record_id,pubmedID,title,authors,abstract,year,label_included,label_abstract_screening
1,10070306,Docetaxel (Taxotere) plus cisplatin: an active and well-tolerated combination in patients with advanced non-small cell lung cancer.,T Le Chevalier; A Monnier; J Y Douillard; P Ruffie; X S Sun; L Belli; N Ibrahim; N Bougon; J Bérille,"The activity of the combination of intravenous docetaxel 75 mg/m2 plus cisplatin 100 mg/m2 administered every 3 weeks for 3 cycles then every 6 weeks was investigated in 51 chemotherapy naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The population was 92% male, with a median age of 54 years and median performance status of 1; 80% of patients had metastatic disease, including 37% with bone involvement. All patients received prophylactic premedication (ondansetron, dexamethasone plus cetirizine) and standard hyperhydration. With a median of 4 treatment cycles (range 1-9), 14 of 42 evaluable patients responded (overall response rate 33.3%, 95% CI 19.6-49.6%); the median response duration was 7.3 months, median survival 8.4 months, and 1-year survival rate 35%. The most common adverse event was neutropenia, occurring in two-thirds of patients. Neurosensory effects were cumulative but generally mild. No treatment-related deaths occurred. This combination of docetaxel/cisplatin showed activity in advanced NSCLC. While it was not clearly superior to single-agent docetaxel, due to differences in prognostic factors among the patients in open trials, a randomised study would be needed to demonstrate definitively whether cisplatin adds to the activity of docetaxel or not.",1999.0,0,0
2,10090440,Link between patient preferences and treatment outcomes in seasonal allergic rhinitis: an empiric investigation.,N Ricard; P Kind; S Christian; M Jensen; J Stewart,"In a multicenter, parallel-group, double-masked, randomized study, two questionnaires were administered to a clinical study population to identify which specific symptoms of seasonal allergic rhinitis patients perceived as most important to relieve (personal preferences) and to learn whether any relationship existed between patient preferences and the severity of their symptoms during treatment with antihistamines. The group was composed of 256 males and 313 females. Their mean age was 32.4 years, and mean duration of seasonal allergic rhinitis was 14.5 years, with mean age of onset of 17.7 years. After receiving placebo for 1 week, patients were randomly allocated to receive an antihistamine (fexofenadine or loratadine) for 2 weeks. Patient preferences for relief of individual allergy symptoms (rhinitis; sneezing; itchy, watery, red eyes; itchy nose, palate, or throat) and related conditions (fatigue, physical limitations) were scored using 2 different questionnaires before treatment (0-to-10 category rating scale for assessing the 4 symptoms of allergic rhinitis) and after receiving placebo for 1 week (Feeling Thermometer). Symptom severity was reported in patient diaries after 1 and 2 weeks of antihistamine treatment and was measured by patient self-assessment. All symptoms were considered by the patients to be important to relieve, the most important being itchy, watery, red eyes and rhinorrhea. The severity of allergy symptoms was consistently related to the importance of symptoms identified before treatment. Therefore, including patient preferences in medical evaluations might be a useful tool in evaluating the success of their treatment.",1999.0,1,1
3,10099066,Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis.,H B Kaiser; C H Banov; R R Berkowitz; D I Bernstein; E A Bronsky; J W Georgitis; L M Mendelson; A R Rooklin; L J Sholler; W W Stricker; J E Harrison; M R Danzig; R R Lorber,"The objective of this study was to compare the efficacy and safety of Claritin-D 24 Hour (once daily) with that of Claritin-D 12 Hour (twice daily) and placebo in the treatment of patients with seasonal allergic rhinitis (SAR). In this double-blind, placebo-controlled, multicenter study, 469 patients with moderate-to-severe SAR symptoms were treated for 2 weeks with one of the following: Claritin-D 24 Hour (a combination tablet formulation of loratadine 10 mg in the coating and pseudoephedrine sulfate 240 mg in an extended-release core), Claritin-D 12 Hour (a combination tablet formulation of loratadine 5 mg in the tablet coating and 120 mg pseudoephedrine sulfate, 60 mg in the coating and 60 mg in the core), or placebo. Claritin-D 24 Hour and Claritin-D 12 Hour were consistently superior to placebo (P < 0.01) in reducing total, nasal, and nonnasal symptom scores. Patients in the Claritin-D 24 Hour and Claritin-D 12 Hour groups also had significantly greater (P </= 0.05) relief of rhinorrhea and nasal stuffiness as compared with placebo. Insomnia was reported significantly more often (P < 0.01) in Claritin-D 12 Hour (15%) patients compared with Claritin-D 24 Hour (4%) and placebo (2%) patients. Dry mouth was reported significantly more often (P < 0.05) in Claritin-D 24 Hour (13%) and Claritin-D 12 Hour (13%) groups compared with placebo (4%). Claritin-D 24 Hour has efficacy comparable to Claritin-D 12 Hour in relieving allergic rhinitis symptoms while producing significantly less insomnia.",2000.0,0,0
4,10099074,Nasal effect of cetirizine and loratadine at 24 hours in patients with allergic rhinitis.,N Frossard; O Benabdesselam; M Melac; N Glasser; J Lacronique; G Pauli,"Numerous studies have compared the duration of the cutaneous effect of cetirizine and loratadine. We assessed their nasal effects 24 hours after administration in patients with allergic rhinitis, using a randomized, double-blind, crossover, placebo-controlled trial. Nasal challenge was performed by nebulization of increasing doubling dosages of histamine (0.04-1.28 mg/nostril) in 12 patients (seven males, five females, aged 31 +/- 7 years). Nasal airway resistance was measured by posterior rhinomanometry 24 hours after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline nasal airway resistance was identical on all study days (2.86 +/- 0.10 cm H2 O/L per second). Twenty-four hours after intake, the dose-response curve of nasal obstruction to histamine was significantly lower after treatment with cetirizine compared with placebo (P < 0.05). However, although the curve was lower on loratadine than on placebo, the curves did not differ significantly. In conclusion, our study shows significant efficacy of cetirizine, but not of loratadine, in the nose at 24 hours after a single dose. This suggests that the nasal action of cetirizine is longer lasting than that of loratadine in patients with allergic rhinitis.",1999.0,0,1
5,10173369,Comparison of intranasal triamcinolone acetonide with oral loratadine in the treatment of seasonal ragweed-induced allergic rhinitis.,S M Gawchik; J Lim,"A double-blind, randomized, multicenter, parallel-group controlled study compared the efficacy and safety of intranasal triamcinolone acetonide (220 micrograms/day) and oral loratadine (10 mg/day) in patients with at least two seasons of ragweed-induced seasonal allergic rhinitis. A 28-day screening period, including a 5-day baseline period, preceded a 4-week treatment period. Reduction in rhinitis symptom scores was evident in both groups as early as day 1, with no significant between-group differences during week 1. At weeks 2, 3, and 4, patients treated with triamcinolone acetonide were significantly (P < 0.05) more improved in total nasal score, nasal itch, nasal stuffiness, and sneezing than were patients treated with loratadine. At weeks 3 and 4, rhinorrhea and ocular symptoms were significantly (P < 0.05) more improved from baseline among triamcinolone acetonide patients compared with loratadine patients. There was no significant between-group difference in relief from postnasal drip at any time point. Physicians' global evaluations significantly (P = 0.002) favored triamcinolone acetonide at the final visit, with moderate to complete relief of symptoms attained by 68% of triamcinolone acetonide patients and 59% of loratadine patients. Over the 4-week treatment period, triamcinolone acetonide patients had significantly greater improvement in total nasal score, nasal itch, nasal stuffiness, sneezing, and ocular symptoms. Both treatments were well tolerated, with headache being the most frequently reported drug-related adverse effect in both the triamcinolone acetonide (15%) and loratadine (11%) groups. These results indicate that triamcinolone acetonide is more effective than oral loratadine in relieving the symptoms of ragweed-induced seasonal allergic rhinitis.",1997.0,0,0
6,10206720,Administration of acetylcholine and vasoactive intestinal polypeptide to atopic eczema patients.,R Rukwied; G Heyer,"Responses to acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) were investigated in atopic eczema (AE) patients. To elucidate the involvement of histamine to ACh-provoked vasoreactions and sensations, we applied a selective H1-antagonist (cetirizine) 3 h prior to the ACh-administration. Solutions of acetylcholine (ACh, 0.55 M) and vasoactive intestinal polypeptide (VIP, 1.5x 10(-5) M) were injected (10 microl) intracutaneously into the volar forearm of 14 healthy subjects and 14 atopic eczema (AE) patients. The substances were applied as single stimulus as well as in combination. Sensations evoked by the stimulation were recorded using 2 visual analog scales (VAS). Vasoreactions were analyzed with the new technique of computer assisted video image analysis. With this method we measured the dynamics of the flare development and the extension of the final flare size independent of the observer's assessment. In control subjects the development and extension of the final flare size was almost similar, regardless whether ACh and VIP were applied in combination or separately. Compared to healthy controls, after injection of ACh, VIP and the combination of VIP and ACh smaller flare sizes were recorded in AE patients. After VIP was given, the control subjects reported pruritus, which was significantly augmented compared to AE patients. In contrast, controls reported a burning pain after the injection of ACh, whereas AE patients felt predominantly pruritus. Itch sensation after the combined application of VIP and ACh was significantly elevated in AE patients. Consequently, we assume that mediators of sudomotor neurons, i.e., VIP and ACh meet in AE patients apparently sensitized nociceptive primary afferents and induce exaggerated itch, pain and flare responses. When pretreated with the selective H1-antagonist cetirizine before ACh was injected, pain and erythema due to ACh was diminished in healthy controls. In contrast, cetirizine did not influence the size of erythema and the magnitude of sensation in AE patients. We conclude, that the release of histamine is not involved in ACh-induced erythema and pruritus in AE. These data provide evidence that pruritus can be elicited in atopic eczema by a cholinergic, histamine independent mechanism.",1999.0,0,0
7,10215756,Risk of ventricular arrhythmias associated with nonsedating antihistamine drugs.,F J de Abajo; L A Rodríguez,"To quantify and compare the incidence of ventricular arrhythniias associated with the use of five nonsedating antihistamines: acrivastine, astemizole, cetirizine, loratadine and terfenadine. The effects of age, sex, dose, duration of treatment, and the interaction with P450 inhibitor drugs were also examined. We carried out a cohort study with a nested case-control analysis using the UK-based General Practice Research database (GPRD). The study cohort included persons aged less than 80 years old who received their first prescription for any of the five study drugs between January 1, 1992 and September 30, 1996. We estimated relative risks and 95% confidence intervals of idiopathic ventricular arrhythmias with current use of antihistamines as compared with non use. The study cohort included 197425 persons who received 513012 prescriptions. Over the study period 18 valid cases of idiopathic ventricular arrhythmias were detected. Nine occurred during the current use of any antihistamine, resulting in a crude incidence of 1.9 per 10000 person-years (95%CI: 1.0-3.6) and a relative risk of 4.2 (95%CI: 1.5-11.8) as compared with non use. Astemizole presented the highest relative risk (RR= 19.0; 95%CI: 4.8-76.0) of all study drugs, while terfenadine (RR=2.1; 95%CI:0.5-8.5) was in the range of other nonsedating antihistamines. Older age was associated with a greater risk of ventricular arrhythmias (RR=7.4; 95%CI: 2.6-21.4) and seemed to increase the effect of antihistamines (RR=6.4; 95%CI: 1.7-24.8). The proportions of high dose terfenadine and the concomitant use with P450 inhibitors among current users of terfenadine were 2.7% and 3.4%, respectively over the study period with no single case of ventricular arrhythmias occurring in the presence of these two risk factors. The use of nonsedating antihistamines increases the risk of ventricular arrhythmias by a factor of four in the general population. Yet, the absolute effect is quite low requiring 57000 prescriptions, or 5300 person-years of use for one case to occur. The risk associated with terfenadine was no different from that with other nonsedating antihistamines.",1999.0,0,1
8,10230583,Treating allergic rhinitis in pregnancy. Safety considerations.,P Mazzotta; R Loebstein; G Koren,"Allergic rhinitis affects approximately one-third of women of childbearing age. As a result, symptoms ranging from sneezing and itching to severe nasal obstruction may require pharmacotherapy. However, product labels state that medications for allergic rhinitis should be avoided during pregnancy due to lack of fetal safety data, even though the majority of the agents have human data which refute these notions. We present a systematic and critical review of the medical literature on the use of pharmacotherapy for the management of allergic rhinitis during pregnancy. Electronic databases and other literature sources were searched to identify observational controlled studies focusing on the rate of fetal malformations in pregnant women exposed to agents used to treat allergic rhinitis and related diseases compared with controls. Immunotherapy and intranasal sodium cromoglycate (cromolyn) and beclo-methasone would be considered as first-line therapy, both because of their lack of association with congenital abnormalities and their superior efficacy to other agents. First-generation (e.g. chlorpheniramine) and second-generation (e.g. cetirizine) antihistamines have not been incriminated as human teratogens. However, first-generation antihistamines are favoured over their second generation counterparts based on their longevity, leading to more conclusive evidence of safety. There are no controlled trials with loratadine and fexofenadine in human pregnancy. Oral, intranasal and ophthalmic decongestants (e.g. pseudoephedrine, phenylephrine and oxymetazoline, respectively) should be considered as second-line therapy, although further studies are needed to clarify their fetal safety. No human reproductive studies have been reported with the ophthalmic antihistamines ketorolac and levocabastine, although preliminary data reported suggest no association between pheniramine and congenital malformations. There are no documented epidemiological studies with intranasal corticosteroids (e.g. budesonide, fluticasone propionate, mometasone) during pregnancy; however, inhaled corticosteroids (e.g. beclomethasone) have not been incriminated as teratogens and are commonly used by pregnant women who have asthma. In summary, women with allergic rhinitis during pregnancy can be treated with a number of pharmacological agents without concern of untoward effects on their unborn child. Although the choice of agents in part should be based on evidence of fetal safety, issue of efficacy needs to be addressed in order to optimally manage this condition.",1999.0,0,1
9,10335761,Cardiovascular safety of fexofenadine HCl.,C M Pratt; J Mason; T Russell; R Reynolds; R Ahlbrandt,"Fexofenadine HCl is the acid metabolite of terfenadine (Seldane). The effect of this recently approved nonsedating antihistamine on the corrected QT interval (QTc) was evaluated in dose-tolerance, safety, and drug-interaction studies with healthy volunteers, and in clinical studies in patients with seasonal allergic rhinitis (SAR). Twelve-lead electrocardiographic data were collected once before and after dosing or serially throughout these studies. Outliers were defined as QTc > 440 ms with a > or = 10 ms increase from baseline. The recommended fexofenadine HCl dose is 60 mg twice daily. Fexofenadine HCl doses up to 800 mg once daily or 690 mg twice daily for 28 days resulted in no dose-related increases in QTc. Longer term studies indicated no statistically significant QTc increases compared with placebo in patients receiving fexofenadine HCl 80 mg twice daily for 3 months, 60 mg twice daily for 6 months, or 240 mg once daily for 12 months. Interaction studies showed no significant increases in QTc when fexofenadine HCl 120 mg twice daily was administered in combination with erythromycin (500 mg 3 times daily) or ketoconazole (400 mg once daily) after dosing to steady state (6.5 days). Clinical trials in patients with SAR (n = 1,160) treated with 40, 60, 120, or 240 mg twice-daily fexofenadine HCl or placebo indicated no dose-related increases in QTc and no statistically significant increases in mean QTc compared with placebo. In controlled trials with approximately 6,000 persons, no case of fexofenadine-associated torsades de pointes was observed. The frequency and magnitude of QTc outliers were similar between fexofenadine HCl and placebo in all studies. Based on a large clinical database, we conclude that fexofenadine HCl has no significant effect on QTc, even at doses > 10-fold higher than that is efficacious for SAR.",2000.0,0,0
10,10335901,Variations among non-sedating antihistamines: are there real differences?,M J Mattila; I Paakkari,"Most of the modern non-sedating H1 receptor antagonists (antihistamines) penetrate the brain poorly, allowing the use of doses large enough to counteract allergic processes in peripheral tissues without important central effects. The antihistamines reviewed here are acrivastine, astemizole, cetirizine, ebastine, fexofenadine, loratadine, mizolastine, and terfenadine. However, these drugs are not entirely free from central effects, and there are at least quantitative differences between them. Although psychomotor and sleep studies in healthy subjects in the laboratory may predict that an antihistamine does not cause drowsiness, the safety margin can be narrow enough to cause a central sedating effect during actual treatment. This might result from a patient's individual sensitivity, disease-induced sedation, or drug dosages that are for various reasons relatively or absolutely larger (patient's weight, poor response, reduced drug clearance, interactions). Mild to even moderate sedation is not necessarily a major nuisance, particularly if stimulants need be added to the regimen (e.g. in perennial rhinitis). Furthermore, patients can adjust doses themselves if needed. Sedating antihistamines are not needed for long-term itching, because glucocorticoids are indicated and more effective. It is wise to restrict or avoid using antihistamines (astemizole, terfenadine) that can cause cardiac dysrhythmias, because even severe cardiotoxicity can occur in certain pharmacokinetic drug-drug interactions. Histamine H1 receptor antagonists (antihistamines) are used in the treatment of allergic disorders. The therapeutic effects of most of the older antihistamines were associated with sedating effects on the central nervous system (CNS) and antimuscarinic effects causing dry mouth and blurred vision. Non-specific ""quinidine-like"" or local anaesthetic actions often led to cardiotoxicity in animals and man. Although such adverse effects varied from drug to drug, there was some degree of sedation with all old antihistamines. Non-sedating antihistamines have become available during the past 15 years. Some of them also have antiserotonin or other actions that oppose allergic inflammation, and they are not entirely free from sedative effects either. In small to moderate ""clinical"" concentrations they are competitive H1 receptor antagonists, although large concentrations of some of them exert non-competitive blockade. Daytime drowsiness and weakness are seldom really important, and they restrict patients' activities less than the old antihistamines. Some new antihistamines share with old antihistamines quinidine-like effects on the cardiac conducting tissues, and clinically significant interactions have raised the question of drug safety. This prodysrhythmic effect has also been briefly mentioned in comparisons of non-sedative H1 antihistamines.",1999.0,0,1
11,10348091,Comparative tolerability of second generation antihistamines.,F Horak; U P Stübner,"Second generation histamine H1 receptor antagonists, the so-called 'nonsedating' antihistamines, have high potency and additional antiallergic properties as well as H1 antagonism and are associated with fewer adverse effects compared with the first generation antihistamines. A number of drugs in this class are approved for use: acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine, mizolastine and terfenadine. All of them have a more favourable risk-benefit ratio with regard to the CNS adverse effects. Even those second generation antihistamines that are not actually 'nonsedating' are less impairing than their predecessors, but not one of them is entirely devoid of CNS activity. Under certain circumstances some antihistamines may affect cardiac repolarisation resulting in cardiovascular adverse effects. Serious cardiovascular effects have been reported with terfenadine and astemizole when they are used in high dosages or when they are given to 'at risk' patients. Animal models indicate that there might be a potential risk of cardiovascular adverse effects with other antihistamines as well. However, up to now there is no clinical evidence for this assumption, despite some confusing reports. Likewise there has been much discussion about a link between these agents and carcinogenicity. However, there is no evidence that any of the second generation antihistamines increase the risk of tumour growth in humans. Small children, elderly patients and persons with chronic renal or liver impairment are special groups in which the individual adverse effects of the second generation antihistamines must be kept in mind. The dosage for an individual has to be modified with respect to their metabolic situation. Despite the fact that some of the second generation antihistamines are listed in the US Food and Drug Administration pregnancy risk classification as class B, the use of second generation antihistamines should be avoided during pregnancy and they should never be administered to nursing mothers. Taking into account their negligible CNS activity, the low incidence of cardiovascular adverse effects, their lack of anticholinergic effects and other benefits, this class of antiallergic drugs represents a definite advance in therapy.",1999.0,0,1
12,10349070,New treatments for allergic rhinitis.,S J Tkachyk,"To review new treatments for allergic rhinitis. Most studies supporting the principles in this paper are double-blind, placebo-controlled trials. Good evidence supports use of antihistamines, nasal steroid sprays, and immunotherapy. Fewer trials have been done on the new antileukotrienes. Allergic rhinitis causes significant morbidity, which can be successfully treated. Newer antihistamines, developed to replace terfenadine and astemizole which have potential side effects, include loratadine, cetirizine, and the newest, fexofenadine. Intranasal steroid sprays are also effective, particularly for people with nasal stuffiness. One study showed some growth retardation in children using beclomethasone over a prolonged period (1 year). The newer steroid sprays, such as fluticasone, budesonide, and mometasone furoate aqueous, however, have not been studied in the same way and are usually recommended for shorter periods. The newest group of medications showing real promise are the antileukotrienes, including zafirlukast and montelukast. Taken orally, these medications avoid the discomfort of nasal sprays and seem to have few side effects. Immunotherapy offers a new option: a short-course, preseasonal series of six to 11 injections that reduces the burden on patients for year-round therapy. Combinations of these therapies are also possible. With new medications and immunotherapy options, family physicians can offer effective treatment to patients with allergic rhinitis.",1999.0,0,0
13,10417497,"A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function.",I Hindmarch; Z Shamsi; N Stanley; D B Fairweather,"To assess whether fexofenadine in a range of doses from 80 to 180 mg has any disruptive effects on aspects of psychomotor and cognitive function in comparison with placebo, loratadine and promethazine, an antihistamine known to produce psychomotor and cognitive impairment. Twenty-four healthy volunteers received fexofenadine 80 mg, 120 mg and 180 mg, loratadine 10 mg, promethazine 30 mg (as a positive internal control) and placebo in a six-way crossover, double-blind study. Following each dose, subjects were required to perform a series of tests of cognitive function and psychomotor performance at 1.5, 3, 6, 9, 12 and 24 h post dose. The test battery included critical flicker fusion (CFF), choice reaction time (CRT) and assessment of subjective sedation (LARS). Overall levels of activity were monitored by means of wrist mounted actigraphs throughout each of the 24 h experimental periods. Fexofenadine at all doses tested was not statistically different from placebo in any of the tests used and loratadine did not cause any significant impairment of cognitive function. Significant impairments were found following promethazine. Promethazine caused a significant reduction in CFF threshold and this effect was evident up to 12 h post dose (P<0.05). There was a significant increase in recognition reaction time at 3 and 6 h post promethazine administration, and the drug caused a significant (P<0. 002) increase in the percentage of 'sleep-like' activity from actigraph records during the daytime. Fexofenadine at doses up to 180 mg appears free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the verum control promethazine 30 mg.",1999.0,0,0
14,10417499,Histamine response and local cooling in the human skin: involvement of H1- and H2-receptors.,M Grossmann; M J Jamieson; W Kirch,"Histamine may contribute locally to cutaneous blood flow control under normal and pathologic conditions. The objective of this study was to observe the influence of skin temperature on histamine vasodilation, and the roles of H1-and H2-receptors using novel noninvasive methods. Eleven healthy subjects received, double-blind, single doses of the H1-receptor antagonist cetirizine (10 mg), cetirizine (10 mg) plus the H2-receptor antagonist cimetidine (400 mg), or placebo on separate occasions. Histamine was dosed cumulatively by iontophoresis to the forearm skin at 34 degrees C and 14 degrees C. Laser-Doppler flux (LDF) was measured at the same sites using customised probeholder/iontophoretic chambers with Peltier cooling elements. Finger mean arterial pressure (MAP) was measured and cutaneous vascular conductance calculated as LDF/MAP. Histamine vasodilation was reduced in cold skin. Cetirizine shifted the histamine dose-response at both temperatures: statistically significantly at 14 degrees C only. Combined H1- and H2-receptor antagonism shifted the response significantly at both temperatures. H1- and H2-receptors mediate histamine-induced skin vasodilation. The sensitivity of these receptors, particularly the H1- receptor, is attenuated at low skin temperature. Whether the reduced effect in cold skin represents specific receptor or postreceptor desensitization, or nonspecific attenuation of cutaneous vasodilation remains to be elucidated.",1999.0,0,0
15,10423657,Double-blind comparison of cetirizine and loratadine in children ages 2 to 6 years with perennial allergic rhinitis.,J J Sienra-Monge; A Gazca-Aguilar; B Del Rio-Navarro,"Antihistamines are the pharmacologic cornerstone of treatment for allergic rhinitis. The comparative effects of the newer, more specific H (1) -antagonists cetirizine and loratadine among younger patients are not well characterized. The efficacy and safety of cetirizine and loratadine were compared in a prospective, randomized, double-blind, longitudinal, parallel-group study of 80 children, 2 to 6 years of age, with perennial allergic rhinitis caused by house dust mites or plant pollens (verified by a radioallergosorbent or skin test). Patients received cetirizine or loratadine at 0.2 mg/kg once daily in the morning for 28 days. Histamine skin tests and eosinophil counts from nasal smears were performed at baseline and at the end of treatment. Individual rhinitis symptoms were assessed by the investigator at baseline and on day 28 and by parents at baseline and daily in symptom diaries. Global assessments were made by using a visual analog scale at baseline and at the end of treatment. Cetirizine produced significantly greater inhibition of the wheal response compared with loratadine (P <.0001). Eosinophil counts were improved to a comparable degree with both agents. Cetirizine and loratadine produced comparable improvements in symptoms and according to a global evaluation as assessed by the investigator at the end of treatment. Both agents produced substantial symptomatic relief according to patients' daily diary assessments; however, cetirizine was more effective than loratadine in relieving the symptoms of rhinorrhea, sneezing, nasal obstruction, and nasal pruritus (P <. 0001). Both treatments were well tolerated; two patients receiving cetirizine were dropped from the study because of adverse events. Cetirizine and loratadine provided effective, well-tolerated relief of the symptoms of perennial allergic rhinitis in small children. Cetirizine was more effective than loratadine in inhibiting the wheal response to histamine challenge and afforded greater reductions in most individual symptoms assessed daily by the parent.",1999.0,1,1
16,10442525,"A double-blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine-induced wheal and flare response for 24 h in healthy male subjects.",J A Grant; L Danielson; J P Rihoux; C DeVos,"New H1-antagonists have become available, but there has been no comparison of their potency for inhibiting histamine in the skin. Cetirizine 10 mg, ebastine 10 mg, epinastine 20 mg, fexofenadine 60 mg, terfenadine 60 mg, loratadine 10 mg, or placebo was given to 14 healthy male volunteers in a double-blind, crossover randomized manner. Inhibition of the wheal and flare response to epicutaneous histamine phosphate (100 mg/ml) challenge was measured at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 h after doses. Epinastine inhibited the wheal and flare after 30 min. Cetirizine commenced acting at 1 h and was superior to other treatments. Ebastine was no better than placebo until 4 h, but was efficacious thereafter until 24 h. Terfenadine induced potent inhibition after 1 h and was superior to its metabolite fexofenadine. Loratadine was the least potent inhibitor. Inhibition of the flare response paralleled the patterns seen for wheals. The rank order for area under the curve (0-24 h) was cetirizine, epinastine, terfenadine, ebastine, fexofenadine, loratadine, and placebo. The inhibition of histamine effects in the skin may be useful in predicting the clinical utility of newly introduced antihistamines in treating allergic disorders.",1999.0,0,0
17,10484575,Comparison of the response to histamine challenge of the nose and the maxillary sinus: effect of loratadine.,F M Baroody; A Gungor; M deTineo; L Haney; C Blair; R M Naclerio,"To study the response of the maxillary sinus to histamine provocation, we performed a double-blind, randomized, crossover trial during which nonallergic subjects without symptoms of rhinitis (n = 25) received either 10 mg loratadine or placebo once daily for a week and then underwent nasal challenge with histamine (3, 10, and 30 mg/ml) followed, 24 h later, by a maxillary sinus challenge while still receiving the medication. Nasal challenge with histamine led to significant increases in vascular permeability, reflex nasal secretions, sneezing, and other nasal symptoms. Sinus challenge resulted in significant increases in vascular permeability within the sinus cavity (P < 0.01) and some nasal symptoms but no significant change in reflex nasal secretions. The response of the sinus mucosa to histamine was lower in magnitude than that of the nose. Treatment with loratadine resulted in a significant inhibition of the histamine-induced changes in both nasal and sinus cavities. Our data suggest the lack of a sinonasal reflex response to histamine provocation of the maxillary sinus of nonallergic individuals.",1999.0,0,1
18,10496299,Clinical pharmacokinetics of troglitazone.,C M Loi; M Young; E Randinitis; A Vassos; J R Koup,"Troglitazone is a new thiazolidinedione oral antidiabetic agent approved for use to improve glycaemic control in patients with type 2 diabetes. It is rapidly absorbed with an absolute bioavailability of between 40 and 50%. Food increases the absorption by 30 to 80%. The pharmacokinetics of troglitazone are linear over the clinical dosage range of 200 to 600 mg once daily. The mean elimination half-life ranges from 7.6 to 24 hours, which facilitates a once daily administration regimen. The pharmacokinetics of troglitazone are similar between patients with type 2 diabetes and healthy individuals. In humans, troglitazone undergoes metabolism by sulfation, glucuronidation and oxidation to form a sulfate conjugate (M1), glucuronide conjugate (M2) and quinone metabolite (M3), respectively. M1 and M3 are the major metabolites in plasma, and M2 is a minor metabolite. Age, gender, type 2 diabetes, renal impairment, smoking and race do not appear to influence the pharmacokinetics of troglitazone and its 2 major metabolites. In patients with hepatic impairment the plasma concentrations of troglitazone, M1 and M3 increase by 30%, 4-fold, and 2-fold, respectively. Cholestyramine decreases the absorption of troglitazone by 70%. Troglitazone may enhance the activities of cytochrome P450 (CYP) 3A and/or transporter(s) thereby reducing the plasma concentrations of terfenadine, cyclosporin, atorvastatin and fexofenadine. It also reduces the plasma concentrations of the oral contraceptive hormones ethinylestradiol, norethindrone and levonorgestrel. Troglitazone does not alter the pharmacokinetics of digoxin, glibenclamide (glyburide) or paracetamol (acetaminophen). There is no pharmacodynamic interaction between troglitazone and warfarin or alcohol (ethanol). Pharmacodynamic modelling showed that improvement in fasting glucose and triglyceride levels increased with dose from 200 to 600 mg. Knowledge of systemic troglitazone exposure within a dose group does not improve the prediction of glucose lowering response or adverse effects beyond those based on the administered dose.",1999.0,0,0
19,10541777,Consistency and efficacy of cetirizine (10 mg) versus ebastine (20 mg) at 4 h on skin reactivity.,A Purohit; C Duvernelle; M Melac; O Benabdesselam; G Pauli; N Frossard,"We compared the consistency and efficacy of the two antihistamines, cetirizine (10 mg) and ebastine (20 mg) on histamine skin reactivity 4 h after treatment. Twenty-four healthy volunteers participated in a randomised double-blind cross-over study. The areas of wheals and flares induced by increasing (0, 5, 10, 50, 100, 200, 300 mg/ml) histamine concentrations, administered by prick tests, were measured before and 4 h after intake of cetirizine or ebastine. Before treatment, concentration-response curves were similar and threshold concentrations identical (0.57 mg/ml and 0.57 mg/ml for cetirizine and ebastine, respectively). Both treatments exerted a significant effect. However, cetirizine was significantly more efficient than ebastine 20 mg (P < 0.01 both for wheals and flares). After cetirizine, the threshold concentration inducing a 3-mm(2 )wheal was significantly higher (266 mg/ml) than after ebastine (77 mg/ml) (P < 0.01), and total inhibition of the wheal was obtained in 18 of 24 patients for cetirizine and in 4 of 24 for ebastine (P < 0.001). The variation coefficient for the wheal reaction was 31% for cetirizine and 159% for ebastine, indicating a much lower variability after cetirizine. Our study shows clearly that the efficacy of a single therapeutic dosage of cetirizine is greater and consistently better than that of ebastine for suppression of cutaneous reactivity to histamine 4 h after treatment in healthy volunteers. The need for ebastine to metabolise into the active carebastine might explain this difference.",1999.0,0,0
20,10557567,,,,,0,0
21,10566703,"A prospective evaluation of esophageal testing and a double-blind, randomized study of omeprazole in a diagnostic and therapeutic algorithm for chronic cough.",T M Ours; M S Kavuru; R J Schilz; J E Richter,"Recent studies suggest an association between chronic cough and gastroesophageal reflux. Our study aims were 1) to define the prevalence of acid reflux induced cough in the general community, 2) to examine the ability of esophageal testing to identify gastroesophageal reflux related cough, and 3) to assess the utility of omeprazole in a chronic cough algorithm. Patients with chronic cough of unknown etiology, who were mostly from the community, were evaluated. Subjects underwent a chest x-ray, methacholine challenge test, and empiric trial of postnasal drip therapy, and completed daily cough symptom diaries subjectively evaluating cough frequency and severity on a graded scale of 0-4 (combined maximum 8). After excluding other causes of cough, the remaining patients underwent esophageal and pH testing. Those testing positive were randomized to omeprazole 40 mg b.i.d. or placebo for 12 weeks. Follow-up was 1 yr. A total of 71 patients were screened; 48 were excluded. Twenty-three patients were evaluated for gastroesophageal reflux disease; six (26%) were eventually determined to have an acid-related cough. Of these patients, 17 had a positive pH test, six (35%) of whom showed a striking improvement or resolution of their cough during omeprazole treatment which was sustained for up to 1 yr. Six had a negative pH test, none of whom responded to omeprazole therapy. No significant differences were seen between responders (n = 6) and nonresponders (n = 11) for demographic factors, baseline symptom frequency and duration, or physiological parameters (motility/pH). Acid-related chronic cough was present in 26% (six of 23) of patients evaluated for gastroesophageal reflux disease. Esophageal testing does not reliably identify patients with acid induced chronic cough responsive to proton pump inhibitor therapy. We suggest that the best diagnostic and therapeutic approach, after excluding asthma and postnasal drip syndrome, is empiric treatment for 2 wk with a high dose proton pump inhibitor.",1999.0,0,0
22,10606058,An evidence-based review of the efficacy of antihistamines in relieving pruritus in atopic dermatitis.,P A Klein; R A Clark,"To critically review the body of clinical trials that refute or support the efficacy of antihistamines in relieving pruritus in patients with atopic dermatitis. Review of MEDLINE from 1966 through March 1999, the Cochrane Database of Systematic Reviews, and Best Evidence to identify therapeutic trials of antihistamines in patients with atopic dermatitis. All randomized controlled trials or clinical trials of antihistamines used in the treatment of atopic dermatitis. We found 16 studies throughout the literature. Large, randomized, double-blind, placebo-controlled clinical trials with definitive conclusions (grade A trials) have not been performed. Two grade B trials (small, rigorous, randomized trials with uncertain results due to moderate to high alpha or beta error) refuted the use of antihistamines in relieving pruritus. One grade B trial supported the efficacy of antihistamines in relieving pruritus. All remaining trials (grade C) lacked placebo controls or randomization, or contained fewer than 20 patients in each treatment group. Although antihistamines are often used in the treatment of atopic dermatitis, little objective evidence exists to demonstrate relief of pruritus. The majority of trials are flawed in terms of the sample size or study design. Based on the literature alone, the efficacy of antihistamines remains to be adequately investigated. Anecdotally, sedating antihistamines have sometimes been useful by virtue of their soporific effect and bedtime use may be warranted. There is no evidence to support the effectiveness of expensive nonsedating agents.",1999.0,0,1
23,10664928,"Inhibition of histamine or allergen-induced wheals by a single dose of acrivastine, fexofenadine or cetirizine.",B K Ballmer-Weber; C Gex-Collet; B Wüthrich,"Certirizine, a potent H1-blocking agent, is often recommended as an emergency drug in anaphylactic reactions because of its well documented fast onset of action. In this randomized, cross-over study we compared the onset of action after a single dose of two recently introduced antihistamines, acrivastine and fexofenadine, with that of cetirizine. The inhibition of the wheal-and-flare reaction produced by skin prick test with histamine in 20 healthy volunteers and with a relevant pollen allergen in 20 atopic patients, respectively, were measured before and at regular intervals up to 60 min after the ingestion of acrivastine (8 mg and 16 mg), fexofenadine (120 mg) and cetirizine (10 mg and 20 mg). Wheal-and-flare reaction were significantly inhibited 20 min after the intake of 16 mg acrivastine in atopic patients and 30 min after intake of 8 mg acrivastine in healthy volunteers, whereas cetirizine produced a significant inhibition of the wheal-and-flare reaction within 40-60 min. No significant inhibition could be observed within 60 min after fexofenadine intake. Therefore, in clinical settings when a fast onset of the H1-blocking action is mandatory (e.g., after insect stings or for short-term prophylaxis) we recommend acrivastine.",2000.0,1,1
24,10691585,"Effects of fexofenadine, diphenhydramine, and alcohol on driving performance. A randomized, placebo-controlled trial in the Iowa driving simulator.",J M Weiler; J R Bloomfield; G G Woodworth; A R Grant; T A Layton; T L Brown; D R McKenzie; T W Baker; G S Watson,"Sedating antihistamines may impair driving performance as seriously as alcohol. To compare the effects of fexofenadine, diphenhydramine, alcohol, and placebo on driving performance. Randomized, double-blind, double-dummy, four-treatment, four-period crossover trial. The Iowa Driving Simulator. 40 licensed drivers with seasonal allergic rhinitis who were 25 to 44 years of age. One dose of fexofenadine (60 mg), diphenhydramine (50 mg), alcohol (approximately 0.1% blood alcohol concentration), or placebo, given at weekly intervals before participants drove for 1 hour in the Iowa Driving Simulator. The primary end point was coherence, a continuous measure of participants' ability to match the varying speed of a vehicle that they were following. Secondary end points were drowsiness and other driving measures, including lane keeping and response to a vehicle that unexpectedly blocked the lane ahead. Participants had significantly better coherence after taking alcohol or fexofenadine than after taking diphenhydramine. Lane keeping (steering instability and crossing the center line) was impaired after alcohol and diphenhydramine use compared with fexofenadine use. Mean response time to the blocking vehicle was slowest after alcohol use (2.21 seconds) compared with fexofenadine use (1.95 seconds). Self-reported drowsiness did not predict lack of coherence and was weakly associated with minimum following distance, steering instability, and leftlane excursion. Participants had similar performance when treated with fexofenadine or placebo. After alcohol use, participants performed the primary task well but not the secondary tasks; as a result, overall driving performance was poorer. After participants took diphenhydramine, driving performance was poorest, indicating that diphenhydramine had a greater impact on driving than alcohol did. Drowsiness ratings were not a good predictor of impairment, suggesting that drivers cannot use drowsiness to indicate when they should not drive.",2000.0,0,1
25,10691592,Nonsedating antihistamines should be preferred over sedating antihistamines in patients who drive.,S Hennessy; B L Strom,,2000.0,0,0
26,10725819,Comparative therapeutic effect and safety of mizolastine and loratadine in chronic idiopathic urticaria. URTILOR study group.,F Leynadier; C Duarte-Risselin; M Murrieta,"Mizolastine, a new second-generation H1 receptor antagonist with additional anti-allergic properties, was compared with loratadine in 61 patients suffering from severe chronic idiopathic urticaria (CIU). In this double-blind study, patients were randomly allocated to receive either mizolastine 10 mg (n = 26) or loratadine 10 mg (n = 35) once-daily for 28 days. Both compounds were well tolerated, safe and efficacious. The reduction in the number of episodes per week (5. 6+/-16.3 and 6.4+/-12.4 for mizolastine and loratadine, respectively) and the reduction in the symptom severity score, measured using a Visual Analogue Scale (VAS), were comparable (30.2 +/- 39.0 mm and 30.5 +/- 28.5 mm for mizolastine and loratadine, respectively). Mizolastine had a positive effect on angioedema (85% CI 95% [0.69-1.00]) of patients improved compared with 75% (CI 95% [0.59-0.91]) of the loratadine group and the differential reduction of the mean total duration of episodes in the mizolastine group was higher when compared with the loratadine group (from 13.7 +/- 33.5 hours on day 0 to 5.1 +/- 9.0 hours over the treatment period and from 8.2 +/- 8.8 hours on day 0 to 5.1 +/- 7.8 hours over the treatment period for mizolastine and loratadine, respectively). Prick test analysis demonstrated that both drugs caused a significant decrease of histamine-induced wheal and flare with no development of tolerance, with a significant superiority of mizolastine over loratadine for some histamine concentrations. Mizolastine and loratadine both proved very efficacious and safe. In addition mizolastine demonstrated a superiority in prick tests, beneficial effects on angioedema and seemed to provide a faster onset of action.",2000.0,0,0
27,10778521,Modification of antihistaminic activity of cetirizine by nimesulide.,S Rewari; U Gupta,"To study the effect of nimesulide (4-nitro-2-phenoxymethane sulfonanilide) a non-steroidal anti-inflammatory drug, on antihistaminic activity of cetirizine. A randomized, double blind, cross over study was conducted in ten healthy male volunteers. Wheal and flare responses to histamine were measured by performing intradermal injection of histamine (2 micrograms base) diluted in 100 microliters volume of saline on the volar surface of forearm, on four occasions (0, 2, 4, and 6 hrs. post-dosing). Each volunteer was randomized to receive either treatment A (cetirizine 10 mg + placebo) or treatment B (cetirizine 100 mg + nimesulide 100 mg), with one week wash out period in between each administration. Wheal and flare responses were measured ten minutes after each histamine injection. Both cetirizine 10 mg alone and cetirizine 10 mg + nimesulide 100 mg, decreased wheal and flare responses significantly at 2 hrs. and this continued till 6 hrs. post-dosing. This decrease was highly significant when cetirizine was given along with nimesulide. The results suggest a synergistic effect exhibited by the combined use of cetirizine with nimesulide.",2000.0,0,0
28,10780795,Double-blind study of cetirizine and loratadine versus placebo in patients with allergic rhinitis.,C Nunes; S Ladeira,"The aim of this double-blind study was to evaluate the effectiveness of cetirizine and loratadine versus placebo in patients with allergic rhinitis. The study included a total of 90 patients suffering from moderate to severe allergic rhinitis as determined by a symptom score, with hypersensitivity to house mites and with high IgE. The study lasted 7 weeks, including 1 for pretreatment, 4 for treatment and 2 posttreatment (washout). During the study, each patient received either one tablet of placebo, 10 mg of cetirizine or 10 mg of loratadine daily. The evaluation was carried out by rhinomanometry to analyze the symptoms on days 1, 15, 29 and 43. The nasal cytology was analyzed on days 1 and 29. For statistical analysis we used the Mantel-Haenszel method and chi-square test. We found that antihistamines showed good effectiveness in improving the symptomatology in patients with allergic rhinitis. The improvement by rhinomanometry and by symptom score versus placebo was good. It was concluded that both antihistamines were significantly superior to placebo and that cetirizine performed better in comparison to loratadine versus placebo, although not as statistically significant.",2000.0,0,1
29,10782522,"House-dust-mite sublingual-swallow immunotherapy (SLIT) in perennial rhinitis: a double-blind, placebo-controlled study.",S Guez; C Vatrinet; R Fadel; C André,"The safety and efficacy of sublingual-swallow immunotherapy (SLIT) in rhinitis caused by house-dust mite were evaluated in a double-blind, placebo-controlled study including 75 patients for 24 months. Patients received either placebo or SLIT with a standardized Dermatophagoides pteronyssinus (D.pt.) - D. farinae (D.f) 50/50 extract. The mean cumulative dose was 90,000 IR, equivalent to 2.2 mg of Der p 1 and 1.7 mg of Der f I. Symptom and medication scores were assessed throughout the study. Exposure to house-dust mite, skin sensitivity, and serum specific IgE and IgG4 were assessed before starting treatment and after 12 and 24 months. Seventy-two patients (36 active-36 placebo) were eligible for intent-to-treat analysis. Thirty-six patients dropped out of the study. The number of patients who dropped out due to lack of efficacy was eight out of 37 (21.6%) in the active treatment group compared to 15 out of 38 (39.5%) in the placebo group (chi-square=2.81, P=0.09). Total symptom and medication scores decreased significantly after 12 and 24 months (P<0.05) of treatment in both groups, but no significant difference was observed between the active and placebo groups. After 24 months, the number of patients with high levels of indoor allergenic load decreased significantly in both groups compared to baseline data (P=0.01). Specific IgE (D.pt. and D.f.) increased significantly in the active treatment group after 12 and 24 months, while no change was observed in the placebo group. Specific IgG4 levels were not significantly modified in either group. Two patients in each group reported mild adverse effects. No severe adverse effects were reported. We conclude that SLIT in rhinitis caused by house-dust mite was safe, but there was a lack of consistent clinical benefit compared to placebo, probably due to the impact of the allergen avoidance measures that lowered the allergen burden.",2000.0,0,0
30,10782524,Cetirizine inhibits bradykinin-induced cutaneous wheal and flare in atopic and healthy subjects.,R Fadel; I Ramboer; N Chatterjee; J P Rihoux; M P Derde,"Kinins are vasoactive mediators involved in allergic reactions. When applied on the skin or in the nose, bradykinin (BK) elicits inflammation that is poorly affected by previous H1-blockade. The aim of this study was to compare the possible effect of cetirizine (an H1-antagonist) on wheal and flare responses to BK, histamine, and compound 48/80 in atopic and healthy subjects. In a randomized, double-blind, crossover study, eight atopic and eight healthy subjects received cetirizine (10 mg/day) or placebo for 3 days before cutaneous tests. Intradermal tests (IDT) and prick tests (PT) were performed with BK (20 nmol/ml for IDT and 20 micromol/ml for PT), histamine (100 microg/ml IDT and 100 mg/ml PT), and compound 48/80 (100 microg/ml IDT and 100 mg/ml PT) as positive controls and saline as negative control. The skin responses were monitored by measurement of wheal and flare areas. BK, histamine, and 48/80 induced wheal and flare reactions in all placebo-treated subjects. Histamine elicited larger wheal and flare reactions than BK and 48/80. IDT with BK induced four- to sixfold larger wheal and flare reaction than PT. No differences in BK-induced wheal and flare were observed between atopic and healthy subjects. In atopic subjects, cetirizine induced a significant reduction of flare reactions after the BK test (80% for IDT, and 94% for PT [P < 0.01]). Moreover, cetirizine reduced significantly BK-induced wheals by 70% for IDT (P < 0.01) and 65% for PT (P < 0.01). A similar inhibiting effect of cetirizine was also observed in healthy subjects. These findings showed that the wheal and flare reactions induced by BK challenge were markedly inhibited by previous intake of cetirizine. The mechanism by which this effect is mediated cannot be established at present.",2000.0,0,0
31,10784544,"Sedation with ""non-sedating"" antihistamines: four prescription-event monitoring studies in general practice.",R D Mann; G L Pearce; N Dunn; S Shakir,"To investigate the frequency with which sedation was reported in post-marketing surveillance studies of four second generation antihistamines: loratadine, cetirizine, fexofenadine, and acrivastine. Prescription-event monitoring studies. Prescriptions were obtained for each cohort in the immediate post-marketing period. Event data were obtained for a total of 43 363 patients. Reporting of sedation or drowsiness. The odds ratios (adjusted for age and sex) for the incidence of sedation were 0.63 (95% confidence interval 0.36 to 1.11; P=0.1) for fexofenadine; 2.79 (1.69 to 4.58; P<0.0001) for acrivastine, and 3.53 (2.07 to 5.42; P<0.0001) for cetirizine compared with loratadine. No increased risk of accident or injury was evident with any of the four drugs. Although the risk of sedation was low with all four drugs, fexofenadine and loratadine may be more appropriate for people working in safety critical jobs.",2000.0,0,1
32,10786387,"Loratadine/pseudoephedrine for nasal symptoms in seasonal allergic rhinitis: a double-blind, placebo-controlled study.",E A McFadden; A Gungor; B Ng; B Mamikoglu; R Moinuddin; J Corey,"In this double-blind, placebo-controlled, crossover, parallel study, we treated 20 adults who had seasonal allergic rhinitis with once-daily fixed-combination loratadine/pseudoephedrine sulfate to observe its effect on relieving symptoms, primarily nasal congestion. Acoustic rhinometry detected a trend toward improvement in nasal patency, although the difference between pre- and post-treatment measures was not statistically significant. Endoscopic inferior turbinate photography documented that treatment led to statistically significant reductions in the amount of nasal edema and nasal secretions. The results of a quality-of-life questionnaire suggested that treatment alleviated nasal and ocular symptoms of rhinoconjunctivitis. An analysis of subjective visual analog scale scores showed a trend toward improvement in most but not all nasal symptoms. We conclude that once-a-day fixed-combination loratadine/pseudoephedrine is effective in relieving nasal congestion in patients with seasonal allergic rhinitis.",2000.0,0,0
33,10804041,Montelukast: a review of its therapeutic potential in persistent asthma.,B Jarvis; A Markham,"Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged > or = 6 years. The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed beta2-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged > or = 15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials. In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged > or = 15 years with persistent asthma [forced expiratory volume in 1 second (FEV1) = 50 to 85% predicted] there was significantly (p < 0.05) greater improvement in FEV1, symptom scores, peak expiratory flow (PEF), as-needed beta2-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in patients treated with montelukast 10 mg/day than in recipients of placebo. Improvements were significantly greater in patients treated with inhaled beclomethasone 400 microg/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced > or = 11% improvement in FEV1, the median improvement in this parameter in beclomethasone-treated patients. In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV1 50 to 85% predicted), montelukast 5 mg/day produced significantly greater improvements in FEV1, clinic PEF, as-needed beta2-agonist use, peripheral eosinophil counts, asthma exacerbations and QOL scores than placebo. The combination of montelukast 10 mg/day plus inhaled beclomethasone 200 microg twice daily provided significantly better asthma control than inhaled beclomethasone 200 microg twice daily in adults with poorly controlled asthma (mean FEV1 = 72% predicted) despite 4 weeks treatment with inhaled beclomethasone. Patients receiving the combination experienced significant improvements in FEV1 and morning PEF, significant reductions in daytime symptom scores, as-needed beta2 agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks in this multicentre, randomised, double-blind, placebo-controlled study. Among adults (FEV1 > or = 70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downward by 47% (vs 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a multicentre, randomised, double-blind study. During clinical studies, the frequency of adverse events in montelukast-treated adults, adolescents and children was similar to that in placebo recipients. In conclusion, montelukast is well tolerated and effective in adults and children aged > or = 6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma.",2000.0,0,0
34,10805062,Pharmacokinetics and pharmacodynamics of the novel H1-receptor antagonist emedastine in healthy volunteers.,B Jansen; U Graselli; S Dallinger; B Kiss; V Wacheck; H Schlagbauer-Wadl; A Assandri; M Müller,"Emedastine is a novel H1-receptor antagonist with pre-clinically well-documented anti-allergic effects. Here, we set out to study the relationship between emedastine pharmacokinetics and the suppressive effect on histamine-induced wheals and flares, and to compare these effects to placebo and cetirizine. Emedastine (4 mg q.d.), emedastine (2 mg b.i.d.), cetirizine (10 mg q.d.) and placebo were administered to healthy volunteers in a double-blind, cross-over fashion. On day 1 and day 5 (steady state) following drug administration, wheals and flares were induced by skin-prick testing with 1 mg ml(-1) or 10 mg ml(-1) histamine. Following the administration of 4 mg emedastine q.d., mean area under the concentration-time curve (AUC)0-24 values of 34.49 +/- 24.07 ng h ml(-1) and 47.05 +/- 36.12 ng h ml(-1) were attained on day 1 and day 5, respectively. Following the administration of emedastine (2 mg b.i.d.) mean AUC0-24 values were 29.75 +/- 19.92 ng h ml(-1) and 46.13 +/- 38.50 ng h ml(-1) on day 1 and day 5, respectively. Histamine-induced wheals and flares were significantly more effectively suppressed by emedastine and cetirizine than placebo. At pharmacokinetic steady-state levels, no significant difference could be found in the potency between cetirizine and emedastine (2 mg b.i.d.). Emedastine displays pharmacodynamic properties comparable with cetirizine and therefore qualifies as a safe and alternative compound with H1-receptor antagonist properties. Additional larger studies may be needed to substantiate potential benefits of cetirizine over emedastine after single-dose administration.",2000.0,0,1
35,10843430,"Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine: a double-blind, placebo-controlled trial.",A Reimers; Y Hari; U Müller,"Immunotherapy with Hymenoptera venoms is highly effective but causes allergic side-effects frequently, especially when honeybee venom is used. Therefore, our objective was to investigate the effect of pretreatment with the antihistamine fexofenadine on the incidence of allergic side-effects during ultrarush immunotherapy with bee venom. In a double-blind, placebo-controlled trial, 57 patients with a history of systemic allergic reactions to honeybee stings and positive diagnostic tests (skin tests, serum specific IgE to honeybee venom) were investigated. Bee venom immunotherapy was started with an ultrarush protocol and patients were randomized to pretreatment with either fexofenadine 180 mg or placebo on days 1, 8, 22, and 50 of the protocol. Local and systemic allergic side-effects were registered. Fifty-four patients completed the study, 28 on fexofenadine and 26 on placebo pretreatment. On day 1, large local reactions were significantly reduced in both extension and duration by fexofenadine pretreatment (P<0.025). Systemic allergic side-effects on the whole were not reduced. However, the symptoms pruritus, urticaria, and angioedema occurred less frequently with fexofenadine (P<0.05). Pretreatment with fexofenadine during venom immunotherapy reduces local allergic reactions and generalized symptoms of the urticaria and angioedema type.",2000.0,0,0
36,10867385,[Projection of new antihistamines].,J Eseverri,"The metabolic fate of most antihistamines is not clearly established. The drugs usually appear to be extensively metabolized,mainly in the liver. Some second generation antihistamines are metabolized principally by the cytochrome P-450 microsomal enzyme system, mainly by the isoenzyme 3A4 (CYP3A4), although other isoenzyme,including CYP1A2 and CYP2D6, also may be involved. However,other second generation antihistamines appear to be only minimally metabolized in the liver. Serious cardiac effects (prolongation of the QT interval, arrhythmias, torsades de pointes, ventricular fibrillation, arrest, hypotension, palpitations, syncope, dizziness, and/or death) have been reported rarely in patients receiving terfenadine or astemizole. Cardiotoxic effects ussually were associated with higher than recommended dosages and/or increased plasma concentrations of the drugs and their active metabolites. No clinically important adverse effects or changes in the QT intervals were reported after concomitant administration of ketoconazole with fexofenadine. Patients receiving an azole, antifungal, a macrolide, quinine or grapefruit juice also appear to be at substantial risk of such toxicity, probably secondary to interference with metabolism of the antihistamine. Second-generation H1 receptor antagonist have been studied extensively in the treatment of asthma. Many of these drugs have been reported to inhibit eosinophil and basophil chemotaxis and therefore might have an effect on the inflammatory reactions that characterise this disease. Safe use of antihistamines during pregnancy has not been established; therefore, the drugs should not be used in women who are or may become pregnant unless the potential benefits justify the possible risks to the fetus. Antihistamines should not be administered to premature or full-term neonates. Young children may be more susceptible than adults to the toxic effects of antihistamines.",2000.0,0,0
37,10868555,Loratadine versus cetirizine: assessment of somnolence and motivation during the workday.,L M Salmun; D Gates; M Scharf; L Greiding; F Ramon; K Heithoff,"This parallel-group, double-blind study compared the somnolence and motivation profiles of 2 second-generation antihistamines, loratadine and cetirizine, in patients with allergic rhinitis. Second-generation antihistamines were developed to provide symptomatic relief from allergic disorders without the unwanted side effects of first-generation antihistamines, including somnolence. Recent research has indicated that not all second-generation antihistamines are comparable with respect to somnolence and other cognitive processes. Patients aged > or = 12 years and actively exhibiting symptoms of allergic rhinitis were randomized to 2 treatment groups to receive 10 mg loratadine or 10 mg cetirizine daily at 8:00 AM for 1 week. After patients took the medication, their somnolence and degree of motivation to perform activities were recorded in an electronic diary using a visual analog scale 4 times during the workday (8:00 AM, 10:00 AM, noon, and 3:00 PM). Sixty patients (31 men, 29 women) were randomized to treatment. Somnolence scores were similar for both groups at baseline and at the time of dosing (8:00 AM). However, there was a statistically significant difference in somnolence scores between the loratadine and cetirizine groups at 10:00 AM (P = 0.008), noon (P = 0.001), and 3:00 PM (P < 0.001), with the cetirizine group showing a greater degree of somnolence. The scores on motivation to perform activities were similar for both groups at the baseline and 8:00-AM measurements. In parallel with the somnolence scores, there were statistically significant differences in motivation scores between the loratadine and cetirizine groups at 10:00 AM (P = 0.014), noon (P = 0.001), and 3:00 PM (P < 0.001), indicating that patients taking loratadine were relatively more motivated during the workday. The results of this study demonstrate that in patients aged > or = 12 years who had allergic rhinitis, cetirizine use promoted somnolence and decreased motivation to perform activities during the workday compared with loratadine.",2000.0,0,1
38,10868558,,,,,0,0
39,10879992,Further improvement of quality of life by cetirizine in perennial allergic rhinitis as a function of treatment duration.,B Burtin; J Duchateau; J C Pignat; F Donnelly; J Bousquet,"The SF-36 Health Status Questionnaire is a generic quality of life questionnaire based on 36 questions selected to represent nine health concepts. Perennial allergic rhinitis is a disease which causes variable restrictions on the physical, psychological and social aspects of patients' lives. According to the SF-36 questionnaire assessment, quality of life is impaired in these patients. Cetirizine, a potent, reliable histamine H1-receptor antagonist, has already been found to induce significant improvement in the quality of life of patients with chronic rhinitis, as assessed by the same SF-36 questionnaire after 1 and 6 weeks of treatment. This paper further investigates the extent to which cetirizine continues to improve quality of life after a long-term treatment (6 weeks) compared to a shorter treatment (1 week). The analyses show that, despite the significant improvement found after 1 week of treatment with cetirizine compared to placebo, a further 5-week course of therapy not only maintains this improvement but continues to enhance quality of life significantly above and beyond this.",2000.0,0,1
40,10898119,Cetirizine and loratadine: a comparison using the ED50 in skin reactions.,I Ramboer; R Bumtbacea; D Lazarescu; J R Radu,"To quantify objectively the comparative potencies of the antihistamines, loratadine and cetirizine, we determined the dose that inhibits histamine-induced skin reactions by 50% of the maximum response (ED50) for each drug. Cetirizine at 2.5, 5 or 10 mg, loratadine at 10, 20 or 40 mg or placebo were given to 14 healthy female subjects in a randomized double-blind crossover design. Inhibition of the wheal and flare response to the histamine prick test (10, 100 and 500 mg/ml) was evaluated. Depending on the histamine concentrations, the ED50s for wheals were in the ranges 4.3 - 4.7, 2.1 - 2.2 and 1.7 - 1.9 mg cetirizine, 2, 4 and 6 h after dosing, respectively. For loratadine, the ED50 for wheals were in the ranges 35.6 - > 40, 9.1 - 24.1 and 9.1 - 13.9 mg, 2, 4 and 6 h after dosing, respectively. Calculation of the ED50 demonstrated that, on average, cetirizine is seven to nine times more potent than loratadine at inhibiting wheal and flare reactions.",2001.0,0,0
41,10921468,Loratadine in the treatment of mosquito-bite-sensitive children.,A Karppinen; H Kautiainen; T Reunala; L Petman; T Reunala; H Brummer-Korvenkontio,"Children frequently experience harmful whealing and delayed papules from mosquito bites. Whealing is mediated by antisaliva IgE antibodies and histamine, but the effect of antihistamines on mosquito-bite symptoms has not been evaluated in children. The effect of loratadine (0.3 mg/kg) was examined in 28 mosquito-bite-sensitive children (aged 2-11 years). The double-blind, placebo-controlled, crossover study was performed with exposure to Aedes aegypti laboratory mosquitoes. The size of the bite lesion and the intensity of pruritus (visual analog scale) were measured at 15 min and at 2, 6, and 24 h. Loratadine decreased the size of the wheals by 45% (P < 0.001, 25 children) and accompanying pruritus by 78% (P = 0.011, 12 children) at 15 min compared to placebo. The size of the 24-h delayed bite lesion also decreased significantly (P = 0.004), but there was no change at 2 or 6 h. Loratadine was well tolerated and no marked side-effects were recorded. This study in children shows that prophylactically given loratadine decreases significantly the whealing and pruritus caused by mosquito bites and also reduces the size of the 24-h bite lesions. Therefore, the therapeutic profile of loratadine extends from immediate to delayed allergic symptoms in mosquito-bite-sensitive children.",2001.0,0,0
42,10921472,Nitrate intolerance.,R Asero,,2001.0,0,0
43,10921473,Hypersensitivity to H1-antihistamines.,P Demoly; D Messaad; S Benahmed; H Sahla; J Bousquet,,2001.0,0,0
44,10927716,SOAP: solutions to often asked problems. Choice of antihistamines for urticaria.,B S Alper,,2000.0,0,0
45,10929922,Efficacy and tolerability of loratadine versus fexofenadine in the treatment of seasonal allergic rhinitis: a double-blind comparison with crossover treatment of nonresponders.,B M Prenner; D Capano; A G Harris,"Nonsedating antihistamines are well-established treatment for seasonal allergic rhinitis (SAR), but patients do not always respond to the first antihistamine prescribed. This double-blind, double-dummy, randomized, 2-phase, multicenter study was designed primarily to compare the therapeutic responses to loratadine and fexofenadine in patients who failed initial therapy with the other drug. Male and female patients aged 12 to 60 years received loratadine 10 mg once daily (n = 331) or fexofenadine 60 mg twice daily (n = 328) for 14 days (phase 1); nonresponders (ie, those who had <25% reduction in the sum of 5 SAR symptoms rated by the investigator on a 4-point scale) subsequently received the alternate medication for 14 days (phase 2). The investigator's rating of relief (complete, marked, moderate, or slight relief of symptoms or treatment failure) at the end of phase 2 was the primary efficacy measure; changes in total symptom severity (TSS) assessed by the investigator (4-point scale) and the patient (11-point visual analog scale) were secondary measures. Mean decreases in TSS were significantly greater with loratadine than with fexofenadine for the 659 patients who completed phase 1 (-12.7 vs -10.2, respectively; P = 0.019; patient assessment) and for the 389 patients who responded to initial therapy (-6.6 vs -6.1, respectively; P = 0.037; investigator assessment). Of the 389 patients who responded to initial therapy, 61.0% had received loratadine and 57.0% had received fexofenadine. More nonresponders to initial therapy had moderate, marked, or complete relief of symptoms after switching to loratadine than after switching to fexofenadine (62.4% vs 51.2%, respectively; P = 0.005) and treatment failure in 10.6% vs 21.7%, respectively (P = 0.011). Overall, ioratadine provided significantly better therapeutic response than fexofenadine in patients who failed to respond to initial therapy with the other drug.",2001.0,1,1
46,10951147,Randomized double-blind study of cyclosporin in chronic 'idiopathic' urticaria.,C E Grattan; B F O'Donnell; D M Francis; N Niimi; R J Barlow; P T Seed; A Kobza Black; M W Greaves,"Histamine-releasing activity (HRA) is detectable in up to 50% of patients with chronic ordinary urticaria. To determine the effect of cyclosporin on clinical features and HRA in patients with chronic urticaria. Thirty patients with severe unremitting disease, responding poorly to antihistamines and showing a positive autologous serum skin test (ASST) as a marker of HRA, were randomized to 4 mg kg-1 daily of cyclosporin (Sandimmun, n = 20) or placebo (n = 10) for 4 weeks. Non-responders were offered open-label cyclosporin for 4 weeks. All were followed for up to 20 weeks or until clinical relapse; all took cetirizine 20 mg daily throughout the study. The primary measure of efficacy was a daily urticaria activity score (UAS) of weal numbers and itch (maximum score 42 per week). A positive response was defined as a reduction to < 25% of baseline weekly UAS and relapse as a return to > 75%. The effect of cyclosporin on serum HRA was assessed by in vitro basophil histamine release assays and ASSTs before and after treatment. Twenty-nine patients (19 active, 10 controls) completed the randomized trial medication. Eight of 19 on active treatment but none on placebo had responded at 4 weeks (P < 0.05). Three others on active drug met the criterion for response at 2 weeks but not at 4 weeks. Mean reduction in UAS between weeks 0 and 4 was 12.7 (95% confidence interval, CI 6.6-18.8) for active and 2.3 (95% CI - 3.3-7.9) for placebo (P = 0.005). Seventeen non-responders (seven randomized to active and 10 to placebo) chose open-label cyclosporin and 11 responded after 4 weeks. Six of the eight randomized active drug responders relapsed within 6 weeks. Of the 19 responders to randomized and open-label cyclosporin, five (26%) had not relapsed by the study end-point. Mean in vitro serum HRA fell from 36% (95% CI 22-49%) to 5% (95% CI 1-8%) after cyclosporin treatment (n = 11, P < 0.0001). The ASST response to post-treatment serum was also reduced (P < 0.05). This study shows that cyclosporin is effective for chronic urticaria and provides further evidence for a role of histamine-releasing autoantibodies in the pathogenesis of this chronic 'idiopathic' disease.",2000.0,0,0
47,10955697,Clinical and pathologic methods to assess the long-term safety of nasal corticosteroids. French Triamcinolone Acetonide Study Group.,F Laliberté; M F Laliberté; S Lécart; J Bousquet; J M Klossec; N Mounedji,"The main objective of this long-term prospective local safety study was to evaluate endoscopic and histologic changes in nasal epithelium after 6-month treatment with triamcinolone acetonide (TAA). We describe here a method to measure quantitatively epithelium thickness. Results were compared with those seen with the use of cetirizine (an antihistamine) and another oral intranasal corticosteroid, beclomethasone dipropionate (BDP). Patients were examined by an ENT specialist who first performed an endoscopic evaluation of the nasal cavities, assessing any morphologic abnormalities and the aspect of the mucosa. Biopsies were taken from the inferior turbinate before and after 24 weeks of treatment. Biopsies were immediately fixed in cold acetone (-20 degrees C) and embedded in glycolmethacrylate; sections of 2 microm were cut on an ultramicrotome. Morphometric evaluations were done in a blinded fashion by computerized image analysis to measure an epithelial area over a minimum length of 50 microm. The thickness was ascertained by the ratio of area to length. 1) For all three treatment groups, the nasal epithelium thickness decreased slightly from pretreatment to the end of treatment. 2) No statistically significant differences between the three treatment groups were found in epithelium thickness. 3) Macroscopically, nasal tissues in all treated groups were normal. These results clearly indicate that long-term treatment with TAA has no atrophic effect on nasal mucosa.",2001.0,0,0
48,10979060,"Montelukast, a leukotriene receptor antagonist, in combination with loratadine, a histamine receptor antagonist, in the treatment of chronic asthma.",A Reicin; R White; S F Weinstein; A F Finn; H Nguyen; I Peszek; L Geissler; B C Seidenberg,"Montelukast sodium, a potent, oral, specific leukotriene-receptor antagonist, has demonstrated clinical efficacy in the treatment of chronic asthma. Loratadine, a selective histamine type 1 (H(1))-receptor antagonist, has demonstrated antiallergic properties. Leukotriene-receptor antagonists given concomitantly with H(1)-receptor antagonists have been shown to have additive effects in the prevention of bronchospasm in antigen-challenge models. To determine whether montelukast plus loratadine provides improved efficacy to montelukast alone in the treatment of chronic asthma. The efficacy of montelukast alone vs montelukast-loratadine was studied in a 10-week, multicenter, randomized, double-blind, 2 x 2 crossover study. After a 2-week placebo run-in period, patients received montelukast sodium (10 mg) plus loratadine (20 mg), or montelukast sodium (10 mg) plus placebo once daily for 2 weeks. After a 2-week placebo washout period, patients were crossed over to receive 2 weeks of the other active treatment regimen, followed by another 2-week placebo washout period. Montelukast given concomitantly with loratadine caused significant improvement in percentage of change from baseline in forced expiratory volume in 1 second (FEV(1)) compared with montelukast alone (13.86% vs 9.72%; P =.001). The average additional effect of loratadine (least square mean difference in percentage of change from baseline in FEV(1)) was 4.15% (95% confidence interval, 1.65%-6.65%). Key secondary end points (mean daily beta-agonist use, daytime and nighttime symptom scores, morning and evening peak expiratory flow rate, and the Patient Global Evaluation) all showed significant improvement with montelukast-loratadine (P<.05). Montelukast-loratadine significantly improved end points of asthma control during a 2-week treatment period.",2000.0,0,0
49,10999590,Loratadine toxicity.,Y Gokel; S Satar; A Sebe,,2000.0,0,1
50,11003455,Cetirizine inhibits bradykinin-induced cutaneous wheal and flare in atopic and healthy subjects.,R Fadel; I Ramboer; N Chatterjee; J P Rihoux; M P Derde,"Kinins are vasoactive mediators involved in allergic reactions. When applied on the skin or in the nose, bradykinin (BK) elicits inflammation that is poorly affected by previous H1-blockade. The aim of this study was to compare the possible effect of cetirizine (an H1-antagonist) on wheal and flare responses to BK, histamine, and compound 48/80 in atopic and healthy subjects. In a randomized, double-blind, crossover study, eight atopic and eight healthy subjects received cetirizine (10 mg/day) or placebo for 3 days before cutaneous tests. Intradermal tests (IDT) and prick tests (PT) were performed with BK (20 nmol/ml for IDT and 20 micromol/ml for PT), histamine (100 microg/ml IDT and 100 mg/ml PT), and compound 48/80 (100 microg/ml IDT and 100 mg/ml PT) as positive controls and saline as negative control. The skin responses were monitored by measurement of wheal and flare areas. BK, histamine, and 48/80 induced wheal and flare reactions in all placebo-treated subjects. Histamine elicited larger wheal and flare reactions than BK and 48/80. IDT with BK induced four- to six-fold larger wheal and flare reaction than PT. No differences in BK-induced wheal and flare were observed between atopic and healthy subjects. In atopic subjects, cetirizine induced a significant reduction of flare reactions after the BK test (80% for IDT, and 94% for PT [P<0.01]). Moreover, cetirizine reduced significantly BK-induced wheals by 70% for IDT (P<0.01) and 65% for PT (P<0.01). A similar inhibiting effect of cetirizine was also observed in healthy subjects. These findings showed that the wheal and flare reactions induced by BK challenge were markedly inhibited by previous intake of cetirizine. The mechanism by which this effect is mediated cannot be established at present.",2001.0,0,0
51,11012550,"Macrolide - induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin.",J F Westphal,,2001.0,0,0
52,11019835,A randomized phase 2 study of PBPC mobilization by stem cell factor and filgrastim in heavily pretreated patients with Hodgkin's disease or non-Hodgkin's lymphoma.,P Stiff; R Gingrich; S Luger; M R Wyres; R A Brown; C F LeMaistre; J Perry; D P Schenkein; A List; J R Mason; W Bensinger; C Wheeler; C Freter; ; C Emmanouilides,"This randomized, controlled study compared the ability to mobilize and collect an optimal target yield of 5 x 10(6) CD34+ cells/kg using stem cell factor (SCF; 20 microg/kg/day) plus filgrastim (G-CSF; 10 microg/kg/day) vs filgrastim alone (10 microg/kg/day) in 102 patients diagnosed with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), who were prospectively defined as being heavily pretreated. Leukapheresis began on day 5 of cytokine administration and continued daily until the target yield was reached, or until a maximum of five leukaphereses had been performed. Compared with the filgrastim-alone group (n = 54), the SCF plus filgrastim group (n = 48) showed an increase in the proportion of patients reaching the target yield within five leukaphereses (44% vs 17%, P = 0.002); reduction in the number of leukaphereses required to reach the target yield (P = 0.003); reduction in the proportion of patients failing to reach a minimum yield of 1 x 10(6) CD34+ cells/kg to proceed to transplant (16% vs 26%, P = NS); increase in the median yield of CD34+ cells per leukapheresis (0.73 x 10(6)/kg vs 0.48 x 10(6)/kg, P = 0.04); and an increase in the median total CD34+ cells collected within five leukaphereses (3.6 x 10(6)/kg vs 2.4 x 10(6)/kg, P = 0.05). All patients receiving SCF were premedicated (antihistamines and albuterol), and treatment was generally well tolerated. Five patients experienced severe mast cell-mediated reactions, none of which were life-threatening. In this study of heavily pretreated lymphoma patients, SCF plus filgrastim was more effective than filgrastim alone for mobilizing PBPC for harvesting and transplantation after high-dose chemotherapy.",2001.0,0,0
53,11030030,Impact of interventions designed to increase market share and prescribing of fexofenadine at HMOs.,S R Benedetto; A S Sloan; B S Duncan,"The impact of interventions designed to shift prescribing from loratadine to fexofenadine at HMOs was studied. Pharmacy claims data for a six-month preintervention period at four HMOs were analyzed to identify all new and refill prescriptions for loratadine, fexofenadine, astemizole, and cetirizine. The interventions consisted of a mandatory lockout of loratadine in favor of fexofenadine (at HMO A), a voluntary switch to fexofenadine promoted through letters to both physicians and members (HMO B), and a voluntary switch promoted through letters to physicians only (HMO C). There was no intervention at HMO D. Pharmacy claims data for the six months after each intervention program was implemented were analyzed to determine changes in the market share and prescribing of the study drugs. After the intervention programs were implemented, the market share of fexofenadine increased from 18.9% to 65.2% at HMO A, from 14.8% to 21.0% at HMO B, and from 20.7% to 23.8% at HMO C. Loratadine's market share decreased from 62.3% to 8.7% at HMO A, from 67.5% to 58.6% at HMO B, and from 70.5% to 65.3% at HMO C. HMOs A, B, and C each had greater shifts in market share for fexofenadine and loratadine than the control HMO. Changes in prescribing followed a similar pattern for the 25 physicians at each HMO who had most frequently prescribed loratadine during the preintervention period. The average cost per antihistamine prescription decreased 22.3% at HMO A. Prescription costs continued to rise at HMOs B, C, and D. Mandating the use of fexofenadine produced a significant increase in its market share, reduced the cost of nonsedating antihistamines, and successfully influenced prescribing behavior. Voluntary programs had a more modest impact on market share and did not stop increases in prescription costs.",2001.0,0,0
54,11030449,Activity of ebastine (10 and 20 mg) and cetirizine at 24 hours of a steady state treatment in the skin of healthy volunteers.,N Frossard; O Benabdesselam; A Purohit; N Mounedji; G Pauli,"We have compared the inhibitory effects of ebastine (10 mg), ebastine (20 mg) and cetirizine (10 mg) on histamine-induced wheal and flare skin reactions 24 h following a 6-day-long treatment. This was a double-blind, randomised, crossover, placebo-controlled study involving 24 healthy volunteers (18-65 years) with negative skin prick tests and the absence of specific IgEs to common allergens. Subjects were randomised to receive each of the following treatments once daily for 6 days: ebastine (10 mg), ebastine (20 mg), cetirizine (10 mg) or placebo with a washout period of 5 days. Twenty-four hours after the last dose of each treatment, histamine skin prick tests were performed (0, 0.5, 1, 2.5, 5, 10, 20, 50, 100 and 200 mg/mL), and wheal and flare responses were measured. All active treatments produced significant inhibition of the wheal responses compared to placebo (P < 0.001). Wheal response inhibition was significantly better with 20 mg of ebastine compared with 10 mg of ebastine and 10 mg of cetirizine. In a comparison to histamine concentrations required to produce a wheal surface area of 10 mm2, 20 mg of ebastine was also significantly better than ebastine 10 mg and cetirizine (P < 0.001), and 10 mg ebastine was significantly better than cetirizine (P < 0.05). Highly significant (P < 0.001) effects on the flare response were observed with each active treatment compared to placebo, with no difference between groups. The frequency of adverse events, primarily somnolence, was similar among the four treatment groups. Our results clearly indicate that ebastine, at either recommended dosage of 10 and 20 mg, and cetirizine produced significant inhibition of the histamine-induced wheal and flare reaction compared to placebo for up to 24 h. A superior efficacy of 20 mg of ebastine is observed compared with 10 mg of ebastine and 10 mg of cetirizine on the skin wheal response 24 h after the last dose of a 6-day-long treatment. This study clearly proves ebastine to be an effective, truly once-daily antihistamine.",2001.0,0,0
55,11042709,Role of cetirizine in treatment of eosinophilia.,T P Yadav; R Singh; R Yadav; M Bhardwaj; L Satyanarayana,,2001.0,0,0
56,11049015,Consequences of a change in reimbursement status on prescription patterns.,M L Bouvy; T C Egberts,,2001.0,0,0
57,11108443,Local nasal immunotherapy and bronchial hyperreactivity in seasonal allergic rhinitis: an observational pilot study.,M Olivieri; M R Mohaddes Zadeh; G Talamini; G Lampronti; V Lo Cascio,"The clinical efficacy of local nasal immunotherapy (LNIT) in patients with allergic rhinitis is amply documented. The aim of the study was to determine the effect on bronchial hyperresponsiveness (BHR) assessed at baseline and after 3 years of LNIT or pharmacological treatment alone. Forty-three randomized patients with allergic oculorhinitis were enrolled (26 positive to Graminaceae and 17 to Parietaria judaica pollens). All patients were asked whether they were willing to follow a 3-year treatment course involving preseasonal LNIT with a powder extract of Graminaceae or Parietaria pollens. Twenty-four patients (16 allergic to Graminaceae and eight to Parietaria) selected LNIT and the other 19 opted for symptomatic pharmacological treatment only. The latter was considered the control group. On the basis of positive or negative bronchial hyperresponsiveness and the LNIT, four subgroups were established and followed in open conditions, during which a record was kept of symptom scores, drug use, spirometry and methacholine test findings. After 3 years, patients treated with LNIT had a significant reduction of symptoms and drug intake. In the controls, symptoms worsened, thus requiring more drugs to control them. Bronchial hyperresponsiveness significantly improved in hyperreactive patients receiving LN7IT 10 of whom were no longer hyperreactive and one at a higher threshold. Among controls, bronchial hyperresponsiveness did not change, with the exception of three nonreactive patients who became hyperreactive, one of them with asthma. These findings confirm the efficacy of LNIT in allergic rhinitis suggesting that it might have systemic activity interfering with bronchial hyperresponsiveness and hence the onset of bronchial asthma.",2001.0,0,0
58,11136297,Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine.,T Kosoglou; M Salfi; J M Lim; V K Batra; M N Cayen; M B Affrime,"To evaluate whether ketoconazole or cimetidine alter the pharmacokinetics of loratadine, or its major metabolite, desloratadine (DCL), or alter the effects of loratadine or DCL on electrocardiographic repolarization in healthy adult volunteers. Two randomized, evaluator-blind, multiple-dose, three-way crossover drug interaction studies were performed. In each study, subjects received three 10 day treatments in random sequence, separated by a 14 day washout period. The treatments were loratadine alone, cimetidine or ketoconazole alone, or loratadine plus cimetidine or ketoconazole. The primary study endpoint was the difference in mean QTc intervals from baseline to day 10. In addition, plasma concentrations of loratadine, DCL, and ketoconazole or cimetidine were obtained on day 10. Concomitant administration of loratadine and ketoconazole significantly increased the loratadine plasma concentrations (307%; 90% CI 205-428%) and DCL concentrations (73%; 62-85%) compared with administration of loratadine alone. Concomitant administration of loratadine and cimetidine significantly increased the loratadine plasma concentrations (103% increase; 70-142%) but not DCL concentrations (6% increase; 1-11%) compared with administration of loratadine alone. Cimetidine or ketoconazole plasma concentrations were unaffected by coadministration with loratadine. Despite increased concentrations of loratadine and DCL, there were no statistically significant differences for the primary electrocardiographic repolarization parameter (QTc) among any of the treatment groups. No other clinically relevant changes in the safety profile of loratadine were observed as assessed by electrocardiographic parameters (mean (90% CI) QTc changes: loratadine vs loratadine + ketoconazole = 3.6 ms (-2.2, 9.4); loratadine vs loratadine + cimetidine = 3.2 ms (-1.6, 7.9)), clinical laboratory tests, vital signs, and adverse events. Loratadine 10 mg daily was devoid of any effects on electrocardiographic parameters when coadministered for 10 days with therapeutic doses of ketoconazole or cimetidine in healthy volunteers. It is concluded that, although there was a significant pharmacokinetic drug interaction between ketoconazole or cimetidine and loratadine, this effect was not accompanied by a change in the QTc interval in healthy adult volunteers.",2001.0,0,0
59,11143865,The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.,W A Shaikh,"Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a group of workers in the Netherlands was later rectified by the same group. Clinically speaking, the cardiovascular safety of fexofenadine has been convincingly demonstrated at various dose levels and various time intervals, alone and together with other drugs of potential toxigenicity. All things put together, it appears reasonable to conclude that fexofenadine is free from cardiovascular ADRs of clinical significance. It could also be concluded that cardiac side-effects of antihistamines is not a class effect.",2001.0,0,0
60,11154865,Effects of cetirizine and epinastine on the skin response to histamine iontophoresis.,M Furue; H Terao; T Koga,"Epinastine and cetirizine are second-generation, nonsedating and long-lasting antihistamines that are now frequently used for the allergic disorders. We have examined the inhibitory effects of these two drugs on the histamine-induced flare and wheal responses using iontophoresis at 1, 2, 4, 8 and 24 h after the oral administration by a double-blind, cross-over and placebo-controlled study. Both cetirizine and epinastine significantly inhibited the histamine-induced flare and wheal responses at 2 h after the oral administration when compared with placebo. The inhibitory effects of cetirizine and epinastine on the flare response lasted long until at 24 h, however, epinastine was less potent than cetirizine. The inhibitory effects on the wheal response was also clearly and significantly evident at 2-8 h by cetirizine and epinastine. At 24 h cetirizine only showed the significant inhibition on the histamine-induced wheal response. In contrast, epinastine seemed to exhibit the inhibitory capacity earlier than did cetirizine. The inhibitory action of the drugs on the histamine-induced wheal response peaked at 4 h after the oral administration. The histamine-induced itch sensation was also markedly or completely suppressed at 2-8 h by the drugs. Thus, both drugs exhibited the potent and long-lasting antihistamine activity on the skin responses induced by histamine iontophoresis.",2001.0,0,0
61,11167352,"A randomized, double-blind, crossover comparison among cetirizine, levocetirizine, and ucb 28557 on histamine-induced cutaneous responses in healthy adult volunteers.",J L Devalia; C De Vos; F Hanotte; E Baltes,"Cetirizine is a highly efficacious and long-acting second-generation H1-receptor antagonist for the treatment of allergic diseases, such as allergic rhinitis and chronic idiopathic urticaria, in adults and children. Pharmacologic studies have demonstrated that cetirizine, a racemate mixture composed of equal amounts of two enantiomers, does not undergo hepatic metabolism to any significant level. The enantiomers are excreted mainly unchanged, predominantly in the urine and to a lesser extent in the faeces. The pharmacologic activity and potency of the two enantiomers of cetirizine in the management of allergic skin conditions were investigated by studying the effect of treatment with 5.0 mg cetirizine; 2.5 mg levocetirizine, the (R)-enantiomer; and 2.5 mg ucb 28557, the (S)-enantiomer, on histamine-induced wheal and flare response in 18 healthy volunteers. Each treatment was administered as a single oral dose in randomized, double-blind, and crossover manner, and the efficacy of treatment was assessed over a period of 32 h, as per cent inhibition of the histamine-induced wheal and flare areas before treatment. Blood and urine samples were collected in a time-dependent manner and analyzed for the total amounts of each study drug, to elucidate their pharmacokinetic profiles. Both cetirizine and levocetirizine caused a marked inhibition of histamine-induced wheal and flare, whereas ucb 28557 was inactive in this model. Inhibition of the wheal response observed for cetirizine and levocetirizine was apparent by 1 h after dosage and lasted for mean durations of 24.4 and 28.4 h, respectively. In addition, the response for cetirizine and levocetirizine became maximal by 6 h after treatment, rising to 79.5% and 83.8%. Similarly, cetirizine and levocetirizine also markedly inhibited the histamine-induced flare response. This effect was evident for both drugs by 1 h after dosage and lasted over a mean period of 28.4 and 26.0 h, respectively, for cetirizine and levocetirizine. The inhibitory effect of these compounds on histamine-induced flare response was also maximal by approximately 6 h after dosage, peaking at 88.5%) and 83.6%, respectively. Statistical evaluation showed that cetirizine and levocetirizine were equivalent for maximum inhibition of histamine-induced wheal and flare. However, levocetirizine was found to be superior to cetirizine when area under the curve was compared. In contrast, ucb 28557 was not found to inhibit histamine-induced wheal and flare responses at any time during the study period. Plasma concentrations of levocetirizine were found to be approximately double those of ucb 28557 at 4 and 8 h after dosing, and 50-60% of the drugs were excreted unchanged in urine over a period of 32 h. The finding that, in this model, levocetirizine 2.5 mg has comparable antihistaminic activity to cetirizine 5 mg, whereas its other enantiomer ucb 28557 has no pharmacodynamic effect, suggests that the antihistaminic properties of cetirizine observed in the management of allergic skin conditions are likely to be attributable to levocetirizine.",2001.0,0,1
62,11176678,Comparison of montelukast and fexofenadine for chronic idiopathic urticaria.,E Nettis; P Dambra; L D'Oronzio; M P Loria; A Ferrannini; A Tursi,,2001.0,0,0
63,11223899,Sure outcomes of random events: a model for clinical trials.,A Bouckaert; M Mouchart,"We consider the outcomes of a clinical trial as determined by one, or several, possibly hidden causes. This paper proposes a statistical model that allows such a distinction of causes not only for the main, or therapeutic, effects but also for the side, or toxic, effects. More specifically, we focus on trials where the effects are naturally dichotomized, that is, where the health of a patient has improved or not, and where a specific adverse effect has occurred or not. A case study provides an example of the way this model can help to solve some problems of suspected drug toxicity. Finally, the model is shown to be a part of a hierarchy of models and the way to select a best model is investigated.",2001.0,0,0
64,11224725,New combination therapies for asthma.,J F Donohue; J A Ohar,"Combination products often have useful clinical benefits in asthma. The scientific rationale for combination therapy includes the fact that different agents have complimentary modes of action. Long-acting beta(2)-agonists have effects on airway smooth muscle, and inhaled corticosteroids have potent topical antiinflammatory effect. This combination has been shown to effectively reduce exacerbations and improve symptoms. Substantial clinical trial data provide a rationale for dual-control therapy supported by basic scientific data. Another combined therapy is inhaled steroids plus leukotriene-receptor antagonists, which provides the patient with two effective therapies. Leukotriene-receptor antagonist can also be combined with antihistamines for improved asthma control. Older therapies including theophylline and controlled release albuterol have been effectively added to inhaled corticosteroids, enabling a reduction in the dose of the inhaled steroids. Many other combination therapies are presently being tested.",2001.0,0,0
65,11269898,Effects of sublingual immunotherapy in patients sensitised to Ambrosia. An open controlled study.,C Valle; S Bazzi; D Berra; V Sillano; P Puccinelli; S Parmiani,"Allergy to Ambrosia is a disease of growing importance in Europe. Injective and non-injective immunotherapy have been recognised as safe and effective but no evidence is currently available for sublingual immunotherapy (SLIT) in patients sensitised to Ambrosia. This study was planned to assess the effects and the safety of SLIT in patients clinically sensitised to Ambrosia. 19 patients clinically sensitised to Ambrosia and treated with SLIT were compared to 14 patients treated only with drugs. Diary cards with symptoms and drug consumption were filled-in by patients during the pollen season whereas specific nasal challenge and skin prick test were run two months before and after the pollen season. Patients and doctors were also asked to express their subjective assessment about symptoms and drug consumption during the season. SLIT-treated patients had less symptoms and a significantly minor drug intake (p = 0.04) as compared to untreated patients. Nasal challenge test improved significantly in the SLIT group (p = 0.0001) but not in the control group (p = 0.6875) with a significant difference between groups at the end (p = 0.0413) but not at the beginning of the trial (p = 0.213). The decrease in skin reactivity was significant in the control group (p = 0.0186) and highly significant in the SLIT group (p < 0.0001), with no difference between groups (p = 0.2987). Subjective assessment from both patients and doctors was favorable to SLIT (p = 0.0005 for symptoms; p = 0.0019 for drug consumption). Only one minor local side effect was registered during SLIT. According to our data, SLIT in patients allergic to Ambrosia is safe and able to improve both subjective and objective parameters.",2001.0,0,0
66,11270088,,,,,0,1
67,11277962,"Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled study.",J Ring; R Hein; A Gauger; E Bronsky; B Miller,"Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12-79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period.",2001.0,0,1
68,11284803,"Effect of cetirizine, levocetirizine, and dextrocetirizine on histamine-induced nasal response in healthy adult volunteers.",D Y Wang; F Hanotte; C De Vos; P Clement,"Cetirizine, an effective H1-receptor antagonist, is a racemate mixture of two enantiomers: levocetirizine (R enantiomer) and dextrocetirizine (S enantiomer). To investigate the pharmacologic activity of the two enantiomers of cetirizine, we conducted a randomized, double-blind, four-way, crossover study to assess the effect of treatment with 5 mg levocetirizine, 5 mg dextrocetirizine, and 10 mg cetirizine and matched placebo, on histamine-induced changes in the nasal airways of 24 healthy volunteers. Four hours after a single oral intake, all subjects were challenged by nasal aerosol application with increasing doubling concentrations (from 0.25 to 32 mg/ml) of histamine in both nostrils. Nasal resistance was measured by passive anterior rhinomanometry (PAR), and changes in histamine threshold were calculated together with the absolute number of sneezes after each challenge. Both levocetirizine and cetirizine significantly attenuated the histamine-induced increase in nasal airway resistance by nearly 50% (from a median resistance of 2.51 Pa per cm3/s to 1.29 and 1.31 Pa per cm3/s, respectively) at the maximal concentration, and they concomitantly increased the histamine threshold by fourfold (from 8 to 32 mg/ml), compared with placebo. Sneezing was also attenuated by both levocetirizine and cetirizine. However, these antihistaminic effects were not seen with dextrocetirizine. This study shows a similar activity of levocetirizine and cetirizine on the inhibition of histamine-induced increase in nasal resistance, indicating that the antihistaminic properties of cetirizine are probably attributable to levocetirizine.",2001.0,0,0
69,11318079,"Pharmacokinetic and safety profile of desloratadine and fexofenadine when coadministered with azithromycin: a randomized, placebo-controlled, parallel-group study.",S Gupta; C Banfield; B Kantesaria; M Marino; R Clement; M Affrime; V Batra,"Significant cardiac toxicity has been associated with some older antihistamines (eg, terfenadine and astemizole) when their plasma concentrations are increased. There is thus a need for a thorough assessment of the cardiac safety of newer antihistamine compounds. This study was undertaken to assess the effects of coadministration of desloratadine or fexofenadine with azithromycin on pharmacokinetic parameters, tolerability, and electrocardiographic (ECG) findings. Healthy volunteers aged 19 to 46 years participated in this randomized, placebo-controlled, parallel-group, third-party-blind, multiple-dose study. Subjects received desloratadine 5 mg once daily, fexofenadine 60 mg twice daily, or placebo for 7 days. An azithromycin loading dose (500 mg) followed by azithromycin 250 mg once daily for 4 days was administered concomitantly starting on day 3. Group 1 received desloratadine and azithromycin, group 2 received desloratadine and placebo, group 3 received placebo and azithromycin, group 4 received fexofenadine and azithromycin, and group 5 received fexofenadine and placebo. The results of the pharmacokinetic analysis revealed little change in mean maximum concentration (Cmax) and area under the concentration-time curve (AUC) values for desloratadine with concomitant administration of azithromycin: Cmax ratio, 115% (90% CI, 92-144); AUC, ratio 105% (90% CI, 82-134). The corresponding ratios for 3-hydroxydesloratadine were 115% (90% CI, 98-136) and 104% (90% CI, 88-122), respectively. A substantial increase was observed in mean Cmax and AUC values for fexofenadine when administered with azithromycin: Cmax, ratio, 169% (90% CI, 120-237); AUC ratio, 167% (90% CI, 122-229). Compared with the group receiving desloratadine and azithromycin, subjects receiving fexofenadine and azithromycin also displayed greater variability in pharmacokinetic parameters for the antihistamine. Mean Cmax and AUC values of azithromycin were slightly higher when administered with desloratadine (Cmax ratio, 131% [90% CI, 92-187]; AUC ratio, 112% [90% CI, 83-153]) but were lower when given in combination with fexofenadine (Cmax ratio, 87% [90% CI, 61-124]; AUC ratio, 88% [90% CI, 65-1201). The most common adverse event for all regimens was headache, reported in 20 (22%) subjects. All combinations of desloratadine or fexofenadine with and without azithromycin were well tolerated, and no statistically significant changes in PR, QT, or QT, interval, QRS complex, or ventricular rate were observed. Small increases (<15%) in mean pharmacokinetics of desloratadine were observed with coadministration of azithromycin. By contrast, peak fexofenadine concentrations were increased by 69% and the AUC was increased by 67% in the presence of the azalide antibiotic. Based on the reported adverse-events profile and the absence of changes in ECG parameters, the combination of desloratadine and azithromycin was well tolerated. This study suggests that desloratadine has a more favorable drug-interaction potential than does fexofenadine.",2001.0,0,0
70,11340690,Local safety of intranasal triamcinolone acetonide: clinical and histological aspects of nasal mucosa in the long-term treatment of perennial allergic rhinitis.,J M Klossek; F Laliberté; M F Laliberté; N Mounedji; J Bousquet,"Intranasal corticosteroids are increasingly used to treat allergic rhinitis and their long-term use is generally safe. However, the long-term safety of each molecule should be assessed. The main aim of this multicenter, prospective, randomized, open-label study was to evaluate the effect of triamcinolone acetonide aqueous intranasal spray on nasal mucosal thickness, macroscopic appearance, and mucociliary function. Patients with perennial allergic rhinitis were treated with triamcinolone acetonide 220 micrograms/day for six months. Nasal biopsies taken before and after treatment were compared with biopsies from patients who had been randomized to oral cetirizine 10 mg day or intranasal beclomethasone dipropionate 400 micrograms/day. In the evaluable population (n = 70), there were no significant differences between groups in terms of histologically evaluated thickness and endoscopically evaluated macroscopic appearance of the nasal mucosa, or indigocarmine saccharine test mucociliary function. In the intent-to-treat population (n = 92), there was no difference between treatment groups in the incidence of overall adverse events. This study indicates that sustained treatment with intranasal triamcinolone acetonide does not lead to atrophy of the nasal mucosa or impairment of mucociliary function.",2001.0,0,0
71,11343039,Children's school performance is not impaired by short-term administration of diphenhydramine or loratadine.,B G Bender; D R McCormick; H Milgrom,"The purpose of this study was to determine whether a second-generation H1 antihistamine produces less sedation in children and permits greater learning in a school setting than a classic antihistamine. Sixty-three 8- to 10-year-old children who had histories of seasonal allergic rhinitis but had no symptoms at the time of the study were randomly assigned to 1 of 3 treatment groups: placebo, diphenhydramine, or loratadine. Medications were administered on 3 of 4 study days, twice 6 hours apart, while participants attended a laboratory school. Classroom testing at the end of each school day evaluated the children's retention of curriculum material. Potential sedative effects were additionally evaluated by self-report of somnolence and computerized reaction-time testing. No treatment-related differences emerged on the verbal instruction score, reading test score, reaction time, or somnolence scale. Learning and response time in children attending a laboratory school were not significantly affected by either antihistamine.",2001.0,0,0
72,11358726,A randomized trial of leukotriene receptor antagonist montelukast in moderate-to-severe atopic dermatitis of adults.,G L Capella; E Grigerio; G Altomare,"Leukotriene receptor antagonists are recommended for the treatment of asthma, and have proved anecdotally successful even in atopic dermatitis. Standard treatments of atopic dermatitis are often unsatisfactory. Accordingly, we compared montelukast, 10 mg/day, with a combined regimen (orally administered cetirizine and clarythromycin, topical corticosteroids and hydrating preparations) for treatment of moderate-to-severe atopic dermatitis of adults. The trial was designed as a randomized single-blind study. SCORAD, eosinophilic cationic protein (ECP), eosinophilic protein X (EPX) serum levels were assessed at baseline and after 6 weeks in 32 adult patients with atopic dermatitis (16 treated with montelukast; 16 treated with the combined regimen). Similar improvements, evaluated in term of SCORAD reductions, were detected in both groups (Mann-Whitney, p < 0.05), while ECP and EPX levels significantly reduced within each group (Welch's approximate t, p < 0.05). We conclude that montelukast is as effective as the comparison combined regimen to treat atopic dermatitis of adults.",2001.0,0,0
73,11361264,Efficacy of nimesulide alone and in combination with cetirizine in acute allergic rhinitis.,A Kotwani; R Puri; U Gupta,"To study the effect of cetirizine and nimesulide given alone and in combination in allergic rhinitis. A double blind, double dummy, randomised, parallel controlled clinical study in three groups consisting of 18 patients each suffering from allergic rhinitis was conducted. Group A was given nimesulide alone (100 mg BD), Group B received combination (nimesulide 100 mg + cetirizine 10 mg) and Group C was given cetirizine alone (10 mg) for one week. The efficacy of each treatment in reducing nasal stuffiness, nasal discharge, itching nose and watery eyes was assessed at base line (day 0), on days four and eight of treatment. Patients used diary cards twice daily to rate symptom severity on a four point scale. Nimesulide and cetirizine alone could decrease nasal discharge, nasal stuffiness and sneezing significantly in allergic rhinitis patients by day four. Cetirizine was more effective in relieving nasal discharge and sneezing compared to nimesulide. By combining cetirizine and nimesulide four symptoms of allergic rhinitis, i.e., nasal discharge, nasal stuffiness, sneezing and watery eyes decreased significantly. Present study has shown that nimesulide alone could decrease three symptoms of allergic rhinitis like certirizine and combination of cetirizine (anti-histaminic) and nimesulide (anti-inflammatory) exerts synergistic action in reducing symptoms in patients of allergic rhinitis.",2001.0,0,0
74,11372583,Modulation of the immediate allergic wheal reaction in the skin by drugs inhibiting the effects of leukotriene C4 and prostaglandin D2.,J V Saarinen; R J Harvima; M Horsmanheimo; I T Harvima,"To study the effect of nordihydroguaiaretic acid (NDGA), zafirlukast and indomethacin on the size of the size of the allergic prick-test wheal. In the first part of the study, NDGA and indomethacin, as well as the mepyramine control (10 micrograms/ml and 100 micrograms/ml), were injected intracutaneously 10 min before prick-testing with the cow dander allergen in 51 sensitised atopic subjects. In the second part, five other subjects were prick-tested with several allergens followed by administration of 40 mg zafirlukast or 100 mg indomethacin and re-prick-testing 2 h or 4 h later. The intracutaneous indomethacin at both concentrations enlarged the wheal by 27 +/- 50% and 29 +/- 51% (P < 0.02, n = 51), respectively. Likewise, the peroral indomethacin significantly increased the wheal area by 17 +/- 30% (P = 0.035, n = 5). Neither intracutaneous NDGA in 51 subjects nor peroral zafirlukast in 5 subjects had marked effects on the size of the prick-test wheal. As expected, mepyramine (10 micrograms/ml) decreased the wheal area by 33 +/- 32% (P < 0.001, n = 51), but 14 subjects did not show any decrease after administration of this H1-antihistamine. The prostaglandin synthesis inhibitor (indomethacin) augments the prick-test wheal, but the leukotriene synthesis inhibitor (NDGA) and leukotriene C4 antagonist (zafirlukast) have no marked effects on the size of the prick-test wheal.",2001.0,0,0
75,11398910,Desloratadine.,K McClellan; B Jarvis,"Desloratadine is the orally active major metabolite of the nonsedating H1-antihistamine loratadine. The drug had no adverse cardiovascular effects in various animal models or when administered at 9 times the recommended adult dosage for 10 days in volunteers. Therapeutic dosages had no effects on wakefulness or psychomotor performance in healthy volunteers. No clinically significant interactions have been reported between desloratadine and drugs that inhibit the cytochrome P450 system, nor does the drug potentiate the adverse psychomotor effects of alcohol. Oral desloratadine 5 mg once daily for up to 4 weeks in patients with seasonal allergic rhinitis (SAR) significantly reduced nasal (including congestion) and non-nasal symptoms and improved health-related quality of life compared with placebo. Similar beneficial effects were observed in patients with SAR and coexisting asthma (in whom asthma symptoms and use of beta2-agonists were reduced). Desloratadine 5 mg once daily for 6 weeks significantly improved pruritus and reduced the number of hives compared with placebo in patients with chronic idiopathic urticaria (CIU). Sleep and daytime performance also improved. Desloratadine was well tolerated in clinical trials and had an adverse event profile similar to that of placebo in patients with SAR (with or without asthma) or CIU.",2001.0,0,1
76,11416103,Cancer fatigue: one drug fails but more are in the pipeline.,C McNeil,,2001.0,0,0
77,11420028,The comparison of the efficacy of fluticasone propionate with cetirizine in perennial allergic rhinitis.,O Karaman; A Günbay; N Uzuner; U Günbay; Z Gülay; S Sarioğlu; N Yuluğ,"Allergic rhinitis is an IgE mediated hypersensitivity reaction of the nasal mucosa characterised by nasal discharge, obstruction, and pruritus. In this study, 43 patients with perenneal allergic rhinitis were enrolled in order to compare the efficacy of Fluticasone Propionate (FP), a corticosteroid nasal spray, with Cetirizine, a systemic oral antihistaminic preparation, which is supposed to have nonsteroidal antiinflammatory activity. Cetirizine (10 mg daily as a single dose) was administered to 22 patient for 45 days. On the other hand, FP (400 micrograms/day) was administered into each nostril twice a day in the remaining 21 patients for 45 days. Skin test was obtained from each patient before therapy. Total eosinophil count, eosinophil count in nasal smear, electrorhinomanometric investigation, PGE2 and ratio of LTC4 to LTD4 both in the serum and in the nasal secretions were determined before and after therapy. In addition, percentage of eosinophils, and mast cells count in the biopsy specimens taken from anterior edge of middle choncha were evaluated before and after therapy, and than the results were graded for each patients. When we compared the eosinophil count in nasal smear, eosinophil percentage and total eosinophil parameters between two groups, it was shown that FP was more effective than Cetirizine. On the other hand, when we compared the ratio of LTC4 to LTD4 in serum and nasal smear, level of PGE2 and mast cell and nasal airway resistance measured by ERM, there were non statistical difference between two groups. These results suggest that FP and Cetirizine may be used alternatively in case of an adverse reaction to any of them.",2001.0,0,0
78,11436969,"Treatment of severe seasonal rhinoconjunctivitis by a combination of azelastine nasal spray and eye drops: a double-blind, double-placebo study.",C Duarte; M Baëhre; S Gharakhanian; F Leynadier; French Azelastine Study Group,"Evaluation of combined azelastine nasal spray and eye drops treatment in patients with severe rhinoconjunctivitis. Phase III, multicenter, randomized, double-blind study of patients with a history of grass pollen allergy, confirmed by skin testing/specific IgE, total symptom scores > or =6 (ocular) or > or =8 (nasal). Intent-to-treat analysis. 99 patients (azelastine = 53, placebo = 46) enrolled homogeneously from May to September 1997 in 7 venues in France. The efficacy of azelastine was significantly higher compared to placebo (49% vs. 28%, p = 0.04), considering response as a decrease of the total sum of ocular and nasal scores by at least 50% and no use of cetirizine by day 7. The decrease of total ocular and nasal scores by at least 50% at day 7, with cetirizine rescue <3 tablets was higher, but not significantly, in azelastine patients (43% vs. 30%). Cetirizine rescue was more frequent, from day 0 to 7, in the placebo patients (4.9 +/- 5.0 vs. 2.7 +/- 4.1, p = 0.02). Global efficacy was rated higher for azelastine by investigators (26% vs. 10%, p = 0.05) and patients (28% vs. 7%, p = 0.01). Adverse events were burning sensation, ""red eyes,"" nasal irritation, bitter taste. No serious adverse events were reported. Tolerance of azelastine was ""very good/good""/""satisfactory"" in the majority (62%/82% assessed by investigators, or 55%/79% by patients, respectively). Combining azelastine eye drops and nasal spray is a safe and effective treatment of severe seasonal rhinoconjunctivitis.",2002.0,0,0
79,11436970,Controlled study of preseasonal immunotherapy with grass pollen extract in tablets: effect on bronchial hyperreactivity.,C Lombardi; S Gargioni; S Venturi; P Zoccali; G W Canonica; G Passalacqua,"Based on experimental results, the sublingual route for immunotherapy (IT) has been accepted as a viable alternative to the injection route, but few data on the effects on asthma are so far available. In the present open controlled trial we evaluated whether a preseasonal IT with grass polllen in orosoluble tablets added to pharmacotherapy, can improve non-specific bronchial hyperreactivity. The clinical efficacy was evaluated as well. Fifty-one patients (mean age 27.4 years) suffering from rhinoconjunctivitis and/or mild-intermittent/mild-persistent asthma due to grass pollen were allocated to two groups receiving pharmacotherapy alone (n = 25) or pharmacotherapy plus IT in tablets (n = 26). A methacholine test was performed in asthmatic subjects out of the pollen seasons at baseline and after 3 years of treatment. Symptom scores and drug intake were evaluated during pollen seasons by a diary card. A significant increase p = .01) in the PD20 at the methacholine test was observed in the IT group compared to the control group. A significant clinical improvement both for rhinitis (p = .001) and asthma (p = .001) was observed in the IT group, and this improvement was paralleled by a clear-cut reduction of drug intake (p = .001). An improvement of rhinitis symptoms without modification of drug intake was seen in the control group (p = .01) The treatment was well tolerated and no relevant side effect was reported during the 3 years. The investigated local IT reduced the nonspecific bronchial hyperreactivity. Furthermore, it was clinically effective and safe.",2002.0,0,0
80,11476107,"Stanozolol in chronic urticaria: a double blind, placebo controlled trial.",D Parsad; R Pandhi; A Juneja,"H1-type antihistamine drugs are mainstays in the management of chronic urticaria. For patients with refractory, chronic, idiopathic urticaria who have failed to benefit from conventional therapy, other safe therapeutic modalities are required. To evaluate the role of stanozolol as an adjunctive therapeutic agent with H1-antihistamine in refractory chronic idiopathic urticaria, we conducted this study. Fifty-eight patients with chronic refractory urticaria were enrolled in this trial and were randomly assigned to two groups (A and B). Patients in group A received 2 mg stanozolol twice daily along with cetrizine 10 mg daily. Patients in group B received cetrizine 10 mg daily and placebo tablets twice daily. The improvement was monitored by estimation of severity score. Of the 58 patients, 26 in group A and 24 in group B could be evaluated. At the end of 12 weeks, 17 patients in group A showed marked to complete resolution as compared to 7 patients in group B (chi-square p<0.01). The intention to treat analysis p value was a found to be <0.007. There was a highly significant decrease in mean severity score at 12 weeks (p<0.001) in group A patients. The present study demonstrated that stanozolol is an effective and safe adjuvant therapy for treatment of chronic refractory urticaria.",2001.0,0,0
81,11482684,Burn wound itch control using H1 and H2 antagonists.,R A Baker; R A Zeller; R L Klein; R J Thornton; J H Shuber; R E Marshall; A G Leibfarth; J A Latko,"This study investigated the use of a combination of H1 and H2 antagonists and topical medications to control burn wound itch. Graeco-Latin square assignment provided an oral combination of 1) cetirizine and cimetidine or 2) diphenhydramine and placebo in four divided doses. The study protocol lasted 16 days divided into 4-day intervals, scoring itch before the initial dose of medication and at 1-hour, 6-hour, and 12-hour intervals after the first medication. A significant difference between mean itch scores across the four times was observed (Wilks' Lambda F = 26.52, df = 3, P <.0005). A three-way nested repeated measures interaction effect (Wilks' Lambda F = 9.85, df = 9, P <.0005) was observed representing a significantly different pattern on days 1 to 4 of the study compared with the remaining days. Controlling for the effect of topical medications, the cetirizine/cimetidine combination demonstrated a dramatic improvement at 1 and 6 hours, and a moderate improvement at 12 hours after initial medication for the day when compared with the diphenhydramine/placebo combination.",2002.0,0,0
82,11511142,Update in general internal medicine.,J V Sheffield; E B Larson; M R Gillock; D A Cramer; P T Kefalides,,2001.0,0,0
83,11517856,Cetirizine reduces the number of tryptase-positive mast cells in psoriatic patients: a double-blind controlled study.,E Pestelli; M Caproni; B Giomi; W Volpi; A Spallanzani; C Cardinali; I Floriani; P Fabbri,"Psoriatic plaque contains an increased number of mast cells that are thought to play an important role in the initiation and maintenance of the disease through the release of mediators such as histamine, proteoglycans, proteinases and cytokines. To verify the possible participation of these cells in the chronic inflammatory cutaneous response in psoriasis, we performed a double-blind controlled study to investigate the presence and activation of tryptase-positive mast cells in the lesional skin of 19 patients affected by active psoriasis vulgaris minima compared with five healthy, age-matched subjects. Psoriatic patients were randomized into two groups (A and B). The first group was treated with cetirizine (10 mg/three times a day for 15 days) and the second one was treated with placebo. Both groups underwent clinical staging [psoriasis area and severity index (PASI) score] and immunohistochemical evaluation [alkaline phosphatase antialkaline phosphatase (APAAP) procedure] before and after treatment. In group A, the PASI score ranged from 3.8 (SE +/- 1.00) to 1.8 (SE +/- 0.68) and in group B, from 5.0 (SE +/- 0.98) to 3.4 (SE +/- 0.47). The mean number of tryptase-positive mast cells for field, mainly distributed in the perivascular and periadnexal sites, ranged from 40.8 (SE +/- 7.15) to 21.6 (SE +/- 3.04) in group A and from 25.1 (SE +/- 3.78) to 26.3 (SE +/- 3.59) in group B (ANOVA test f = 6.95; gl = 1.16; p = 0.02). In our psoriatic patients, cetirizine significantly reduced the expression of tryptase-positive mast cells and produced a clinical improvement in erythema, suggesting a multilevel immunopharmacologic modulation of this antihistamine in psoriasis.",2002.0,0,1
84,11521794,Phase I dose-finding and pharmacokinetic study of docetaxel and vinorelbine as first-line chemotherapy for metastatic breast cancer.,M Campone; P Fumoleau; V Delecroix; R Deporte-Fety; G Perrocheau; L Vernillet; O Borg-Olivier; J P Louboutin; M C Bissery; A Riva; N Azli,"Anthracycline-containing regimens are widely used in advanced breast cancer. However, there is a need for new, non-anthracycline regimens that are active in patients for whom anthracyclines are contraindicated. The aim of this study was to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs) and recommended doses of docetaxel and vinorelbine as first-line chemotherapy in patients with metastatic breast cancer. The pharmacokinetics of both drugs was also evaluated. Thirty-four women with first-line metastatic breast cancer were treated with docetaxel, 60-100 mg/m2 (day 1), and vinorelbine, 20-22.5 mg/m2 (days 1 and 5), repeated every three weeks and administered on an outpatient basis. Two MTDs were determined: MTD1 was defined at the dose level using docetaxel 75 mg/m2, and vinorelbine 22.5 mg/m2 DLT being a grade 3 stomatitis that was more related to the dose of vinorelbine than that of docetaxel. Therefore, the study continued with a fixed dose of vinorelbine, 20 mg/m2, and docetaxel 85-100 mg/m2. MTD2 was defined at the dose level combining docetaxel, 100 mg/m2, and vinorelbine, 20 mg/m2; DLTs were grade 3 stomatitis and severe asthenia. Fluid retention was observed in 41% of patients but was never severe or a reason for patient discontinuation. In comparison with historical experience, Daflon 500 did not seem to increase the efficacy of the three-day corticosteroid premedication by further reducing the incidence or severity of fluid retention. No significant neurotoxicity was observed and no patient discontinued the study due to this site effect. Activity was observed at all dose levels and at all metastatic sites, with an overall response rate of 71% (95% CI: 52.0%-85.8%). The median time to progression was 31.4 weeks (95% CI: 12-48 weeks) and median survival was 15.6 months (95% CI: 2.6-26.6 months). The pharmacokinetics of docetaxel and vinorelbine were not modified between day 1 and day 3 when the two drugs were combined with the day 1 administration schedule used in this study. The recommended doses for phase II studies are docetaxel, 75 mg/m2 (day 1), plus vinorelbine, 20 mg/m2 (days 1 and 5), repeated every three weeks. At these doses, the combination was found to be active and well tolerated.",2002.0,0,0
85,11549210,Evaluation of the safety of fexofenadine from experience gained in general practice use in England in 1997.,P M Craig-McFeely; N V Acharya; S A Shakir,"Fexofenadine is the active metabolite of the non-sedating anti-histamine terfenadine. Pre-licensing clinical trials in over 6000 patients suggested it was effective and well tolerated. To assess the tolerability and safety of fexofenadine immediately after its availability on the UK market in March 1997. Post-marketing non-interventional observational cohort study using the methodology of prescription-event monitoring. Exposure data derived from dispensed prescription details supplied in confidence by the Prescription Pricing Authority. Outcome data derived from questionnaires returned by general practitioners (GPs) in England between March and August 1997. Of the 35,817 questionnaires sent, 18,238 (50.9%) were returned, of which 16,638 contained useful data. These included 40% male (mean age 36+/-19 years) and 59% female (mean age 39+/-19 years). Most common indications were allergic rhinitis (55%), not specified (28%), urticaria, pruritus or rash (10%) and other indications (7%). There were 40 reports of adverse drug reactions in 27 patients. Less than 2% of patients stopped the drug because of side effects. Events reported after exposure to fexofenadine were uncommon and already reported in clinical trials. There were eight reports of possible cardiac side effects (palpitations, three; chest pain, three; arrhythmia, one; and chest tightness, one). None was felt to be serious. There were no drug interactions reported. None of the 30 deaths was related to fexofenadine. None of the three adverse outcomes from the 47 pregnancies reported was related to fexofenadine. Within the limitations for an observational cohort study, fexofenadine was found to be well tolerated and safe in 16,638 users in general practice in England.",2002.0,0,1
86,11564134,"Absorption and disposition of levocetirizine, the eutomer of cetirizine, administered alone or as cetirizine to healthy volunteers.",E Baltes; R Coupez; H Giezek; G Voss; C Meyerhoff; M Strolin Benedetti,"The primary objective of the present study was to compare the absorption and disposition of levocetirizine, the eutomer of cetirizine, when administered alone (10 mg) or in presence of the distomer. An additional objective was also to investigate the configurational stability of levocetirizine in vivo in humans. The study was performed in a randomized, two-way cross-over, single-dose design with a wash-out phase of 7 days between the two periods. A total of 12 healthy male and 12 healthy female volunteers were included in the study. Bioequivalence can be concluded from the analysis of the pharmacokinetic parameters of levocetirizine when administered alone or as the racemate cetirizine. No chiral inversion occurs in humans when levocetirizine is administered, i.e. there is no formation of the distomer. When comparing the pharmacokinetic characteristics of levocetirizine and the distomer, the apparent volume of distribution of the eutomer is significantly smaller than that of the distomer (0.41 and 0.60 L/kg, respectively). For an H1-antagonist a small distribution volume can be considered as a positive aspect, both in terms of efficacy and safety. Moreover the non-renal clearance of levocetirizine is also significantly lower than that of the distomer (9.70 and 28.70 mL/min, respectively), which constitutes an additional positive aspect particularly as far as metabolism-based drug interactions are concerned. The information collected in the present study on the pharmacokinetics of levocetirizine and the distomer provide additional reasons for eliminating the distomer and developing levocetirizine as an improvement on cetirizine.",2002.0,0,0
87,11570300,Direct-to-consumer advertising. Finasteride for male pattern hair loss.,A Cassels; J M Wright; B Mintzes; C Jauca,,2002.0,0,0
88,11576078,"Comparison of the effects of levocetirizine and loratadine on histamine-induced wheal, flare, and itch in human skin.",G F Clough; P Boutsiouki; M K Church,"This randomized, double-blind, crossover study compared the effects of the R-enantiomer of cetirizine, levocetirizine, with those of loratadine on the wheal, flare, and itch response to histamine in human skin. Levocetirizine (5 mg), loratadine (10 mg), or placebo was taken orally 4 h before the intradermal injection of histamine (20 microl, 100 microM) or the control vehicle into the forearm skin of healthy volunteers. Flare areas were assessed by scanning laser Doppler imaging before and at 30-s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s with a visual analogue scale. After placebo administration, the mean peak flare area was 23.01+/-1.94 cm(2), the wheal area 248+/-27 mm(2), and the cumulative itch score 28.8+/-4.6% (mean+/-SEM). Levocetirizine reduced the flare, wheal, and itch by 60%, 68%, and 91%, respectively (all P<0.001, Student's t-test for paired data). The effects of loratadine were variable and not statistically significant. Levocetirizine (5 mg) is a potent inhibitor of the effects of histamine in human skin with an efficacy that exceeded that of loratadine (10 mg) when single doses of the drugs were administered 4 h before the test.",2001.0,0,1
89,11577794,Intranasal corticosteroids for allergic rhinitis: superior relief?,L P Nielsen; N Mygind; R Dahl,"Whether first-line pharmacological treatment of allergic rhinitis should be antihistamines or intranasal corticosteroids has been discussed for several years. First-generation antihistamines are rarely used in the treatment of allergic rhinitis, mainly because of sedative and anticholinergic adverse effects. On the basis of clinical evidence of efficacy, no second-generation antihistamine seems preferable to another. Similarly, comparisons of topical and oral antihistamines have been unable to demonstrate superior efficacy for one method of administration over the other. Current data documents no striking differences in efficacy and safety parameters between intranasal corticosteroids. When the efficacy of antihistamines and intranasal corticosteroids are compared in patients with allergic rhinitis, present data favours intranasal corticosteroids. Interestingly, data do not show antihistamines as superior for the treatment of conjunctivitis. Safety data from comparative studies in patients with allergic rhinitis do not indicate differences between antihistamines and intranasal corticosteroids. Combining antihistamines and intranasal corticosteroids in the treatment of allergic rhinitis does not provide any additional effect to intranasal corticosteroids alone. On the basis of current data, intranasal corticosteroids seem to offer superior relief in allergic rhinitis than antihistamines.",2002.0,0,0
90,11583068,Triamcinolone: new and old indications.,S A Doggrell,"Triamcinolone is a commonly used synthetic corticosteroid that has recently been tested in a large clinical trial for chronic obstructive pulmonary disease and shown to have some benefits. To our knowledge, there are no reviews of the pharmacotherapy of triamcinolone. This review has a brief overview of the pharmacology of triamcinolone, followed by a discussion of the clinical trials with triamcinolone. Triamcinolone is used in the treatment of respiratory inflammation, rheumatoid arthritis and a variety of other inflammatory conditions.",2001.0,0,0
91,11584993,Treatment of acute cryptococcal disease.,A Apisarnthanarak; W G Powderly,"Successful treatment outcome for cryptococcal disease has been available since the introduction of the polyene antifungal, amphotericin B. Over the past 15-20 years, treatment of acute cryptococcal disease has dramatically improved. Several therapeutic strategies have been introduced which improve overall outcome of therapy and help decrease the duration of treatment. Not surprisingly, most data now exists on the treatment of AIDS-associated cryptococcal disease, especially cryptococcal meningitis. Currently, amphotericin B with or without flucytosine is regarded as the best initial therapy for patients with meningitis or more severe illness, although, the azoles and other formulations of amphotericin B can considered in other situations. The choice of treatment for cryptococcal disease depends on both the anatomic sites of involvement and the host's immune status, all of which will be addressed in this article.",2002.0,0,0
92,11588693,Variant effect of first- and second-generation antihistamines as clues to their mechanism of action on the sneeze reflex in the common cold.,P S Muether; J M Gwaltney,"Treatment with first-generation antihistamines reduces sneezing, rhinorrhea, nasal mucus weight, and, in some instances, cough in subjects with experimental or natural colds; however, treatment with second-generation antihistamines has not been effective for these complaints in trials in subjects with natural colds. This article reports the negative results of a clinical trial with loratadine, a second-generation antihistamine, in adults in the rhinovirus challenge model. This finding in the highly controlled setting of the challenge model confirms the earlier negative studies with second-generation antihistamines in natural colds. First-generation antihistamines block both histaminic and muscarinic receptors as well as passing the blood-brain barrier. Second-generation antihistamines mainly block histaminic receptors and do not pass the blood-brain barrier. The effectiveness of first-generation antihistamines in blocking sneezing in colds may be due primarily to neuropharmacological manipulation of histaminic and muscarinic receptors in the medulla.",2002.0,1,1
93,11665867,Causality assessment of adverse effects: when is re-challenge ethically acceptable?,A L Po; M J Kendall,"One of the most difficult tasks in the evaluation of a medicine is whether it causes a particular rare and unusual (idiosyncratic) adverse effect. Such causality assessments are sometimes done by drug de-challenge and re-challenge. When the adverse effect is potentially serious, there is clearly an important decision to be made as to whether the re-challenge is justifiable and hence ethical. The recent controversy about the potential cardiotoxicity of fexofenadine, the fatalities associated with penicillin re-challenge and the fatalities associated with abacavir re-challenge highlight some of the potential serious risks of drug re-challenge. The associated important ethical issues are discussed. In particular, there is the need to ensure respect for the patient and to consider the scientific and social value of the re-challenge. A framework for evaluating and assessing the appropriateness of a particular drug re-challenge is proposed in the light of recent as well as long-standing discussions of drug re-challenge, patient informed consent and the ethics of human experimentation, in general. It is suggested that a drug re-challenge should be approached with the same rigour and standards of documentation as are currently required of clinical trials. Given the potential conflicts of interest inherent with any drug study, it is argued that the safeguards, as may be provided by scrutiny by an ethics committee, are necessary for a drug re-challenge. For the investigator contemplating the conduct of a drug re-challenge we would recommend the following: (i) a careful risk-benefit assessment as part of the decision-making process; (ii) careful scientific preparation, including appropriate expert support and emergency back-up facilities, if re-challenge is deemed necessary; (iii) the writing of a detailed protocol for independent approval and for safeguarding all concerned; and (iv) meticulous record keeping.",2002.0,0,0
94,11674900,Do antihistamines impair school performance in children?,T W Marsland; W P Newton,,2002.0,0,0
95,11674922,"Sublingual immunotherapy in tree pollen allergy. Double-blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule.",S Voltolini; P Modena; P Minale; D Bignardi; C Troise; P Puccinelli; S Parmiani,"sublingual immunotherapy has been recognised as safe and effective but it is still poorly documented in tree pollen allergy. Allergy to alder, birch and hazel is important in Northern European countries but its clinical relevance is increasing in Southern Europe. thirty patients, selected and observed for one pollen season, were randomised to receive placebo (15 patients) or active treatment (15 patients). Twenty-seven patients completed the first year and 24 of them were treated with active therapy during the second year of the study in comparison to a parallel group of ten patients treated only with drugs. Symptom and drug scores during each pollen season, birch-specific IgE, changes in skin test reactivity, changes in specific Nasal Provocation Test and the daily average pollen count for the relevant trees were considered for the assessment of the efficacy of the treatment. both active and placebo group showed a statistically significant improvement in scores in comparison to the previous year, under a lower allergenic pressure. The improvement was higher in the active group (76.04 % reduction of drugs) but not significantly different from that registered in the placebo group (37.05 % reduction). In the open phase of the study, treated patients showed significantly better scores in comparison to the control group. No significant changes in skin reactivity, specific IgE and Nasal Provocation Test were registered. SLIT tolerance was very good. our data show a better but not statistically significant clinical outcome for patients actively treated with SLIT, but the placebo effect and the year-by-year variability of the environmental allergenic load in our small-size pilot study do not allow for a conclusive statement about the efficacy of this form of therapy.",2002.0,0,0
96,11702618,Treatment of urticaria. An evidence-based evaluation of antihistamines.,E E Lee; H I Maibach,"Urticaria is a cutaneous syndrome characterized by dermal edema (wheal) and erythema (flare) that blanches with pressure. The lesions typically last less than 24 hours and are usually pruritic. In 1983, Christensen and Maibach summarized the theory behind the use of histamine H1 receptor antagonists (antihistamines) in clinical dermatology. These agents remain the mainstay of treatment for urticaria. This article reviews the medical literature on the effectiveness of antihistamines in urticarial syndromes, including acute, chronic idiopathic and the physical urticarias. Older antihistamines, such as chlorpheniramine and hydroxyzine, are effective in the treatment of urticarias, but they also have marked sedative and anticholinergic effects. Newer nonsedating antihistamines (second-generation antihistamines) have been developed that have reduced adverse effects because they do not cross the blood-brain barrier; these agents (acrivastine, cetirizine, loratadine, mizolastine, fexofenadine, ebastine, azelastine and epinastine) cause significantly less sedation and psychomotor impairment than their older counterparts. A review of the literature reveals that there are few studies which document the efficacy of second-generation antihistamines in the treatment of acute urticaria, a biologic entity that usually resolves within 3 weeks. We did not identify controlled studies that suggested superiority of any antihistamine in the treatment of acute urticaria. Loratadine or cetirizine, and possibly mizolastine, appear to be treatments of choice for chronic idiopathic urticaria. For symptomatic dermatographism, the combination of an antihistamine and an H2 antagonist, e.g. chlorpheniramine and cimetidine, appears to be effective. Very few studies have been conducted on the use of antihistamines in the treatment of cold, cholinergic, and pressure urticaria. Antihistamines are the mainstay of urticarial therapy. This evidence-based review suggests that there are efficacy differences between newer, nonsedating antihistamines and older agents in some forms of the disorder. Clearly, further well-controlled clinical trials in larger numbers of patients are needed to clarify the role of these agents in the treatment of urticaria.",2002.0,0,0
97,11703220,Fexofenadine reduces nasal congestion in perennial allergic rhinitis.,G Ciprandi; C Cosentino; M Milanese; C Mondino; G W Canonica,"Nasal congestion is the predominant symptom in perennial allergic rhinitis (PAR), and it seems to be mainly related to the late-phase inflammatory events. The present pilot study aimed to evaluate the therapeutic effect exerted by fexofenadine in patients with PAR due to mite allergy. This study was a parallel, double-blind, randomized, three-arm (1:1:1), placebo-controlled study. Thirty-one subjects with PAR were enrolled and received double-blind medication: fexofenadine 120 or 180 mg, or placebo, once a day for 28 days. The total symptom score was reduced by fexofenadine (both dosages) at V2 (P=0.007), whereas placebo did not modify it. Nasal congestion decreased after 1 week of treatment with fexofenadine 120 (P=0.027) and 180 (P=0.01), but not with placebo (P=NS). At V3, fexofenadine (both dosages) significantly reduced nasal congestion (P=0.011 and P=0.007, respectively), by placebo did not show any significant effect. This pilot study represents the first evidence of the efficacy of fexofenadine in PAR, and also the control of the nasal congestion. We suggest performing larger trials to confirm these preliminary findings.",2002.0,0,1
98,11703222,Desloratadine reduces nasal congestion in patients with intermittent allergic rhinitis.,A S Nayak; E Schenkel,"Nasal congestion is among the most bothersome of the symptoms of intermittent allergic rhinitis (IAR). Decongestants such as pseudoephedrine are often accompanied by adverse effects and should be avoided by patients with hypertension, arrhythmia, and other medical conditions. Most of the currently available antihistamines are ineffective for nasal congestion. Oral desloratadine, a new, potent H1-receptor antagonist, was examined for its ability to relieve nasal congestion/stuffiness in 346 patients (172 in the desloratadine group and 174 in the placebo group) with IAR. Desloratadine, administered once daily at a dose of 5 mg, demonstrated significant improvement in nasal congestion/stuffiness at all time points assessed in the study. This benefit was observed as early as the first patient evaluation on day 2 and continued throughout the 2 weeks of the study. Desloratadine is a new treatment option for patients with IAR and nasal congestion.",2002.0,0,0
99,11718589,Superiority of an intranasal corticosteroid compared with an oral antihistamine in the as-needed treatment of seasonal allergic rhinitis.,S M Kaszuba; F M Baroody; M deTineo; L Haney; C Blair; R M Naclerio,"The daily use of either intranasal corticosteroids or histamine(1) (H(1)) receptor antagonists has proved to be efficacious in the treatment of seasonal allergic rhinitis. Most patients, however, use these medications as needed. Our objective was to compare the effectiveness of as-needed use of H(1) receptor antagonists with that of intranasal corticosteroids in the treatment of seasonal allergic rhinitis. We performed a randomized, open-label, parallel-group study comparing the as-needed use of an H(1) receptor antagonist (loratadine) with that of an intranasal corticosteroid (fluticasone propionate) in the management of fall seasonal allergic rhinitis in the fall of 1999. Subjects kept a diary of their daily symptoms and were examined at enrollment into the study and biweekly for 4 weeks during treatment. Outcome measures were the Rhinoconjunctivitis Quality of Life Questionnaire score, daily symptom diary scores, and the number of eosinophils and the levels of eosinophilic cationic protein in nasal lavage samples. Patients in the fluticasone-treated group reported significantly better scores in the activity, sleep, practical, nasal, and overall domains (P<.05) of the Rhinoconjunctivitis Quality of Life Questionnaire. The median total symptom score in the fluticasone-treated group was significantly lower than that in the loratadine-treated group (4.0 vs 7.0; P<.01). After treatment, the number of eosinophils was significantly smaller in the fluticasone-treated group compared with the loratadine-treated group (P =.001). Eosinophilic cationic protein levels followed the same pattern, with a significant correlation between the levels of eosinophilic cationic protein and the number of eosinophils (r(s) = 0.70, P<.01). As-needed intranasal corticosteroids reduce allergic inflammation and are more effective than as-needed H(1) receptor antagonists in the treatment of seasonal allergic rhinitis.",2002.0,0,0
100,11721215,Controlled clinical study of the efficacy of loratadine in Nigerian patients with allergic rhinitis.,C C Nwawolo; A D Olusesi,"An observer blind clinical study was carried out among 64 Nigerian patients with allergic rhinitis to assess the efficacy and tolerance of loratadine a new generation H1 antihistamine. Patients were allotted randomly to receive treatment for 1 week with either loratadine + Vit. C (group A), chlorpheniramine + Vit. C (group B), or Vit. C alone (group C). Assessment was by subjective symptom scoring of three nasal symptoms namely; sneezing, rhinorrhoea and nasal blockage. Difference between pre treatment and post treatment mean symptom scores was used as degree of improvement for statistical analysis and this formed the primary efficacy parameter. Adverse effects namely; anticholinergic effects, gastrointestinal effects and drowsiness were assessed following treatment. The results showed that loratadine was significantly better than Vit. C. alone (P = 0.0002) and chlorpheniramine was also significantly better than Vit. C. alone (P = 0.039). However, loratadine was significantly better than chlorpheniramine P = 0.046. Drowsiness was noted in 19.2% of patients on loratadine compared with 57.1% of patients on chlorpheniramine. lt is concluded that though both loratadine and chlorpheniramine were effective in the relief of symptoms of allergic rhinitis in Nigerian patients, loratadine was significantly more effective with minimal sedating effect.",2002.0,0,0
101,11736946,"Pruritus in polycythaemia vera: prevalence, laboratory correlates and management.",F Diehn; A Tefferi,"In a retrospective cohort, 192 (48%) out of 397 patients with polycythaemia vera had a documented history of pruritus. At diagnosis, the presence of pruritus was significantly associated with a lower mean corpuscular volume and a higher leucocyte count. Among 66 patients with documentation of treatment for pruritus, 389 'patient visits' were reviewed, revealing a significant correlation between active pruritus and low mean corpuscular volume, but not platelet, leucocyte or basophil count. Paroxetine and hydroxyzine were rated by patients to be the most effective drugs in controlling pruritus. These observations suggest a pathogenetic role for both iron deficiency and biogenic amines in polycythaemia vera-associated pruritus.",2002.0,0,0
102,11758635,"Absorption, distribution, metabolism and excretion of [14C]levocetirizine, the R enantiomer of cetirizine, in healthy volunteers.",M S Benedetti; M Plisnier; J Kaise; L Maier; E Baltes; C Arendt; N McCracken,"The main goal of the present study was to investigate the absorption and disposition of levocetirizine dihydrochloride, the R enantiomer of cetirizine dihydrochloride, following a single oral administration (5 mg) of the 14C-labelled compound in healthy volunteers. Configurational stability was also investigated. Levocetirizine was rapidly and extensively absorbed: 85.4% and 12.9% of the radioactive dose were recovered 168 h post-dose in urine and faeces, respectively. Levocetirizine and/or its metabolites were not, or only very poorly, associated with blood cells, as the blood-to-plasma ratio was 0.51 to 0.68. The mean apparent volume of distribution (Vz/F) was 26.9 1 (0.3 l/kg) indicating that the distribution of levocetirizine is restrictive. The protein binding of radiolabelled levocetirizine was 96.1% l h after administration. In vitro, at concentrations ranging from 0.2 microg/ml to 1 microg/ml, the protein binding was 94.8% to 95.0%. Levocetirizine is very poorly metabolised. The cumulative 48-h excretion as parent compound accounted for 85.8% of the oral dose, equivalent to 95% of the total radioactivity excreted at this time. At least 13 minor metabolites were detected in urine and represented 2.4% of the dose at 48 h. The metabolic pathways involved in levocetirizine metabolism are oxidation (hydroxylation, O-dealkylation, N-oxidation and N-dealkylation), glucuroconjugation, taurine conjugation and glutathione conjugation with formation of the mercapturic acids. There was no evidence of chiral inversion of levocetirizine in humans. This result is consistent with that obtained in preclinical studies.",2002.0,0,0
103,11765592,Efficacy and safety of an oral formulation of cetirizine and prolonged-release pseudoephedrine versus xylometazoline nasal spray in nasal congestion.,U P Stübner; J Toth; B Marks; U E Berger; B Burtin; F Horak,"The aim of this study was to compare the decongestant properties and tolerability of the sympathomimetic xylometazoline hydrochloride 0.1% (CAS 1218-35-5, XMZ) and an oral formulation of cetirizine hydrochloride 5 mg and pseudoephedrine hydrochloride 120 mg (CAS 83881-51-0 and 90-82-4, CTZ/PSE; Cirrus). Thirty-six asymptomatic patients suffering from perennial allergic rhinitis from house dust mite were randomized to this open two-period crossover study. Patients received the study medications for four days each. In each period, treatments were taken twice a day. On day 1 in each period, immediately after the first dose of medication, patients were challenged with Dermatophagoides pteronyssinus extract 1 in the Vienna Challenge Chamber for 5 h. Primary efficacy parameters were nasal congestion evaluated by digital analysis of nasal cavity photographs and nasal airflow. Furthermore amounts of nasal secretions, nasal and ocular symptoms were recorded. In addition, 5 independent Ear-Nose-Throat specialists also assessed nasal cavity photographs. Statistical analyses were conducted at the 5% level of significance. Digital analysis of the nasal cavity photographs as well as nasal airflow measurements did not differentiate XMZ from CTZ/PSE. Ratings of the photographs of the nasal cavity emphasized the rapid onset of XMZ. No clinically relevant adverse events were recorded. This rapid onset of action but short-lived effect of topical xylometazoline 0.1% should be balanced against the consistent and prolonged effect of systemic cetirizine/pseudoephedrine combination in the treatment of perennial allergic rhinitis as no significant differences between these 2 medications were noted regarding their decongestant properties. With the exception of nasal obstruction, all subjective symptoms as well as the global condition were significantly better under CTZ/PSE. Amounts of nasal secretions during these sessions were significantly lower with CTZ/PSE.",2002.0,0,0
104,11772135,Cetirizine/pseudoephedrine.,K Wellington; B Jarvis,"Cetirizine is the carboxylated metabolite of hydroxyzine, and has high specific affinity for histamine H(1) receptors. Pseudoephedrine is a sympathomimetic drug that acts directly on alpha-adrenergic receptors. black triangle Cetirizine/pseudoephedrine 5/120 mg twice daily was significantly more effective than intranasal budesonide 100 microg or placebo at improving nasal obstruction, nasal patency and reducing the volume of nasal secretion, and was significantly more effective than intranasal xylometazoline 0.1% with respect to nasal secretion, during house dust mite faeces challenge in three randomised, cross- over studies among volunteers with seasonal or perennial rhinitis. The onset of action of cetirizine/pseudoephedrine was reported to be approximately 30 minutes. black triangle The bioavailability of cetirizine and pseudoephedrine is similar after administration of cetirizine/pseudoephedrine 5/120 mg bilayer tablets or coadministration of cetirizine 5 mg tablets plus pseudoephedrine sustained-release (SR) 120 mg caplets. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was significantly more effective than each drug given alone at reducing mean total symptom scores for seasonal or perennial allergic rhinitis in two randomised, double-blind, multicentre trials. In both studies, the mean proportion of days during which the five measured symptoms (nasal obstruction, sneezing, rhinorrhoea, nasal pruritus and ocular pruritus) were absent or mild was significantly greater in recipients of the cetirizine plus pseudoephedrine SR. black triangle In one study, cetirizine 5 mg plus pseudoephedrine SR 120 mg was significantly more effective at reducing nasal obstruction than either drug alone. black triangle Cetirizine 5mg plus pseudoephedrine SR 120 mg twice daily for 2 to 3 weeks was well tolerated in patients with seasonal or perennial allergic rhinitis. The most common adverse events were dry mouth, insomnia, headache, somnolence, asthenia and nervousness.",2002.0,0,0
105,11799030,Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis.,Andreas Schapowal; Petasites Study Group,"To compare the efficacy and tolerability of butterbur (Petasites hybridus) with cetirizine in patients with seasonal allergic rhinitis (hay fever). Randomised, double blind, parallel group comparison. Four outpatient general medicine and allergy clinics in Switzerland and Germany. 131 patients were screened for seasonal allergic rhinitis and 125 patients were randomised (butterbur 61; cetirizine 64). Butterbur (carbon dioxide extract tablets, ZE 339) one tablet, four times daily, or cetirizine, one tablet in the evening, both given for two consecutive weeks. Scores on SF-36 questionnaire and clinical global impression scale. Improvement in SF-36 score was similar in the two treatment groups for all items tested hierarchically. Butterbur and cetirizine were also similarly effective with regard to global improvement scores on the clinical global impression scale (median score 3 in both groups). Both treatments were well tolerated. In the cetirizine group, two thirds (8/12) of reported adverse events were associated with sedative effects (drowsiness and fatigue) despite the drug being considered a non-sedating antihistamine. The effects of butterbur are similar to those of cetirizine in patients with seasonal allergic rhinitis when evaluated blindly by patients and doctors. Butterbur should be considered for treating seasonal allergic rhinitis when the sedative effects of antihistamines need to be avoided.",2002.0,0,0
106,11802289,[Efficacy and safety of fexofenadine and cetirizine in the treatment of allergic rhinitis].,A López García; D Paz Martínez; M Orea Solano; G Hernández Valencia; A Ramírez García; H Ramírez Ojeda; L F Sánchez Medal; A Soda Mehry; T Velarde Domínguez; M A Betancourt Suárez; J L Méndez Vera,"Allergic rhinitis affects 20 million of people in United States and a higher figure all around the world. To evaluate the efficacy and safety of fexofenadine compared with certirizine in the treatment of allergic rhinitis. It was carried out a prospective, double blind, comparative, randomized and multicentric study in patients with allergic rhinitis, with ages between 12 and 65 years. In the first phase, placebo was administered during three days to all the patients; and then, they were randomly allocated to receive fexofenadine 120 mg or cetirizine 10 mg in one dose a day during 14 days. Laboratory and cabinet tests at the beginning and at the end were performed to value security, as well as a global evaluation of the researcher to estimate effectiveness. 176 patients were included, 63.6% were women, average age was 27 years (+/- 12), 47.7% received fexofenadine and 52.2%, cetirizine. There was not significant difference in parameters of effectiveness nor of security in the studied group. The results of the present study confirm the efficacy and safety of the antihistaminic fexofenadine in the treatment of allergic rhinitis.",2002.0,0,1
107,11806304,[H1 antihistaminics: can we precisely define the characteristics of the ideal molecule?].,J P Rihoux,"The experience of the past twenty years in the field of H1 antihistamines prompts us to consider that these drugs are more dissimilar than has previously been reported in the scientific literature. In fact, the H1 antihistamines that are used in man seem to be effective, even if there are some differences in clinical efficacy. Nevertheless they may have marked differences as far as the following aspects are concerned: their possible binding to various biological targets, their pharmacokinetics, their metabolism and their volume of distribution. All these differences must be taken into consideration when judging the real quality of each of these drugs.",2002.0,0,0
108,11806881,The effect of loratadine in exercise-induced asthma.,A Baki; F Orhan,"To assess the effect of loratadine in exercise induced asthma. Randomised, double blind, placebo controlled study of 10 mg oral loratadine, once daily for three days in 11 children. At the end of the treatment period FEV(1) was measured, and patients were exercised on a treadmill. FEV(1) measurements were repeated at intervals after exercise. Loratadine significantly reduced the decrease in FEV(1) after exercise at two, five, 10, 15, and 30 minutes, compared with placebo (p < 0.05). However, the mean decrease in FEV(1) at five minutes was more than 15% of baseline in the loratadine group. Loratadine reduces, but does not prevent, exercise induced asthma in children.",2002.0,0,0
109,11818765,Effects of the selective H1 and H2 histamine receptor antagonists loratadine and ranitidine on autonomic control of the heart.,Michael A Nault; Brian Milne; Joel L Parlow,"H1 and H2 histamine receptor subtypes are present throughout the heart and may be involved in disturbances of cardiac rhythm that occur during anaphylaxis. Although H1 and H2 receptor antagonists are used in the treatment of anaphylaxis, there have been reports implicating these drugs in the genesis of dysrhythmias. This study was designed to investigate the effects of the selective H1 and H2 receptor antagonists loratadine and ranitidine on physiologic autonomic control of the healthy cardiovascular system. Using a double-blind, crossover design, 14 healthy volunteers completed the protocol and were randomized to receive one dose of loratadine (20 mg), ranitidine (300 mg), or placebo on each of three separate testing sessions. Continuous electrocardiogram and BP recordings were obtained before and 3 h after administration of study drug. Effects on cardiac autonomic control were quantified using power spectral analysis of heart rate variability and calculation of spontaneous baroreflex sensitivity. Neither placebo nor loratadine significantly altered indices of autonomic cardiovascular control. Conversely, H2 antagonism with ranitidine resulted in a 23.3% decrease in baroreflex sensitivity (P < 0.05) and a corresponding 25.0% decrease in the ratio of high frequency to total power of heart rate variability, both indices of parasympathetic modulation (P < 0.01). Furthermore, ranitidine evoked a concomitant 103.8% increase in the ratio of low to high frequency power of heart rate variability, an index of sympathetic control (P < 0.01). H1 receptor antagonism with loratadine does not influence physiologic cardiovascular control in young healthy subjects. However, the altered cardiac sympathovagal balance after oral administration of the H2 receptor antagonist ranitidine indicates a shift toward sympathetic predominance in heart rate control. The authors postulate that this could have implications regarding susceptibility to arrhythmias in conditions of heightened sympathetic stimulation.",2002.0,0,0
110,11834560,Systematic review of randomised controlled trials of over the counter cough medicines for acute cough in adults.,Knut Schroeder; Tom Fahey,"To determine whether over the counter cough medicines are effective for acute cough in adults. Systematic review of randomised controlled trials. Search of the Cochrane Acute Respiratory Infections Group specialised register, Cochrane Controlled Trials Register, Medline, Embase, and the UK Department of Health National Research Register in all languages. All randomised controlled trials that compared oral over the counter cough preparations with placebo in adults with acute cough due to upper respiratory tract infection in ambulatory settings and that had cough symptoms as an outcome. 15 trials involving 2166 participants met all the inclusion criteria. Antihistamines seemed to be no better than placebo. There was conflicting evidence on the effectiveness of antitussives, expectorants, antihistamine-decongestant combinations, and other drug combinations compared with placebo. Over the counter cough medicines for acute cough cannot be recommended because there is no good evidence for their effectiveness. Even when trials had significant results, the effect sizes were small and of doubtful clinical relevance. Because of the small number of trials in each category, the results have to be interpreted cautiously.",2002.0,0,0
111,11859651,,,,,0,1
112,11874388,Comparative activity of cetirizine and mizolastine on histamine-induced skin wheal and flare responses at 24 h.,A Purohit; M Mélac; G Pauli; N Frossard,"The aim of our study was to compare the activity of cetirizine 10 mg with that of mizolastine 10 mg vs placebo at 24 h after intake in healthy volunteers. This was a double-blind, randomized, placebo controlled, three-way cross-over study with a wash-out period of 7 +/- 2 days between each period. The study included 36 healthy volunteers (18--50 years, mean age = 32 years; 9 males). The objective measurement was the cutaneous reactivity to increasing concentrations of histamine (0, 5, 10, 20, 40, 80, 160 mg ml(-1)) administered by prick tests. The reactivity was evaluated by the wheal and flare areas (mm2). The AUC (area under curves) values of the wheal and flare areas as a function of the log2 transformed histamine concentration were calculated for each subject and treatment, and compared. A highly significant treatment effect was evidenced both for wheal and flare responses (P = 0.0001). This indicates the good activity of both cetirizine 10 mg and mizolastine 10 mg in inhibiting skin wheal and flare reactions to histamine. In addition, the mean AUC values significantly differed between cetirizine and mizolastine (64.8 and 117.8 log2 (mg ml(-1)) x mm2 for wheal, and 939.4 and 2340.8 for flare, respectively; P = 0.0001), with a superior activity of cetirizine than mizolastine at 24 h after intake both on wheal and flare responses. The tolerance of cetirizine and mizolastine was good. The severity of the adverse events was never more than 'moderate', 'fatigue' being the most frequent reported symptom [cetirizine (6 subjects), placebo (3), mizolastine (5)], followed by 'somnolence' [cetirizine (0), placebo (1), mizolastine (3)]. There was no serious adverse event. This study shows that cetirizine (10 mg) suppresses skin reactivity to histamine more effectively than mizolastine (10 mg) 24 h after intake in healthy volunteers.",2002.0,0,0
113,11888359,Montelukast: a review of its therapeutic potential in asthma in children 2 to 14 years of age.,Richard B R Muijsers; Stuart Noble,"Montelukast is a cysteinyl leukotriene receptor antagonist which is used as a preventive treatment for persistent asthma in patients > or =2 years of age. In children aged 6 to 14 years montelukast (5 mg/day) treatment resulted in a significant increase in FEV(1) (forced expiratory volume in 1 second, primary clinical outcome) during an 8-week randomized, double-blind trial. Moreover, significant improvements were observed for a range of secondary endpoints assessing symptoms, exacerbation rates, beta-agonist usage and quality of life. Concomitant administration of montelukast (5 mg/day) and inhaled budesonide (200 microg twice daily) resulted in a trend towards an increase in FEV(1) (p = 0.06, primary endpoint) and a statistically significant reduction in both as-needed beta(2)-agonist usage and the percentage of days with asthma exacerbations compared with budesonide plus placebo. No significant differences were observed in asthma-related quality of life between the two groups. During clinical trials both improvements in lung function and reductions in as-needed beta(2)-agonist usage were generally observed within 1 day after initiation of therapy in children 2 to 14 years of age with persistent asthma. Data from a randomized, nonblind trial in 6- to 11-year-old children and a 6-month extension to this trial suggest that both compliance to therapy and patient satisfaction are greater for montelukast than for either inhaled sodium cromoglycate or inhaled beclomethasone. In addition, patients and parents preferred oral montelukast over sodium cromoglycate. In 2- to 5-year-old children with persistent asthma, montelukast (4 mg/day) treatment resulted in significant improvements in a range of outcomes, such as as-needed beta(2)-agonist usage, symptom scores and percentage of days with asthma symptoms, as assessed during a randomized, double-blind trial primarily designed to assess tolerability. Data from small randomized, double-blind trials suggest that montelukast reduces exercise-induced bronchoconstriction in 6- to 14-year-old children. Montelukast is generally well tolerated. The frequency of adverse events in montelukast-treated children of all ages was comparable to that in patients receiving placebo. Oral montelukast has shown efficacy as a preventive treatment for asthma during clinical trials in children aged 2 to 14 years. The drug offers benefits over more standard therapies such as inhaled sodium cromoglycate and nedocromil in terms of compliance and convenience. In addition, the drug offers significant benefits when added to inhaled corticosteroids (according to secondary endpoints). Montelukast offers an effective, well tolerated and convenient treatment option for children with asthma.",2002.0,0,0
114,11903961,Dose-dependent inhibition of the CYP2D6 catalyzed oxidation of sparteine by mepyramine in healthy volunteers.,S Kortunay; A Bozkurt; N E Basci; K Brøsen; S O Kayaalp,,2002.0,0,0
115,11949773,"Effects of emedastine and cetirizine, alone and with alcohol, on actual driving of males and females.",Annemiek Vermeeren; Johannes G Ramaekers; James F O'Hanlon,"Emedastine is registered in its country of origin (Japan) as an antihistamine for the indication of seasonal allergic rhinitis. Further research on the drug's sedating properties was needed to secure its registration elsewhere. The present study was designed to compare the effects of emedastine 2 mg and 4 mg twice daily after single and repeated doses, on actual driving performance versus those of cetirizine 10 mg once daily and placebo; and to determine how repeated doses of each drug interact with alcohol to affect driving. Each treatment was administered for 5 days to 19 healthy volunteers (nine men and ten women, aged 21-45 years) according to a four-period double-blind cross-over design. Driving performance was measured in a standardized test between 3 and 4 h after administration of the morning dose on days 1, 4 and 5. Alcohol, sufficient for achieving a blood alcohol concentration of 0.05 g/dl was given before driving on day 5 of each period. Both emedastine doses similarly and significantly impaired driving in every test. The effects of cetirizine were less. They were significant over days 1, 4 and 5 combined, although not separately. Women were more impaired by both drugs. Alcohol increased driving impairment similarly in every condition. Subjects were only able to discriminate the sedating and impairing effects of the first dose of emedastine 4 mg from placebo. Emedastine, in oral doses of 2 mg and 4 mg twice daily, is sedating and impairs driving. The drug could therefore constitute a traffic hazard and its users should be warned accordingly.",2002.0,0,0
116,11952027,"A randomized, double-blind, placebo-controlled comparison of emedastine 0.05% ophthalmic solution with loratadine 10 mg and their combination in the human conjunctival allergen challenge model.",Mark B Abelson; Allen P Kaplan,"When selecting treatment for allergic conjunctivitis, a primary concern is whether to choose local or systemic therapy. This study compared the efficacy of topical emedastine 0.05% ophthalmic solution with that of oral loratadine 10 mg and their combination in the conjunctival allergen challenge model of allergic conjunctivitis. This was a single-center, randomized, double-masked, placebo-controlled, parallel-group study. At visit 1, eligible subjects underwent conjunctival allergen challenge to identify the dose required to elicit a positive allergic reaction. After 7 days, subjects returned for visit 2, at which the allergen dose was confirmed. At visit 3, which took place 2 weeks later, subjects were randomized to receive either emedastine plus placebo capsules, loratadine plus placebo eyedrops, or both emedastine and loratadine. One hour after receiving study drug, subjects were challenged with allergen in both eyes. Allergic signs and symptoms were graded using standardized 5-point scales. The primary efficacy variables were itching and conjunctival hyperemia. Secondary efficacy variables were ciliary and episcleral hyperemia, chemosis, lid swelling, and tearing. Itching was graded subjectively at 3, 5, and 10 minutes after challenge. All other variables were assessed at 5, 10, and 20 minutes after challenge. Eighty subjects (mean age, 43.68 years) were randomized to receive study treatment. Forty subjects (20 men, 20 women) received emedastine plus placebo capsules, 20 (7 men, 13 women) received loratadine plus placebo eyedrops, and 20 (12 men, 8 women) received both active treatments. In the between-group efficacy comparison at visit 3, the difference in itching and hyperemia scores between emedastine and loratadine was statistically significant at all time points (all, P < 0.05). Efficacy scores for the combination of emedastine and loratadine were significantly better than those for loratadine alone at 2 of 3 time points for itching and all time points for hyperemia (P < 0.05). The combination was significantly better than emedastine alone at I of 3 time points for itching and 6 of 9 time points for hyperemia (P < 0.05). In this study, emedastine was more efficacious than loratadine for reducing the itching and redness associated with allergic conjunctivitis in the human conjunctival allergen challenge model.",2002.0,0,0
117,11978146,Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine.,Christopher Banfield; Samir Gupta; Mark Marino; Josephine Lim; Melton Affrime,"Certain foods, such as grapefruit juice, are known to substantially alter the bioavailability of some drugs. These effects may be mediated by interactions with enzyme systems, such as cytochrome P450, or with active transporter systems, such as P-glycoprotein and organic anion transporting polypeptides. To assess the effect of consumption of grapefruit juice on the oral bioavailability of two nonsedating antihistamines, fexofenadine and desloratadine. Non-blinded, randomised, single-dose, four-way crossover study. Twenty-four healthy adult volunteers. Single oral doses of desloratadine 5mg and fexofenadine 60mg taken without and with grapefruit juice (pretreatment with 240ml of double-strength juice three times daily for 2 days prior to administration of study drug, plus the same amount simultaneously with, and 2 hours after, the drug dose). Each treatment was separated by at least 10 days. Log-transformed pharmacokinetic parameters [peak plasma concentration (C(max)) and area under the curve (AUC)], time to maximum concentration, elimination half-life and electrocardiographic (ECG) parameters. Comparing the ratio of the pharmacokinetic parameter means (C(max) and AUC) with and without grapefruit juice (expressed as a percentage), the rate (C(max)) and extent (AUC) of absorption of fexofenadine were reduced by 30% by consumption of grapefruit juice. In contrast, the bioavailability of desloratadine was unaffected by grapefruit juice. No clinically significant changes in ECG parameters were observed following coadministration of grapefruit juice with desloratadine or fexofenadine compared with either antihistamine given alone. The bioavailability of drugs that do not undergo significant intestinal or hepatic metabolism, such as fexofenadine, may be altered when administered with agents that influence drug transport mechanisms.",2002.0,0,0
118,12000385,Laser-induced weal and flare reactions: clinical aspects and pharmacological modulation.,B Algermissen; B Hermes; B M Henz; U Müller; H P Berlien,"Among the adverse effects of cutaneous laser therapy, weal and flare reactions immediately after treatment have received little attention, and the pathomechanisms are unclear. To study clinical features and possible mechanisms of laser-induced weal and flare reactions in order to identify means of possible therapeutic intervention. Normal skin from the inner arm of 20 volunteers was treated with an argon laser, and the size of weal and flare reactions was measured over a 60-min period. Skin biopsies were taken from four volunteers before and up to 24 h after laser treatment and examined histologically and immunohistologically. Possible underlying mechanisms were also explored using various topical or systemic pharmacological agents. Wealing was noted in 19 of 20, and flare reactions in all volunteers, with peak values at 15 min. Skin biopsies showed central coagulation of the tissue, cleft formation between epidermis and dermis, normal numbers of morphologically intact mast cells on toluidine blue staining close to the lesion, and only minor upregulation of endothelial and leucocyte adhesion molecules. In agreement with these findings, pretreatment with acetylsalicylic acid, the H1-blocker loratadine and triamcinolone cream was ineffective or resulted in a non-significant reduction of weal and flare reactions. In contrast, local anaesthetics as well as neuropeptide depletion of skin with capsaicin abolished the reactions almost completely. Transient weal and flare reactions in response to laser treatment occur in almost all persons and are based primarily on a neurogenic rather than a histamine- or mast cell-dependent mechanism.",2002.0,0,0
119,12014063,"[Chronic idiopathic urticaria: effectiveness of fexofenadine. A double-blind, placebo controlled study with 21 patients].",M Degonda; W J Pichler; A Bircher; A Helbling,"Chronic urticaria defined as repeated or daily eruptions of wheals within a week over a period of at least 1 1/2 months is a frustrating problem not only for the patient but also for the physician. Since a cause will seldom be identified, therapy is symptomatic. In this study the effect of fexofenadine the active metabolite of terfenadine on pruritus, wheal formation and subjective feedbacks has been investigated in 21 patients with chronic urticaria. The study was double-blind, placebo-controlled designed. Following a 1-week washout period all study subjects received fexofenadine 180 mg OD for 3 weeks; thereafter the subjects were randomized for another 3 weeks in a placebo and fexofenadine arm. This study showed that fexofenadine had a beneficial effect on urticaria, particularly pruritus, and the patient-reported symptoms. Reports on side effects were non characteristic and not different between fexofenadine and placebo. Prolongation of QTc intervals or other cardiac side effects have not been observed. Fexofenadine 180 mg is a new antihistamine that is effective in the treatment of chronic urticaria and that has a profile of side effects similar to placebo.",2002.0,0,0
120,12028119,"Comparison of cetirizine, ebastine and loratadine in the treatment of immediate mosquito-bite allergy.",A Karppinen; H Kautiainen; L Petman; P Burri; T Reunala,"People frequently experience whealing and delayed papules from mosquito bites. Whealing is mediated by antisaliva immunoglobulin (Ig)E antibodies and histamine. Cetirizine, ebastine and loratadine have earlier shown effects on mosquito-bite reactions but no comparative studies exist. A double-blind, placebo-controlled, cross-over study was performed with cetirizine 10 mg, ebastine 10 mg and loratadine 10 mg in 29 mosquito-bite-sensitive adults exposed to Aedes aegypti mosquito-bites. The size of the bite lesion and the intensity of pruritus (visual analog scale) were measured at 15 min and 2, 6 and 24 h. Cetirizine and ebastine, but not loratadine, decreased significantly the size of whealing (P < 0.01) and accompanying pruritus (P < 0.001) compared to placebo. Cetirizine was most effective on pruritus but caused more often sedation than ebastine or loratadine. The delayed bite symptoms remained too faint for any statistical comparison. This comparative study in mosquito-bite-sensitive adults shows that cetirizine and ebastine decrease significantly whealing and accompanying pruritus, and that cetirizine seems to be the most effective against pruritus.",2002.0,1,1
121,12052668,Cardiotoxicity of new antihistamines and cisapride.,Ilari Paakkari,"Although the new second-generation nonsedative antihistamines terfenadine and astemizole were launched as highly selective and specific H(1)-receptor antagonists, they were later found to cause prolongation of the QT-interval and severe cardiac arrhythmias. The prolongation of the QT-interval is caused by the blockade of one or more of the cardiac potassium channels, among which the delayed rectifier I(Kr), encoded by the HERG-gene, appears to be the most significant. The potency of the prokinetic drug cisapride to block I(Kr) appears to be similar to that of terfenadine (IC(50) about 50 nmol/l). These drugs cause problems when overdosed, used in combination with inhibitors of their CYP3A4-mediated metabolism, or when given to individuals with altered drug kinetics (the aged) or patients with existing cardiac disease (congenitally long QT). Moreover, interactions with other QT-interval prolonging drugs require special attention. Active hydrophilic metabolites of the second-generation antihistaminic compounds (ebastine-carebastine, loratadine-desloratadine, terfenadine-fexofenadine, astemizole-norastemizole) are new compounds with probably reduced risk for drug interactions and cardiac toxicity.",2002.0,0,1
122,12100225,"Lack of effect of single and repeated doses of levocetirizine, a new antihistamine drug, on cognitive and psychomotor functions in healthy volunteers.",J M Gandon; H Allain,"Levocetirizine (R-cetirizine), is the active enantiomer of cetirizine, an antihistamine indicated in the treatment of allergic rhinitis and chronic idiopathic urticaria. The purpose of this trial was to analyse the effects of levocetirizine single and multiple doses on CNS using integrated measures of cognitive and psychometric performance. A battery of psychometric tests was used: critical flicker fusion (CFF), choice reaction time (CRT), body sway (BS), learning memory test (LMT) and subjective assessments of alertness compared with placebo. Nineteen (19) healthy male volunteers received either levocetirizine 5 mg (therapeutic dose), diphenhydramine 50 mg or placebo once daily for 5 consecutive days (3-way cross-over). Diphenhydramine was used as a positive control. CFF tests were performed on days 1 and 5 at baseline and up to 24 h following drug intake. Subjects used the Bond-Lader visual analogue scales (VAS) to assess their mood and vigilance. In contrast to diphenhydramine, when compared with placebo, levocetirizine did not modify the CFF (primary endpoint), regardless of the dosing scheme (-1.62 Hz [-2.61, -0.64] and -0.81 Hz [-1.80, 0.19], respectively, 3 h after dosing on day 1). CRT was decreased with both levocetirizine and placebo up to 5 h after dosing on day 1 and up to 3 h after dosing on day 5. Body sway data were similar with levocetirizine and placebo but increased with diphenhydramine. LMT was similar in all three groups. No relevant difference between placebo and levocetirizine was recorded by the subjects on their assessment of alertness using the VAS, whilst decreased alertness was reported following diphenhydramine 50 mg. This study showed that levocetirizine does not produce any deleterious effect on cognitive and psychometric functions compared with placebo in healthy male volunteers.",2003.0,0,0
123,12118496,Therapeutic efficacy and safety of loratadine syrup in childhood atopic dermatitis treated with mometasone furoate 0.1 per cent cream.,Amornsri Chunharas; Wanee Wisuthsarewong; Siriwan Wananukul; Suchitra Viravan,"Atopic dermatitis is a common skin disease in Thai children. The treatment of atopic dermatitis requires topical corticosteroids, emollients, systemic antihistamine as well as avoidance of the precipitating factors. A double blind multicenter placebo controlled study was conducted to assess the therapeutic efficacy of topical mometasone furoate 0.1 per cent cream in combination with loratadine syrup. Forty-eight patients, 23 boys and 25 girls, mean age 73.67 months, with atopic dermatitis were included in the study. The severity of the disease was measured by using the SCORAD index including the degree of erythema, dryness, edema/papulation, oozing/crusting, lichenification, and excoriation. Total area involved was measured and a target area of dermatitis was selected for specific evaluation. The degree of clinical signs and pruritic symptom was graded. The sensation of pruritus, disturbance of sleep due to pruritus, and feeling of sleepiness in the morning were recorded. Mometasone furoate 0.1 per cent cream was applied to all patients once daily. One group received loratadine syrup and another group received placebo syrup. They were followed-up on day 5, 8 and 15. The severity of atopic dermatitis and pruritus significantly decreased after 14 days of treatment in both groups (p < 0.001). There was no difference in therapeutic response between the loratadine and placebo groups (p = 0.99). All signs examined had decreased by the end of the study. The result demonstrated that 0.1 per cent mometasone therapy is very effective for treating childhood atopic dermatitis. Loratadine did not show beneficial effect when combined with good topical corticosteroid but it was safe and had no serious side effect on the children.",2002.0,0,0
124,12149503,"Long-term evaluation of the impact of the h1-receptor antagonist cetirizine on the behavioral, cognitive, and psychomotor development of very young children with atopic dermatitis.",Jim Stevenson; Deborah Cornah; Philippe Evrard; Valere Vanderheyden; Catherine Billard; Martin Bax; Anne Van Hout; ETAC Study Group,"The impact of the prolonged use of cetirizine at high dose (0.25 mg/kg twice a day over 18 mo) on behavior and cognitive ability was examined in a double-blind, randomized, placebo-controlled trial (ETAC-Early Treatment of the Atopic Child) designed to establish whether it was possible to prevent young children (1-2 y old at study entry) with atopic dermatitis from developing asthma. Well-validated and standardized measures of behavior (Behavior Screening Questionnaire) and cognition (McCarthy Scales of Children's Abilities) were used. In addition, the ages of attainment of psychomotor milestones were established. These measures were taken between an average of 32 and 53 mo of age, both during the study treatment with cetirizine or placebo and after the study treatment had been discontinued. The Behavior Screening Questionnaire was completed at least once on approximately 300 children in each group and on approximately 200 children on five occasions. The McCarthy Scales of Children's Abilities were administered to approximately 100 in each group at three different times. There were no significant differences between the cetirizine and placebo groups on either of the behavior and cognition measures or in psychomotor milestones during or after the study treatment. These findings suggest that there are no adverse effects on behavior or learning processes associated with the prolonged use of cetirizine in young children with atopic dermatitis.",2003.0,0,0
125,12162793,24-hour efficacy of once-daily desloratadine therapy in patients with seasonal allergic rhinitis [ISRCTN32042139].,Luis M Salmun; Richard Lorber,"Early studies with desloratadine demonstrated efficacy in treating seasonal allergic rhinitis (SAR). A dose-ranging study was conducted to characterize its 24-hour efficacy in patients with SAR. Patients (N = 1,026) were randomly assigned once-daily (QD) desloratadine (2.5, 5, 7.5, 10, or 20 mg) for 2 weeks in a placebo-controlled, double-blind study. The end point of 24-hour efficacy was assessed by the mean change from baseline in the average AM instantaneous total symptom score (TSS) over the treatment period. Day 2 data were assessed for efficacy of desloratadine following the first dose. Other efficacy variables included AM/PM previous total nasal and nonnasal symptom scores and individual symptom scores. Desloratadine 5-20 mg was significantly (P <.01) more effective than placebo in improving total AM instantaneous TSS and AM/PM previous total nasal and nonnasal symptom scores. This dosing range also was significantly (P <.01) more effective than placebo for reducing AM instantaneous TSS beginning with the first dose; thus, demonstrating the full 24-hour efficacy of desloratadine. AM/PM previous scores for all individual symptoms, including nasal congestion, were also significantly improved versus placebo (P <.05) with desloratadine at 5, 7.5, and 20 mg. All treatments were well tolerated. There were no clinically meaningful changes in electrocardiogram parameters. Desloratadine 5-20 mg provided significant 24-hour relief of SAR signs and symptoms. There were no statistically significant differences between the 4 largest doses suggesting that desloratadine 5 mg QD offers the best therapeutic profile for patients with SAR.",2003.0,0,1
126,12166555,The combination of single-dose montelukast and loratadine on exercise-induced bronchospasm in children.,D G Peroni; G L Piacentini; A Pietrobelli; A Loiacono; W De Gasperi; A Sabbion; R Micciolo; A L Boner,"The aim of the study was to evaluate the protective effect of single-dose, combination treatment comprising montelukast (5 mg) and loratadine (10 mg), on exercise-induced bronchoconstriction in asthmatic children. The combination was compared to placebo, loratadine and montelukast alone. Nineteen children were enrolled in a double-blind randomised, single-dose, crossover study. For each treatment patients undertook two treadmill exercise tests, 2 and 12 h respectively after single-dose administration. No significant differences were seen in the maximum fall in forced expiratory volume in one second (FEV1) 2 h after treatment and placebo. Whereas significant differences in maximum fall in FEV1 were observed between treatment groups 12 h after administration. Loratadine alone did not show any significant protection or any additional effect in comparison with montelukast alone. Single doses of montelukast and montelukast plus loratadine were significantly more effective than loratadine at 12 h. The present study, performed using single-dose treatments, demonstrated that maximal protective effect by montelukast was obtained 12 h after dosing and that montelukast plus loratadine did not result in significant additive bronchoprotective effects on exercise-induced bronchoconstriction.",2003.0,0,0
127,12169044,Lack of clinically relevant interaction between desloratadine and erythromycin.,Christopher Banfield; Thomas Hunt; Larisa Reyderman; Paul Statkevich; Desmond Padhi; Melton Affrime,"To evaluate the bioavailability, cardiac safety and tolerability of desloratadine when given in combination with the CYP3A4 inhibitor erythromycin. A randomised, 2-way crossover, placebo-controlled, third party-blind, multiple dose study. 24 healthy volunteers (12 men, 12 women) aged 19 to 46 years. Oral desloratadine 7.5mg daily in combination with either placebo (n = 24) or erythromycin 500mg every 8 hours (n = 24) for 10 days. After a minimum 7-day washout period, participants crossed over to the alternative regimen. ECG parameters. Desloratadine/erythromycin did not induce clinically or statistically significant changes in any ECG parameter. The maximum corrected QT (QT(c)) interval was 445 msec for both treatments. The peak plasma concentration and area under the plasma concentration-time curve from 0 to 24 hours of desloratadine were slightly increased by 1.2- and 1.1-fold by concomitant administration of erythromycin compared with desloratadine/placebo. Gastrointestinal adverse events were more frequent after desloratadine/erythromycin than desloratadine/placebo (46 vs 4%), reflecting the poor gastrointestinal tolerability of erythromycin. There were no reports of syncope. Combined desloratadine/erythromycin therapy was well tolerated and had no clinically relevant electrocardiographic effects at a dose that was 50% higher than the recommended dose of 5mg. Although coadministration of erythromycin slightly increased plasma concentrations of desloratadine, this change did not correlate with any prolongation of the QT(c) interval, and no toxicity was observed clinically.",2002.0,0,0
128,12169045,Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole.,Christopher Banfield; Jerry Herron; Anther Keung; Desmond Padhi; Melton Affrime,"This study was performed to assess the electrocardiographic safety and pharmacokinetics of desloratadine in combination with the CYP3A4 inhibitor ketoconazole. A randomised, placebo-controlled, third-party-blind, 2-way crossover study. 24 healthy volunteers (12 men, 12 women; age 19 to 50 years). 7.5mg of desloratadine orally per day in combination with placebo or with 200mg of ketoconazole every 12 hours for 10 days. After a minimum 7-day washout period, participants received the alternative treatment. ECG parameters. Comparable maximum corrected QT (QT(c)) intervals were observed after coadministration of desloratadine and placebo or ketoconazole (431 and 435 msec, respectively). The desloratadine/ketoconazole combination did not induce any statistically significant or clinically relevant changes in QT(c), QT, PR or QRS intervals compared with desloratadine alone; ventricular rate was slightly slower when desloratadine was given with ketoconazole. At steady state, coadministration of ketoconazole resulted in no significant change in area under the desloratadine concentration-time curve (AUC) from 0 to 24 hours compared with desloratadine/placebo. Coadministration of desloratadine and ketoconazole resulted in a 1.3-fold increase in desloratadine maximum concentration (C(max)) that was not clinically relevant. The most common adverse event was headache, reported in 42 and 38% of individuals, respectively, after coadministration of desloratadine/placebo and desloratadine/ketoconazole. There were no reports of dizziness or syncope. Coadministration of desloratadine and ketoconazole was well tolerated and was associated with minimal increase in AUC and C(max). The combination did not induce any clinically relevant electrocardiographic changes.",2002.0,0,0
129,12182260,Comparison of the efficacy of combined fluticasone propionate and olopatadine versus combined fluticasone propionate and fexofenadine for the treatment of allergic rhinoconjunctivitis induced by conjunctival allergen challenge.,Bob Q Lanier; Mark B Abelson; William E Berger; David B Granet; Peter A D'Arienzo; Dennis L Spangler; Martin K Kägi,"One approach to treating allergic rhinoconjunctivitis is the concomitant use of an intranasal spray such as fluticasone propionate to alleviate nasal symptoms and a topical or systemic agent to relieve ocular symptoms. It has not yet been determined whether a topical or systemic agent is more effective for the latter purpose. This study compared the efficacy of combined use of fluticasone and olopatadine with combined use of fluticasone and fexofenadine in the treatment of the signs and symptoms of allergic rhinoconjunctivitis. This 2-site, randomized, double-masked, placebo-controlled, parallel-group study employed the conjunctival allergen challenge (CAC) model, a standardized method of inducing ocular and nasal signs and symptoms of allergic rhinoconjunctivitis. At visit 1, subjects underwent CAC to determine the dose of allergen required to elicit a positive reaction. The allergen dose was confirmed at visit 2, and, according to a randomization schedule, subjects were dispensed fluticasone, olopatadine, and placebo pill; fluticasone, fexofenadine, and tear substitute; or placebo nasal spray, placebo pill, and tear substitute. CAC took place at visit 3, after patients had used the assigned medications for 2 weeks. Study medication was instilled 2 hours before CAC, after which allergic signs and symptoms were graded on standardized scales. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms. Eighty subjects completed the study: 30 received fluticasone and olopatadine, 30 fluticasone and fexofenadine, and 20 placebo. Women constituted 63.8% of the study population and men 36.3%; 91.3% were white, 3.8% black, 2.5% Hispanic, 1.3% Asian, and 1.3% other. Concomitant use of fluticasone and olopatadine produced significantly greater improvements in ocular itching at 3 and 7 minutes after CAC compared with fluticasone and fexofenadine (P < 0.05). There were no significant differences in redness scores between groups; however, concomitant use of fluticasone and olopatadine produced significantly greater improvements in redness at 2 time points in each of the 3 vessel beds (ciliary, conjunctival, and episcleral) compared with placebo, and fluticasone and fexofenadine produced significantly greater improvement in redness at 1 time point in I vessel bed compared with placebo (both comparisons, P < 0.05). The 2 treatments had similar effects on total nasal symptom efficacy scores. In this study, concomitant use of the topical agents fluticasone and olopatadine was more effective than concomitant use of fluticasone plus fexofenadine for overall treatment of the signs and symptoms of induced allergic rhinoconjunctivitis.",2003.0,0,0
130,12196053,Single-patient drug trial methodology for allergic rhinitis.,Donald P Reitberg; Eve Del Rio; Sidney L Weiss; Gerbert Rebell; Nardo Zaias,"Historically, single-patient trials (SPTs) have been specifically designed for each patient, requiring significant time and effort for execution. There has been no previous attempt to standardize an SPT for routine commercial availability. To validate the use of an SPT method to discriminate effectiveness and adverse events while comparing drugs/doses in patients with allergic rhinitis. Double-blind, randomized, 4 paired-period, multiple-crossover SPT. Academic and commercial investigative sites. Thirty-six patients with allergic rhinitis were evaluated for the most appropriate treatment; 6 of these participated in 2 different SPTs. Treatment of symptoms of allergic rhinitis by comparing either loratadine with chlorpheniramine maleate or loratadine with placebo in a series of SPTs. Effectiveness endpoints were selected from a modern, Food and Drug Administration (FDA)-approved new drug application. Expected adverse events were directly solicited; unsolicited events were also recorded. Total signs and symptoms cumulatively included sneezing, runny nose, itchy nose, teary eyes, and itchy eyes. Quality of life was measured by the most bothersome symptom and the patient's global evaluation. Of 42 initiated SPTs, 40 (95%) provided complete data and 1 (2%) provided partial data, resulting in 41 (98%) evaluable tests. Thirty-one evaluable SPTs compared loratadine 10 mg/d with chlorpheniramine maleate 12 mg twice daily, and 10 SPTs compared loratadine 10 mg/d with placebo. Four of 31 SPTs (13%) showed significant superiority for loratadine over chlorpheniramine maleate and 5 of 31 (16%) for chlorpheniramine maleate over loratadine. Twenty-two of 31 (71%) showed parity performance between loratadine and chlorpheniramine maleate. Loratadine was significantly superior to placebo in 3 of 10 trials (30%), consistent with rates found in 3 pivotal group trials used for FDA approval (24%, 17%, and 0%). Sleepiness could be discriminated for loratadine versus placebo and for chlorpheniramine maleate versus loratadine. The allergic rhinitis SPT proved to be acceptable to patients, feasible to administer, and reproducible. It can statistically discriminate effectiveness and adverse events, serving as a useful, prognostic tool in community practice.",2003.0,0,1
131,12322847,A comparative study of the side effects between pseudoephedrine in Loratadine plus Pseudoephedrine Sulfate Repetabs Tables and loratadine + pseudoephedrine tablet in treatment of allergic rhinitis in Thai patients.,Pakpoom Supiyaphun; Ladda Chochaipanichnon; Virachai Kerekhanjanarong; Supinda Saengpanich,"The objective of the study was to evaluate the adverse reactions of Loratadine plus Pseudoephedrine Sulfate Repetabs Tables (LTD+PSE Repetabs) (Loratadine 5 mg + Pseudoephedrine 120 mg) twice daily with that of loratadine (5 mg) twice daily and pseudoephedrine (60 mg) quarter daily in the treatment of patients with allergic rhinitis. The study was designed as an investigator-blind, parallel group study. In this study, 56 patients were equally separated into 2 groups and treated for 14 days with either LTD+PSE Repetabs or loratadine + pseudoephedrine tablet. Both groups were comparable in age, gender, weight; baseline systolic blood pressure, diastolic blood pressure and pulse rate. The change of systolic blood pressure, diastolic blood pressure, and pulse rate did not reach clinical significance throughout the study period. There was no significant difference in occurrences of insomnia, palpitation, mouth dryness and anxiety. However, the incidence of patients with tremor at day 14 in the loratadine + pseudoephedrine tablet group was significantly higher than the LTD+PSE Repetabs group (39% vs 10.7%, p-value = 0.03). Furthermore, one patient in the loratadine + pseudoephedrine tablet group had to discontinue medication at day 7 due to insomnia. In conclusion, LTD+PSE Repetabs is well tolerated and has fewer adverse effects when compared to the loratadine + pseudoephedrine tablet.",2002.0,0,1
132,12392861,The use of handheld computers in clinical trials.,Andreas Koop; Ralph Mösges,"A recently completed, randomized, double-blind placebo-controlled clinical trial is presented in which Palm handheld computers were used as a substitute for normal paper-based patient diaries. In this nasal provocation study, a common antihistamine approved for the treatment of seasonal allergic rhinitis was tested against placebo for evidence of additional properties. In addition to their medical examinations, the 12 study volunteers rated subjective complaints in a diary program on 4 examination days, for a duration of 4.5 hours every 15 minutes at each visit. This resulted in 903 data sets consisting of five questions each, or 4515 data points total. In this study the use of handheld computers resulted in an increase in data quality and shortened the time needed to close the database. Moreover, the benefit of electronic reminders for protocol compliance is clearly demonstrated. Our findings support the results found in the literature we reviewed. For more than 16 years, mobile computers have been supporting the implementation of clinical trials. Our review of 27 articles out of more than 100 clinical trials in which mobile computers have been used elaborates on the advantages and problems of this technology. We give a comprehensive overview of the various technologies as used in different settings, and then discuss the methodology of using mobile devices in comparison to traditional methods, the considerations that need to be made and things to be avoided in order to conduct a successful clinical trial with mobile tools. We conclude that mobile devices are very useful in most cases, especially when design and software validation aspects have been taken into account.",2002.0,0,0
133,12396959,[Cold urticaria: review of 12 cases].,M Santaolalla Montoya; María I Martínez Molero; F Santaolalla San Juana; María L Baeza; E Alonso Lebrero; L Zapatero Remón,"Cold urticaria is caused after exposition to cold air, water and food. It is the third more frequent physical urticaria in pediatric population. We reviewed twelve patients, studied different characteristics and obtained following results: mean age is 12 years and 9 months and it is more frequent in female subjects, atopy is present in 67 % of patients, other physical urticaria are present in 25 % and there is not familial inheritance. 83 % of patients have localized and generalized symptoms. Cold stimulation test is positive in 92 %. Cryoglobulins and cold agglutinins are negative in 100 % of patients in which these tests were made. There is infectious disease in only two patients. Cetirizine was used in most of patients and it was successful in 70 %. Mean duration is 3 years and 6 months. Only patient with negative cold stimulation test remains without symptoms. Cold urticaria must be initially diagnosed by cold stimulation test and clinical history. Cetirizine is effective and cause less adverse effects than other antihistamines traditionally used.",2003.0,0,0
134,12425364,"Dermal objective pharmacodynamic profile of cetirizine and epinastine: two controlled, randomised, double-blind, crossover studies.",T Leroy; D van Neste,"Two double-blind clinical pharmacology studies were performed in healthy volunteers to compare the dermal pharmacodynamic profile of epinastine with cetirizine, a well-documented anti-H1 antagonist, after oral administration at the usual recommended dosage, i.e. 10 mg cetirizine and 20 mg epinastine (versus placebo). Histamine skin challenges (prick test) were evaluated before and at 1, 2, 4, 8 and 24 hr after drug intake by measuring the wheal and flare area (studies 1 and 2) along with laser Doppler monitoring of the microvascular responses (study 2). A decrease in wheal and flare areas was observed following intake of both drugs compared with placebo controls. With the notable exception of 1 hr post dose wheal values, which were consistently smaller after epinastine, cetirizine was superior to epinastine for both wheal and flare at all other times. At the prick test site, treatment with epinastine and cetirizine accentuated the increase in blood flow induced by histamine. This reflects the decrease of the whealing but there was no significant difference between the two active test compounds. At 1 cm from the prick test site, the administration of both active treatments inhibited the increase of blood flow, and cetirizine showed a more potent inhibitory effect from 8 hr post dose. This reflects the reduction of the flare induced after histamine-receptor activation of the axon reflex. In conclusion, epinastine shows a rapidly greater (within 1 hr post dose on the wheal only) but vanishing effect than cetirizine. At all other time points, cetirizine was generally more effective than epinastine.",2002.0,0,1
135,12464165,[Immunotherapy with an oral Alternaria extract in childhood asthma. Clinical safety and efficacy and effects on in vivo and in vitro parameters].,A Criado Molina; F Guerra Pasadas; J C Daza Muñoz; C Moreno Aguilar; E Almeda Llamas; E Muñoz Gomariz; P Font Ugalde; C Alonso Díaz; M Germán Cárdenas; P Sánchez Guijo,"Studies of immunotherapy with oral Alternaria extracts are scarce. We decided to perform a clinical trial of the clinical safety and efficacy of this extract as well as of its effects on in vivo and in vitro parameters in 39 patients with Alternaria allergy, aged between 7 and 17 years, who are also sensitized extract was used. Allergic activity was determined through RAST inhibition and skin prick test. Quantification of the principal allerten (Alt a 1) was performed through the 2-site binding assay, with a mean content of 34.2 ng Alt a 1/micro g protein. The parameters analyzed were the symptom-medication score, skin prick using the end-point technique, specific bronchial challenge test, peak flow, total and specific IgE and IgG4. Nineteen patiens received active treatment with oral immunotherapy and another 19 received symptomatic treatment. The initial phase of immunotherapy lasted 3 months until the maximum dose was reached. This was maintained for 12 months; the mean accumulated dos was 280,000 PNU. Significant differences were found in reduction in the symptom-medication score in the treated group after 12 months of immunotherapy. No differences were found in the control group. Immunotherapy was well tolerated with 0.42 adverse reactions per 100 doses administered. All adverse reactions were mild-to-moderate. In the treated group, papule size was significantly reduced. Values for the specific bronchial challenge test, expressed through PD20, were significantly higher in the immunotherapy group. Peak flow showed no changes in either group. Values of IgG4 were significantly higher in the immunotherapy group. Total and specific IgE levels showed no significant changes in either group. In conclusion, oral immunotherapy with Alternaria extract is clinically effective in pediatric patients. In general, the therapy was well tolerated. It modified specific cutaneous and bronchial reactivity in our sample and increased levels of specific IgG4, wich are implicated in humoral response.",2003.0,0,0
136,12467881,Roles of histamine in regulation of arousal and cognition: functional neuroimaging of histamine H1 receptors in human brain.,Manabu Tashiro; Hideki Mochizuki; Kentaro Iwabuchi; Yumiko Sakurada; Masatoshi Itoh; Takehiko Watanabe; Kazuhiko Yanai,"Brain histamine is involved in a wide range of physiological functions such as regulation of the sleep-wake cycle, arousal, cognition, and memory mainly through interactions with histamine H1 receptors (H1Rs). Neurons producing histamine, histaminergic neurons, are exclusively located in the posterior hypothalamus and transmit histamine to almost all regions of the brain. Histamine H1 antagonists, or antihistamines, often prescribed for treatment of allergic disorders, sometimes induce sleepiness and cognitive deficits. It is understood that the mechanism of such CNS side effects is that antihistamine blocks H1Rs in the brain. The purpose of the present study was to compare the CNS side effects of different antihistamines. Subjective sleepiness was measured using the Stanford Sleepiness Scale (SSS) and psychomotor performance was examined by a tachistoscope testing system in healthy, young, Japanese volunteers (16 males, 20-28 yrs.) before and after oral administration of antihistamines such as fexofenadine (FEX) and cetirizine (CET). Additionally, H1R occupancy by antihistamines was examined by PET with 11C-doxepin in 8 volunteers. The results of SSS and psychomotor tests demonstrated that FEX tended to be less sedative than CET though the difference was not statistically significant. PET measurements revealed that no H1Rs in the cerebral cortex were occupied by FEX while about 30% of H1Rs were occupied by CET. In summary, it was confirmed that histamine and H1Rs are involved in maintaining arousal and cognition in humans, and that the severity of clinical symptoms is correlated to the amount of antihistamine that penetrated into the brain.",2003.0,0,0
137,12476276,Optimising parameters for peripheral blood leukapheresis after r-metHuG-CSF (filgrastim) and r-metHuSCF (ancestim) in patients with multiple myeloma: a temporal analysis of CD34(+) absolute counts and subsets.,I H Chin-Yee; M Keeney; A K Stewart; A Belch; I Bence-Buckler; S Couban; K Howson-Jan; M Rubinger; D Stewart; R Sutherland; V Paragamian; M Bhatia; R Foley,"Patients (n = 69) with multiple myeloma undergoing peripheral blood stem cell collection (PBSC) were treated with cyclophosphamide and a combination of recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF, filgrastim) and recombinant methionyl human stem cell factor (r-metHuSCF, ancestim). The objectives of this study were to determine: (1) The proportion of patients reaching a target yield of >or=5 x 10(6) CD34(+) cells/kg in one or two successive large-volume (20 liter) leukapheresis procedures; (2) the optimal collection time for leukapheresis; (3) mobilization kinetics of CD34(+) subsets in response to G-CSF/SCF. All patients were mobilized with cyclophosphamide (2.5 g/m(2)) on day 0 followed by filgrastim (10 microg/kg ) plus ancestim (20 microg/kg) commencing day 1 and continuing to day 11 or 12. Of the 65 evaluable patients, 57 were considered not heavily pretreated and 96.5% obtained a target of >or=5 x 10(6)/kg in one collection. The median CD34(+) cells/kg was 39.5 x 10(6) (range: 5.2-221.2 x 10(6)). Subset analysis demonstrated the number of CD38(-), CD33(-), and CD133(+) peaked at day 11; and CD34(+), CD90(+) cells peaked at day 10. The optimum day for leukapheresis was determined to be day 11. The median absolute peripheral blood CD34(+) cell numbers on day 11 was 665 x 10(6)/l (range: 76-1481 x 10(6)/l). Eight of the 10 heavily pretreated patients were evaluable: three achieved the target dose in one leukapheresis (37.5%) and three (37.5%) achieved the target dose with two leukaphereses. Use of this mobilization strategy allowed the collection of high numbers of CD34(+) cells and early progenitors and the ability to predictably schedule leukapheresis.",2003.0,0,0
138,12484432,Rapid effects of olopatadine hydrochloride on the histamine-induced skin responses.,Keisuke Morita; Tetsuya Koga; Yoichi Moroi; Kazunori Urabe; Masutaka Furue,"Olopatadine hydrochloride is one of the second-generation nonsedating antihistamines that are used for treating allergic disorders such as urticaria, rhinitis, and atopic dermatitis. We examined the inhibitory effects of this drug on the flare and wheal responses induced by histamine iontophoresis at 30, 60, and 90 min after oral administration in a double-blind, cross-over, and placebo-controlled study. Olopatadine hydrochloride significantly inhibited the histamine-induced flare and wheal responses as early as 60 min after oral administration when compared with placebo. Significant inihibitory effects of olopatadine hydrochloride on the itch responses were seen at 90 min after administration. Thus, olopatadine hydrochloride exhibited a very rapid and potent antihistamine effect on the histamine-induced skin responses.",2003.0,0,0
139,12503949,"Why aren't lower, effective, OTC doses available earlier by prescription?",Jay S Cohen,"Many popular oral over-the-counter (OTC) drugs were originally available only by prescription, but not at the low doses contained in their OTC counterparts. Yet, if OTC doses are effective for treating mild symptoms, why weren't these low, often safer doses made available at least by prescription when the drugs were first approved? To examine issues surrounding the delayed approval of OTC doses by the Food and Drug Administration (FDA). Information reviewed included package inserts, data obtained from manufacturers, and articles published in MEDLINE (1966 to December 2001). Medications examined included presently available and potentially approved OTC antiinflammatory, gastrointestinal, and antihistamine drugs. Considerable data demonstrate the effectiveness of ibuprofen, naproxen, ranitidine, famotidine, nizatidine, diphenhydramine, and clemastine at OTC doses. Published studies also show the effectiveness of celecoxib, omeprazole, and fexofenadine at doses 33-50% lower than currently recommended for prescription use. OTC doses are effective for many patients with mild symptoms and for some with serious symptoms. However, OTC-like doses are usually not offered when drugs are approved for prescription use because new drugs are usually studied in patients with serious conditions requiring higher doses; manufacturers and the FDA seem to prefer a middle-dose approach; >75% of subjects in premarketing dose studies are male; and averaging the responses of study subjects may obscure a wide range of interindividual variation in drug response. Simplistic dosage guidelines make therapeutic decisions easier. Because dose-related adverse effects frequently diminish quality-of-life and reduce adherence, the early availability of OTC-like doses, at least by prescription, would allow healthcare professionals greater flexibility in matching medication doses to patients' widely differing needs.",2003.0,0,0
140,12549941,Failure of cetirizine and fexofenadine to prevent motion sickness.,Bob S Cheung; Raquel Heskin; Kevin D Hofer,"To determine the effectiveness of 2 second-generation antihistamines in modulating motion sickness induced by Coriolis vestibular cross-coupling stimulation. This prospective, randomized, double-blind, crossover, placebo-controlled study was conducted in 18 healthy adults. Subjects were exposed to Coriolis vestibular cross-coupling in the laboratory using the Staircase Profile Test for baseline susceptibility and when under the influence of cetizirine, fexofenadine, and placebo. Subjective evaluation of sickness symptoms was based on the Graybiel diagnostic criteria of acute motion sickness, Golding's scale, and the Coriolis Sickness Susceptibility Index. Repeated measures ANOVA and Friedman nonparametric ANOVA of rank tests revealed that there were significant differences in symptom assessments based on Graybiel's diagnostic criteria (p < or = 0.001), subjective symptoms of motion sickness (p < or = 0.001), and state-anxiety (p < or = 0.001) before and after motion exposure. However, there are no significant differences between the baseline susceptibility to motion sickness and treatment with placebo, cetirizine, or fexofenadine. The failure of the second-generation antihistamines cetirizine and fexofenadine to prevent motion sickness suggests that the therapeutic actions of this class of antihistamines against motion sickness may be mediated through central versus peripheral receptors. The sedative effect of other antihistamines, such as hydroxyzine, may play a more significant role in alleviating motion sickness than previously thought.",2003.0,0,1
141,12549956,Desloratadine: a nonsedating antihistamine.,Lynn Limon; Denise R Kockler,"To review information on desloratadine, a nonsedating antihistamine. An English-language MEDLINE search was conducted (1966-July 2002). References of identified articles were subsequently reviewed for additional data. Schering Corporation provided unpublished information. Articles and abstracts pertaining to desloratadine were considered for inclusion, with emphasis on randomized, placebo-controlled, double-blind trials. Desloratadine is approved for the treatment of symptoms associated with seasonal allergic rhinitis (SAR), perennial allergic rhinitis (PAR), and chronic idiopathic urticaria (CIU) in patients aged > or =12 years. In placebo-controlled trials, desloratadine demonstrated superior efficacy as a once-daily treatment of SAR, PAR, and CIU. Data suggest that desloratadine has antiinflammatory and decongestant activity. Desloratadine appears to be a ""me-too"" agent, with no major differences compared with other second-generation antihistamines.",2003.0,0,1
142,12564104,[Therapeutic advances in 2002 (1)].,A J Scheen,"The most important drugs registered and/or launched in Belgium during the last year in the various disciplines of internal medicine will be briefly described. The main characteristics of each molecule and its modalities of appropriate use in clinical practice will be emphasized. For all these molecules, both the efficacy and tolerance have been proven in randomised clinical trials according to the rules of Evidence-Based Medicine.",2003.0,0,0
143,12608555,Plasma serotonin and histamine levels in hemodialysis-related pruritus are not significantly influenced by 5-HT3 receptor blocker and antihistaminic therapy.,E Weisshaar; N Dunker; U Domröse; K H Neumann; H Gollnick,"Elevated plasma histamine levels are considered to play a part in the pathophysiology of hemodialysis-related pruritus. However, antihistaminic therapy often fails to provide sufficient relief. Elevated serotonin levels in patients on dialysis therapy have also been described but the effects of 5-HT3 receptor antagonists on hemodialysis-related pruritus remain controversial. we conducted a study to determine plasma histamine and serotonin levels before and after treatment with 5-HT3 receptor antagonists (tropisetron 5 mg and ondansetron 8 mg) and an antihistamine (cetirizine 10 mg). Eleven hemodialysis patients with a history of pruritus participated in this study,10 healthy volunteers served as control group. Histamine and serotonin values were normal in patients and controls. Treatment with cetirizine did not significantly reduce histamine levels in patients or in controls. Tropisetron and ondansetron likewise did not alter serotonin levels in patients. Tropisetron treatment did not significantly change serotonin levels in controls. Histamine and serotonin are no major mediators of pruritus in hemodialysis patients. Elevated histamine levels are occassionally seen and may be due to the increased mast cell number found in a subgroup of hemodialysis patients. Our findings explain the only marginal relief of antihistamines and the controversial antipruritic effect of serotonin receptor antagonists in hemodialysis-related pruritus.",2003.0,0,0
144,12633131,"A double-blind, placebo-controlled trial of the safety and efficacy of selegiline transdermal system without dietary restrictions in patients with major depressive disorder.",Jay D Amsterdam,"The monoamine oxidase (MAO) inhibitor selegiline has demonstrated antidepressant efficacy superior to placebo. A selegiline transdermal system (STS) has been developed with unique pharmacokinetic and pharmacodynamic properties that allow inhibition of central nervous system MAO-A and MAO-B enzymes while substantially avoiding inhibition of intestinal and liver MAO-A enzyme. This novel transdermal system provides targeted MAO inhibition without clinically significant increases in sensitivity to dietary tyramine. We investigated the safety and efficacy of STS in patients with major depressive disorder. 365 outpatients 18 to 65 years old with a DSM-IV diagnosis of major depressive disorder were enrolled at 16 sites. A 17-item Hamilton Rating Scale for Depression (HAM-D-17) score of > or = 20 was required for entry. Patients were randomly assigned to receive either STS, 20 mg/20 cm(2), daily or placebo patch for up to 8 weeks. A tyramine-restricted diet was neither required nor advised. Efficacy, safety, and vital sign measures were obtained regularly. 289 patients were randomly assigned to treatment and received at least 1 on-therapy evaluation (STS, N = 145; placebo, N = 144). Although the effect size was modest, at endpoint, STS was statistically superior to placebo on the MADRS (p =.001) and HAM-D-28 (p =.039) ratings and showed a nonsignificant superiority on the HAM-D-17 (p =.069) and Clinical Global Impressions-Severity ratings (p <.055). Side effect profiles were similar for STS and placebo with the exception of application-site reaction, which was observed in 31.5% of STS patients and 15.1% of placebo-treated patients (p =.001). No significant differences were observed in blood pressure measures between treatment groups. Results from this double-blind, placebo-controlled clinical trial demonstrate that STS may have a modest, but statistically significant, antidepressant benefit compared with placebo and a similar safety profile compared with placebo in the absence of a tyramine-restricted diet.",2003.0,0,0
145,12634728,Successful mobilization of peripheral blood stem cells after addition of ancestim (stem cell factor) in patients who had failed a prior mobilization with filgrastim (granulocyte colony-stimulating factor) alone or with chemotherapy plus filgrastim.,L B To; J Bashford; S Durrant; J MacMillan; A P Schwarer; H M Prince; J Gibson; I Lewis; B Swart; J Marty; T Rawling; L Ashman; S Charles; B Cohen,"This study assessed the ability of recombinant human stem cell factor (rHuSCF) to mobilize stem cells in 44 patients who had failed a prior mobilization (CD34(+) yield 0.5-1.9 x 10(6)/kg BW) with filgrastim-alone or chemotherapy-plus-filgrastim. The same mobilization regimen was used with the addition of rHuSCF. In the filgrastim-alone group (n=13), rHuSCF 20 microg/kg was started 3 days before filgrastim and continued for the duration of filgrastim. In the chemotherapy-plus-filgrastim group (n=31), rHuSCF 20 microg/kg/day plus filgrastim 5-10 microg/kg/day were administered concurrently. Leukaphereses were continued to a maximum of four procedures or a target of >or=3 x 10(6) CD34(+) cells/kg. In both groups, CD34(+) yield (x 10(6)/kg BW) of the study mobilization was higher than that of the prior mobilization (median: 2.42 vs 0.84 P=0.002 and 1.64 vs 0.99 P=<0.001, respectively). In all 54 and 45% of patients in the filgrastim-alone group and chemotherapy-plus-filgrastim group, respectively, reached the threshold yield of 2 x 10(6)/kg. The probability of a successful mobilization was the same in those with a CD34+ yield of 0.5-0.75 x 10(6)/kg BW in the prior mobilization as in those with 0.76-1.99 x 10(6)/kg BW. Downmodulation of c-kit expression and a lower percentage of Thy-1 positivity in the mobilized CD34(+) cells were noted in the successful mobilizers compared with those in the poor mobilizers. This study shows that rhuSCF is effective in approximately half the patients who had failed a prior mobilization and allows them to proceed to transplant. It also points to the likely role of the SCF/c-kit ligand pair in mobilization.",2003.0,0,0
146,12653769,The selective cyclooxygenase-2 inhibitor rofecoxib may improve the treatment of chronic idiopathic urticaria.,W-H Boehncke; R J Ludwig; T M Zollner; F Ochsendorf; R Kaufmann; B F Gibbs,,2003.0,0,0
147,12664016,"Efficacy and safety of desloratadine 5 mg once daily in the treatment of chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial.",Eugene Monroe; Albert Finn; Piyush Patel; Robinson Guerrero; Paul Ratner; David Bernstein; Desloratadine Uritcaria Study Group,"Chronic idiopathic urticaria (CIU) has a major impact on patient well-being. Antihistamines are the first-line treatment for CIU; however, some cause sedation. Our purpose was to study the efficacy and safety of desloratadine, 5 mg, a new H(1)-receptor antagonist, in patients with moderate to severe CIU. This study was a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial of 6 weeks' duration. Compared with placebo, desloratadine significantly improved the total CIU symptom score as well as pruritus, the number of hives, and the size of the largest hive. Overall therapeutic response and global CIU status improved significantly with desloratadine; interference with sleep was reduced and the performance of daily activities improved. Statistically and clinically significant improvements were seen within the first 24 hours of treatment and were sustained throughout the full duration of the study. The incidence of adverse events, including somnolence, was similar in the desloratadine and placebo groups. Desloratadine is a well-tolerated and effective treatment of CIU.",2003.0,0,1
148,12668896,Aspirin desensitization in patients with AERD.,Donald D Stevenson,"All patients with aspirin exacerbated respiratory disease (AERD) can be desensitized to ASA. After achieving this state, patients can then take ASA daily without adverse effect. ASA desensitization can be maintained indefinitely as long as the patient takes ASA each day. Crossdesensitization with older NSAIDs also occurs. After ASA desensitization, patients can take daily ASA in order to treat their underlying respiratory disease. In AERD patients treated with ASA 650 BID for at least a year, 115/172 (67%) improved in their clinical courses while decreasing systemic and topical corticosteroids. Sixteen failed to improve, 24 stopped ASA because of intractable side effects (gastritis or hives) and 17 patients discontinued ASA treatment in the first year of study for unrelated reasons. Therefore, treatment with daily ASA is a significant therapeutic option for patients afflicted with AERD. It should be used for AERD patients who do not respond to topical corticosteroids and leukotriene modifier drugs. Those who respond to systemic steroids or have intractable or recurrent nasal polyps are particularly well-suited for this therapeutic intervention.",2003.0,0,0
149,12688835,Chronic urticaria: a role for newer immunomodulatory drugs?,Alberto Tedeschi; Lorena Airaghi; Maurizio Lorini; Riccardo Asero,"Chronic urticaria is now recognized as an autoreactive disorder in a substantial fraction of patients. A serologic mediator of whealing has been demonstrated in 50-60% of patients with chronic urticaria, and autoantibodies against the high affinity IgE receptor or IgE have been detected in about half of these patients. The demonstration that chronic urticaria is frequently autoimmune has encouraged a more aggressive therapeutic approach, with the use of immunomodulatory drugs.A step-by-step approach to the management of chronic urticaria is proposed, based on our personal experience and review of current medical literature, identified through Medline research and hand searching in medical journals. The non- or low-sedating H(1) receptor antagonists (antihistamines), such as cetirizine, fexofenadine, loratadine, mizolastine and, more recently, levocetirizine, desloratadine and ebastine, represent the basic therapy for all chronic urticaria patients. Older sedating antihistamines, such as hydroxyzine and diphenhydramine, may be indicated if symptoms are severe, are associated with angioedema, and if the patient is anxious and disturbed at night.Corticosteroid therapy with prednisone or methylprednisolone can be administered for a few days (7-14) if urticarial symptoms are not controlled by antihistamines and a rapid clinical response is needed. In cases of relapse after corticosteroid suspension, leukotriene receptor antagonists, such as montelukast and zafirlukast, should be tried. In our experience, remission of urticarial symptoms can be achieved in 20-50% of chronic urticaria patients unresponsive to antihistamines alone. When urticaria is unremitting and is not controlled by combined therapy with antihistamines and leukotriene receptor antagonists, prolonged corticosteroid therapy may be needed. Long-term corticosteroid therapy should be administered at the lowest dose able to control urticarial symptoms, in order to minimize adverse effects. In a few patients, however, high-dose corticosteroid therapy may have to be administered for long periods. In these patients, immunosuppressive treatment with low-dose cyclosporine can be started. This type of treatment has a corticosteroid-sparing effect and is also generally effective in patients with severe, unremitting urticaria, but requires careful monitoring of cyclosporine plasma concentration and possible adverse effects. Other immunomodulating drugs that have been tried in chronic urticaria patients include hydroxychloroquine, dapsone, sulfasalazine and methotrexate, but their efficacy has not been proven in large controlled studies. Warfarin therapy may also be considered in some patients with chronic urticaria and angioedema unresponsive to antihistamines.",2003.0,0,1
150,12757449,Herbal supplements and skin testing: the lack of effect of commonly used herbal supplements on histamine skin prick testing.,D R More; D C Napoli; L L Hagan,"The use of herbal supplements is common, yet little is known about their pharmacologic properties. The purpose of this study was to assess the effects of 23 commonly used herbal supplements on histamine skin prick testing (SPT). Fifteen healthy volunteers participated in a double-blind, placebo-controlled, single-dose, crossover study. Wheal and flare responses to SPT with histamine phosphate (1 mg/ml) were measured before and 4 h after administration of each of the 23 popular herbal supplements, fexofenadine (60 mg) and placebo. Wheal and flare areas were recorded with tracings performed 10 min after the prick test and measured with a PC-digitizer using stereometric software. Fexofenadine significantly suppressed the wheal (P < 0.001) and flare (P = 0.02) areas compared with placebo. None of the herbal supplements caused significant suppression of the wheal and flare areas compared with placebo (P > 0.10). When taken in single-doses, the popular herbal supplements tested did not significantly affect the histamine skin response. Therefore, it seems unnecessary for clinicians to ask patients to discontinue these herbal supplements prior to allergy skin testing.",2003.0,0,0
151,12759270,Fluticasone nasal spray and the combination of loratadine and montelukast in seasonal allergic rhinitis.,Supinda Saengpanich; Marcy deTineo; Robert M Naclerio; Fuad M Baroody,"To compare the effectiveness of an intranasal steroid treatment with that of the combination of a histamine1 receptor antagonist and a leukotriene D receptor antagonist in the treatment of seasonal allergic rhinitis. A 2-week, parallel, randomized, double-blind, double-dummy study with rolling enrollment. Tertiary care medical center. Subjects A total of 63 adults with a 2-year history of ragweed sensitivity in the Chicago, Ill, area and a positive skin-prick reaction to ragweed pollen. Intervention Subjects were randomized to receive either 100 micro g of fluticasone propionate aqueous nasal spray in each nostril or 10 mg of loratadine and 10 mg of montelukast sodium by mouth once daily in the evening for 2 weeks. At visits 1 and 2, subjects completed a quality-of-life questionnaire and underwent nasal lavage to determine total eosinophil count and eosinophil cationic protein (ECP) measurements. Daily symptom diaries were kept for 2 weeks. Questionnaire answers, daily nasal symptom scores, eosinophil counts, and ECP levels. Median total nasal symptom scores were lower in the fluticasone group (4.5 vs 6), but the difference was not statistically significant. The questionnaire answers showed dramatic improvement in overall and individual domains for both groups (P<.01 vs visit 1) with significantly greater reduction in nasal symptoms in the fluticasone group (P<.05). Eosinophil counts and ECP levels were significantly reduced in the fluticasone group. Both treatments provided clinically meaningful responses, but the overall results favored fluticasone propionate.",2003.0,0,0
152,12786770,Supplementation of fexofenadine therapy with nedocromil sodium 2% ophthalmic solution to treat ocular symptoms of seasonal allergic conjunctivitis.,Michael Alexander; Piyush Patel; Stacey Allegro; Angela Hicks,"Ocular symptoms are often under-treated in patients with allergic rhinoconjunctivitis. The efficacy of fexofenadine hydrochloride 60 mg capsules supplemented with nedocromil sodium 2% ophthalmic solution was evaluated to determine the optimal drug regimen for control of ocular allergic symptoms. In this 5-week, open-label, randomized, multicentre comparative study, 89 patients with documented ragweed pollen allergy received fexofenadine b.i.d. with nedocromil rescue, fexofenadine q.d. with nedocromil b.i.d., or fexofenadine rescue with nedocromil b.i.d. during the ragweed pollen season. For all regimens, mean symptom severity scores for itching, burning, tearing, redness, grittiness, discharge, light sensitivity and swelling improved significantly (P < 0.003). Similarly, all groups experienced significant (P < 0.02) improvement in all clinical signs: erythema, oedema, discharge, conjunctival injection and conjunctivitis, as well as quality-of-life scores (P < 0.0001). All regimens reduced overall symptom severity scores after 5 min (P < 0.05) with relief persisting over 12 h (P < 0.03). Improvements in mean symptoms, signs and quality-of-life scores were similar among the treatment groups as were onset and duration of action even though patients in two of the three study arms were taking one-half or less of the recommended fexofenadine dosage. Patients and physicians judged the regimens containing lower fexofenadine dosages (with nedocromil b.i.d.) to be more effective overall than the regimen containing the highest fexo-fenadine dosage (with nedocromil as rescue only). Supplementation of oral fexofenadine therapy with nedocromil sodium 2% ophthalmic solution relieves ocular symptoms of seasonal allergic rhinoconjunctivitis, allowing control of rhinal symptoms with half the recommended dosage of fexofenadine.",2003.0,0,0
153,12806876,[H1 histamine antagonists].,J Duchateau; M Heenen; J Sternon,"Histamine is an important mediator for early phase allergic reactions that are involved in atopic diseases, mediated by specific IgE antibodies. After allergenic contact, its liberation induces unpleasant symptoms like itching, several manifestations as local vasodilatation, bronchoconstriction, mucus hypersecretion. Antagonists of H1 histamine receptors are the most prescribed drugs, due to their symptomatic effects at the levels of nasal or conjunctival mucosa, and the skin. Their major indications cover allergic rhinitis, either seasonal or perennial, and idiopathic chronic urticaria, as a first line medication. The pharmacological evolution allows to distinguish three generations of products differing at the levels of specificity, long acting period, and toxicity. The authors are discussing the respective benefits of two recent molecules presented as 3rd generation molecules: fexofenadine and levocetirizine, while repositioning their use among available treatment strategy.",2003.0,0,0
154,12814463,The effects of histamine and leukotriene receptor antagonism on nasal mannitol challenge in allergic rhinitis.,Daniel K C Lee; Kay Haggart; Graeme P Currie; Sandra D Anderson; Brian J Lipworth,"It is unclear as to which mediators are involved in mediating the response to nasal mannitol challenge, a novel osmotic stimulus. A double-blind, randomized, placebo-controlled, crossover design was employed. Nine patients with allergic rhinitis were randomized to receive a single-dose of desloratadine 5 mg, montelukast 10 mg or placebo, and underwent nasal mannitol challenges with nasal peak inspiratory flow recordings over 60 min. The change in peak nasal inspiratory flow was calculated as percentage change from baseline as the peak response and area under the time-response curve (AUC). Desloratadine and montelukast conferred a significant degree of protection compared to placebo for peak and AUC response, but there were no significant differences between the two drugs. For the peak response as percentage fall, the mean difference (95% CI) vs placebo was 27.7 (8.0, 47.4)% for desloratadine and 17.6 (1.9, 33.3)% for montelukast. Our results suggest that histamine and cysteinyl-leukotrienes are involved in mediating the response to nasal mannitol in allergic rhinitis.",2003.0,0,0
155,12828751,"Addition of fexofenadine to a topical corticosteroid reduces the pruritus associated with atopic dermatitis in a 1-week randomized, multicentre, double-blind, placebo-controlled, parallel-group study.",M Kawashima; T Tango; T Noguchi; M Inagi; H Nakagawa; S Harada,"Fexofenadine, a nonsedating, H1-receptor selective antihistamine, exhibits consistent efficacy and safety in the treatment of allergic rhinitis and urticaria. The pruritus associated with atopic dermatitis is considered to be induced, in part, by histamine. Therefore, we thought that fexofenadine may be useful in the relief of pruritus associated with atopic dermatitis. To compare the efficacy of twice-daily fexofenadine hydrochloride (HCl) 60 mg vs. placebo in reducing the pruritus associated with atopic dermatitis. In this randomized, multicentre, double-blind, placebo-controlled study, patients (aged >or= 16 years) with atopic dermatitis underwent a 1-week placebo lead-in period, followed by randomization to fexofenadine HCl 60 mg twice daily or placebo for 1 week. All patients also received topical treatment with 0.1% hydrocortisone butyrate twice daily throughout the study. The primary efficacy endpoint was mean change in pruritus score from baseline. Patients reflectively recorded pruritus scores twice daily (day and night) using a five-point scale (0 = none; 4 = very severe). Fexofenadine (n = 201) significantly decreased the severity of pruritus compared with placebo (n = 199) (mean change in score -0.75 (unadjusted 95% confidence interval [-0.88, -0.62]) vs. -0.5 [-0.62, -0.38], respectively; P = 0.0005). This improvement was seen after just 1 day of treatment (P = 0.039) and was maintained throughout the treatment period (P = 0.019). Compared with placebo, fexofenadine significantly improved both diurnal (P = 0.0001) and nocturnal pruritus (P = 0.013). In addition, significantly more patients in the fexofenadine group experienced a reduction in the ratio of pruritus area to body surface area compared with those in the placebo group (P = 0.007). The incidence of adverse events was low and similar across all treatment groups. Fexofenadine HCl 60 mg twice daily demonstrated a rapid, significant improvement in the pruritus associated with atopic dermatitis, with a safety profile equivalent to that of placebo.",2003.0,0,0
156,12847854,[Multicenter study of the effectiveness and tolerability of desloratadine in seasonal allergic rhinitis].,Henriette Farkas,"The authors appraised the clinical efficacy of desloratadine in patients with seasonal allergic rhinitis and rhinoconjunctivitis. An open, two-week trial was conducted on 428 patients between 3 June and 31 July 2002 in 11 centres. Nasal obstruction, rhinorrhea, sneezing, and itching as well as ocular clinical signs were characterized using a symptom score. Desloratadine tablet was administered in 5 mg doses. After two weeks of treatment, the symptom score was re-evaluated. Potential adverse events that had occurred during the treatment period were recorded. Desloratadine significantly alleviated all four nasal symptoms and ocular effectively. In particular, treatment resulted from 76 percent to 12% percent decrease of overall symptom score. One of the participants discontinued treatment due to the occurrence of adverse effects. These results demonstrate that desloratidine is a safe and effective systemic antihistamine--with complex antiallergic effect--for the therapy of seasonal allergic rhinitis and rhinoconjunctivitis. It can reduce nasal congestion with greater magnitude than other known antihistamines.",2003.0,0,0
157,12867226,"A single-center, randomized, double-blind, placebo-controlled, crossover investigation of the effects of fexofenadine hydrochloride 180 mg alone and with alcohol, with hydroxyzine hydrochloride 50 mg as a positive internal control, on aspects of cognitive and psychomotor function related to driving a car.",Fran Ridout; Ziba Shamsi; Robert Meadows; Sigurd Johnson; Ian Hindmarch,"Antihistamines (H(1)-receptor antagonists) are the mainstay of symptomatic therapy for allergic disorders. Antihistamines are needed that cause no disruptive effects on cognitive and psychomotor function. It is essential that antihistamines maintain the integrity of the cognitive system, not only in ambulatory patients at increased risk of drug-induced traffic- or work-related accidents, but also in students and others whose cognitive or intellectual impairment may adversely affect their performance.Objective; The goal of this study was to investigate the acute effects of fexofenadine hydrochloride 180 mg, alone and with a ""social"" dose of alcohol, on subjective feelings of sedation and on a battery of objective measures related to driving a car. These measures included information processing, psychomotor speed, and reaction time in an on-the-road car-driving task. Hydroxyzine hydrochloride 50 mg was included in the study as a positive internal control to validate the sensitivity of the psychometri tests to nonspecific impairment. In this randomized, double-blind, 6-way, crossover study conducted at the Human Psychopharmacology Research Unit, Medical Research Centre (University of Surrey, Guildford, United Kingdom), 18 healthy volunteers received fexofenadine 180 mg, hydroxyzine 50 mg, and placebo alone and with alcohol (0.3 g/kg body weight or approximately 0.43-0.50 g/L blood-alcohol concentration). Treatment periods were separated by a washout period of at least 6 days. Subjects performed tests of cognitive and psychomotor performance at 1, 3, and 5 and hours after dosing. The test battery included subjective ratings of sedation, critical flicker fusion (CFF), choice reaction time (including recognition reaction time [RRT], motor reaction time [MRT], total reaction time [TRT], and brake reaction time [BRT]. Eighteen healthy male volunteers (median age, 30.5 years [range, 23-44 years]) were entered into the study. Fexofenadine alone and with alcohol had no significant effect on performance compared with placebo and was not distinguishable from placebo in any of the objective or subjective tests at any point. However, impairment was evident following the administration of hydroxyzine. Hydroxyzine caused significant impairment in CFF (P < 0.05), RRT (P < 0.001), and TRT (P < 0.001) compared with placebo. Hydroxyzine with alcohol significantly disrupted performance on all of the above measures with respect to both placebo and fexofenadine (P < 0.05) as well as MRT (P < 0.001). No significant treatment effects on BRT were found. Fexofenadine 180 mg did not have disruptive effects on objective measures related to driving a car and aspects of psychomotor and cognitive function, even when combined with a dose of alcohol equivalent to 0.3 g/kg body weight, in a study in which the psychometric assessments were shown to be sensitive to impairment.",2003.0,0,1
158,12911418,Levocetirizine is effective for symptom relief including nasal congestion in adolescent and adult (PAR) sensitized to house dust mites.,P C Potter; Study Group,"Antihistamines are the most commonly prescribed class of medication for perennial allergic rhinitis (PAR). The primary objective of this study was to determine whether levocetirizine (Xyzal(R)), the active enantiomer of cetirizine, could achieve at least a 50% improvement in PAR symptoms compared to the placebo over the first week of treatment. A total of 294 patients with PAR due to house dust mites were randomized in this 8-week double-blind, placebo-controlled, multicentre trial to receive either levocetirizine 5 mg/day or placebo. Mean Total Four-Symptom Scores (T4SS) (nasal pruritus, ocular pruritus, rhinorrhoea and sneezing) were compared between treatment groups over weeks 1, 4 and 6. All individual symptom scores, including nasal congestion, were also studied. Levocetirizine showed an 86% improvement in T4SS over the first week of treatment and a 47% improvement over the entire treatment period compared with placebo. Absolute changes from baseline were 3.64 and 2.47 for levocetirizine and placebo, respectively. Individual symptom scores showed statistically significant (P < or = 0.01) differences in favour of levocetirizine for all study time-points. Nasal congestion was unexpectedly significantly improved (P < 0.001). The incidence of reported adverse events was comparable between treatment and placebo group. Levocetirizine 5 mg/day is an effective and well-tolerated treatment of PAR. In addition, levocetirizine is effective for the relief of nasal congestion.",2003.0,0,1
159,12917016,Assessing satisfaction with desloratadine and fexofenadine in allergy patients who report dissatisfaction with loratadine.,Daniel J Glass; Anne S Harper,"The FDA recently moved loratadine (Claritin) from prescription only status to over-the-counter (OTC). In response to the availability of an OTC non-sedating antihistamine, many managed care organizations are reevaluating which if any prescription antihistamines should remain on formulary. From a managed care perspective, determining which of the remaining prescription antihistamines results in the greatest patient satisfaction with allergy treatment would be informative. We report on a weighted cross sectional survey (n = 10,023) delivered online to a sample of allergy sufferers in the U.S. during the month of December 2002. Two segments were identified for analysis: patient who were dissatisfied with loratadine and converted to desloratadine (Clarinex; n = 61), and patients who were dissatisfied with loratadine and converted to fexofenadine (Allegra; n = 211). The two segments were compared along a series of measures that the literature suggests are related to treatment satisfaction. The survey found that two of the satisfaction measures differentiated desloratadine converters from fexofenadine converters (p <.05): mean sum of self-reported adverse events and nighttime awakening due to allergy symptoms. For the remainder of satisfaction measures though, patients who were dissatisfied with loratadine reported equal duration of coverage and satisfaction with desloratadine as fexofenadine. When severity of disease was controlled for in the analysis, a pattern emerged suggesting greater levels of satisfaction amongst loratadine dissatisfied patients who converted to desloratadine. Point estimates suggest a consistent pattern favoring desloratadine patient satisfaction, with statistically significant results reported for sum of adverse effects, nighttime awakening due to symptoms, symptom severity just prior to the next dose, and overall satisfaction (p < 0.05). On average, patients who were dissatisfied with loratadine reported equal or better satisfaction with desloratadine as fexofenadine. Patients with severe allergic rhinitis reported greater satisfaction when converted from loratadine to desloratadine than fexofenadine for select satisfaction measures. These results suggest that if managed care intends to position prescription antihistamines as second line for OTC loratadine treatment dissatisfaction, desloratadine is a useful treatment alternative. These findings, while informative to formulary decision-makers, must be interpreted with caution. Only through head-to-head controlled clinical trials can differences in efficacy and safety be established.",2003.0,0,1
160,12946545,"Comparison of ketotifen fumarate ophthalmic solution alone, desloratadine alone, and their combination for inhibition of the signs and symptoms of seasonal allergic rhinoconjunctivitis in the conjunctival allergen challenge model: a double-masked, placebo- and active-controlled trial.",H Jerome Crampton,"Ketotifen fumarate is a topical antiallergic combination mast-cell stabilizer and antihistamine indicated for the temporary prevention of ocular itching due to allergic conjunctivitis. Desloratadine is a systemic antihistamine indicated for the treatment of seasonal and perennial allergic rhinitis. The purpose of this study was to compare the efficacy of ketotifen 0.025% ophthalmic solution instilled in the eye, desloratadine 5-mg tablets taken orally, and their combination for prevention of the signs and symptoms of allergic rhinoconjunctivitis, as induced by the conjunctival allergen challenge (CAC) model. This was a randomized, double-masked, placebo- and active-controlled, single-center clinical trial. At visit l, the dose of allergen necessary to elicit a qualifying allergic reaction was determined for subjects meeting the entry criteria. At visit 2, the allergen dose determined at visit 1 was confirmed, and all subjects who had a qualifying ocular and nasal allergic reaction were randomized to 1 of 3 treatment groups: ketotifen ophthalmic solution and placebo tablet, desloratadine tablet and placebo eyedrop, or ketotifen and desloratadine. Subjects were instructed to instill 1 drop into each eye twice daily and take 1 tablet with water once daily at the same time as the morning eyedrop for approximately 4 weeks. At visit 3, subjects brought in their medication and were given 1 drop of the eyedrop bilaterally and 1 tablet with water. Bilateral CAC was performed 2 hours after administration of medication. Using standardized scales, subjects rated ocular itching at 3, 5, and 7 minutes after CAC; ocular tearing and eyelid swelling at 10, 15, and 20 minutes after CAC; and nasal signs and symptoms (sneezing, rhinorrhea and postnasal drip, pruritus, and nasal congestion) at 10, 20, 30, 40, and 50 minutes after CAC. The investigator graded ocular redness and chemosis at 10, 15, and 20 minutes after CAC. At all visits, subjects were offered an anti-allergy eyedrop to relieve any immediate ocular discomfort caused by CAC. One hundred two subjects were screened-82 (55 women, 27 men; mean age, 42.8 years [range, 21-70 years]) were randomized to treatment, and 80 completed the study. Subjects in the group that received ketotifen (n = 27) and the group that received ketotifen with desloratadine (n = 26) had significantly lower mean itching scores compared with those in the group that received desloratadine alone (n = 27) at all time points (P </= 0.05). Total ocular redness, calculated by summing the mean redness scores for each of the 3 vessel beds, was significantly lower in the ketotifen group than in the other treatment groups at most time points (P </= 0.05). All treatments attenuated nasal symptoms; no statistically significant differences were noted between treatment groups, with the exception of the 50-minute time point, at which combination treatment was significantly more effective than ketotifen alone (P </= 0.05). The proportion of subjects who requested relief drops after CAC was significantly lower in both the ketotifen alone and combination treatment groups compared with the desloratadine alone group (P = 0.004). Ketotifen ophthalmic solution significantly decreased the signs and symptoms of ocular and nasal allergic rhinoconjunctivitis. The addition of ketotifen to the oral desloratadine regimen improved the overall antiallergic efficacy of both medications.",2003.0,0,0
161,12968983,Twenty-four-hour activity and consistency of activity of levocetirizine and desloratadine in the skin.,Ashok Purohit; Michel Melac; Gabrielle Pauli; Nelly Frossard,"Levocetirizine, the active enantiomer of cetirizine, and desloratadine, the active metabolite of loratadine, are two recently introduced anti-H1 agents. We set out to compare their antihistaminic activity in the skin for 24 h in a double-blind, randomized cross-over trial. The skin reaction to histamine administered by prick tests (100 mg ml(-1)) was measured by the surface areas of weals and flares for 24 h [before treatment, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 h after a single dose of levocetirizine (5 mg), desloratadine (5 mg) or placebo] in 18 healthy volunteers (34.8 +/- 9.4 years; 14 women). The areas under the curves (AUC) of the weal and flare areas as a function of time were compared by ANOVA. A highly significant overall treatment effect (P < 0.0001) was observed and both weals and flares were inhibited. The pairwise comparisons showed that the activity of levocetirizine and desloratadine was significantly superior to that of placebo (P < 0.0001), and the activity of levocetirizine was significantly superior to that of desloratadine (P < 0.0001). 'Total' weal inhibition (> or = 95%) occurred only with levocetirizine. Median values of maximal weal inhibition were 44.2% with placebo, 55.0% with desloratadine and 100% with levocetirizine. The time to maximal weal inhibition was 4 h (median value) for all three study drugs, but scattered over a wider range for desloratadine (3-24 h) than levocetirizine (2-4 h). With desloratadine, five of 18 (28%) subjects reached weal inhibition of at least 70% at between 3 and 10 h, whereas with levocetirizine all subjects [18/18 (100%)] reached this level of weal inhibition at between 1 and 3 h. The median duration of 70% weal inhibition was zero with placebo and desloratadine, and was 21.4 h with levocetirizine (P < 0.0001 between the three study drugs, and P < 0.0001 between the two active drugs). No uncommon adverse events were reported, and no subject withdrew from the study due to an adverse event. This study shows that the activity of levocetirizine in suppressing skin reactivity to histamine was clearly superior to that of desloratadine for 24 h after a single dose. In addition, its activity was more consistent and lasted longer.",2003.0,0,0
162,12968987,Leukotriene C4 synthase polymorphisms and responsiveness to leukotriene antagonists in asthma.,Graeme P Currie; John J Lima; Jim E Sylvester; Daniel K C Lee; Wendy J R Cockburn; Brian J Lipworth,"Cysteinyl leukotrienes are important pro-inflammatory mediators in the pathogenesis of asthma, while leukotriene C4 synthase is a key enzyme in their biosynthesis. Our aim is to evaluate whether responsiveness to leukotriene receptor antagonists was determined by expression of the variant (C) or wild-type (A) polymorphism of this enzyme. We carried out a retrospective analysis of 8 randomised, placebo-controlled trials performed in our department in mild-to-moderate asthmatics. In all trials, effect of leukotriene receptor antagonist was compared to placebo, where the primary outcome was bronchial hyperresponsiveness to adenosine monophosphate or methacholine. Secondary outcomes were forced expiratory volume in 1 second, exhaled nitric oxide and peripheral blood eosinophils. For the primary outcome of attenuation of bronchial hyperresponsiveness by leukotriene receptor antagonist vs placebo, there were significant effects within each genotype on adenosine monophosphate (AMP) (n = 78): 2.21 and 2.07-fold improvements for AA and AC/CC, respectively; while for methacholine (n = 81) there were 1.39 and 1.36-fold improvements, respectively. There were no significant differences between genotypes (i.e. AA vs AC/CC): geometric mean fold-differences of 1.07 (95%CI 0.63-1.81) and 1.02 (95%CI 0.70-1.50) for AMP and methacholine, respectively. There were also no differences between genotypes for all secondary outcomes. Polymorphisms of leukotriene C4 synthase did not determine responsiveness, in terms of attenuation of bronchial hyperresponsiveness, to leukotriene receptor antagonists in mild-to-moderate asthmatics. Further prospective large pharmacogenetic studies are required in more severe patients, where there may be greater improvements in pharmacodynamic outcome measures such as bronchial hyperresponsiveness and exhaled nitric oxide.",2003.0,0,0
163,1342896,Multicenter double-blind comparative study of terfenadine and cetirizine in hay fever.,M F Caiaffa; A Iudice; L Macchia; A Tursi; G Vergallo; G Sacerdoti; A Venuti; F Della Torre; A Musarra,"The efficacy and safety of terfenadine in the management of hay fever were compared with those of cetirizine in a multicenter, double-blind, parallel-group study, carried out during the 1990 spring pollen season. The patients were randomly assigned to one of two groups of treatment, 70 patients being given terfenadine 120 mg, and 72 patients cetirizine 10 mg, once daily for 7 days. The severity of the main symptoms was evaluated at baseline and after treatment by a 4-point rating scale. In addition, the overall symptom severity was recorded daily by the patient on a diary card. Both terfenadine and cetirizine produced significant relief of symptoms by the end of treatment, with a decrease in symptom severity ranging from 46 to 69% for terfenadine and from 40 to 55% for cetirizine. Adverse effects experienced by terfenadine- and cetirizine-treated patients were mainly drowsiness, with minor differences between the two groups. The results of this study confirmed previous experiences, showing that both terfenadine and cetirizine once daily should be regarded as effective drugs for the management of hay fever.",1992.0,0,1
164,1364168,A comparison of new nonsedating and classical antihistamines in the treatment of primary acquired cold urticaria (ACU).,F Villas Martínez; F J Contreras; J M López Cazaña; M C López Serrano; F Martínez Alzamora,"The efficacy of the new nonsedating antihistamines loratadine and cetirizine was compared in a randomized, single-blind, crossover, controlled study with that of the classical antihistamines cyproheptadine and ketotifen in seven patients with primary acquired cold urticaria (ACU). The patients received each of the four drugs for 14 consecutive days with a 7-day interval between drugs. We evaluated clinical symptomatology, adverse effects, minimum time of cold contact stimulation required to induce an immediate coalescent wheal (CSTT), and inhibition of histamine-induced wheal response. Both loratadine and cetirizine showed suppression of symptoms with infrequent adverse effects. Important side-effects were observed in patients receiving cyproheptadine. Improvement in CSTT was statistically significant for all drugs compared with baseline values, without differences among them. The histamine-induced skin test was significantly inhibited by all antihistamines. Wheal reductions were 34.6% for loratadine and 50.9% for cetirizine. This study suggests that both loratadine and cetirizine may be effective in the treatment of primary ACU.",1992.0,0,1
165,14520518,"Comparison of the effects of desloratadine and levocetirizine on histamine-induced wheal, flare and itch in human skin.",K J Denham; P Boutsiouki; G F Clough; M K Church,"A previous study showed the inhibitory effects of loratadine on histamine-induced wheal, flare and itch in human skin to be very variable between individuals. It was hypothesised that this variability may have been due to differences in the rates of metabolism of loratadine to its active form, desloratadine. This double blind, crossover study examined the effects of desloratadine in 12 healthy volunteers. Levocetirizine was used as a comparator. Desloratadine (5 mg), levocetirizine (5 mg) or placebo was taken orally 4 h before an intradermal injection of histamine (20 microL, 100 microM) or vehicle control into the forearm skin. Flare areas were assessed by scanning laser Doppler imaging before and at 30 s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s for 5 min using a visual analogue scale. Following placebo administration, the mean (+/- SEM) wheal area at 10 min was 79.3 +/- 6.9 mm(2), mean flare area for the first 5 min following challenge 26.6 +/- 2.7 cm(2), and itch score for the same period 48.5 +/- 7.6%. The effects of desloratadine were variable between individuals, mean reductions in the wheal and flare areas being 17% (P = 0.033) and 12% (P = 0.036). Desloratadine did not reduce itch significantly. Levocetirizine was more consistent in its effects, mean reductions in wheal, flare and itch being 51%, 67% 78% respectively (all P < 0.001). A single dose of 5 mg levocetirizine produced more consistent and greater inhibitory effects on histamine-induced wheal, flare and itch than did 5 mg desloratadine. The difference is suggested to reflect the basic pharmacokinetics of the two drugs.",2003.0,0,0
166,14556322,Pre and post treatment mucociliary function in allergic rhinitis in three different treatment modalities.,L M Lee; B S Gendeh,"Allergic rhinitis causes an impairment of the mucociliary function in the nose. It is hoped that treatment of perennial allergic rhinitis would be able to revert mucociliary function to normal. This study aims to compare pre and post treatment mucociliary transport time in 3 different treatment modalities. Ninety-two newly diagnosed patients with allergic rhinitis were randomised into 3 groups and started on different treatment regimes. At the end of 8 weeks, the group treated with only intranasal beclomethasone showed some, though not significant, improvement in the mucociliary function. There were no changes in the mucociliary function in the other two groups treated with beclomethasone and loratidine or loratidine alone.",2003.0,0,0
167,14558336,[Acute interstitial nephritis induced by loratadine].,R Alvarez Navascués; Z Bastardo; M Fernández Díaz; J Guerediaga; L Quiñones; J Pinto,"Loratadine is a second generation histamine H1 receptor antagonist, that has high potency antiallergic properties and is associated with low adverse effects compared with other antihistamines. Acute interstitial nephritis is a cause of acute renal failure that is most often induced by drugs or, less frequently, infection or sarcoidosis. Although the number of drugs associated with acute intersticial nephritis is too large, the antihistaminic loratadine have never been reported before. We report a case of an interstitial nephritis with acute renal failure that suggesting hypersensitivity reaction in a 77 old man who had received loratadine (10 mg/day) during ten days before his assessment to our hospital by disseminated pruritic syndrome. The initial suspect was rapidly progressive glomerulonephitis and renal biopsy was practice and treatment with corticosteroids were initiated (prednisone bolus of 500 mg three days and 1 mg/kg/day/later). The loratadine therapy was cessation. He exhibiting a slow and progressive improvement on renal function and one month later, urea and creatinine levels was normal and hematuria and proteinuria had disappeared. The corticosteroids therapy were progressive decreased until withdrawal. We think that this is an interesting case, basing in its clinical presentation and that it had never been reported before.",2003.0,0,1
168,14626470,Changing medication use in managed care: a critical review of the available evidence.,Sallie-Anne Pearson; Dennis Ross-Degnan; Ann Payson; Stephen B Soumerai,"To review the effectiveness of strategies to improve the quality and efficiency of medication use in managed care organizations (MCOs). Systematic review of published intervention studies. Studies were identified by using computerized and manual literature searches and personal contacts, and were categorized by intervention type and adequacy of research design according to commonly accepted criteria. Reported significance and magnitude of the changes in key outcomes were used to summarize the effects of studies with adequate research designs. The searches identified 105 studies, 70 of which were reported since 1996. Overall, 46% of the studies met the minimum criteria for methodologic adequacy (n = 48). Consistently effective interventions included dissemination of educational materials with drug samples, participatory clinical guideline development, group or one-to-one educational outreach, and enhanced patient-specific feedback. Disease management (primarily for depression and diabetes) showed promise in improving short-term outcomes. Dissemination of educational materials and aggregated feedback alone were ineffective. Interventions in staff-model health maintenance organizations were more effective than those conducted in group-model health maintenance organizations. High-quality studies of interventions to improve drug use in MCOs are increasing in frequency. There is evidence for the effectiveness of several strategies to change drug use, but little is known about longer-term clinical outcomes. Few well-designed, published studies have assessed the efficacy or safety of financial incentives for physicians, tiered copayments for patients, or formularies--despite their widespread use.",2003.0,0,0
169,1669595,Comparative effects of terfenadine and loratadine in the treatment of hay fever.,G Ciprandi; A Iudice; M A Tosca; S Ruffoni; S Buscaglia; G W Canonica,"This double-blind, double-dummy, parallel-group study was undertaken in 40 patients with seasonal allergic rhinoconjunctivitis during the 1990 hay fever season. The patients were randomized and treated for seven days with either 120 mg terfenadine or 10 mg loratadine, each drug taken once daily in the morning. The severity of nasal congestion, rhinorrhea, sneezing, nasopharyngeal itching, and itchy, watery, red eyes was evaluated before and at the end of treatment. The global severity of symptoms was ranked daily by the patient on a diary card. Both treatment groups experienced a significant improvement of symptoms after treatment (p < 0.01), without any significant difference between the two study drugs. Terfenadine and loratadine significantly improved symptom severity by 69 and 55% compared with the baseline values, respectively. Headache and fatigue were reported in three loratadine-treated patients, and sedation in one patient. No side effects were observed in patients receiving terfenadine. This study confirmed that terfenadine 120 mg once daily is a safe and effective treatment for hay fever.",1991.0,0,1
170,7528133,Loratadine. A reappraisal of its pharmacological properties and therapeutic use in allergic disorders.,M Haria; A Fitton; D H Peters,"Loratadine is a long-acting antihistamine agent, exhibiting partial selectivity for peripheral histamine H1-receptors. To date, loratadine has been evaluated in allergic rhinitis, urticaria and, to a limited extent, in asthma. In several large controlled comparative clinical studies, loratadine was superior to placebo, faster acting than astemizole and as effective as azatadine, cetirizine, chlorpheniramine (chlorphenamine), clemastine, hydroxyzine, mequitazine and terfenadine in patients with allergic rhinitis and chronic urticaria. The clinical effectiveness of loratadine in asthma is at present unclear. Loratadine is well tolerated. At dosages of 10 mg daily, commonly reported adverse events were somnolence, fatigue and headache. Sedation occurred less frequently with loratadine than with azatadine, cetirizine, chlorpheniramine, clemastine and mequitazine. Serious ventricular arrhythmias, as reported with some other second generation histamine H1-receptor antagonists, have not been observed with loratadine to date. Thus, loratadine, with its attributes of once daily administration, fast onset of action and essentially nonsedating properties, would appear to be an appropriate first-line agent for the treatment of allergic rhinitis or urticaria.",1994.0,0,0
171,7530629,"Urticaria. Recognition, causes and treatment.",A D Ormerod,"The urticarias are a complex group of disorders characterised by transient whealing or swelling of the skin. Understanding the many possible causes is the first step in assessing urticaria. Allergic and drug-induced urticaria respond to removal of the cause. The physical urticarias, particularly delayed pressure urticaria and also urticarial vasculitis, require separate consideration. For the majority of patients with chronic idiopathic urticaria, nonsedating antihistamines are the mainstay of treatment. There are several to choose from, including cetirizine, astemizole, loratadine, terfenadine and acrivastine, each with its own pharmacokinetics and antiallergic properties. When these fail, histamine H2-antagonists may help either alone or in combination with H1-antagonists. Older sedative antihistamines are still useful. Ketotifen, oxatomide and azelastine have mast cell stabilising effects that are considered an advantage in treating these disorders. Second-line therapies include a wide range of drugs such as doxepin, dapsone, attenuated androgens, calcium antagonists, antimalarials, gold and methotrexate. The most effective and regularly used second-line agents are corticosteroids. These are best limited to short term crisis management, except in severe recalcitrant cases, and in patients with pressure urticaria or urticarial vasculitis. Recent work on circulating histamine releasing autoantibodies suggests that there is scope for more aggressive immunosuppression in selected patients. However, effective treatment with immunosuppression often requires plasma exchange and more toxic agents such as cyclosporin. Such treatments are only likely to be entertained in exceptional cases.",1994.0,0,1
172,7536515,[The effect of loratadine on skin and bronchial reactivity and histamine liberation from basophils in patients with atopic asthma and allergic rhinitis].,Z Siergiejko; I Michalska; Z Buko; M Swiderska; S Chyrek-Borowska,"The effect of the therapy with Loratadine on skin and bronchial reactivity to histamine and on a specific histamine release from isolated basophils of allergic patients was assessed. The studies were carried out on a 34 patients (23 with pollen rhinitis and 11 with a mild bronchial asthma). The effect loratadine versus placebo on the skin reactivity to histamine was measured in patients suffering from pollen rhinitis. Outside the pollen season in 12 patients from the above group a histamine release from isolated basophils was evaluated by Shore method, using a-IgE and pollen allergen as liberators, before and after 4 days therapy with loratadine. In the group of the 11 asthmatic patients the effect of the single dose of 10 mg Loratadine on spirometric parameters and on a bronchial response to histamine was studied. The Bronchial Provocation Test with histamine was performed by the Ryan's method. The results were expressed as PC20 FEV1. It was shown that loratadine statistically significant limited of the skin reactivity to histamine and specific histamine release from basophils. The one tablet of Loratadine have not changed of spirometric parameters in the patients with mild asthma, but statistically significant reduced their bronchial response to histamine.",1994.0,0,0
173,7542992,[Efficacy and safety of loratadine vs terfenadine in the treatment of children with perennial allergic rhinitis. Capacity for inhibiting the positive cutaneous response after antihistaminic treatment].,J I Canseco Villarreal,"We studied 104 medical student from the UANL with symptoms of Perennial Allergic Rhinitis, including only 30 patients for this study; seven patients with Loratadine 10 mg, eight with Loratadine 20 mg, and 15 with Terfenadine 120 mg/day/21 days, 20 mg of Loratadine and 120 mg of Terfenadine demonstrated significant decrease of the symptoms (P > 0.005). Two patients had collateral effects with Terfenadine, but Terfenadine were more effective than the Loratadine in the reduction of the skin reactivity.",1995.0,1,1
174,7551204,Comparative study of terfenadine and cetirizine in hay fever: assessment of efficacy and central nervous system effects.,F Bonifazi; L Provinciali; L Antonicelli; M B Bilò; S Pucci; M Signorino; B Franciolini; B Censori; P Pagelli; A Iudice,"A daily dose of either terfenadine 120 mg or cetirizine 10 mg was compared in two parallel groups of patients suffering from hay fever. According to a double-blind, double-dummy, randomized design, 28 patients were treated with one of the two drugs once daily in the morning for 2 weeks during the 1990 grass pollen season. The severity of nasal congestion, rhinorrhea, sneezing, nasopharyngeal itching and itchy, watery, red eyes was evaluated by the investigator after a 1-week run-in period and at the end of the treatment. The patients made a daily record of the severity of symptoms on a diary card. In addition, drug-related central nervous system (CNS) effects were assessed at baseline and at the end of the treatment by neuropsychological tests aimed at investigating selective and sustained attention, visuomotor abilities and anxiety, and by quantitative, bit-mapped EEG. Both terfenadine and cetirizine produced a significant improvement in symptoms at endpoint without any significant difference between the two drugs. Drowsiness was referred by one patient in each treatment group. No significant impairment of psychomotor performance occurred with either drug. Quantitative EEG showed a significant power increase in the relative (%) delta band in both groups of treated patients. Although the difference was not statistically significant, a tendency towards greater involvement of the CNS was observed with the use of cetirizine. In conclusion, the results of this study confirm that terfenadine and cetirizine are equally effective in the management of hay fever. Some differentiated untoward EEG changes were also observed in relation to the drugs used, without any variation in neuropsychological performance.",1995.0,0,1
175,7572544,[Non-sedative antihistaminics in the treatment of chronic urticaria].,J M Negro; F Sarrió; J C Miralles; F J García Sellés; J D López Sánchez; J a Pagán; J Hernándéz,"Antihistamines are the drugs of choice in the symptomatic relief of chronic idiopathic urticaria; however, the usefulness of classic antihistamines has been limited by side effects. In the 1980s a new class of antihistamines has been developed that maintains effectiveness and produces less side effects (eg anticholinergic side effects, daytime sedation, etc). This review analyzes each of the new nonsedating antihistamines commercially available in Spain (astemizole, ebastine, cetirizine, loratadine and terfenadine) and evaluates its clinical efficacy and safety in the treatment of chronic idiopathic urticaria.",1995.0,0,0
176,7573830,"Effects of loratadine on anti-IgE-induced inflammation, histamine release, and leukocyte recruitment in skin of atopics.",A Roquet; J Raud; G Halldén; M van Hage-Hamsten; J Hed; L O Hansson; O Zetterström; R Grönneberg,"The aim of this study was to assess the ability of the H1-receptor antagonist loratadine to modify anti-IgE-induced cutaneous wheal-and-flare and late-phase reactions (WFR and LPR), as well as histamine release and leukocyte accumulation in skin chambers. For this purpose, 10 atopics with allergic rhinitis were entered into a double-blind crossover study in which they received either placebo or loratadine (20 mg/day orally) for 8 days separated by a 7-day washout period. Blisters were induced on both forearms on day 7 of each treatment period, and were unroofed on day 8 and covered with plastic skin chambers. Chamber fluids were collected during 7 h after 1-h incubation with anti-IgE or control IgG. Intradermal challenge with histamine and anti-IgE was performed at the same occasion. As compared to placebo treatment, loratadine inhibited the immediate WFRs to anti-IgE by 35% (wheal) and 65% (flare), respectively (P < 0.01), and corresponding reactions to histamine challenge by 50% and 70% (P < 0.001), respectively. Moreover, the initial phase (0-2 h) of the LPR induced by anti-IgE was attenuated by up to approximately 60% (P < 0.001) during loratadine treatment. Thereafter, no inhibition of the LPR was observed. The magnitude and time course of histamine release into skin chambers was virtually the same after loratadine and placebo treatment, with a peak during 0-1 h and a progressive decline during the following 2 h. Accumulation of alpha 2-macroglobulin, reflecting extravasation of large plasma proteins, also peaked during the first hour and was unaffected by loratadine during the 8-h observation period.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
177,7581058,"[Effect of loratadine, selective antagonist of histamine H1 receptors, on histamine-induced bronchoconstriction].",G Cieślewicz; K Gondorowicz; I Grzelewska-Rzymowska; J Rozniecki,The aim of this study was to assess the duration of Loratadine effect on histamine H1 receptor in the airway. Six patients with mild or moderate asthma were examined. Bronchial reactivity to histamine was measured according to Cockcroft. The significant blockade of histamine H1 receptors in airway was observed from the 2nd day when 10 mg of Lo was given daily. The maximal protection with 10 mg doses was observed after 3-4 days. After another 5-6 days without Loratadine bronchial responsiveness return to the initial values. Single dose of 30 mg Loratadine given better protection against histamine bronchoconstriction than 10 mg given for 5 days. This effect was observed as early as 60 minutes after administration of Loratadine.,1995.0,0,0
178,7585852,Comparison of intranasal triamcinolone acetonide with oral loratadine for the treatment of patients with seasonal allergic rhinitis.,W Schoenwetter; J Lim,"This multicenter, double-blind, randomized, controlled, parallel-group study compared the safety and efficacy of intranasal triamcinolone acetonide with oral loratadine in relieving symptoms of ragweed-induced seasonal allergic rhinitis. Patients from community-based allergy practices with a history of at least two seasons of seasonal allergic rhinitis verified by a positive skin test received either once-daily treatment with intranasal triacinolone acetonide 220 micrograms plus 1 placebo capsule or oral loratadine 10 mg plus placebo nasal spray. Other medications for rhinitis were prohibited. Changes in rhinitis symptoms were assessed by using patient evaluations, physician global evaluations, and withdrawal rates. Efficacy was evaluated in 274 of 298 patients randomized to treatment (134 to triamcinolone acetonide and 140 to loratadine). Mean total nasal symptom scores for weeks 1, 2, 3, and 4 and the overall score showed greater improvement (P = 0.001) with triamcinolone acetonide than with loratadine. Improvement in all rhinitis symptoms was significantly greater with triamcinolone acetonide than with loratadine; there was a trend for greater improvement in ocular symptoms with triamcinolone acetonide. Physicians' global evaluations indicated triamcinolone acetonide provided moderate-to-complete relief in 78% of patients compared with 58% of loratadine-treated patients (P < or = 0.0001). Both treatments were well tolerated; headache was the most commonly reported adverse event in both groups. Intranasal triamcinolone acetonide was significantly more effective than oral loratadine in relieving the symptoms of seasonal allergic rhinitis.",1995.0,0,0
179,7589029,"Lack of interaction between two antihistamines, mizolastine and cetirizine, and ethanol in psychomotor and driving performance in healthy subjects.",A Patat; D Stubbs; C Dunmore; N Ulliac; B Sexton; I Zieleniuk; A Irving; W Jones,"The pharmacodynamic interaction between mizolastine, a new H1 antihistamine, and ethanol was assessed in a randomized, double-blind, three-way crossover, placebo-controlled study. Eighteen healthy young male volunteers received mizolastine 10 mg, or cetirizine 10 mg or placebo once daily for 7 days with a 1-week wash-out interval. An oral dose of ethanol or ethanol placebo, given 2 h after dosing on days 5 or 7 of each treatment period, was administered to achieve a peak blood alcohol concentration (BAC) of 0.7 g/l then maintained for 1 h by two further doses of ethanol. Driving ability and psychomotor performance were evaluated using actual and simulated driving tests, critical flicker fusion threshold (CFF), adaptive tracking and divided attention (DAT) tasks. Ethanol produced a significant decrement in all tasks up to 5.5 h after administration: an increase in steering movements of 4.6, in lateral deviation of 0.45 m, in braking reaction time of 80 ms, in driving test and DAT performance of + 3.2; and a decrease in CFF and in tracking speed of 2.6 m.s-1. Neither mizolastine nor cetirizine significantly impaired driving ability or arousal (CFF) compared with the placebo. However, both drugs significantly impaired DAT performance 6:00 h post-dose (increase of + 2.1 for mizolastine and + 2.4 for cetirizine). The tracking speed was significantly decreased 7:50 h after mizolastine administration (-1.3 m.s-1) and more consistently from 1:30 to 7:50 h after cetirizine administration (-1.4 m.s-1). No significant adverse interaction, i.e. potentiation, occurred between ethanol and either antihistamine.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
180,7591422,Pharmacologic modulation by cetirizine of some adhesion molecules expression in psoriatic skin lesions.,M Caproni; G M Palleschi; D Falcos; C Papi; T Lotti,"Adhesion molecules play a major role in the pathogenesis of inflammatory skin diseases by regulating lymphocyte trafficking and homing in an inflamed area. The expression of the lymphocyte function-associated antigen-1 (LFA-1) and of its ligand, the intercellular adhesion molecule-1 (ICAM-1) has been studied in psoriatic skin lesions of 10 patients with guttate, nummular, and palmoplantar psoriasis. In addition, the peculiar immunophenotype of infiltrating cells (CD3, CD4, CD8, CD25) and their correlation with HLA-DR expression before and after treatment with oral cetirizine, a highly selective, third generation H1-receptor antagonist has been examined using the labeled avidin biotin (LAB) system. Cetirizine treatment modulated in vivo the expression of adhesion molecules LFA-1/CAM-1 as shown in all cases by decreased levels of their expression on keratinocytes and on dermal endothelial cells (P < 0.001). The expression of HLA-DR on keratinocytes and endothelial cells was also inhibited after treatment. The numbers of infiltrating CD3-, CD4-, CD8-positive cells were reduced, whereas there was no significant modification of CD25-positive cells within the epidermis and the dermis. This open clinical trial suggests that cetirizine could be effective in treating psoriasis: (1) for its symptomatic control on itching; (2) for its immunopharmacologic modulation of leukocyte integrins and on the immunophenotype pattern of infiltrating and resident cells, and (3) for contributing to the clearing of the lesions clinically.",1995.0,0,0
181,7591715,The influence of betahistine on the dynamics of the cutaneous hypersensitivity reaction in patients with grass pollen allergy.,J R Snyman; D K Sommers; M van Wyk; M D Gregorowski,"Histamine has been well documented as an immune modulator, but the dynamics of a number of histamine receptor agonists and antagonists have not been similarly established. The aim of this study was to determine the effect of betahistine (an H3-receptor blocker with partial H1- and H2-agonism) on the dynamics of the cutaneous hypersensitivity reaction. The skin blister technique was used to collect inflammatory cells after intradermal (i.d.) administration of grass pollen antigen, histamine and betahistine to 11 atopic volunteers. In this open, cross-over study, volunteers were randomly allocated to five treatment protocols i.e. (a) histamine 1 microgram i.d.; (b) betahistine 57, 114 and 285 micrograms i.d.; (c) i.d. grass pollen antigen; (d) (c) plus oral betahistine; (e) (c) plus oral betahistine, cetirizine, (H1-blocker) and cimetidine (H2-blocker). Blister fluid containing cells were collected on microscope slides at 6 and 24 h after i.d. injections. The areas of the wheal and flare and of induration were measured, respectively, at 0.25, and, 1, 6 and 24 h. Combined oral therapy with cetirizine, cimetidine and betahistine reduced the area of grass pollen-induced induration significantly at all time periods, but caused a significant increase in eosinophil and neutrophil vacuolisation during the late phase reaction. This did not occur with orally administered betahistine alone. Intradermal betahistine induced significantly more neutrophil and eosinophil vacuolization than histamine and, in contrast to the latter, also mediated a concentration-dependent late phase induration. The results of this study suggest that the H3-receptor regulates a feedback system in conjunction with that previously proven for the H2-receptor.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
182,7600792,Echographic evaluation of patch test inhibition by oral antihistamine.,A Motolese; G Ferdani; B M Manzini; S Seidenari,,1995.0,0,0
183,7604646,Efficacy of cetirizine in cholinergic urticaria.,T Zuberbier; W Aberer; B Burtin; J P Rihoux; B M Czarnetzki,"In order to examine the efficacy of cetirizine in cholinergic urticaria, we studied 24 patients in a double-blind crossover design during 3-week treatment periods, with either 10 or 20 mg/d cetirizine or placebo. The placebo period was always placed in between the two verum treatments to allow for a washout of the drug. Evaluation of the patients' daily symptom scores based on itching, erythema and whealing showed a highly significant improvement (p < 0.01). The percentage of days with mild or no symptoms was also increased significantly with the drug (p < 0.05). Except for whealing (p < 0.05), no significant differences between the two dosages of cetirizine could be determined. Since antihistamines have previously been shown to be frequently unsatisfactory in the treatment of cholinergic urticaria, the present data are encouraging regarding the control of symptoms in this condition.",1995.0,0,1
184,7622644,"Cetirizine and astemizole therapy for chronic idiopathic urticaria: a double-blind, placebo-controlled, comparative trial.",D Breneman; E A Bronsky; S Bruce; J T Kalivas; G L Klein; H L Roth; M D Tharp; C Treger; N Soter,"Cetirizine and astemizole have been shown to be safe and effective in the treatment of patients with chronic idiopathic urticaria. Cetirizine brings about clinical benefit more rapidly. The purpose of this study was to compare the efficacy of single daily doses of cetirizine and astemizole in relieving the symptoms of chronic idiopathic urticaria, with particular emphasis on the commencement of action. Patients with chronic idiopathic urticaria were randomly assigned to relieve either 10 mg of cetirizine, 10 mg of astemizole, or placebo for 4 weeks in a multicenter double-blind trial. Patients rated symptom severity each night, and investigators rated symptoms weekly. One hundred eighty-seven patients were enrolled in the trial; 180 were included in the safety analysis and 177 were included in at least one efficacy analysis. Both cetirizine and astemizole were significantly superior to placebo in relieving symptoms of chronic idiopathic urticaria. Both patients' and investigators' ratings indicated that cetirizine acted more rapidly. Both active treatments were well tolerated, and the incidence of somnolence did not differ statistically between cetirizine (14.5%) and astemizole (10.3%). Both cetirizine and astemizole provide effective relief of the symptoms of chronic idiopathic urticaria with similar side-effect profiles. However, clinical benefit occurs significantly more rapidly with cetirizine.",1995.0,1,1
185,7649340,Astemizole-D causes less sleep impairment than loratadine-D.,M M Janssens; R L Lins,"This randomized, double-blind, double-dummy, parallel-group trial was initiated to evaluate and compare the tolerability of once-daily astemizole-D capsules (10 mg astemizole/240 mg pseudoephedrine) and twice-daily loratadine-D tablets (5 mg loratadine/120 mg pseudoephedrine), with particular reference to the impact of treatment on quality of sleep. A total of 240 healthy volunteers participated in this study with a treatment duration of 3 days. Astemizole-D consistently produced less sleep impairment than loratadine-D with statistically significant differences in favour of astemizole-D reported for night-time waking on days 4 and 5 (P = 0.004 and P = 0.006, respectively), as well as for night-time restlessness on day 4 and the total score for all sleep parameters on day 4 (P < 0.05). Global evaluations of overall sleep quality at the end of the trial also revealed some statistically significant differences in favour of astemizole-D. Both drugs were well tolerated and there were no differences in the incidence and type of adverse events reported in the two treatment groups. Slight changes in heart rate and blood-pressure were observed in both treatment groups, but these were small and were not considered to be of clinical significance. In conclusion, once-daily astemizole-D is well tolerated and appears to cause less sleep impairment than twice-daily loratadine-D.",1995.0,0,1
186,7653736,Assessment of the efficacy and safety of three dose levels of cetirizine given once daily in children with perennial allergic rhinitis.,S Jobst; W van den Wijngaart; A Schubert; H van de Venne,"The present study compared the efficacy and safety of three dose levels of cetirizine (2.5, 5, and 10 mg) once a day with placebo over 14 days in 6-12-year-old children with perennial allergic rhinitis. The design was a double-blind, randomized, multicenter, parallel-group study. Five symptoms (sneezing, nasal discharge, nasal obstruction, nasal pruritus, and ocular pruritus) were rated according to severity by investigators at the visits and daily by patients. Eighty-three patients were randomized to placebo, 84 to 2.5 mg cetirizine, 85 to 5 mg cetirizine, and 76 to 10 mg cetirizine. Groups were comparable at inclusion. The primary efficacy variable was the percentage of days with no or only mild symptoms: at all doses, cetirizine appeared to be more effective than placebo, but a significant difference was reached only in the 10-mg group (difference in medians of 22%; P = 0.016). The test of linearity was significant (P = 0.026) for the percentage of asymptomatic days. The investigators' assessments at each visit scored the symptoms in the placebo group higher, i.e., more severe, than in the active groups, the 10-mg dose causing the greatest reduction in symptoms. Adverse events were infrequent and generally mild or moderate in severity. It was concluded that cetirizine at a 10-mg, once daily dose could be used to treat effectively 6-12-year-old children with perennial allergic rhinitis.",1994.0,0,0
187,7653738,Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis. Swedish GP Allergy Team.,,"This multicenter, double-blind, double-dummy, parallel-group trial was initiated to compare the efficacy and tolerability of two antihistamines, topical levocabastine (eye-drops and nasal spray) and oral loratadine, for the treatment of seasonal allergic rhinoconjunctivitis in the primary care setting. A total of 95 adult patients participated in the study with a treatment duration of 5 weeks. Forty-seven patients were randomized to receive twice daily levocabastine eye-drops and nasal spray plus an oral placebo, and 48 to receive once daily oral loratadine with placebo eye-drops and nasal spray. Naphazoline eye-drops and xylometazoline nasal spray were permitted as rescue medication. No statistically significant intergroup differences in therapeutic efficacy were observed. Symptom severity was comparable in the two treatment groups throughout the trial period. At the end of the study, 86% of levocabastine-treated patients considered global therapeutic efficacy to be excellent or good, as compared with 77% of those who received loratadine. This difference was not statistically significant. There were no significant differences in the use of rescue medication or in the incidence or severity of adverse events in the two treatment groups. In conclusion, levocabastine eye-drops and nasal spray appear to be as effective and well tolerated as oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis.",1994.0,0,0
188,7653747,"Dose-ranging, placebo-controlled study of cetirizine nasal spray in adults with perennial allergic rhinitis.",P Clement; M H Roovers; C Francillon; P Dodion,"A total of 360 patients with perennial allergic rhinitis were randomized in a placebo-controlled, dose-finding study comparing three concentrations (0.06%, 0.125%, and 0.25%) of a cetirizine nasal spray, administered three times a day for 2 weeks. The primary criterion of efficacy was the percentage of days with no or only mild symptoms of rhinitis (PDMax1), as evaluated by the patients. The median PDMax1 were 16.7%, 30.8%, 42.9%, and 26.7% for the placebo, 0.06%, 0.125%, and 0.25% groups, respectively. Although the global comparison among the four groups only approached statistical significance (P = 0.076), the difference (26.2%) between the placebo and 0.125% groups was clinically and statistically significant (P = 0.011). For the global evaluation by the investigator, the best results were seen in the 0.125% group (P = 0.03). The occurrence of adverse events did not differ among the four treatment groups and consisted mainly of nasal events, occurring in 22.5%, 17.1%, 12.9%, and 24.4% of the patients for the placebo, 0.06%, 0.125%, and 0.25% groups, respectively (P = 0.184). These results indicate that the 0.125% concentration is significantly better than placebo and offers the best therapeutic ratio.",1994.0,0,1
189,7655699,The effects of a new generation of H1 antihistamines (cetirizine and loratadine) on histamine release and the bronchial response to histamine in atopic patients.,S Chyrek-Borowska; Z Siergiejko; I Michalska,"The effects of two selective H1 receptor blockers, cetirizine and loratadine, in comparison with placebo, on basophil histamine release and the bronchial response to histamine were assessed. The studies were performed in a group of 18 patients with pollinosis and 22 with atopic asthma. Both tests were performed before and after medication. Histamine release from isolated basophils was evaluated by Shore's method using anti-IgE and pollen antigen as stimulants. The bronchial provocation tests were performed by Ryan's method. The results were expressed as PC20FEV1. It was shown that both drugs significantly inhibited basophil histamine release induced by anti-igE or specific allergen. It was also found that these drugs effectively reduced the bronchial response to histamine challenge. These findings confirm the beneficial clinical effect of a new generation of selective H1 blockers in the treatment of IgE-mediated allergic diseases, and also the possible role of these drugs in the therapy of atopic asthma.",1995.0,0,1
190,7677241,"Antihistamine effects on actual driving performance in a standard test: a summary of Dutch experience, 1989-94.",J F O'Hanlon; J G Ramaekers,"The review summarizes the major results of eight double-blind, placebo-controlled, volunteer studies undertaken by three independent institutions for showing the effects on actual driving performance of ""sedating"" and ""nonsedating"" antihistamines (respectively, triprolidine, diphenhydramine, clemastine and terfenadine, loratadine, cetirizine, acrivastine, mizolastine, and ebastine). A common, standardized test was used that measures driving impairment from vehicular ""weaving"" (i.e., standard deviation of lateral position (SDLP)). Logical relationships were found between impairment and dose, time after dosing, and repeated doses over 4-5 days. The newer drugs were generally less impairing, but differences existed among their effects, and none was unimpairing at doses 1-2x the currently recommended levels. One or possibly two of the newer drugs possessed both performance-enhancing and -impairing properties, depending on dose, suggesting two mechanisms of action.",1995.0,1,1
191,7718472,Interferon-alpha in combination with corticosteroids improves systemic mast cell disease.,E Delaporte; E Piérard; B G Wolthers; P Desreumaux; A Janin; A Cortot; F Piette; H Bergoend,,1995.0,0,0
192,7719255,[Test for efficacy of cetirizine and loratadine as a treatment for seasonal allergic rhinitis in a 6 week cross-over comparative study].,B Tarchalska-Kryńska; E Zawisza,"Cetirizine and loratadine-two new antihistaminic drugs were evaluated in 56 patients with seasonal rhinitis in cross-over open study. I our study, no difference between loratadine and cetirizine has been seen. Both evaluated drugs significantly inhibited the symptoms of allergic rhinitis and conjunctivitis. Adverse reaction and inhibition of histamine and codeine skin tests were similar.",1994.0,1,1
193,7719467,Investigation of the stereoselective metabolism of the chiral H1-antihistaminic drug terfenadine by high-performance liquid chromatography.,A Terhechte; G Blaschke,"The enantiomers of the racemic H1-antihistaminic drug terfenadine (1) have been resolved by fractional crystallization of the diastereomeric salts with optically active 2-chlorotartranilic acid. The enantiomeric excess of both terfenadine enantiomers was determined using an achiral and a chiral HPLC system after formation of diastereomers with S-(+)-naphthylethylisocyanate. To investigate the metabolism of terfenadine after oral administration, an achiral HPLC system, equipped with a conventional reversed-phase column, was used to quantify the main metabolite MDL 16.455 (2) in human serum and urine. The determination of the enantiomeric composition of 2 was achieved using an Ultron ES-OVM column as chiral stationary phase. Metabolite 2, extracted from human blood plasma, was found to be enriched in the R-enantiomer, but was excreted in urine as racemate. The results of a study including six volunteers are presented.",1995.0,0,0
194,7748542,,,,,0,0
195,7761882,Efficacy and safety of loratadine compared with astemizole in Malaysian patients with allergic rhinitis.,S T Lee; M J Amin,"Nonsedating selective peripheral H1 receptor antagonists are an important advance in antihistaminic therapy in allergic patients. This is a randomised, double-blind parallel group study comparing the use of two such agents viz loratadine 10mg daily and astemizole 10mg daily for two weeks in 39 Malaysian allergic rhinitis patients. At these dosages, both drugs were demonstrated to be efficacious (p < 0.05) for controlling nasal symptoms and safe in terms of short term biochemical and haematological changes and adverse effects noted. Evaluating efficacy criteria utilised in this study loratadine and astemizole were comparable but loratadine was significantly more effective in three areas viz: (i) in diminishing nasal symptoms after 2 weeks of treatment (p = 0.03); (ii) physician's efficacy evaluation after 2 weeks' treatment (p = 0.009); (iii) patient's efficacy evaluation after 2 weeks' treatment (p = 0.019).",1994.0,0,1
196,7834324,[Loratadine versus terfenadine in perennial allergic rhinitis: ability to inhibit skin response].,J I Canseco Villarreal,"We studied 104 medical student from the UANL, with symptoms of perenneal allergic rhinitis, including only 30 patients for this study; seven patients with loratadin 10 mg, eight with loratadine 20 mg and 15 with terfenadine 120 mg/day/21 days, 20 mg of loratadine and 120 mg of terfenadine demonstrated significant decrease of the symptoms (P). Two patients had collateral effects with terfenadine, but terfenadine were more effective than the loratadine in the reduction of the skin reactivity.",1994.0,1,1
197,7854994,[Results of treatment with loratadine in patients with chronic urticaria].,Z Siergiejko; S Chyrek-Borowska,"This study aimed at evaluating loratadine efficiency versus placebo in the treatment of patients with chronic urticaria. The single blind trial involved 31 patients divided into the group treated with active drug (21 patients), and placebo (10 patients). Loratadine in a daily dose of 10 mg (1 tablet in the evening) was administered for 28 days whereas placebo was given for 14 days. Patients filled so-called self-observation charts in which a severity of disease symptoms and/or adverse reactions were noted every day. Skin test with histamine was performed in the hospital before the trial, after 2 weeks, and in the last day of the treatment. The obtained results showed a marked decrease in erythema, wheals, and prurigo in patients treated with loratadine. No such an improvement was seen in placebo group. Skin reaction to histamine was also markedly reduced in loratadine group. Loratadine proved an efficient agent in the treatment of the chronic urticaria in 71% of patients.",1994.0,0,0
198,7903515,Nonsedating H1 antihistamines in chronic urticaria.,E W Monroe,"Histamine type 1 (H1) receptor antagonists are the principal therapy for chronic urticaria. Their usefulness, however, is sometimes compromised by undesirable central nervous system (CNS) side effects such as daytime sedation and anticholinergic side effects such as dry mouth. Second-generation, nonsedating antihistamines (terfenadine, astemizole, loratadine, and cetirizine hydrochloride) are just as effective as the potent first-generation antihistamines such as hydroxyzine. Yet they do not cause the CNS and anticholinergic side effects seen with the older agents. Cardiovascular side effects, which have been recently reported with terfenadine and astemizole, are dose related and rare, generally occurring in patients who overdose or who take concomitant medications that increase serum antihistamine levels. The second-generation antihistamines also offer twice daily and once daily dosage schedules, which are more convenient than the two- to four-times daily schedules of the older agents. They should therefore be considered first-line agents for the treatment of chronic urticaria. This article is a review of the role of the nonsedating antihistamines in the treatment of chronic urticaria.",1993.0,0,0
199,7903516,H1-receptor antagonists: does a dose-response relationship exist?,F E Simons,"Objective dose-response studies of histamine receptor blockade in the skin have been performed using suppression of the histamine-induced wheal and flare. Results with second-generation H1-antagonists indicate a dose-dependent increase in histamine skin test suppression. Few dose-response studies of H1-antagonists in allergic rhinitis or chronic urticaria have been published. The manufacturers' recommend doses for H1-antagonists appear to be optimal with regard to safety and should not be exceeded, as the incidence of adverse effects may increase when higher doses are used. Also, even if higher doses are given, complete symptom relief may not occur in all patients, as total H1-blockade still leaves the effects of other chemical mediators of inflammation unopposed.",1993.0,0,0
200,7904400,Initiation of the effects of acrivastine and cetirizine on histamine-induced wheals and itch in human skin.,A Lahti; T Haapaniemi,"The initiation of the antihistamine effect of a single dose of acrivastine (8 mg) or cetirizine (10 mg) on wheals and itch induced by histamine dihydrochloride (10 mg/ml) in the prick test was studied in a randomized cross-over design employing 20 healthy medical students. The prick test was performed before ingestion of the drug and after 15, 20, 25, 30, 60 and 90 min and 2, 3 and 4 h. Local symptoms (itching) were recorded on a visual analogue scale. The inhibitory effect of acrivastine on the histamine wheal was first noticed 20 min (p < 0.01) after ingestion of the drug and that of cetirizine after 60 min (p < 0.001). The maximum effect of cetirizine, at 4 h, was greater than that of acrivastine, at 3 h (p < 0.001). The suppression of itching was first noticed 25 min after ingestion with both drugs.",1993.0,0,0
201,7906659,A comparison of the efficacy of azelastine nasal spray and loratidine tablets in the treatment of seasonal allergic rhinitis.,R Gambardella,"A total of 30 patients suffering from seasonal allergic rhinitis were treated in a 6-week randomized, double-blind, double-dummy parallel-group study, comparing azelastine nasal spray (0.14 mg/nostril administered twice daily) and loratidine tablets (10 mg once daily). Symptoms evaluated were sneezing, nose and/or eye itching, lacrimation, rhinorrhoea, photophobia, nasal occlusion, throat irritation, smell loss, nasal mucosa swelling, conjunctivitis, and pharyngeal mucosa reddening. Each symptom was assessed according to severity and given a score on a four-point rating scale. Compared with baseline, total symptom scores for both the azelastine and loratidine treatment groups were reduced at each of the assessments during treatment. No significant differences were observed between the two treatment groups. The investigator concluded that azelastine, formulated as a nasal spray, is as effective as loratidine tablets in the relief of the symptoms of seasonal rhinitis and that it has a rapid onset of action.",1993.0,1,1
202,7907893,"Assessment of the wheal size and skin blood flow of the erythema induced by histamine and its modification with cetirizine and ebastine: a crossover, double-blind study.",J de la Cuadra; M Teruel; P Teixidó; J Roma,"In order to assess the antihistaminic power of cetirizine and ebastine, we designed a randomized, double-blind, crossover study, measuring their capacity to modify skin blood flow induced by a histamine prick test. The vasomotor response was compared using a laser Doppler flowmeter. Two hours after intake of the antihistaminic drug, there were significant differences between both drugs: at 4 h, the antihistaminic effect of cetirizine persists, whereas ebastine only showed moderate activity. The reduction of the cutaneous blood flow values (CBFV) showed good activity in both groups, but cetirizine was more potent and showed faster activity than ebastine.",1994.0,0,1
203,7911402,Comparative study of SCH 434 and CTM-D in the treatment of seasonal allergic rhinitis.,M Prevost; Y Turenne; D W Moote; J Mazza; A Clermont; C PetitClerc; M R Danzig,"The efficacy and safety of an extended-release combination of loratadine plus pseudoephedrine sulfate (SCH 434) was compared with that of a tablet containing chlorpheniramine maleate plus pseudoephedrine sulfate (CTM-D) in 131 patients with symptomatic seasonal allergic rhinitis. Patients were randomly assigned to receive either SCH 434 (loratadine 5 mg and pseudoephedrine sulfate 120 mg) or CTM-D (chlorpheniramine maleate 12 mg and pseudoephedrine sulfate 120 mg) twice daily for 2 weeks. Evaluations were made after 3, 7, and 14 days of treatment. Demographics (age, race, sex, and duration of seasonal allergic rhinitis) and baseline total symptom scores were comparable between groups. Both combination products were effective in relieving the symptoms of allergic rhinitis. Improvement in total symptom scores was 54% on day 3 and 65% on day 14 in the SCH 434 group versus 57% on day 3 and 64% on day 14 in the CTM-D group. Individual symptom scores (nasal discharge, stuffiness, nasal itching, sneezing, and ocular symptoms) responded similarly. A smaller proportion of patients in the SCH 434 group reported side effects, especially dry mouth (7% vs 19%, P = 0.07), fatigue (6% vs 25%, P < 0.01), and sedation (7% vs 22%, P < 0.03). In conclusion, the combination of loratadine plus pseudoephedrine sulfate was equally as effective as a classic antihistamine (chlorpheniramine maleate) plus pseudoephedrine sulfate but had a lower incidence of side effects.",1994.0,0,0
204,7913608,H1-receptor antagonists. Comparative tolerability and safety.,F E Simons,"First-generation histamine H1-receptor antagonists, such as diphenhydramine, triprolidine, hydroxyzine or chlorpheniramine (chlorphenamine), frequently cause somnolence or other CNS adverse effects. Second-generation H1-antagonists, such as terfenadine, astemizole, loratadine and cetirizine, represent a true advance in therapeutics. In manufacturers' recommended doses, they have a more favourable benefit/risk ratio than their predecessors with regard to lack of CNS effects, and do not exacerbate the adverse CNS effects of alcohol or other CNS-active chemicals. Rarely, some of the newer H1-antagonists may cause cardiac dysrhythmias after overdose or under other specific conditions. The concept of a risk-free H1-antagonist is proving to be an oversimplification. An H1-antagonist absolutely free from adverse effects under all circumstances is not yet available for use. The magnitude of the beneficial effects of each H1-antagonist should be related to the magnitude of the unwanted effects, especially in the CNS and cardiovascular system, and a benefit-risk ratio or therapeutic index should be developed for each medication in this class.",1994.0,0,0
205,7942320,Lectin-induced increase in microvascular permeability to colloidal carbon in vitro may involve protein kinase C activation.,A M Northover; B J Northover,"Two plant lectins, wheat germ agglutinin (WGA) and concanavalin A (Con A), which are known to bind to endothelial cells (ECs), were found to increase the leakage of colloidal carbon (CC) into the walls of microvessels in the villi of rat small intestine, when added to a gelatin-containing perfusate (GPSS) at a concentration of 10 micrograms/ml. Pretreatment of the microvessels with the protein kinase C (PKC) inhibitor Ro 31-8220 (1 x 10(-6) M) significantly reduced this effect. In contrast, the leakage of CC in response to A23187 (1 x 10(-4) M) was not affected by Ro 31-8220. Peanut agglutinin (PNA) and succinyl concanavalin A (SuccCon A), which do not bind to ECs, had no effect at a concentration of 10 micrograms/ml. A lower concentration of WGA (1 microgram/ml) had no significant effect of its own, but significantly reduced the leakage of CC in response to both platelet-activating factor (PAF, 5 x 10(-6) M) and 5-hydroxytryptamine (5-HT, 1 x 10(-4) M), but not to beta-phorbol 12,13-dibutyrate (PDB, 1 x 10(-6) M). These results suggest that all these effects of WGA and Con A involve cell surface receptors, albeit in a non-specific way. A possible mode of action is discussed.",1994.0,0,0
206,8067592,Once daily loratadine versus astemizole once daily.,P Chervinsky; J Georgitis; C Banov; P Boggs; R Vande Souwe; S Greenstein,"This study was designed to compare the efficacy and safety of loratadine and astemizole for the treatment of seasonal allergic rhinitis. A total of 167 adult patients with seasonal allergic rhinitis was enrolled in a randomized double-blind, parallel group study. Patients were treated once daily for 2 months during a spring allergy season. Both treatment groups showed significant reduction of symptoms (P < .01) from baseline. The physicians' and patients' evaluations of response to treatment were generally higher for loratadine than astemizole but only reached statistical significance (P < .05) at the 1-week evaluation. Astemizole-treated patients showed statistically significantly more weight gain than did loratadine-treated patients. Loratadine and astemizole were comparable in reducing the signs and symptoms of seasonal allergic rhinitis. Both treatments were well tolerated, although less weight gain was observed in patients treated with loratadine.",1994.0,1,1
207,8067594,Double-blind study of cetirizine in atopic eczema in children.,M La Rosa; C Ranno; I Musarra; F Guglielmo; A Corrias; J A Bellanti,"An 8-week, double-blind study of the clinical efficacy of cetirizine was performed in a group of 6 to 12-year-old children suffering from atopic eczema. Patients were enrolled in the study if they presented the diagnostic criteria of atopic dermatitis established by Hanifin and Rajka. Pruritus in the cetirizine-treated group diminished significantly more rapidly than in the control group receiving only placebo. During the 8 weeks of the study, diary card scores showed a statistically significant decrease in erythema and other cutaneous symptoms, such as lichenification, in the cetirizine group. The children's parents did not observe any side effects (somnolence or decreased attention) during the study. The results of this preliminary study suggest that cetirizine can effectively control pruritus and other cutaneous symptoms in children suffering from atopic eczema without noticeable side effects.",1994.0,0,0
208,8075442,Evaluation of the efficacy of H1 blockers by noninvasive measurement techniques.,K Hoffmann; T Auer; M Stücker; T Dirschka; S el-Gammal; P Altmeyer,"Evaluation techniques for determining the strength of action and the onset of activity of H1 receptor blockers have not yet been sufficiently standardized. The clinical efficacy of the H1 receptor blocker loratadine was to be measured upon a wheal response subsequent to an intracutaneous injection of 0.1 ml histamine (0.1%). In a pilot study, 10 patients were treated with the H1 receptor blocker loratadine for a period of 7 days. Various noninvasive measurement techniques, i.e. 20-MHz sonography, laser-Doppler flowmetry, chromatometry using the Lab* system and computer-assisted planimetry, were applied to provide a quantitative evaluation of the wheal and the marginal erythema. Using these quantification methods, the development of the urticarial reaction 20 min after injection and its decline were evaluated. The urticarial reaction was reduced substantially under treatment with 10 mg loratadine over a period of 7 days. The methods we used could accurately quantify different aspects of the urticarial reaction noninvasively. All of the chosen measurement techniques are widely recognized. For objective assessment of the urticarial reaction with high-frequency ultrasound, we recommend the measurement of the distance between skin entrance echo and fascia since the demarcation of the wheal is often impossible by ultrasound. In order to improve comparison of results of various workgroups in the future, we therefore suggest the use of the selected combination of noninvasive procedures as a standard for evaluating the efficacy of H1 receptor blockers.",1994.0,0,0
209,8092558,Efficacy of loratadine versus placebo in the prophylactic treatment of seasonal allergic rhinitis.,J Dolovich; D W Moote; J A Mazza; A Clermont; C PetitClerc; M Danzig,"The efficacy of loratadine as prophylactic therapy for seasonal allergic rhinitis was evaluated in a randomized, double-blind, parallel group, placebo-controlled study. One hundred eighteen subjects received either loratadine, 10 mg once daily, or placebo for 6 weeks. Treatment was begun prior to the onset of grass pollen seasonal symptoms of allergic rhinitis. Total symptom-free days occurred more frequently in subjects receiving loratadine. More loratadine than placebo subjects (65% versus 49%) had no symptoms or mild rhinitis at the end of the study. In contrast, the differences between loratadine and placebo in symptom scores did not achieve significance. The incidence of sedation and anticholinergic effects were comparable between the groups. Prophylactic loratadine therapy was effective in suppressing symptoms of seasonal allergic rhinitis and providing patients with symptom-free days throughout the pollen season.",1994.0,0,1
210,8148216,Acoustic rhinometry compared with posterior rhinomanometry in the measurement of histamine- and bradykinin-induced changes in nasal airway patency.,C E Austin; J C Foreman,"1. Acoustic rhinometry is a relatively new method for objectively assessing nasal airway patency. In this paper we compare acoustic rhinometry with active posterior rhinomanometry. 2. Twenty normal healthy volunteers underwent nasal challenge with either histamine or bradykinin, 100 micrograms to 1000 micrograms, and responses were assessed by acoustic rhinometry. A further 20 subjects received identical nasal challenges and responses were assessed by active posterior rhinomanometry. 3. On a subsequent occasion, the subjects challenged previously with histamine, were given the selective H1-receptor antagonist, cetirizine, 10 mg orally, 3 h before repeat nasal challenge with histamine, 100-1000 micrograms. Again, responses were assessed by active posterior rhinomanometry and acoustic rhinometry. 4. The acoustic reflection measurements and the nasal airway resistance measurements showed comparable, significant dose-related changes in nasal patency to both histamine and bradykinin. Pretreatment with cetirizine blocked the histamine-induced change in nasal patency as measured by both methods. 5. We conclude that acoustic rhinometry has a number of advantages over posterior rhinomanometry. It is quick to perform, requires minimal subject co-operation and gives a reliable objective, measurement of dose-related changes in nasal airway patency before and after pharmacological treatment.",1994.0,0,0
211,8160562,[Comparative study between 10 and 20 mg of cetirizine in the symptomatic treatment of seasonal allergic rhinoconjunctivitis].,J Hernández; J M Negro; A Pascual; J Sola; J C Miralles; A Mora; J A Pagán; F J García; J D López; F Sarrió,"Our patients with seasonal allergic rhinoconjunctivitis usually present severe clinical symptoms. A single daily dose of cetirizine 10 mg might be insufficient for these patients. To investigate this hypothesis we compared clinical efficacy and adverse side effects between two daily doses of cetirizine, 10 and 20 mg. We designed a comparative open randomized study, including 38 patients, with hay fever sensitized to local pollens (grass, olive, parietaria judaica, chenopodium album, artemisia vulgaris and plantago lanceolata) diagnosed by clinical history and a positive skin prick test (wheal > 3 mm), 20 women and 18 men, aged 17 to 57 years (x: 31.32 +/- 9.73), living in the same geographic area. Randomly, after a week run in period, 21 subjects received a daily dose of cetirizine 10 mg during 2 weeks, and the other 17 received 10 mg twice a day. The symptomatic score used was based on: sneezes number, nasal itching, nasal secretion, nasal congestion, ocular itching, lacrimation, weight gain, sedation and additional methylprednisolone usage. All symptoms were scored on a 0-3 scale (0: absent; 1: mild; 2: moderate; 3: severe). A mean 8 points daily score during the previous week was required for recruitment. Nasal eosinophilia was determined at baseline and at the end of treatment. The study was conducted in may 1992. We did not find significant differences between the two groups, except in sneezes number and sedation. Both groups improved their symptoms, in comparison with the basal week (p < 0.01) and reduced their oral steroid use (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
212,8187941,A comparison of azelastine nasal spray and cetirizine tablets in the treatment of allergic rhinitis.,D Passali; F Piragine,"A total of 40 patients with perennial allergic rhinitis were treated with either azelastine nasal spray 0.14 mg/nostril twice daily (0.56 mg/day) or cetirizine tablets 10 mg once daily. Treatment was for a period of eight weeks. The rhinitis symptoms were evaluated according to a four-point scale (0 = absent, 3 = severe). The Total Rhinitis Symptom Score (TRSS) was derived from the sum of the individual symptom scores. Symptoms were assessed at baseline prior to treatment and at weeks 2, 4 and 8. Compared baseline, TRSS for both the azelastine and cetirizine groups were less at each assessment during treatment, a slight non-significant advantage was seen in the azelastine group. At the end of the study, physicians rated global efficacy as being ""good"" or ""excellent"" in 73.7% of azelastine patients and 55.5% of cetirizine patients. Both treatments were well tolerated and no serious adverse events were reported, however, two cetirizine patients withdrew from the study because of somnolence. In conclusion, azelastine has been shown to be at least as effective as cetirizine in the relief of the symptoms of perennial allergic rhinitis.",1994.0,0,1
213,8198236,Therapeutic effect of loratadine on pruritus in patients with atopic dermatitis. A multi-crossover-designed study.,T Langeland; H E Fagertun; S Larsen,"The aim of the study was to assess the therapeutic efficacy of loratadine on pruritus in patients with atopic dermatitis, considering the patients' sensation of itch. Sixteen patients, mean age 24.8 years, with moderate or severe atopic dermatitis were included in a double-blind and placebo-controlled study with a six-period, multi-crossover design. The patients were given 10 mg loratadine or placebo every day, alternating between loratadine and placebo every 2 weeks. The degree of pruritus during the day and during the night was recorded by the patients every morning and every evening, respectively, on a 10-cm visual analog scale. The study detected a significant effect of loratadine, as compared with placebo, on pruritus during the day, pruritus during the night, and severity of rash. At least nine of the 16 patients included were classified as responders and only one as a nonresponder to loratadine treatment. It is concluded that loratadine may be tried as an adjuvant therapy in the management of severe and moderate atopic dermatitis, in patients complaining of pruritus.",1994.0,0,1
214,8251354,In dermographic urticaria H2 receptor antagonists have a small but therapeutically irrelevant additional effect compared with H1 antagonists alone.,G R Sharpe; S Shuster,"Two studies of the additional effect of an H2 receptor antagonist when given in combination with an H1 antagonist were undertaken in dermographic urticaria. Using a randomized, double-blind, crossover design in 19 patients, a combination of cetirizine (10 mg at night) and ranitidine (150 mg twice daily) was compared with a combination of cetirizine (10 mg at night) and placebo. The addition of ranitidine did not produce any significant difference in linear analogue scores for weal, itch or sleep disturbance. There was a significant depression of the frictional force/wealing response curve with an increase in wealing threshold (P < 0.0001) following the addition of H2 blockade. The wealing threshold was 54.7 +/- 4.4 (mean +/- SEM) g/mm2 for the H1 antagonist alone, and 73.2 +/- 5.7 for the combination of H1 and H2 antagonists. In a second similar study involving nine different patients, comparing terfenadine (120 mg twice daily) with a combination of terfenadine and ranitidine (150 mg twice daily), the weal threshold was 59.8 +/- 6.6 for the H1 antagonist alone, and 73.0 +/- 6.4 for the combination of H1 and H2 antagonists. Thus, in dermographic urticaria, adding an H2 antagonist to treatment with a potent H1 antagonist gives a small, significant reduction in wealing response, but no symptomatic benefit. We conclude that involvement of the H2 receptor in this urticarial disease is minimal, and does not justify the use of H2 receptor antagonists.",1993.0,0,0
215,8251355,The effect of cetirizine on symptoms and wealing in dermographic urticaria.,G R Sharpe; S Shuster,"The effect of cetirizine, 10 mg at night, on dermographic urticaria, was studied in 19 patients. The study design was a randomized, double-blind, crossover comparison with placebo, each treatment being given for 7 days. Patients kept a daily diary of itch and weal severity (100-mm linear analogue scale), and recorded sleep disturbance. The dermographic weal response was measured objectively with a spring-loaded stylus, and the weal threshold calculated from the force/response curve. There was a small, insignificant subjective response to placebo, but no objective response. On cetirizine, the subjective assessment of wealing was reduced from 34.3 +/- 6.7 (mean +/- SEM, 0-100 scale) to 16.8 +/- 4.1 (P = 0.02), itch was reduced from 43.2 +/- 6.6 to 19.4 +/- 4.1 (P = 0.001), and nights disturbed from 46.2 to 8.8% (P = 0.03). There was a shift to the right in the position of the force/response curve, and the wealing threshold increased from 24.6 +/- 3.2 to 54.7 +/- 4.4 g/mm2 (P = 0.00001), but there was no correlation between change in itch scores and wealing threshold. Cetirizine 10 mg daily is an effective treatment in dermographic urticaria, and its usefulness will depend on the prevalence of unwanted effects.",1993.0,0,1
216,8269452,A comparative study of the efficacy and safety of loratadine syrup and terfenadine suspension in the treatment of 3- to 6-year-old children with seasonal allergic rhinitis.,B N Lutsky; P Klöse; J Melon; J L Menardo; P Molkhou; R Ronchetti; J Suonpää; U Wahn; F Wessel,"The efficacy and safety of loratadine and terfenadine in the treatment of 3- to 6-year-old children with seasonal allergic rhinitis were compared in a third-party-blind, randomized, parallel-group study. A total of 96 children were included in the efficacy analysis: 49 children received 5 or 10 mg of loratadine once daily, and 47 received 15 mg of terfenadine twice daily, for 14 days. The mean total score for both nasal and non-nasal symptoms was decreased significantly from baseline at days 3, 7, and 14 in both treatment groups. At endpoint, these scores had improved 73% in each group. There were no statistically significant differences between the two groups in the total symptom scores at any point during the study. Both treatments were effective in relieving individual nasal and nonnasal symptoms. Therapeutic response to treatment was good or excellent in 82% of loratadine-treated children and in 60% of terfenadine-treated children. Few adverse events were reported during the study; all were mild or moderate and were not significantly different between the two treatment groups. There were no reports of sedation or dry mouth in either group. Once-daily treatment with 5 or 10 mg of loratadine was as effective as twice-daily treatment with 15 mg of terfenadine in improving the symptoms of seasonal allergic rhinitis in children 3 to 6 years old. Both treatments were well tolerated.",1993.0,0,0
217,8281352,The effect of loratadine on activated cells of the nasal mucosa in patients with allergic rhinitis.,M Raptopoulou-Gigi; G Ilonidis; H Orphanou-Koumerkeridou; C Preponis; J Sidiropoulos; T Lazaridis; G Goulis,"The effect of loratadine on the numbers of activated cells--cells expressing interleukin-2 receptors(IL-2R), HLA-DR antigens and proliferating cell nuclear antigen (PCNA)--in the nasal mucosa was studied in 48 patients with allergic rhinitis. Patients were treated with either loratadine (10 mg) or placebo for 1 month. At the end of treatment, a significant decrease in the symptom scores was noted in both groups of patients. However, the clinical score was significantly lower in the loratadine group compared to the placebo group. At the end of treatment, the numbers of IL-2R+, HLA-DR+ and PCNA+ cells were significantly decreased only in the group on loratadine. An almost significant correlation was also observed between the numbers of IL-2R+ cells and symptoms in the loratadine group. Our results show that loratadine exerts its beneficial effect possibly by inhibiting both the action of histamine and immune activation.",1993.0,0,1
218,8291746,,,,,0,0
219,8292064,Comparative study of the efficacy and safety of loratadine syrup and terfenadine suspension in the treatment of chronic allergic skin diseases in a pediatric population.,B N Lutsky; J L Schuller; R Cerio; M L Chieira; A Giannetti; H M Gonçalves; L J deGroot; A Vareltzides; B Guillot; C W Lynde,"The safety and efficacy of loratadine (Sch 29851, CAS 79794-75-5) syrup (5 or 10 mg QD) was compared to terfenadine (CAS 50679-08-8) suspension (30 mg b.i.d.) in a randomized, third party blind, parallel-group, multicenter trial. Two hundred thirty-six children ages 6-12 years, with chronic allergic skin disorders were treated for 14 days. The predominant skin condition was atrophic dermatitis (88% of the efficacy population). Evaluation of efficacy was based on investigator and patient assessment of symptoms, overall condition of the disease, and therapeutic response to treatment. After 7 and 14 days of treatment, and in the endpoint analysis (last valid study visit for all patients) the decreases from baseline in mean total sign/symptom scores, and all individual symptoms, did not differ significantly (p > 0.05) between treatments. Itching improved 54% in the loratadine group and 58% in the terfenadine group in the endpoint analysis. Forty-five percent of patients treated with loratadine and 46% of terfenadine-treated patients treated had complete or marked relief of their symptoms at endpoint. The efficacy of loratadine increased during the study, suggesting that patients did not develop tolerance to the medication over the 14-day course of therapy. Mild to moderate treatment-related adverse experiences were reported in 7/113 patients (6%) treated with loratadine and 11/119 patients (9%) treated with terfenadine. Single daily doses of 5 mg or 10 mg loratadine syrup were comparable to terfenadine suspension 30 mg twice daily for improving the symptoms of chronic allergic skin disorders in children. Loratadine was safe and well tolerated.",1993.0,0,0
220,8305302,Progesterone-induced urticaria: response to buserelin.,K C Yee; W J Cunliffe,"We report a 41-year-old Caucasian woman with polycystic liver and kidney disease, and a 9-year history of severe cyclical urticaria related to her menses. The urticaria was not adequately controlled by antihistamines or Prempak-C (conjugated oestrogens and norgestrel). Intradermal testing with progesterone was strongly positive at 30 min and 18 h. Buserelin, administered intranasally at doses of up to 800 micrograms daily, controlled the urticaria within 4 weeks, and she was completely symptom-free thereafter. She had therapy-induced amenorrhoea and occasional hot flushes. Unfortunately, her liver cysts progressively enlarged, and a right hepatectomy was performed in June 1992, but she died after complications 3 weeks later. Prior to this she had been free of urticaria for 6 months after starting buserelin. Buserelin, a gonadotrophin-releasing hormone analogue, may be useful in the management of progesterone-induced urticaria, in patients in whom conjugated oestrogens are contraindicated or unhelpful.",1994.0,0,0
221,8546995,Quantifying systemic absorption of topical hydrocortisone in erythroderma.,K Aalto-Korte; M Turpeinen,"The systemic absorption of topical hydrocortisone (HC) was quantified in seven patients with erythroderma, using the ratio of the areas under the curves for plasma concentration vs. time, following topical and intravenous administration. Over a period of 24 h, 19-93 mg of HC was absorbed systemically, corresponding to 4-19% of the total topical dose of 500 mg. Thus, topical HC therapy of erythroderma is accompanied by a pharmacologically significant systemic dose.",1995.0,0,0
222,8581453,[Comparative assessment of astemizole-pseudoephedrine and loratadine-pseudoephedrine in children with allergic rhinitis].,D Paz Martínez; E Rosales Parra,"The purpose of the study was to evaluate the effectiveness and safety of astemizole-pseudoephedrine solution compared to loratadine-pseudoephedrine syrup in the treatment of allergic rhinitis. Fifty children (34 boys and 16 girls) ages between 2 and 7 years were enrolled and randomly assigned to each group. Patients were evaluated before treatment and on the third and seventh days of therapy. Children treated with astemizole-pseudoephedrine had better results with an average effectiveness of 84% compared to 64% for children treated with loratadine-pseudoephedrine. Differences were significant for eye symptoms by medical evaluation and for blocked nose, sneezing and itchy nose according to the patients diary. Both treatment groups started action within 30 minutes after drug intake. 4 hours later, 38% of the patients in the astemizole-pseudoephedrine group and 16% in the loratadine-pseudoephedrine groups had experienced improvement. One patient in the former and three in the latter showed adverse effects.",1995.0,0,0
223,8607569,Evaluation of a composite scoring system in conjunctival challenge with allergen: reproducibility and evolution during loratadine treatment.,J Bousquet; I Chanal; W Czarlewski; F B Michel,"The reproducibility of any challenge and its sensitivity to change during therapeutic interventions should always be examined before any drug trial is conducted. Conjunctival challenge has been widely used to assess objectively the efficacy of antiallergic treatments. A double-blind, placebo-controlled, crossover study was carried out in 26 patients allergic to grass pollen to test the reproducibility of a composite symptom score during placebo and control days, and to check the ability of loratadine to increase the provocative dose inducing a positive challenge. Conjunctival challenge was carried out with increasing concentrations of a standardized orchard grass pollen extract until a composite symptom score of 5 was reached. The provocative dose inducing a positive challenge was similar for the baseline (6.94 +/- 8.7 index of reactivity (IR)) and placebo days (20.0 +/- 32.5 IR) and was significantly increased (P < 0.01 and P < 0.001) when patients received loratadine (117.3 +/- 136.8 IR). This study shows that the composite score used was reproducible and sensitive to change, making it possible to use in drug trials.",1995.0,0,1
224,8607960,Effects of loratadine and terfenadine on the induced nasal allergic reaction.,F M Baroody; M C Lim; D Proud; A Kagey-Sobotka; L M Lichtenstein; R M Naclerio,"To evaluate the effect of terfenadine and loratadine on the early nasal allergic response to challenge and the subsequent cellular influx and hyperresponsiveness. Double-blind, placebo-controlled, triple-crossover study. Fourteen, asymptomatic, allergic volunteers. After an initial challenge with methacholine chloride, subjects received treatment with placebo, loratadine (10 mg by mouth daily), or terfenadine (60 mg by mouth twice daily) for 1 week, followed by a nasal allergen challenge with lavages; 24 hours later, while the subjects were still receiving medication, the quantity of cells in the nasal lavage was determined, and another challenge with methacholine was done. Mediator levels were quantified in the nasal lavages after the allergen c hallenge, and the weight of the methacholine-induced nasal secretions was measured. Both loratadine and terfenadine treatment resulted in significant reductions in allergen-induced sneezing and the levels of histamine, kinins, albumin, and N-alpha-tosyl-L-arginine methyl ester-esterase activity in recovered nasal lavages compared with the reductions that resulted from placebo treatment, with no significant difference among the treatments. Treatment had no effect on the levels of tryptase, prostaglandin D2 or leukotriene C4. A significant eosinophil influx into nasal secretions 24 hours after the allergen challenge in patients who were receiving placebo (P=.006) was not affected by loratidine or terfenadine treatment. Comparing methacholine-induced secretions between screening challenges and challenges with the patients who were being treated with either loratadine or terfenadine, there was a significant decrease in secretions after the use of these antihistamines (P<.05). Both loratadine and terfenadine partially inhibit the early nasal response to allergen challenge and the subsequent reactivity to a challenge with methacholine without affecting the influx of eosinophils into nasal secretions.",1996.0,0,1
225,8612470,"Levocabastine. An update of its pharmacology, clinical efficacy and tolerability in the topical treatment of allergic rhinitis and conjunctivitis.",S Noble; D McTavish,"Levocabastine is a potent and selective histamine H1-receptor antagonist which has been evaluated as a topical treatment (nasal spray and/or eyedrops) for allergic rhinitis and/or conjunctivitis. Data available at the time of the previous review in Drugs, together with more recent results, have clearly demonstrated that levocabastine nasal spray and eyedrops are clinically effective, have a rapid onset of action and are well tolerated in patients with nasal and/or ocular allergic conditions. Previous evidence indicating that topical levocabastine has efficacy similar to or better than that of topical sodium cromoglycate (cromolyn sodium) has been confirmed in more recent studies. Furthermore, results from a number of controlled clinical trials have also shown that topical levocabastine is at least as effective as oral terfenadine for the treatment of allergic rhinoconjunctivitis. Notably, topical levocabastine appears to be more effective than oral terfenadine in improving the severity of selected symptoms. Limited data indicating efficacy equivalent to that of oral loratadine, oral cetirizine or azelastine nasal spray will need to be confirmed. Data from several studies have shown that topical levocabastine has a tolerability profile similar to that of placebo, topical sodium cromoglycate or oral terfenadine. The main adverse events seen in patients treated with topical levocabastine are ocular irritation after application of eyedrops, and headache, nasal irritation, somnolence and fatigue after administration of the nasal spray. Administered doses of topical levocabastine, and subsequent plasma concentrations, are low, and the risk of systemic adverse events is therefore expected to be minimal. Thus, topical administration of levocabastine rapid and effective symptom relief with no apparent serious adverse events in patients with allergic rhinitis and/or conjunctivitis. Topical levocabastine is a useful alternative to topical sodium cromoglycate or oral terfenadine. Additional data supporting current evidence that topical levocabastine can provide more effective symptom relief than oral terfenadine, together with clarification of the relative efficacies of these agents in relation to varying pollen exposure, would help to further confirm its clinical potential. However, the results available to date suggest that the topical formulations of levocabastine are a valuable treatment option in patients with allergic rhinitis and/or conjunctivitis.",1995.0,0,0
226,8669268,The activity of recent anti-allergic drugs in the treatment of seasonal allergic rhinitis.,D Wang; P Clement; J Smitz; M De Waele,"Two experiments were performed during the pollen season to study the activity of different antiallergic drugs in the treatment of seasonal allergic rhinitis. Nasal allergen challenge (NAC) was performed to mimic an acute attack of allergic rhinitis and to objectively evaluate the effect of the drugs on the early-phase reaction during the season. The first study assessed the effect of H1 (Cetirizine 10 mg a day) and of a combination of H1 (Cetirizine 10 mg) plus H2 (Cimetidine 800 mg a day) antagonists on nasal symptoms, mediator release and eosinophil count in a group of 16 patients with seasonal allergic rhinitis. During the same season a second study compared in a randomized way (2 parallel groups) the effect of Budesonide (Rhinocort Aqua) and Azelastine (Allergodil nasal spray) in a group of 14 patients. Results showed that both antihistamines, applied topically of dosed orally, reduced sneezing even when significant increases of histamine concentration in nasal secretions were evidenced immediately after NAC. When a combination of Cetirizine and Cimetidine was administered, a significant (p < 0.01) reduction of nasal airway resistance and increase of nasal airflow after NAC were demonstrated as well. In addition, topical application of Budesonide showed a strong (p < 0.01) effect on the infiltration and activation of eosinophils during the season, and on tryptase release after NAC. These effects lasted at least for one week after therapy.",1996.0,0,0
227,8703650,"Comparative wheal and flare study of mizolastine vs terfenadine, cetirizine, loratadine and placebo in healthy volunteers.",P Rosenzweig; H Caplain; S Chaufour; N Ulliac; M J Cabanis; J J Thebault,"1. Mizolastine, a new benzimidazole derivative with potent selective, non-sedative H1-histamine antagonist activity was compared with terfenadine, cetirizine and loratadine using the histamine-induced wheal and flare model in healthy volunteers. 2. Study design was a five way double-blind crossover design using a single dose of mizolastine 10 mg, terfenadine 120 mg, cetirizine 10 mg, loratadine 10 mg and placebo. 3. Histamine tests were performed on 10 occasions up to +24 h after dosing using an intradermal injection of histamine 2 micrograms with concommittant contralateral injection of a saline control. 4. Mizolastine, terfenadine, cetirizine and loratadine significantly (P < 0.001 vs placebo) inhibited the wheal and flare formation starting 1 to 2 h after dosing up to 24 h after dosing. 5. Mizolastine was significantly more active than loratadine on the wheal (P < 0.01) and flare (P < 0.05) inhibition from 3 up to 6 and 8 h respectively, as active as terfenadine on both parameters and as active as cetirizine on wheal inhibition while less active (P < 0.01) than cetirizine on flare inhibition at 2 and 12 h post-dosing.",1995.0,0,0
228,8719584,A multicenter clinical study of the efficacy and tolerability of azelastine nasal spray in the treatment of seasonal allergic rhinitis: a comparison with oral cetirizine.,D Charpin; P Godard; R P Garay; M Baehre; D Herman; F B Michel,"A new topically administered intranasal antiallergic drug, azelastine, was investigated in a large randomized multicenter study that compared it with oral cetirizine from the aspects of efficacy and safety. Patients were treated for 14 days, and efficacy was assessed on days 7 and 14 by means of an investigator rating scale measuring the severity of eight nasal and ocular symptoms of seasonal rhinitis. In addition, patients recorded the extent of individual symptoms on a visual analogue scale (VAS). Tolerability was assessed on the basis of adverse events reported. Data from a total of 129 patients were included in the analysis of drug efficacy. Treatment groups had significant reductions in the investigators' total symptom score during treatment. These reductions were 47% and 55% for azelastine and cetirizine, respectively, at day 7 and 61% and 67% at day 14. There were no differences between the two groups whether they were analyzed overall or separately for nasal and ocular symptoms. Patients' daily VAS scores showed a significantly better resolution of nasal stuffiness and rhinorrhea in the azelastine-treated group than in the cetirizine-treated group. There were no differences for any other symptom. Adverse events were reported by 12 patients in the azelastine group and 20 patients in the cetirizine group. Drowsiness was the only frequently occurring event and this was reported by 9 patients in the cetirizine group and 2 patients in the azelastine group (P = 0.003).",1995.0,0,0
229,8731671,Pachydermatous eosinophilic dermatitis.,W K Jacyk; I W Simson; D N Slater; K M Leiferman,"We report three South African black teenage girls with extensive pruritic papular lesions arising on a pachydermatous base, resembling severe atopic dermatitis or onchodermatitis. All three had peculiar hypertrophic genital lesions and peripheral blood eosinophilia. Histological studies showed an eosinophil-rich lymphohistiocytic infiltrate and variable fibrosis. Extensive fibrillar extracellular deposition of eosinophil granule major basic protein was demonstrated by an indirect immunofluorescence technique. A beneficial therapeutic effect was obtained using dapsone, prednisolone and cetirizine. The term pachydermatous eosinophilic dermatitis is proposed and its position among other conditions characterized by peripheral blood and skin tissue eosinophilia, is discussed.",1996.0,0,0
230,8741162,Cutaneous antihistaminic action of cetirizine and dose-related EEG concomitants of sedation in man.,W G Sannita; E Crimi; S Riela; G Rosadini; V Brusasco,"The cutaneous antihistaminic action (prick test; 1:100, 1:200 and 1:1000) and neuropsychological and electroencephalographic (EEG) concomitants of sedation following the histamine H1 receptor antagonist cetirizine (10- and 20-mg acute oral doses) and chlorpheniramine, 4 mg, were investigated in a cross-over, placebo-controlled study in healthy male volunteers (age 23-29 years). With an average Cmax of cetirizine of 697.0 ng/ml (10 mg) and 1000.2 ng/ml (20 mg), the diameter of histamine-induced skin weals was reduced by 24.0-74.9% depending on histamine concentration and with no dose dependence for cetirizine. Placebo and chlorpheniramine were ineffective. Behavioral or neuropsychological signs of sedation were never observed. An increase of the 6.5-14.5 Hz EEG power, with anterior scalp preponderance, was observed after chlorpheniramine or cetirizine 20 mg. This effect of cetirizine was accounted for by a substantial increase of power in the 6.5-8.0 Hz frequency subsegment and is regarded, for these experimental conditions, as an established early EEG indication of mild sedation (vigilance 'state A'). No EEG effects were observed after placebo or cetirizine at the 10 mg dose. The existence of some histaminergic (H1) specificity of the mechanisms modulating vigilance and of a threshold dose of cetirizine for sedative action is suggested.",1996.0,0,0
231,8754963,[Bronchial hyperresponsiveness in patients with seasonal allergic rhinitis and the influence of loratadine and beclomethasone on this hyperresponsiveness].,J Kroczyńska-Bednarek; K Gondorowicz; M Kalinowska-Graczyk; I Grzelewska-Rzymowska; J Rozniecki,"60 patients aged 16 to 46 years with seasonal allergic rhinitis were selected for study. Daily symptom scores of seasonal allergic rhinitis and nonspecific bronchial hyperresponsiveness to histamine (PC20H in mg/ml) before, during the pollen season and after 3 weeks of treatment with loratadine, beclomethasone dipropionate were evaluated. The control group received oxymetazoline. Nonspecific bronchial hyperresponsiveness for 11 patients (18.3%) before the seasons was observed. At the beginning of the season frequency of nonspecific bronchial hyperresponsiveness increased to 26.3% and to 36.8% after 3-week treatment course. Bronchial hyperresponsiveness was not related to any of the way of treatment. The patients treated with beclomethasone dipropionate and oxymetazoline showed significant relief of nasal symptoms. The patients without bronchial hyperresponsiveness showed lower value of symptom scores.",1996.0,0,0
232,8776357,Total skin examination during screening for malignant melanoma does not increase the detection rate.,M J De Rooij; F H Rampen; L J Schouten; H A Neumann,"Total skin examination during public screening for malignant melanoma is often advocated, but the benefit of this approach has not been established properly. We assessed the yield of examination of the entire skin, in addition to examination of intentionally shown skin lesions, in people attending melanoma screening clinics in southern Limburg, the Netherlands, in 1993. Of the 4146 attenders, 2910 (70%) showed a specific skin spot. Additional examination of the entire skin was offered to 1385 people. There were 1221 evaluable cases. Fourteen presumptive diagnoses of malignancies were encountered: seven malignant melanomas, all with low clinical suspicion, and seven basal cell carcinomas. Histology revealed three basal cell carcinomas. No malignant melanomas were confirmed by histology. It is concluded that additional total skin examination during screening for malignant melanoma is not worthwhile, except perhaps for persons presenting lesions that are suspicious of melanoma or dysplastic naevi.",1996.0,0,0
233,8795669,"Effect of loratadine, an H1 antihistamine, on induced cough in non-asthmatic patients with chronic cough.",S Tanaka; K Hirata; N Kurihara; J Yoshikawa; T Takeda,"H1 antihistamines have been shown to have an antitussive effect in patients with asthma, postnasal drip, and allergic rhinitis. No study has been performed to determine whether orally administered H1 antihistamines can reduce the number of coughs induced by stimulation of cough receptors in non-asthmatic patients with chronic dry cough. The effect of loratadine (10 mg) on the number of coughs induced by ultrasonically nebulised distilled water (UNDW) was examined in 10 patients with nasal disease and in seven patients with unexplained chronic cough using a randomised, double blind crossover method. Eleven normal volunteers were also studied. Each subject inhaled UNDW for one minute, and the numbers of coughs during the one minute inhalation and the 30 seconds following it were counted. There was no difference in the results of pulmonary function tests performed before and one minute after UNDW inhalation for either patients or normal subjects. There was also no significant difference between the results of pulmonary function tests before or after oral administration of loratadine. Loratadine significantly reduced the number of coughs in patients with nasal disease and in those with unexplained chronic cough, but not in normal subjects. The H1 antihistamine loratadine reduces cough induced by UNDW. The release of histamine may contribute to the chronic cough in patients with unexplained chronic cough or nasal disease.",1996.0,0,0
234,8797551,Safety of antihistamines in the treatment of allergic rhinitis in elderly patients.,J D McCue,"Elderly patients may be more susceptible than younger persons to the sedating and anticholinergic effects of first-generation antihistamines. Second-generation antihistamines, such as loratadine, astemizole, and terfenadine, cause minimal sedation and little if any impairment in cognitive and psychomotor activity in healthy nonelderly patients. Although less extensively studied in elderly patients, it is probable that second-generation antihistamines are also less likely to induce the adverse central nervous system effects in older patients that are characteristic of the first-generation antihistamines. Toxic effects to the cardiovascular system, an issue of greater concern among elderly patients who may have subclinical heart disease, has not been observed with first-generation antihistamines. Among the second-generation antihistamines, however, astemizole and terfenadine, but not loratadine, can cause serious cardiovascular adverse effects, including death, when taken in high doses or coadministered with ketoconazole, itraconazole, or macrolide antibiotics.",1996.0,0,1
235,8828023,Comparison of the efficacy of ebastine 10mg and 20mg once daily with that of cetirizine 10mg once daily in adults with seasonal allergic rhinitis. A multicentre double-blind study.,B Cohen; P Gehanno,,1996.0,0,1
236,8834825,The effect of cetirizine on sulfidoleukotriene production by blood leukocytes in children with allergic rhinitis.,O Kalayci; Y Saraclar; G Adalioglu; B Sekerel; A Tuncer,"Twelve children with allergic rhinitis due to monosensitivity to Dermatophagoides pteronyssinus (Dp) took part in a placebo-controlled, double-blind, crossover study to evaluate the effect of cetirizine, a second-generation, nonsedating H1-blocker-type antihistamine, on sulfidoleukotriene releasability by blood leukocytes and to determine its correlation with clinical findings and nasal challenge scores. Sulfidoleukotriene release by blood leukocytes was determined by the cellular allergen stimulation test (CAST), which measures leukotriene (LT)C4, LTD4, and LTE4, all in one assay. Compared to placebo, cetirizine significantly (P < 0.05) decreased daily symptom scores of nasal discharge, nasal itching, and sneezing, as well as the number of sneezings after nasal challenge with the antigen, without alleviating nasal obstruction (P > 0.05). It also suppressed both early (P < 0.05) and late skin reactions to intradermal tests. Although cetirizine did not influence in vitro sulfidoleukotriene production by blood leukocytes with buffer or anti-IgE (P > 0.05), it substantially reduced the release of these mediators upon challenge with Dp antigen. Furthermore, there was a high correlation between the number of sneezes after challenge and the amount of sulfidoleukotriene released in nine patients (r = 0.78; P < 0.01). It is concluded that the amount of sulfidoleukotrienes produced by blood leukocytes in vitro may reflect the nasal hyperreactivity of the patient, and that cetirizine, which is highly effective in the treatment of allergic rhinitis, owes part of its effect to inhibition of sulfidoleukotriene releasability by blood leukocytes in children.",1995.0,0,0
237,8866630,,,,,0,0
238,8869688,Acute urticaria: clinical aspects and therapeutic responsiveness.,T Zuberbier; J Iffländer; C Semmler; B M Henz,"Although acute urticaria is common, its eliciting factors, clinical course and therapeutic responsiveness have not been intensively investigated. We have therefore prospectively studied all patients with acute urticaria attending the department of dermatology (n = 72) and a rural dermatology office (n = 37) during the course of 1 year. After a standardized history and physical examination, patients were randomized into treatment with either loratadine (10 mg/day for 3 days) or prednisolene (50 mg/day for 3 days). All patients were followed up until complete remission. Most patients suffered from moderate (42%) to severe (40%) disease. Possible eliciting factors were identified in less than 50% of the cases. Associated upper respiratory tract infections were found most commonly (39.5%), followed by possibly eliciting drugs, mostly analgesics (9.2%) and suspected food intolerance (0.9%). The course of the disease was self-limited in all cases, the longest episode lasting for 3 weeks. Both treatment regimens were effective in controlling whealing, but in corticosteroid-treated patients, symptoms ceased earlier, with complete remission occurring within 3 days of treatment in 93.8%, compared to 65.9% of patients treated with loratadine (p < 0.001). Acute urticaria is thus frequently idiopathic and only rarely associated with IgE-mediated events. It is, however, largely self-limited, with prompt response to symptomatic treatment.",1996.0,0,0
239,8874661,Once-daily mometasone furoate aqueous nasal spray (Nasonex) in seasonal allergic rhinitis: an active- and placebo-controlled study.,J R Hebert; K Nolop; B N Lutsky,"Mometasone furoate aqueous nasal spray (Nasonex) was compared with beclomethasone dipropionate (BDP) aqueous nasal spray in a double-blind, randomized, placebo-controlled, double-dummy, parallel-group study of adults with moderate to severe seasonal allergic rhinitis. Patients allergic to at least one tree and/or grass aeroallergen received one of the following regimens for up to 4 weeks; mometasone furoate 100 micrograms once daily [OD] (n = 126) or 200 micrograms OD (n = 126), BDP 200 micrograms twice daily (n = 126), or only placebo spray (n = 123). Physician-rated nasal and total symptom scores, and global evaluation of overall condition and therapeutic response by physicians and patients, showed that the three active treatments were equally effective, and all three were significantly superior to placebo at most time points. Overall, mometasone furoate 200 micrograms OD demonstrated somewhat greater numerical, but not statistical, superiority to mometasone furoate 100 micrograms OD at the earliest evaluation time point. At the end of treatment, complete or marked relief was obtained in 77% of patients with mometasone furoate 100 micrograms/day, 79% with mometasone furoate 200 micrograms/day, and 74% with BDP, compared with 54% of placebo vehicle control patients. Mometasone furoate and BDP were equally well tolerated. It was concluded that mometasone furoate adequately controls symptoms of moderate to severe seasonal allergic rhinitis, offers the advantage of OD treatment, and is well tolerated.",1996.0,0,0
240,8876070,Cetirizine and pseudoephedrine retard alone and in combination in the treatment of perennial allergic rhinitis: a double-blind multicentre study.,B Bertrand; J Jamart; J L Marchal; C Arendt,"We compared the efficacy and safety of 5 mg cetirizine (CTZ), 120 mg pseudoephedrine retard (PER) and their combination (COM), given twice daily for three weeks, for the treatment of perennial allergic rhinitis. Two hundred and ten evaluable patients (97 males and 113 females) were included in the study and randomly allocated to one of three treatment groups, each of 70 patients. Nasal obstruction, sneezing, rhinorrhoea, nasal and ocular pruritus were scored each day throughout the study by patients using a symptom scale ranging from 0 (no symptom) to 3 (severe). The mean proportion of days without symptoms was higher in the COM group (11.8%) than in the CTZ (6.8%) and PER (5.1%) groups, but the differences were not statistically significant. The mean percentage of days when symptoms were absent or at most mild was significantly higher in the COM group (64.8%) than in either CTZ (45.5%; p = 0.003) or PER groups (40.6%; p = 0.0001). In addition, evaluation of symptoms by investigators and their global evaluation at the end of treatment showed statistically significant differences in favour of COM compared, to both CTZ and PER. The most frequent adverse events were somnolence in the CTZ and COM groups (8.6% and 12.9%, respectively) while insomnia was most frequent in the PER group. No clinically significant abnormalities were found in haematological or biochemical tests. These results indicate that the combined treatment was more effective than and as well tolerated as treatment with each individual agent.",1996.0,0,0
241,8876072,Comparison of mizolastine with loratadine in the treatment of perennial allergic rhinitis.,P Bellioni; B Catalano; G Cervellera; F Filiaci; E Mira; A Carraro,"Mizolastine is a new, non-sedating antihistamine providing satisfactory symptomatic relief in seasonal allergic rhinitis. The purpose of this study has been to compare mizolastine to loratadine in perennial allergic rhinitis. This multicentre, double-blind study has involved 68 patients, randomly allocated, after a one-week placebo run-in, to 10 mg mizolastine or 10 mg loratadine, both given on a once-daily basis, for four weeks. Comparable symptom relief occurs in both groups resulting, respectively for mizolastine and loratadine, in a 66.6% and a 61.3% decrease in total nasal score, to a 74.8% and a 76.4% decrease in total ocular score, and to a 69.0% and a 64.8% decrease in global total score. Safety is satisfactory in both groups. Mizolastine is at least as effective as loratadine in relieving perennial allergic rhinitis symptoms and its safety profile allows its use in the treatment of this disease.",1996.0,0,1
242,8876938,Effects of dimethindene maleate on psychomotor performance in the oculodynamic test compared with placebo and loratadine.,W Englisch; D Rehn; K Schaffler; C H Wauschkuhn,"The effects of dimethindene maleate (CAS 3614-69-5) on the central nervous system-as sustained release pellets (Fenistil OAD; OAD = once a day) and sustained release tablets (Fenistil retard) with an immediate release fraction-were investigated by means of the oculodynamic test (ODT) and visual analogue scales and compared to loratadine (CAS 79794-75-5) and placebo. In the confirmatory part of the study 18 healthy volunteers were included in a single-blind, randomised, 3-way change-over design with Fenistil OAD, loratadine, and placebo. An additional, fourth exploratory arm with Fenistil retard was run in 6 (out of the 18) subjects after completing the main part of the study. The ODT includes electro-oculography, choice reaction task, and cardiologic parameters under workload. Visual analogue scales were used for subjective ratings on well-being and drug effects concerning wakefulness (sedation), excitation, dizziness, performance, effort, and dry mouth. The results show no relevant differences between either of the active drugs and placebo. Therefore it can be stated that after a single dose there is no sedating effect of dimethindene maleate compared to loratadine or placebo.",1996.0,0,1
243,8880949,"Sodium cromoglycate and nedocromil sodium in the therapy of asthma, a critical comparison.",M J Parnham,,1996.0,0,0
244,8882207,[Multicenter study on the efficacy of Zyrtec (Cetirizine) in the treatment of perennial allergic rhinitis in 875 adolescents].,P Molkhou; M Billardon; A M Jouan; J Fondarai,"875 adolescents of both sexes, aged between 12 and 15 years, who had presented with a perennial allergic rhinitis, were included in an open study that was conducted by pediatricians and allergologists on the efficacy of ZYRTEC (CETIRIZINE). There were four evaluations in the study, at Day-10, D 0, D15 and D30 and it was conducted according to the following plan: A first period (D-10 to D 0) to establish the eligibility of the subjects to be tested, and to establish the clinical allergic history, before definitive inclusion at D 0. A second period, of therapy, of 30 days, during which the subjects took a 10 mg tablet of ZYRTEC as a daily dose. Efficacy was evaluated at each visit by scores of intensity of major symptoms (sneezing, nasal discharge, nasal obstruction, nasal pruritus) and secondary symptoms (ocular score ... ) of rhinitis, as well as anterior rhinoscopy. The patients made an auto-evaluation of symptoms at different times. Analysis of the different parameters showed a real efficacy of ZYRTEC, for 30 days of treatment, in young patients. Furthermore, the tolerance of the product is excellent. This study has shown an overall improvement in the symptoms of perennial allergic rhinitis in patients who were treated with ZYRTEC in conditions similar to those of usual medical practice by pediatricians and allergologists.",1996.0,0,0
245,8886862,The contribution of histamine to the action of bradykinin in the human nasal airway.,C E Austin; J W Dear; H Neighbour; V Lund; J C Foreman,"Bradykinin, 10 to 1000 micrograms given by aerosol into the nasal cavity of normal, healthy volunteers, produced a dose-related increase of nasal airway resistance. Bradykinin also reduced the minimal nasal cross-sectional area (Amin), increased albumin release into nasal lavage fluid and increased the symptoms of nasal inflammation. Pretreatment with cetirizine (10 mg orally) reduced the fall in Amin induced by bradykinin, 300 micrograms, but not by bradykinin, 100 micrograms. Pre-treatment of the subjects with the H1 histamine receptor antgonist cetirizine (10 mg, orally) or terfenadine (60 mg, orally) 3 h before bradykinin administration caused significant reduction of the bradykinin-induced increase in nasal airway resistance in the upper range of bradykinin doses (300-1000 micrograms) but not in the lower range (10-100 micrograms). Cetirizine reduced the albumin release into the nasal airway and the symptoms induced by bradykinin, 1000 micrograms. Following nasal challenge with bradykinin 300 micrograms or 1000 micrograms, no increase could be detected in the histamine content of nasal lavage fluid. Isolated human nasal cells released histamine in response to bradykinin, 33 and 100 microM, anti-IgE and calcium ionophore, A23187. We conclude that the actions of bradykinin in the human nasal airway are, in part, accounted for by the release of histamine.",1996.0,0,0
246,8888086,Treating allergic rhinitis with second-generation antihistamines.,C H Nightingale,"Allergic rhinitis afflicts close to 40% of the nation's population and costs more than $1.8 billion a year. The toll exacted by this disorder has been greatly alleviated by nonsedating second-generation antihistamines loratadine, terfenadine, and astemizole. The three agents effectively reduce symptoms without the sometimes intolerable adverse effects of older drugs, but they are not completely equivalent. For example, terfenadine requires twice/day dosing, whereas the others can be given once/day. Astemizole has a slow onset and extremely prolonged duration of action. Both terfenadine and astemizole may have cardiotoxic effects (e.g., torsades de pointes) when serum concentrations rise due to overdosing or drug interactions. Cetirizine, a recently approved second-generation antihistamine, has sedative and anticholinergic effects, although to a lesser degree than the first-generation antihistamines.",1996.0,0,1
247,8890140,Sinusitis in children and adolescents.,D A Newton,"Sinusitis is common in children and adolescents, most frequently as a complication of a viral upper respiratory tract infection or allergic rhinitis. The diagnosis usually is suggested by symptoms of a viral upper respiratory tract infection persisting beyond 10 days without improvement or severe symptoms with fever and purulent rhinitis. Young children frequently do not have the symptoms (headache) or physical findings (sinus tenderness) seen in older patients. Radiographic evaluation may be helpful if the clinical presentation is atypical or severe. Antibiotics remain the primary therapeutic agent of choice in pediatric sinusitis, with other therapeutic modalities having little proven efficacy.",1996.0,0,0
248,8891761,The effect of cetirizine and loratadine on codeine-induced histamine release in human skin in vivo assessed by cutaneous microdialysis.,M Perzanowska; D Malhotra; S P Skinner; J P Rihoux; A P Bewley; L J Petersen; M K Church,"To determine whether or not cetirizine and loratadine inhibit codeine- induced histamine release in human skin in vivo, we conducted a placebo-controlled double-blind trial in which histamine release was assessed by dermal microdialysis. A group of ten normal volunteers were studied, each subject visiting the laboratory on three occasions with intervals of at least 2 weeks between visits. Cetirizine, loratadine (both 10 mg) or placebo was given orally 4 h before provocation of weal and flare responses in the skin by intradermal injection of 25 microliters of 3 or 10 mg/ml codeine 1 mm from the centre of individual 216 microns diameter microdialysis fibres inserted in the dermis. Dialysate was collected at 2 min intervals for 4 min before and 20 min after codeine injection and histamine assayed spectrofluorometrically. Weal and flare responses to codeine were assessed in the opposite arm. Histamine concentrations in the microdialysis fibre outflow with 3 and 10 mg/ml codeine were maximal at 2-4 min when 910 +/- 156 and 1194 +/- 304 nM respectively were found in the placebo group. Cetirizine and loratadine did not modify either the kinetics or total histamine release while significantly (p < 0.01) inhibiting weal and flare responses. Neither cetirizine nor loratadine inhibited codeine-induced histamine release or modified the time course of its release in human skin in vivo when given in clinically used doses which are sufficient to significantly reduce weal and flare responses.",1996.0,0,0
249,8893110,Cetirizine versus hydroxyzine and placebo in chronic idiopathic urticaria.,D L Breneman,"To compare the safety and efficacy of cetirizine with that of hydroxyzine and placebo in the treatment of chronic idiopathic urticaria. A 4-week multicenter, randomized, double-blind, double-dummy, placebo-controlled safety and efficacy study. Patients were treated in a variety of allergy practice settings. The study population consisted of 188 patients who were at least 12 years of age, with symptomatic chronic idiopathic urticaria that had occurred episodically for at least 6 weeks. Patients were given either cetirizine 10 mg once daily, hydroxyzine 25 mg tid, or placebo for 4 weeks. Patients and investigators used a 4-point scale to evaluate symptoms of urticaria and adverse effects of treatment. Ratings were compared among those taking cetirizine, hydroxyzine, or placebo. After 1 day of treatment, patients randomized to receive cetirizine 10 mg/d exhibited a reduction in the number of episodes of urticaria (and a reduction in pruritus) compared with patients who received hydroxyzine 25 mg tid and patients who received placebo (p = 0.002). The number of urticarial episodes in patients treated with hydroxyzine did not reach significance until day 2 (p = 0.001). Compared with patients who received placebo, patients who received cetirizine and those who received hydroxyzine showed reductions during weeks 1, 2, and 3 and at end-point analysis in the number and size of lesions and in the severity of pruritus (p < 0.04). Patient and physician evaluations at the end of week 4 revealed an improvement in urticarial symptoms for the hydroxyzine and cetirizine groups compared with the placebo group (p < 0.001). Four patients in the hydroxyzine group, 1 patient in the cetirizine group, and 1 patient in the placebo group discontinued the study because of sedation. No patient withdrew because of lack of efficacy. Cetirizine 10 mg once daily was equivalent to hydroxyzine 25 mg tid in controlling the symptoms of patients with chronic urticaria, as assessed by patient and investigator evaluations.",1996.0,1,1
250,8930779,Influence of food on the oral bioavailability of loratadine and pseudoephedrine from extended-release tablets in healthy volunteers.,A A Nomeir; P Mojaverian; T Kosoglou; M B Affrime; J Nezamis; E Rodwanski; C C Lin; M N Cayen,"The effect of a high-fat breakfast on the bioavailability of the components of an extended-release tablet containing 10 mg loratadine in the immediate-release coating and 240 mg pseudoephedrine sulfate in the extended-release core was studied in 24 healthy male volunteers in a single-dose, two-way crossover study. The drug was administered after a 10-hour overnight fast or within 5 minutes of consuming a standardized high-fat breakfast. Serial blood samples were collected over a 48-hour period, and plasma was analyzed for loratadine and its active metabolite descarboethoxyloratadine (DCL), and pseudoephedrine. For pseudoephedrine, maximum concentration (Cmax) and area under the concentration-time curve extrapolated to infinity (AUCzero-infinity) were similar after both treatments, indicating no relevant food effect on the bioavailability of pseudoephedrine. Also, the absorption profiles of pseudoephedrine (from Wagner-Nelson analysis) were similar for the fed and fasted treatments, indicating no apparent differences in absorption. Plasma concentration-time profiles and values for Cmax and AUCzero-infinity of DCL were similar for the two treatments, indicating no relevant food effect on the pharmacokinetics of DCL. In contrast, for loratadine, administration with food resulted in a significantly increased mean Cmax (53%) and AUC from time zero to the final quantifiable sample (AUCif) (76%). However, the resultant Cmax and AUC of loratadine under fed conditions were well below those previously obtained at steady-state after multiple-dose administration of loratadine (40 mg/day) that were shown to be safe and well-tolerated in several clinical studies. The effect of food on the bioavailability and pharmacokinetic profiles of the components of a combination loratadine/pseudoephedrine extended-release tablet is not likely to be clinically significant.",1996.0,0,0
251,8932546,Inhibition of histamine-induced skin wheal and flare after 5 days of mizolastine.,J L Pinquier; H Caplain; M J Cabanis; C Dubruc; A Stalla-Bourdillon; P Rosenzweig,"Mizolastine is a new, nonsedating antihistamine providing satisfactory symptomatic relief in allergic rhinitis and urticaria. The purpose of this study was to use inhibition of wheal and flare formation after 2-mu g intradermal histamine injections as a measure of the antihistamine effect of repeated doses of mizolastine. Eight volunteers were enrolled in this four-arm, double-blind, cross-over, randomized study. Three dose levels of once-daily mizolastine (5 mg, 10 mg, and 15 mg) were compared with placebo during 5-day dose periods. Histamine tests were performed before drug intake on days 1 and 5, and then 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours after drug intake on day 5. All 3 doses of mizolastine were more effective than placebo in suppressing wheal and flare reactions, and the antihistamine activity was highest at both the 10- and 15-mg dose levels. The effect on the flare reaction appeared within 1 hour, reached a maximum effect 4 hours after administration, and persisted for as long as 24 hours. The relative changes in wheal and flare areas were correlated with mizolastine trough plasma levels on day 5. Safety was satisfactory in all groups. This study confirms that mizolastine is a rapid and potent antihistamine; and its long-lasting effectiveness indicates that a once-daily regimen is acceptable for clinical use.",1996.0,0,0
252,8955868,,,,,0,0
253,8993958,Double-blind crossover study of high-dose cetirizine in cholinergic urticaria.,T Zuberbier; C Münzberger; U Haustein; E Trippas; B Burtin; S D Mariz; B M Henz,"Cholinergic urticaria does not respond well to treatment with conventional antihistamines and is difficult to study because of its highly variable clinical expression which depends on the presence of eliciting factors. We have therefore designed a double-blind, crossover, placebo-controlled trial, with a 3-week treatment period using either 20 mg/day of cetirizine or placebo. Presence of eliciting factors and symptoms were scored daily on a diary card by the patient, with a scale from 0 to 3 for erythema, wheals and pruritus. Statistical analysis was done on 11 evaluable patients during the last 2 weeks of each treatment period (to allow for 1 week of washout) and only for days when eliciting factors were present. Compared to placebo, cetirizine caused a statistically significant reduction of wheals (p = 0.015), erythema (p = 0.033), pruritus (p = 0.006) and all symptoms (p = 0.013). No adverse events were observed. These data show a high efficacy of cetirizine at twice its normally recommended dose which may be related to the specific antiallergic effects of this newer-generation antihistamine.",1996.0,0,1
254,9020417,Sedation in allergic rhinitis is caused by the condition and not by antihistamine treatment.,J Spaeth; L Klimek; R Mösges,"Sedation is regarded as a common side-effect of most H1-antihistamines. This view must be accepted, yet can hardly be assessed under treatment of allergic disorders. Since central sedative potency is hard to evaluate, different methods of measurement have been introduced in the four phases of clinical investigation. While tests of high complexity in early trials can detect true central effects, they seem to have the disadvantage of not taking into consideration the important interactions of drugs with the disorder. Therefore, we used a visual analog scale (VAS) as an instrument to demonstrate sedative effects in five clinical studies carried out between 1989 and 1994 with a total number of 1070 patients. Thereby, we could assess the result of the different components of the central interaction. In 1989, in a double-blind, placebo-controlled trial, we could show that the vigilance of patients suffering from seasonal allergic rhinitis increased significantly more under treatment with an antihistamine (mizolastine) than under placebo. From 1992 until 1994, we compared azelastine nasal spray either by the double-dummy technique with oral antihistamines (cetirizine, loratadine, and astemizole) or by the double-dummy or placebo-controlled design with monotherapy or combined therapy with azelastine tablets. A marked or statistically significant improvement of vigilance was found for all compounds (loratadine: P < 0.0001; cetirizine: P < 0.0254; and azelastine nasal spray: P < 0.1409 to P < 0.0001). Even when taking azelastine as oral application, patients, in spite of the warning, reported a similar increase in vigilance (P < 0.2628 to P < 0.0001). Finally, we assessed the range of physiologic vigilance using the same VAS in healthy volunteers. In conclusion, we could prove that in all trials the baseline values of vigilance of untreated symptomatic patients were far below physiologic condition and improved under treatment to the upper range of healthy persons. Therefore, any sedative properties of modern H1-antihistamines should not limit their therapeutic use, since the truly threatening sedation results from the disorder itself.",1996.0,0,1
255,9065344,Effects of a single dose of loratadine on flying ability under conditions of simulated cabin pressure.,P J Valk; R M Simons; P A Struyvenberg; H Kruit; M T van Berge Henegouwen,"Pilots with allergic diseases, who need antihistaminic drug therapy, have to be grounded temporarily because this therapy is considered to interfere with flight safety due to its sedative effects. There is evidence that loratadine is practically void of these sedative effects, and therefore might be prescribed to pilots. A study was conducted to determine the effects of loratadine on performance and alertness. In a randomized, double-blind, within subjects design, 18 male subjects were studied, employing loratadine 10 mg, triprolidine hydrochloride 5 mg, and placebo. Objective (vigilance, complex tasks) and subjective tests, tailored to the specific tasks of aircrew, were applied under hypobaric conditions that prevail in an intact cockpit. With respect to alertness and performance, the results of this study showed no significant differences between loratadine and placebo during a period of 1 to 6 hours after drug ingestion. Triprolidine, used as a positive control, showed significant detrimental effects on both subjective and objective measures. It is anticipated that a single dose of loratadine 10 mg will not affect flying performance. This finding might also have implications for the treatment of allergic disorders of personnel involved in other highly skilled jobs.",1997.0,0,1
256,9090952,[Can one adjust the distribution of a drug in an organism to its target sites? The example of antihistaminics (anti-H1) and cetirizine].,J P Tillement; E Albengres,"When comparing the fate of a drug in the body with the location of its receptors, it appears that a large amount of the administered dosage will never reach these receptors. Thus this large amount is useless in terms of drug efficacy whereas it may generate side of toxic effects in other tissues. An attempt to optimize drug distribution is to limit or even to suppress its useless localisations. This is possible with H1 antagonists as these drugs develop benefic effects in organs which are distinct from those where toxic effects may occur. Cetirizine is an example of choice of this strategy. It is poorly distributed into tissues, especially in heart and liver which favors preferential binding at its target H1 selected receptors.",1996.0,0,0
257,9105526,Onset of action in the nasal antihistaminic effect of cetirizine and loratadine in patients with allergic rhinitis.,N Frossard; J Lacronique; M Melac; O Benabdesselam; J J Braun; N Glasser; G Pauli,"Several studies have compared the cutaneous efficacy of cetirizine and loratadine and their onset of action. We assessed the nasal effect of these two antihistamines in a randomized, double-blind, crossover, placebo-controlled trial in order to compare objectively their efficacy and onset of action in the noses of patients with allergic rhinitis. Nasal challenge was performed by nebulization of increasing doubling doses of histamine (0, 0.04-1.28 mg/nostril) in 12 patients (eight men, four women, aged 22-39 years). Nasal airway resistance (NAR) was measured by posterior rhinomanometry either 1.5 h or 4 h after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline NAR was identical between all study days (2.60-2.88 cmH2O.l-1.s). One and a half hours after intake, the increase in NAR induced by histamine was significantly reduced by both cetirizine and loratadine in contrast to placebo. However, with cetirizine the nasal obstruction was significantly lower than with loratadine (P < 0.05). Four hours after intake, a similar inhibition of the nasal obstruction caused by histamine was observed with both cetirizine and loratadine (P < 0.05). In conclusion, this study found cetirizine and loratadine to have similar nasal efficacy at therapeutic dosage 4 h after intake, whereas cetirizine was more effective than loratadine 1.5 h after intake. In agreement with the results observed in the skin, our study suggests a more rapid onset of action of cetirizine in the nose in allergic rhinitis.",1997.0,0,1
258,9114992,"Once-daily cetirizine effective in the treatment of seasonal allergic rhinitis in children aged 6 to 11 years: a randomized, double-blind, placebo-controlled study.",D S Pearlman; W R Lumry; J A Winder; M J Noonan,"Cetirizine (once daily), a highly selective H1-antagonist, is efficacious for treating seasonal allergic rhinitis (SAR), perennial allergic rhinitis, and chronic idiopathic urticaria. A 4-week, randomized, double-blind, placebo-controlled trial investigated the safety and efficacy of cetirizine syrup (5 or 10 mg daily) in 209 children ages 6 to 11 years with SAR. Parents assisted patients in recording symptom severity (sneezing, nasal discharge, itchy eyes, itchy nose or mouth, conjunctivitis, nasal congestion) daily. A total symptom severity (TSS) score was derived from all symptoms, excluding nasal congestion. At baseline, TSS was comparable for all groups (range 6.8-7.0). Cetirizine 10 mg produced a significantly greater mean TSS reduction (3.2) than placebo (P < 0.05) over the treatment period. Cetirizine 5 mg once daily produced mean reductions in weekly symptom scores of 2.4; this did not differ statistically from placebo. Furthermore, cetirizine 10 mg significantly improved symptoms of itchy eyes, nose, or mouth. The most commonly reported adverse reactions to both cetirizine and placebo were headache, pharyngitis, and abdominal pain, which did not occur with an incidence statistically different from that of placebo. Once-daily cetirizine is safe for treating SAR in children ages 6-11 years. Once-daily cetirizine 10 mg provides effective improvement in symptoms and is well tolerated.",1997.0,0,0
259,9179528,Clarithromycin. A review of its efficacy in the treatment of respiratory tract infections in immunocompetent patients.,H D Langtry; R N Brogden,"Clarithromycin is a broad spectrum macrolide antibacterial agent active in vitro and effective in vivo against the major pathogens responsible for respiratory tract infections in immunocompetent patients. It is highly active in vitro against pathogens causing atypical pneumonia (Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella spp.) and has similar activity to other macrolides against Staphylococcus aureus. Streptococcus pyogenes, Moraxella catarrhalis and Streptococcus pneumoniae. Haemophilus influenzae is susceptible or intermediately susceptible to clarithromycin alone, but activity is enhanced when the parent drug and metabolite are combined in vitro. Absorption of clarithromycin is unaffected by food. More than half of an oral dose is systemically available as the parent drug and the active 14-hydroxy metabolite. Pharmacokinetics are nonlinear, with plasma concentrations increasing in more than proportion to the dosage. First-pass metabolism results in the rapid appearance of the active metabolite 14-hydroxy-clarithromycin in plasma. Clarithromycin and its active metabolite are found in greater concentrations in the tissues and fluids of the respiratory tract than in plasma. Dosage adjustments are required for patients with severe renal failure, but not for elderly patients or those with hepatic impairment. Drug interactions related to the cytochrome P450 system may occur with clarithromycin use. In addition to the standard immediate-release formulation for administration twice daily, a modified-release formulation of clarithromycin is now available for use once daily. In dosages of 500 to 1000 mg/day for 5 to 14 days, clarithromycin was as effective in the treatment of community-acquired upper and lower respiratory tract infections in hospital and community settings as beta-lactam agents (with or without a beta-lactamase inhibitor), cephalosporins and most other macrolides. Clarithromycin was similar in efficacy to azithromycin in comparative studies and is as effective as and better tolerated than erythromycin. Adverse events are primarily gastrointestinal in nature, but result in fewer withdrawals from therapy than are seen with erythromycin. Clarithromycin provides similar clinical and bacteriological efficacy to that seen with beta-lactam agents, cephalosporins and other macrolides. It offers a cost-saving alternative to intravenous erythromycin use in US hospitals and is available in both once-daily and twice-daily formulations. The spectrum of activity of clarithromycin against common and emerging respiratory tract pathogens may make it suitable for use in the community as empirical therapy of respiratory tract infections in both children and adults.",1997.0,0,0
260,9188928,Can an antihistamine delay appearance of hay fever symptoms when given prior to pollen season?,M A Stern; R Darnell; D Tudor,"Mizolastine is a new, nonsedating antihistamine providing satisfactory symptom relief in allergic conditions. The purpose of this study was to determine whether the onset of hay fever symptoms could be delayed in patients known to suffer seasonal allergic rhinoconjunctivitis symptoms if mizolastine was given before the pollen season. This double-blind study involved 342 patients, randomly allocated to once-daily 10 mg mizolastine (n = 115), once-daily 120 mg terfenadine (n = 116), or placebo (n = 111) groups. All patients started treatment on 1 May, before the onset of the grass pollen season. The prophylactic effect of test drugs was assessed on their ability to delay the time to the first hay fever crisis of the season, which was defined by the occurrence of one of the following events: use of rescue medication, study withdrawal because of treatment failure, or total diary symptom score over 18. Active treatments prolonged the time to the first crisis by approximately 1 week (mizolastine 55 days, terfenadine 57 days) in comparison with placebo (50 days) (survival curve analysis: Logrank test, P = 0.01; Wilcoxon test, P = 0.03). Tolerability was satisfactory and comparable between groups. Thus, mizolastine can be safely used to delay and to treat symptoms of seasonal allergic rhinitis.",1997.0,0,0
261,9188929,Fluticasone propionate aqueous nasal spray compared with oral loratadine in patients with seasonal allergic rhinitis.,P Géhanno; J L Desfougeres,"The effectiveness and safety of fluticasone propionate aqueous nasal spray (200 micrograms once daily for 4 weeks) were compared with those of loratadine (10 mg once daily for 4 weeks) in 114 adults and adolescents with seasonal allergic rhinitis in this multicenter, double-blind, double-dummy, randomized, parallel-group study. Patients recorded their nasal symptoms (nighttime and daytime obstruction, sneezing, itching, rhinorrhea, and overall discomfort) using a 4-point scale (0 = no symptoms, 3 = very frequent symptoms) in daily diaries. Clinicians assessed patients' nasal symptoms (nighttime and daytime obstruction, sneezing, itching, and rhinorrhea) using a 4-point scale at every scheduled visit. Clinicians and patients assessed the overall effectiveness of treatment at the end of the study. Fluticasone propionate improved clinician-rated total nasal symptom scores (defined as the sum of five nasal symptoms) more than loratadine at the 2-week and 4-week assessments (P < or = 0.008). Clinicians give fluticasone propionate better global ratings than loratadine (P = 0.04). After 4 weeks of treatment, between-group differences in clinician-rated individual nasal symptoms favored fluticasone propionate (P < 0.05), with the exception of nasal itching (P = 0.11). These findings were confirmed by between-group differences in the percentages of symptom-free days calculated from patient-recorded daily diary-card data. Both treatments were well tolerated. The incidence of adverse events between groups was similar. Fluticasone propionate aqueous nasal spray 200 micrograms administered once daily in the morning was more effective than loratadine 10 mg administered once daily for the treatment of seasonal allergic rhinitis.",1997.0,0,0
262,9188955,Antihistamines in the treatment of asthma.,A Malick; J A Grant,"Antihistamines were investigated for use in asthma shortly after discovery over fifty years ago. Earlier compounds proved ineffective because of side effects: this class of drugs was not thought useful for asthma, and were actually considered contraindicated. More recent drugs have greater potency, fewer side-effects, and no evidence of adverse effects in asthma. There are some studies showing second generation antihistamines, especially cetirizine, improve certain parameters of asthma.",1997.0,0,0
263,9225677,,,,,0,1
264,9226059,Adjunct effect of loratadine in the treatment of acute sinusitis in patients with allergic rhinitis.,J J Braun; J P Alabert; F B Michel; M Quiniou; C Rat; J Cougnard; W Czarlewski; J Bousquet,"H1-blockers are often added to the standard treatment of acute sinusitis, but this is not supported by a controlled study. A multicentric, randomized, double-blind, placebo-controlled, parallel-group study was done in 139 allergic patients (15-65 years) to assess the adjunct efficacy of loratadine in acute exacerbation of rhinosinusitis. Sinusitis was diagnosed by symptoms and confirmed by rhinoscopy and sinus radiograph. Allergy was characterized by skin tests, RAST, and history. Patients were treated with antibiotics (14 days), oral corticosteroids (10 days), and loratadine (10 mg OD) or placebo (28 days). Treatment efficacy was assessed over 28 days by symptom scores quoted daily by patients. Physicians also rated total symptom scores at entry and at day 28. At entry, both groups had similar symptoms. Placebo-treated patients improved significantly, but patients who received loratadine had a significantly greater improvement in sneezing (P = 0.003) after 14 days, and in nasal obstruction (P = 0.002) after 28 days. Physicians found that patients receiving loratadine were significantly improved compared to placebo patients (P = 0.0125). Loratadine in addition to standard therapy was found to improve the control of some symptoms of sinusitis.",1997.0,0,0
265,9228228,Effect of ebastine on mosquito bites.,T Reunala; H Brummer-Korvenkontio; L Petman; T Palosuo; S Sarna,"Mosquito bites usually cause wealing and delayed bite papules. Cetirizine decreases wealing, bite papules and pruritus but the effect of other antihistamines on mosquito bites is unknown. We studied the effect of ebastine in 30 mosquito bite-sensitive adult subjects. Ebastine 10 mg or 20 mg and placebo were given for 4 days in a cross-over fashion. Aedes aegypti bites were given on forearms. The size of the bite lesions and pruritus (visual analogue score) were measured at 15 min, 2, 6, and 24 h after the bites. Twenty-five subjects were evaluable in the study. At 15 min ebastine decreased significantly the size of the bite lesion (p = 0.0017) and pruritus (p<0.0001). The effects of 10 mg and 20 mg of ebastine were similar. No significant effect was found at 2, 6 or 24 h, but when the measurements at all four time points were compiled the size of the bite lesion and pruritus score decreased significantly. Sedation occurred during ebastine treatment in 6 (21%) and during placebo treatment in 2 (7%) subjects. The present results show that prophylactically given ebastine is effective against immediate mosquito bite symptoms.",1997.0,0,0
266,9259911,Pregnancy outcome following first trimester exposure to antihistamines: meta-analysis.,A Seto; T Einarson; G Koren,"To determine the relative risk for major malformations associated with antihistamine (H1 blockers) exposure in the first trimester of pregnancy, a literature search of all studies examining the association between antihistamines and major malformations for the period 1960 to 1991 was conducted, followed by meta-analysis. Odds ratio was calculated using the Mantel-Haenszel method. Twenty-four controlled studies met the inclusion criteria with more than 200,000 participating women. The summary odds ratio of major malformations associated with antihistamines taken during the first trimester was 0.76 (95% CI: 0.60-0.94). This analysis indicates that H1 blockers used mainly for morning sickness during the first trimester do not increase the teratogenic risk in humans and may, in fact, be associated with a protective effect. More study is needed to verify the possibility that by preventing vomiting, antihistamines may ensure better metabolic conditions to the fetus and thus may reduce some birth defects. Alternatively, it is possible that pregnancies characterized by vomiting are associated with better outcome due to other reasons, such as hormonal status or placental function. Women suffering from morning sickness which is not controlled by nonpharmacological methods can safely use antihistamines.",1997.0,0,1
267,9265991,Cetirizine treatment of allergic cough in children with pollen allergy.,G Ciprandi; M Tosca; V Ricca; G Passalacqua; L Fregonese; L Fasce; G W Canonica,"Cetirizine, an antihistamine widely used in the treatment of allergic rhinoconjunctivitis, also has antiallergic activity. The present study aimed to evaluate cetirizine as a treatment for children with allergic cough due to pollen allergy. This was a parallel-group, double-blind, placebo-controlled, randomized study. Twenty children with pollinosis were enrolled: they were subdivided into two groups receiving a 1-month treatment during the pollen season. The following variables were monitored: 1) clinical symptoms and respiratory data (spirometry and PEF) evaluated at baseline and at the end of the study by allergists and by a daily diary card, and 2) pollen count. This study shows that cetirizine treatment reduces cough intensity (P < 0.05) and frequency (P < 0.01). In conclusion, cetirizine does clinically improve cough due to pollen allergy.",1997.0,0,0
268,9278194,Enantioselective pharmacokinetics of mefloquine during long-term intake of the prophylactic dose.,U Hellgren; I Berggren-Palme; Y Bergqvist; M Jerling,"To investigate the kinetics of the (+)RS- and (-)SR-enantiomers and the carboxylic acid metabolite (MMQ) of the antimalarial drug mefloquine (MQ) in healthy volunteers. Ten subjects of which three were poor metabolizers of debrisoquine received racemic MQ 250 mg once weekly for 16 weeks. The kinetics were followed in plasma and urine and evaluated by individual kinetic modelling as well as by a nonparametric population kinetic method. A two-compartment model adequately described the disposition of (+)RS-MQ. CL/F was 6.5 +/- 1.8 l h(-1), V(ss)/F 815 +/- 165 l, and k 0.0081 +/- 0.0023 h(-1). The kinetics of (-)SR-MQ were time- and/or concentration dependent with a lower oral clearance (0.92 +/- 0.25 vs 2.14 +/- 0.63 l h(-1), 95% CI for the difference 0.86-1.60 l h(-1)) and a longer half-life (345 vs 185 h, 95% CI for the difference 47-291 h) after the last dose compared with the first dose. Clearance of (+)RS-MQ and (-)SR-MQ was significantly correlated within subjects (r = 0.69, P < 0.05). Urinary recovery of unchanged substance was 8.7% for (+)RS-MQ and 12.3% for (-)SR-MQ. The elimination of MMQ was disposition rate-limited and not determined by its rate of formation. Poor metabolizers of debrisoquine did not differ from extensive metabolizers in the kinetics of any compound. The MQ enantiomers differ extensively in their disposition both with regard to parameter values and the kinetic stability over time during repeated dosing with racemic MQ. Kinetic modelling of racemic MQ is therefore inadequate.",1997.0,0,0
269,9283989,A parallel-group comparison of astemizole and loratadine for the treatment of perennial allergic rhinitis.,H al-Muhaimeed,"The efficacy and safety of the two antihistamines, astemizole and loratadine, were compared in a double-blind study of 84 patients with perennial allergic rhinitis. Patients were randomized to receive orally either astemizole 10 mg once daily (n = 40) or loratadine 10 mg once daily (n = 44) for 1 week. No other antirhinitis medication was allowed during the study. By day 7 the mean daily symptom scores, recorded on diary cards, were lower in patients receiving astemizole than in those receiving loratadine for runny nose, itchy nose and sneezing, although not for blocked nose, and treatment differences only reached statistical significance for runny nose. After 7 days, 53.75% of patients on astemizole and 38.6% on loratadine were free of symptoms, and 87% of patients on astemizole described the treatment as good or excellent compared with 62% on loratadine. The present results suggest that astemizole may be more effective than loratadine in controlling symptoms of perennial allergic rhinitis.",1997.0,1,1
270,9294478,Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer.,M J Piccart; J Klijn; R Paridaens; M Nooij; L Mauriac; R Coleman; M Bontenbal; A Awada; J Selleslags; A Van Vreckem; M Van Glabbeke,"To confirm the efficacy of docetaxel in patients with breast cancer previously treated with one chemotherapy regimen for advanced or metastatic disease and to compare the incidence of fluid retention (FR) and skin toxicity when docetaxel is administered with and without prophylactic corticosteroids. Eighty-three patients, pretreated with one chemotherapy regimen for metastatic breast cancer (MBC) with bidimensionally measurable and progressive disease, were eligible for this randomized trial. Docetaxel with prophylactic oral antihistamine was administered at a dose of 50 mg/m2 as a 1-hour infusion on days 1 and 8 every 21 days and patients were randomized to receive methylprednisolone (40 mg days -1, 0, 1, 7, 8, and 9 of each cycle) (arm A) or no methylprednisolone (arm B). Twenty-eight patients (34%, 95% confidence interval [CI], 23% to 45%) achieved on objective response. The median time to disease progression and median overall survival time were 5 and 13.5 months, respectively. In total, 415 cycles of docetaxel were administered (arm A: N = 219, median = six; arm B: N = 196, median = five). The most common toxicity observed was grade 3 or 4 neutropenia, which occurred in 79% of patients. Clinically significant nonhematologic side effects included skin reactions and asthenia. In an intent-to-treat analysis, patients who received methylprednisolone premedication had a delayed onset of FR (median time to onset of FR: arm A, 84 days; arm B, 62 days; P = .01) and received a higher median cumulative dose of docetaxel before the onset of FR (arm A, 333 mg/m2; arm B, 215 mg/m2; P = .001). There was no statistically significant difference in the incidence of skin toxicity between the two arms. Docetaxel, at this dose and schedule, has definite antitumor activity in pretreated MBC patients. Moreover, this is the first randomized trial to show that corticosteroids have a favorable impact on docetaxel-induced FR.",1997.0,0,0
271,9299654,"Cetirizine and pseudoephedrine retard, given alone or in combination, in patients with seasonal allergic rhinitis.",M Grosclaude; K Mees; M E Pinelli; M Lucas; H Van de Venne,"We compared the efficacy and safety of cetirizine (5 mg), pseudoephedrine retard (120 mg), and the combination of cetirizine (5 mg) with pseudoephedrine retard (120 mg), each given twice daily for two weeks to subjects with pollen-associated allergic rhinitis. The study was multicentre and of randomized, double-blind, parallel-group design. Five rhinitis symptoms were rated according to severity on a scale of 0 - 3, daily by patients and at each clinic visit by investigators. A total of 687 patients, aged 9 - 66 years (mean: 32 years) was randomised to treatment (cetirizine: 231; pseudoephedrine: 226; combination: 230). On entry, the three groups were comparable in relevant respects. The primary outcome measure was based on the five symptoms assessed by the patients over the 2-week treatment period. The combination was more effective, providing at least 20% more ""comfortable days"" (symptoms absent or at most mild) than cetirizine or pseudoephedrine given alone (median values: 53.3%, 30.8%, and 33.3%, respectively; p < 0.001). For nasal obstruction, the combination (mean score: 1.19) was more effective than cetirizine (mean score: 1.43; p = 0.0005), but there was little difference between the combination and pseudoephedrine (mean score: 1.22; not significant). Sneezing, rhinorrhoea, nasal and ocular pruritus were better controlled by combination (mean 4-symptom score: 0.77) than by pseudoephedrine alone (mean 4-symptom score: 1.12; p < 0.001) and also better than by cetirizine alone (mean 4-symptom score: 0.93; p < 0.001). No unexpected adverse reactions were observed. A combination of cetirizine and pseudoephedrine retard is well tolerated and superior to each given alone for moderate to severe allergic seasonal rhinitis, especially when nasal obstruction is a predominant symptom.",1997.0,0,0
272,9330784,Effect of food on the bioavailability of fexofenadine hydrochloride (MDL 16455A).,M Stoltz; T Arumugham; C Lippert; D Yu; V Bhargava; M Eller; S Weir,,2000.0,0,0
273,9339388,Flare responses of atopic eczema patients analysed with true colour images.,R Rukwied; M Nischik; C Forster; G Heyer; H O Handwerker,"Attenuated flare responses of atopic eczema (AE) patients to histamine are well documented, but their origin is still unknown. Here we studied the development of erythema after histamine iontophoresis in 12 AE patients and 12 healthy volunteers by means of a RGB-camera for recording true colour images. 10 mg cetirizine or placebo was administered orally 3 h before the experiment in a crossover design. The flare reaction was found to develop after termination of histamine iontophoresis in two phases: a first phase lasting 1-2 min in which the flare increased by about 10 mm2/s and a second phase lasting another 10-15 min characterized by a slower growth in the range of 1 mm2/s. Flare size was diminished in AE patients, mainly due to a slower or absent growth in the second phase. Oral application of the H1-antagonist cetirizine (Zyrtec) reduced the flare reaction in both groups of volunteers significantly, indicating that the reaction is dependent on the activation of chemosensitive nerve fibres via H1-receptors.",1997.0,0,0
274,9360756,Reduction of soluble ICAM-1 levels in nasal secretion by H1-blockers in seasonal allergic rhinitis.,A Campbell; I Chanal; W Czarlewski; F B Michel; J Bousquet,"ICAM-1, a transmembrane glycoprotein promoting adhesion in immunologic and inflammatory reactions, was found to be increased on nasal epithelial cells of patients with allergic rhinitis. Loratadine, an H1-blocker, was found to reduce in vitro the expression of ICAM-1 on nasal epithelial cells. A double-blind, parallel-group study was carried out during the pollen season to compare the effect of two H1-blockers, cetirizine (10 mg OD) and loratadine (10 mg OD), on the release of soluble ICAM-1 in nasal secretions. A group of untreated patients was used as a control group. sICAM-1 was measured by enzyme immunoassay before and after 2 weeks of treatment. Symptoms were significantly decreased in the actively treated groups. sICAM-1 levels were unchanged in the control group but were significantly reduced in the two treated groups (P < 0.015, Wilcoxon's W test). This study shows that two H1-blockers, loratadine and cetirizine, have a similar effect on sICAM-1 released in nasal secretions during the pollen season.",1997.0,0,1
275,9361576,"Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance.",G G Kay; B Berman; S H Mockoviak; C E Morris; D Reeves; V Starbuck; E Sukenik; A G Harris,"The classic, first-generation histamine1-receptor antagonists used to treat allergic disorders frequently cause sedation. In contrast, sedation is reduced or absent after administration of recommended doses of second-generation histamine1-receptor antagonists. We measured the initial and steady-state effects of diphenhydramine, a first-generation antihistamine, and loratadine, a second-generation antihistamine, by means of a comprehensive battery of psychometric tests that mirror real-world tasks. Healthy volunteers (N = 98) were randomly assigned in a double-blind fashion to receive loratadine (n = 33), diphenhydramine (n = 32), or placebo (n = 33). A computerized test battery was administered at baseline, on day 1 after administration of the initial dose, and on days 3 and 5. After the initial dose, subjects taking diphenhydramine demonstrated poorer cognitive performance than subjects taking loratadine or placebo on tasks of divided attention, working memory, speed, and vigilance. Subjects taking diphenhydramine also reported greater fatigue and sleepiness and lower levels of motivation, and rated the quality of their performance as lower than subjects taking loratadine or placebo. On day 3, subjects taking diphenhydramine continued to show more fatigue and lower motivation, and rated the quality of their test performance as poorer than subjects taking loratadine or placebo. There were no differences between loratadine and placebo after the initial dose or steady-state (day 5) dosing for any measure of cognitive or psychomotor test performance, mood, or sedation. Patients taking diphenhydramine may be at risk of lapses and significant errors that may lead to potential hazards and decreased work productivity.",1997.0,0,0
276,9372314,Can a serotonin type 3 (5-HT3) receptor antagonist reduce experimentally-induced itch?,E Weisshaar; B Ziethen; H Gollnick,"Serotonin type 3 (5-HT3) receptor antagonists have been reported to be a novel therapeutic principle for the treatment of cholestatic and uremic pruritus. To determine the antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) on histamine and serotonin-induced itch under experimental conditions in comparison to native skin and after pretreatment with an orally applied antihistamine (cetirizine). Histamine and serotonin were iontophoretically applied in 10 healthy volunteers. Wheals and flares were planimetrically evaluated. Itching and burning sensations were entered on a scale over 24 min. The examination also comprised alloknesis, elicitation of perifocal itch sensation by usually non-itching (e.g. mechanical) stimuli. Tropisetron did not have any significant influence on histamine-induced reactions but could significantly reduce serotonin-induced flares. Cetirizine led to a significant reduction of all histamine-induced parameters and abolished serotonin-induced wheals. Serotonin has an own pruritic potency and does not only act over histamine containing mast cells. The antipruritic effect of tropisetron reported in cholestatic and uremic pruritus could not be verified in healthy persons under experimental conditions.",1997.0,0,0
277,9385487,Pharmacokinetics of loratadine and pseudoephedrine following single and multiple doses of once- versus twice-daily combination tablet formulations in healthy adult males.,T Kosoglou; E Radwanski; V K Batra; J M Lim; D Christopher; M B Affrime,"The pharmacokinetic profiles of single and multiple doses of loratadine, descarboethoxyloratadine (DCL) (the major active metabolite of loratadine), and pseudoephedrine were determined in a randomized, open-label, two-way crossover study in 24 healthy men. Subjects received a single dose (day 1) and multiple doses (days 3 to 10) of a once-daily (QD) formulation of loratadine 10 mg in an immediate-release coating and pseudoephedrine sulfate 240 mg in an extended-release core (CLAR-ITIN-D 24 HOUR tablets), and a twice-daily (BID) formulation of loratadine 5 mg in an immediate-release coating and pseudoephedrine sulfate 120 mg, with 60 mg in an immediate-release coating and 60 mg in the barrier-protected core (CLARITIN-D 12 HOUR tablets) in study sessions, each separated by a 10-day washout period. Both regimens were safe and well tolerated. On day 1, plasma loratadine, DCL, and pseudoephedrine concentrations were higher following the QD formulation than following the BID formulation, as expected. On day 10, loratadine and DCL maximum plasma concentration (Cmax) values were, on average, 87% and 35% higher, respectively, for the QD formulation than for the BID formulation; however, the values of the area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) for loratadine and DCL were equivalent (90% confidence interval [CI]: 83% to 110% for loratadine; 90% to 107% for DCL). On day 10, pseudoephedrine Cmax and AUC0-24 values were equivalent (90% CI for Cmax: 94% to 109%; for AUC: 91% to 106%) for the two formulations, and lower pseudoephedrine concentrations were observed from 16 to 24 hours with the QD formulation. Both loratadine/pseudoephedrine formulations produced equivalent loratadine and DCL AUC0-24 values and equivalent pseudoephedrine Cmax and AUC0-24 values following multiple dosing. The lower pseudoephedrine concentrations in the evening with the QD formulation may minimize the potential for insomnia in patients when compared with the BID formulation.",1998.0,0,0
278,9387943,Effects of antihistamines in adult asthma: a meta-analysis of clinical trials.,E Van Ganse; L Kaufman; M P Derde; J C Yernault; L Delaunois; W Vincken,"A meta-analysis of clinical trials of antihistamines was performed to assess the risk-benefit ratio of this therapeutic class in asthma. Double-blind randomized placebo-controlled trials assessing lung function changes under repeated use of antihistamine in adult asthma were selected, and the quality of studies was scored. Morning peak expiratory flow rate (PEFR) was the primary outcome: an effect size was computed for each study, with a 95% confidence interval (95% CI), and a mean effect size was computed, combining all studies. Effect sizes were also determined for secondary outcomes: evening PEFR, forced expiratory volume in one second (FEV1) and daily use of inhaled beta-agonists. Nineteen studies were included in the meta-analysis. Mean quality score of studies was 59.4%; asthma was generally uncontrolled at study inclusion. Altogether, 582 antihistamine-treated and 557 placebo-treated asthma patients were evaluable. Antihistamines had little effect on airway calibre (mean increase in morning PEFR: 13 L x min(-1); 95 CI: 8-18 L x min(-1)) and on use of inhaled beta-agonists (mean reduction in daily use: 0.4 doses; 95% CI: 0-0.8 doses). Sedation occurred more often with antihistamines than with placebo (p<0.001); additional side-effects were mentioned, including weight gain, altered taste, headache and dry mouth. Respiratory and systemic effects observed after repeated use of antihistamines do not support the use of these medications in the treatment of asthma; better designed studies could affect this appraisal.",1997.0,0,0
279,9408807,Paroxetine does not affect the cardiac safety and pharmacokinetics of terfenadine in healthy adult men.,D E Martin; B D Zussman; D E Everitt; L J Benincosa; R C Etheredge; D K Jorkasky,"Potent CYP3A4 inhibitors such as ketoconazole can cause dangerous increases in plasma concentrations of the H-1 antagonist terfenadine. In light of recent reports that the selective serotonin reuptake inhibitor antidepressants may be weak CYP3A4 inhibitors, this study was designed to investigate the effects of paroxetine on the pharmacodynamic and pharmacokinetic profile of terfenadine. Twelve healthy male volunteers participated in a randomized open-label, two-period, steady-state crossover study. Terfenadine (60 mg twice daily for 8 days) was administered alone and with paroxetine at steady state (20 mg once daily for 15 days, with terfenadine on days 8 through 15). Extensive electrocardiogram monitoring was conducted throughout, and terfenadine and carboxyterfenadine pharmacokinetics were assessed at the end of each treatment period. One subject withdrew because of adverse experiences related to paroxetine, but the other 11 subjects completed the study uneventfully. On the final day of coadministration, the rate-corrected QT interval (QTc) was unaltered compared with terfenadine dosed alone; maximum QTc values (mean [SEM]) were 404 (4) and 405 (5) msec, respectively. Terfenadine pharmacokinetics were also unchanged; geometric mean steady-state area under the curve (AUC)tau values were 30.0 ng.hr/mL during coadministration compared with 30.8 ng.hr/mL when dosed alone (p > 0.05). The corresponding Cmax values were 3.68 and 3.64 ng/mL (p > 0.05). There was, however, a small (on average 17-20%), unexplained reduction in the steadystate Cmax and AUCtau of carboxyterfenadine during coadministration with paroxetine. In conclusion, paroxetine does not affect the pharmacokinetics or cardiovascular effects of terfenadine. The small reduction in carboxyterfenadine plasma concentrations is unlikely to be important clinically.",1997.0,0,0
280,9415511,Opiate and H1 antagonist effects on histamine induced pruritus and alloknesis.,G Heyer; M Dotzer; T L Diepgen; H O Handwerker,"Itching is a well known side-effect of opiate therapy. To gain insight into the possible contribution of opiate receptors to itching we compared the antipruritic effect of naltrexone (Nemexin), an opiate antagonist, to an H1-receptor antagonist and to placebo. In a double blind cross-over study on 15 healthy volunteers, 25 mg naltrexone or placebo was orally given 60 min prior to a histamine stimulus. In a second, otherwise identical experiment, 10 mg cetirizine, an H1 blocker, or placebo was orally given 12 h before the experiment to the same group of volunteers. Histamine was applied iontophoretically to the forearm skin and the following parameters were assessed thereafter: weal and flare size, itch intensity and the extension of the area of alloknesis ('itchy skin') around the application site. Naltrexone had no effect on the vascular histamine reactions 'weal' and 'flare', whereas cetirizine abolished the weal reactions and greatly diminished the flare reactions. Both naltrexone and cetirizine significantly diminished histamine induced itching. In contrast to placebo and cetirizine, naltrexone abolished alloknesis completely in four of 15 volunteers and in the others alloknesis was greatly reduced after naltrexone. Since vascular reactions to histamine are of peripheral origin, whereas alloknesis depends on central nervous mechanisms, our findings suggest a pronounced centrally mediated action of naltrexone on histamine induced pruritus.",1998.0,0,0
281,9443210,Early treatment of the atopic child: first results of the clinical trial.,L Businco,,1998.0,0,0
282,9491231,Effect of continuous allergen challenge on clinical symptoms and mediator release in dust-mite-allergic patients.,F Horak; J Toth; R Hirschwehr; B Marks; U P Stübner; S Jäger; U Berger; K Schleinzer; P Günczler,"This study investigated the early, prolonged immediate, and late-phase reactions of dust-mite-sensitive subjects undergoing long-term challenge in the Vienna challenge chamber (VCC) in terms of clinical symptoms and inflammatory mediator level patterns in nasal lavage fluids. A concentration of 70 ng Der p 1/m3 of air (feces of Dermatophagoides) was maintained over 8 h in the VCC. To show the clinical impact of this challenge model, the effect of a histamine H1-receptor antagonist that also has some antiallergic properties (loratadine) was also investigated. The study followed a double-blind, placebo-controlled, crossover design. Medication was given orally over 7 days before the provocation at a dose of 10 mg once daily. All 12 patients, whose dust-mite sensitivity was confirmed by disease history, skin prick test, and RAST, completed the challenge session. The documentation of the chosen parameters was performed every 30 min. Subjective nasal and ocular symptoms were assessed via a visual analog scale of 100 mm, nasal flow was recorded by active anterior rhinomanometry, and mediator release was evaluated with nasal lavages. Clinical aspect: the whole sample population showed a rise of nasal and ocular symptom severity and a nasal flow reduction, which were perceptibly, but not significantly attenuated by active drug treatment. Mediator pattern: in each patient, prostaglandin (PG)D2 and leukotriene (LT)C4 levels peaked within the first 2 h of provocation, PGD2 then moving toward baseline levels, and LTC4 then again rising continuously. Eosinophil cationic protein (ECP) exhibited a constant level increase over the whole provocation period, and tryptase levels did not change significantly. Whereas the area under the curve values of tryptase and ECP were higher in drug-treated patients than the placebo group, the early PGD2 peak occurring during the first two challenge hours seemed to be mitigated by loratadine. These results reveal that there is no link between the clinical symptoms, the drug efficacy, and the released mediators (LTC4, PGD2, ECP, and tryptase).",1998.0,0,0
283,9491827,"Loratadine-pseudoephedrine in children with allergic rhinitis, a controlled double-blind trial.",H A Serra; O Alves; L F Rizzo; F M Devoto; H Ascierto,"To conduct a randomized placebo controlled double-blind crossover trial in order to evaluate a loratadine-pseudoephedrine combination (L + PS) in children with seasonal allergic rhinitis. Forty children (15 males; 25 females), aged 3-15 years, were included in this study. They were randomized to receive L + PS (0.2 mg kg[-1] body weight-2.4 mg kg[-1] body weight respectively) or placebo (PLA) for 14 days. After 7 days of washout, patients were shifted to the other treatment for a further 14 days. Nasal symptoms (sneezing/itching, congestion, nasal dripping) and signs (turbinal swelling, retronasal drainage), rated on a scale ranging from: 1. absent to 5. very intense, and their sum or mean total symptom score (MTSS) were used as efficacy measurement. Significant relief was observed; post-treatment MTSS difference and its percent change were respectively; L + PS = -4.29; 95% CI: -3.64 and -4.94 (27.8%), and PLA = -1.63; 95% CI: -0.95 and -2.31 (10.7%) (P < 0.001 baseline vs endpoint and between treatments). Furthermore, L + PS and PLA significantly modified symptoms, but only L + PS significantly modified signs. No clinical changes were observed during the trial; only one patient showed slight transient insomnia when receiving L + PS. It is concluded that L + PS is useful and well tolerated in children with seasonal allergic rhinitis. However, elements such as placebo effect must be taken into account for planning future trials.",1998.0,0,0
284,9506246,Fexofenadine.,A Markham; A J Wagstaff,"The nonsedating histamine H1 receptor antagonist fexofenadine is the active metabolite of terfenadine. It reduced the allergic response in animal models of allergy and did not prolong the QT interval (QTc) in dogs or rabbits at plasma concentrations many times higher than those seen after administration of therapeutic dosages. Similarly, relative to placebo, fexofenadine did not affect mean QTc in patients given dosages of up to 480 mg/day for 2 weeks or in volunteers who received up to 800 mg/day for 6 days or 240 mg/day for 12 months. In a double-blind clinical trial, oral fexofenadine 120 or 180mg once daily controlled symptoms in patients with seasonal allergic rhinitis as effectively as cetirizine. Other double-blind clinical trials showed that fexofenadine 40 to 240mg twice daily was significantly more effective than placebo. Fexofenadine 180 or 240mg once daily was significantly more effective than placebo in patients with chronic idiopathic urticaria. The drug was well tolerated in these clinical trials, with an adverse event profile similar to that seen with placebo. The most common adverse events were headache, throat irritation, viral infection, nausea, dysmenorrhoea, drowsiness, dyspepsia and fatigue.",1998.0,0,0
285,9533065,Troglitazone: review and assessment of its role in the treatment of patients with impaired glucose tolerance and diabetes mellitus.,M D Johnson; L K Campbell; R K Campbell,"To introduce troglitazone (CS-045, Rezulin), a new oral antidiabetic agent and discuss its pharmacology, therapeutics, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy. A MEDLINE database search was completed to identify relevant articles including reviews, recent studies and abstracts, and data from Parke-Davis. Due to the small number of published human studies available, some data are derived from animal studies and abstracts of human studies. Studies and abstracts chosen summarize the clinical action of troglitazone in healthy volunteers, in subjects with impaired glucose tolerance, and in patients with diabetes mellitus. Three of the six published human studies used subjects in a placebo-controlled, multicenter, randomized environment (type 2 diabetic patients or obese subjects with insulin resistance). All clinical trials available, including unpublished reports, were reviewed. Troglitazone is the first member of a new class of medications, the thiazolidinediones, to be approved for clinical use. Troglitazone increases insulin sensitivity in skeletal muscle and in hepatic and adipose tissue. It has been shown to decrease hepatic glucose output while having no effect on stimulating insulin secretion from the pancreatic beta-cells. Its metabolic effects decrease fasting and postprandial hyperglycemia, insulin concentrations, and triglyceride concentrations, while increasing high-density lipoprotein concentrations. There is some evidence, based on short-term trials, that troglitazone causes only minimal decreases in glycosylated hemoglobin A1C (HbA1C) concentrations. Data suggest that troglitazone decreases impaired glucose tolerance in nondiabetic obese subjects and leads to a reduction in both systolic and diastolic blood pressure in hypertensive type 2 diabetes mellitus patients. Troglitazone has a mild adverse effect profile, with rare instances of abnormal liver function tests. Troglitazone appears to be a safe, effective, and useful new agent in the treatment of insulin-requiring type 2 diabetes mellitus patients, although its HbA1C-lowering effects have been minimal in short-term trials, and its insulin dosage-reduction activity remains unclear. The Food and Drug Administration has also approved its use as monotherapy and in combination with sulfonylureas for patients with type 2 diabetes. It may have use in the treatment of patients with impaired glucose tolerance, but more clinical experience is needed before definitive conclusions can be made. The role of troglitazone therapy in diabetes mellitus and impaired glucose intolerance will continue to evolve as the results of studies and our clinical experience with this agent become available.",1998.0,0,0
286,9534917,Differential effects of new-generation H1-receptor antagonists in pruritic dermatoses.,B M Henz; P Metzenauer; E O'Keefe; T Zuberbier,"In search of an improved treatment of pruritic dermatoses, we have studied azelastine, a novel H1-receptor antagonist, during a 2-week treatment period, using a double-blind, placebo-controlled design. The potent H1-antagonist cetirizine was used for comparison. Symptoms were recorded daily by the patients on a diary card, using a 4-point scale. The same parameters and adverse events were evaluated at weekly intervals, and global improvement was evaluated at the end of treatment. In all 230 evaluable patients with moderate to severe itching, azelastine caused an overall significant improvement in comparison to placebo (P = 0.02), with significance also for pruritus (P = 0.01 after 1 week and P = 0.02 after 2 weeks). Both drugs reduced itching more effectively in urticaria than in atopic eczema. Azelastine was superior to cetirizine in reducing pruritus, whereas cetirizine caused a more marked reduction of whealing. Both drugs rarely caused fatigue and dry mouth, but taste perversion occurred only in azelastine-treated patients (9.7%) and headaches only with cetirizine (10.4%). Therefore, the two H1-blockers exert differential effects on pruritus verses whealing and a distinctive adverse events pattern. The data also underline the low efficacy of antihistamines in atopic eczema, compared to urticaria.",1998.0,1,1
287,9555615,Cetirizine reduces conjunctival nonspecific hyperreactivity in children with mite allergy.,M Tosca; G Ciprandi; G Passalacqua; G W Canonica,"As mite allergy is characterized by a continuous allergen exposure, persistent inflammation is always detectable even during symptomless periods. It has been reported that mite allergic patients present a nonspecific hyperreactivity to different stimuli, including hyperosmolar solution. Since it has been reported previously that cetirizine is able to reduce minimal persistent inflammation due to mite allergy, the aim of the study was to investigate the effect of cetirizine on nonspecific conjunctival hyperreactivity. Twenty children with mite allergy were studied; two hyperosmolar conjunctival challenges were performed before and after cetirizine or placebo treatment, lasting one week. Patients treated with cetirizine showed a significant reduction in nonspecific conjunctival hyperreactivity compared to the placebo group (p < 0.05). In conclusion, cetirizine was able to reduce nonspecific hyperreactivity related to allergic inflammation.",1998.0,0,0
288,9557493,[From atopic dermatitis to asthma].,L Businco; M Marziali; G Furcolo; P Meglio,"Atopic dermatitis (AD) is the most common chronic skin disorder in infancy and childhood and is the main hallmark of atopic constitution. The disease is multifactorial, and although genetic predisposition is certainly a prerequisite, a number of environmental factors modulate the phenotypic expression of AD. The majority of affected children shows IgE sensitisation towards a large variety of foods and aeroallergens. Since at least 1600, it has been recognized that patients with AD have a high predisposition to develop asthma. Recent epidemiological studies show that AD is commonly seen in individuals from families with a history of asthma. In addition, in population where asthma is uncommon, AD is also uncommon. The sex distribution of AD and asthma is the same, with boys affected significantly more often by these two atopic diseases and in similar proportions. The ETAC project (Early Treatment of the Atopic Child) is a large multicenter, multi-national, double blind, placebo controlled, randomised trial. The main objective of the study is to stop the progression from AD to asthma in young children with AD using early therapeutic intervention with Cetirizine and the second objective is to investigate the main risk factors for the onset of asthma. The results of this study indicate that exposure to potent allergens such as cat or mite significantly increased the risk of sensitisation to these allergens. Prolonged breast feeding was associated with a lowest sensitisation rate to cow milk proteins and to egg. Therefore environmental factors seem to play a crucial role in IgE sensitisation in children with AD.",1998.0,0,0
289,9590467,"Brompheniramine, loratadine, and placebo in allergic rhinitis: a placebo-controlled comparative clinical trial.",H M Druce; W R Thoden; P Mure; S A Furey; E A Lockhart; T Xie; S Galant; B M Prenner; S Weinstein; R Ziering; M L Brandon,"A double-blind, randomized, placebo-controlled, parallel-group, multicenter study was conducted to compare the effectiveness of an extended-release formulation of a classical antihistamine, brompheniramine, and a second-generation compound, loratadine, in the treatment of allergic rhinitis. Subjects with symptoms of allergic rhinitis received brompheniramine 12 mg twice daily (n = 112), loratadine 10 mg once daily (n = 112), or placebo twice daily (n = 114) for 7 days. Study medications were blinded using a double-dummy technique. Subjects completed an overall evaluation of symptom relief on a daily basis and returned on treatment days 3 and 7, at which times the investigator assessed symptom severity. The investigator and subject each completed a global efficacy evaluation, and subjects were interviewed regarding adverse experiences. The primary efficacy variable was the physicians' global efficacy evaluation on day 3. Symptoms also were analyzed as summed severity scores for all symptoms and for the nasal symptom cluster of rhinorrhea, sneezing, and nasal blockage. At all post-baseline evaluations (days 3, 7, and averaged over the two days), brompheniramine was significantly better than loratadine and placebo for both sets of summed symptom scores and all three global assessments. Loratadine was significantly better than placebo for physician ratings of total symptom severity averaged over the two days and for the physician and subject ratings of the nasal cluster on day 3. Central nervous system-related symptoms were the most frequently reported adverse experiences; somnolence was reported most frequently by patients taking brompheniramine, and its occurrence was less frequent as treatment continued. A nonprescription, extended-release formulation of brompheniramine 12 mg twice daily provided significantly better relief of symptomatic allergic rhinitis than loratadine 10 mg once daily.",1998.0,0,1
290,9602225,Antiinflammatory properties of cetirizine in a human contact dermatitis model. Clinical evaluation of patch tests is not hampered by antihistamines.,J J Grob; M Castelain; M A Richard; J P Bonniol; V Béraud; H Adhoute; N Guillou; J J Bonerandi,"The aim of this double-blind, placebo-controlled, randomized, cross-over pilot study was to assess the antiinflammatory properties of cetirizine. A group of 27 patients with a positive patch test to an allergen consecutively received cetirizine 10 mg o.d. or placebo during a 14-day period, respectively. At day 11 of each period, patch testing was performed with the allergen. The image analysis showed a skin reaction significantly reduced under cetirizine (p = 0.03), but the clinical recording and the standardized chromatometry did not show any difference between groups. In the cross-over analysis the results of image analysis were influenced by the period, but this effect disappeared after adjustment of the ambient temperature during the 3 days of the test. These results demonstrate that cetirizine has an impact on the inflammatory process in a clinical model of cell-mediated allergic reaction, although this effect is only detected with a very sensitive technique. They also show that it is useless to stop antihistamines before patch testing, since clinical evaluation of tests is not hampered by a potent antihistamine. Additionally this study suggests that ambient temperature has an influence on the results of tests.",1998.0,0,1
291,9617978,,,,,0,0
292,9620105,Troglitazone in type II diabetes mellitus.,N Sparano; T L Seaton,"Troglitazone, a new antihyperglycemic agent, is approved for use alone, with oral sulfonylureas, or with insulin in the treatment of type II diabetes mellitus. Rather than stimulating insulin secretion, it enhances insulin sensitivity. Potential advantages of troglitazone over oral sulfonylureas include decreased endogenous insulin concentrations, decreased exogenous insulin requirements, reduced hypoglycemic risk, and convenient once/day administration. The effect on morbidity and mortality from lowering endogenous and exogenous insulin concentrations remains to be determined. Troglitazone also has potential disadvantages. It induces cytochrome P450 isoenzyme 3A4, although few drug interactions have been identified to date. Serum transaminases must be monitored routinely because of rarely reported cases of idiosyncratic hepatocellular injury. In addition, the cost of troglitazone is much higher than that of other oral antihyperglycemic agents or insulin. Given the available information, troglitazone has limited benefit over oral sulfonylureas or metformin as monotherapy or in combination with oral sulfonylureas. Until additional combination and comparative studies have been done, the agent should be reserved for patients with poor glycemic control receiving high daily doses of insulin.",1998.0,0,0
293,9636808,"Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, placebo-controlled trial of a standardized five-grass-pollen extract in rhinitis.",R Clavel; J Bousquet; C André,"Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen extracts has been found to be effective in reducing allergic symptoms and medication needs. A double-blind, placebo-controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT. Some 136 patients with grass-pollen rhinitis with or without mild asthma were studied. Patients received either placebo or SLIT with a standardized grass-pollen extract administered daily with increasing doses up to 300 IR (index of reactivity) from January to the end of July 1994. During the grass-pollen season, patients were instructed to use medications as required and to visit their doctors in case of asthma. Symptom-medications scores were assessed during the pollen season, and serum-specific IgG4 was measured before and at the end of SLIT. In the SLIT group, drug consumption dropped significantly throughout the pollen season (P < 0.02). Moreover, at the peak of the pollen season, betamethasone consumption was significantly reduced in the SLIT group (P < 0.02). Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group (P < 0.02). IgG4 levels increased significantly in the SLIT group (P < 0.001) but without correlation with symptoms. Side-effects were comparable in both groups. This study indicates that SLIT in grass-pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumption and the need for oral corticosteroids.",1998.0,0,0
294,9636821,Loratadine reduces the expression of ICAM-1.,G Ciprandi; A Catrullo; P Cerqueti; M Tosca; N Fiorino; G W Canonica,,1998.0,0,0
295,9662080,"Effects of methysergide and loratadine on food intake, mood, and performance of humans living in a residential laboratory.",S D Comer; M Haney; A S Ward; M W Fischman; R W Foltin,"The effects of loratadine, a peripherally acting histamine (H1) antagonist, and methysergide, a serotonin (5-HT) antagonist, were evaluated in seven normal-weight, male research volunteers, participating in a placebo-controlled, double-blind, 17-day residential study. Participants received oral loratadine (10 or 20 mg), methysergide (4 or 8 mg), or placebo at 1000 and 1700 hours daily. Active drug was administered on Days 4, 5, 7, 8, 11, 12, 15, and 16; placebo was administered on all other days. Drug and dose order were counterbalanced across participants. Food intake, performance, and subjective ratings were measured repeatedly throughout the day. Loratadine had no effect on food intake, performance, or subjective ratings. In contrast, total caloric intake significantly decreased from approximately 3500 kcal during placebo administration to 3065 kcal on the first but not the second day of methysergide administration. Consumption of carbohydrate (p < 0.055), protein, and fat decreased on the first day of methysergide administration. This decrease in food intake was due to a decrease in meal size; the number of meals consumed was not affected. The proportion of calories derived from carbohydrates significantly increased on the first day of methysergide administration. Methysergide also significantly impaired performance of a psychomotor task on the first day of high-dose administration and increased ratings of several subjective measures, including ""Vomiting,"" ""Stomach Pain,"" and ""Miserable."" These results suggest that the anorectic effect occurred as a result of the somatic and mood changes produced by methysergide. In addition, the inability of loratadine to affect food intake indicates that antagonism of central histamine receptors may be responsible for the increases in food intake produced by other antihistamines (e.g., diphenhydramine).",1998.0,0,0
296,9666826,Effects of H1 antagonists on the cutaneous vascular response to histamine and bradykinin: a study using scanning laser Doppler imaging.,G F Clough; A R Bennett; M K Church,"Histamine plays an important part in the cutaneous weal and flare response which underlies many allergic skin conditions. It has a direct effect on the local vasculature to promote vasodilatation and increase microvascular permeability and may also initiate the more widely spread neurogenic flare. Quantification of these responses and studies of the mediator mechanisms underlying them have been limited by the lack of appropriate techniques to investigate them. To address this we have used two relatively new techniques, scanning laser Doppler imaging (LDI) and dermal microdialysis to measure changes in skin blood flow and the release of histamine within the weal and flare, following intradermal injection of histamine or bradykinin. These measurements have been made both in the absence and presence of the H1 receptor blockers cetirizine and loratadine. Scanning LDI of the inflammatory response revealed marked differences in both the development and steady state responses to the intradermal injection of histamine (1-3 mumol/L) and bradykinin (1 mumol/L). The development of the flare and the weal response to both histamine and bradykinin was significantly reduced by cetirizine but not by loratadine. The histamine-induced flare area fell by 57 +/- 4% (mean +/- SEM, n = 10, P < 0.001) after cetirizine and the area of the weal fell by 73 +/- 11% (P < 0.009). Bradykinin-induced inflammatory responses were similarly reduced by cetirizine, the weal by 60 +/- 16% (P < 0.02) and the flare by 61 +/- 4% (P < 0.005). Measurement of histamine concentration in skin using microdialysis, in six subjects, confirmed that histamine levels rose in the dialysate collected from the weal to 310 +/- 16 nmol/L following injection of histamine. Histamine levels also rose following bradykinin injection in some subjects (mean 147 +/- 46 nmol/L, range 18-336). Little increase in histamine concentration was seen in the dialysate from the flare following injection of either histamine or bradykinin. The histamine concentration in dialysate from unprovoked skin was 4.19 +/- 0.75 nmol/L. These data reveal differences in the dermal responses to different mediators when assessed using scanning LDI. They confirm that histamine is released within the weal but not the flare response to the intradermal injection of both histamine and bradykinin and that its effects on the local vasculature to cause the oedematous weal and the axon reflex-mediated flare are significantly attenuated by the H1 antagonist cetirizine and to a lesser extent by the H1 antagonist loratadine.",1998.0,0,1
297,9689339,Changes in skin-test reactivity do not correlate with clinical efficacy of H1-blockers in seasonal allergic rhinitis.,J Bousquet; W Czarlewski; J Cougnard; M Danzig; F B Michel,"New-generation H1-blockers may possess antiallergic properties, and their effect may differ, depending on the target organ. A double-blind, placebo-controlled, parallel-group study was carried out during the pollen season to compare the clinical effect on nasal and conjunctival symptoms of astemizole (10 mg o.d.) and loratadine (10 mg o.d.) with their effect on skin-test reactivity to allergen and histamine. Thirty-eight patients (12-56 years of age) were studied. Nasal and ocular symptoms were recorded daily from days 4 to 7. Skin prick tests with serial concentrations of allergens and one concentration of histamine were carried out before and at the end of the 7-day treatment period. Parallel-line bioassay, analysis of variance, and covariance were used to analyze skin test data. Loratadine and astemizole significantly decreased symptoms from baseline (P < 0.004 and P < 0.006). Skin-test reactivity to allergen and histamine was more profoundly decreased by astemizole than loratadine. The histamine covariant was more important in the allergen effect of astemizole than in that of loratadine. Two H1-blockers having the same clinical effect on nasal and ocular symptoms during the pollen season have totally different effects on skin-test reactivity. Skin-test reactivity to allergen or histamine is not predictive of the clinical efficacy of H1-blockers during seasonal allergic rhinitis.",1998.0,0,1
298,9700035,"Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization.",D Vourdas; E Syrigou; P Potamianou; F Carat; T Batard; C André; P S Papageorgiou,"For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergènes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR. were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE, IgG4, eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the pollinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization.",1998.0,0,0
299,9718972,[Levocabastine versus cetirizine for perennial allergic rhinitis in children].,L Arreguín Osuna; R García Caballero; M T Montero Cortés; I Ortiz Aldana,"To compare the efficacy and safety of levocabastine nasal spray asid cetirizine oral for the treatment of perennial allergic rhinitis in children. In this randomized, prospective experimental, open clinical trial. We studied 30 children with ages between 6 and 16 years with perennial allergic rhinitis. Group 1, 17 subjects (7 female, 10 male) received cetirizine once daily, 5 mg children weientig less dian 30 k asid 10 mg in children weighing more trw' 30 k during 15 days. Group 2, 13 subjects (7 male, 6 female) received levocabastine 2 puffs BID on each nostril during tbe same time. A nasal symptoms score, nasal peal: flow vid eosinophils in a nasal smear were performed before and after treatment. There were no statistical differences in age, weight, height and arid duration of symptoms. Both groups showed improvement of symptoms via nasal peak flow with no differences between them (intergroup); nasal eosinophils remained unchanged. We for third statistical differences pre vid postreatment in each group (intragroup): Group 1, nasal congestion p = 0.002, ocular itch p = 0.01, sneezing p = 0.007, nasal secretion p = 0.01, nasal itch O = 0.009, total points O = 0.0005. Group 2, nasal congestion O = 0.02, ocular itch p = 0.05, sneezing p = 0.01, nasal secretion p = 0.01, nasal itch p = 0.04, total points p = 0.005. Significant differences were found in nasal peal' flow in Group 1 (p = 0.01) but no differences in eosinophils between file two groups. Side effects: 3 subjects in Group 1 (drowsiness, 1 appetite increase said 1 rhinorrea with epistaxis) vide 1 in Group 2 sensation of facial edema. Bofil drugs are effective the clinical relief of symptoms of perennial allergic rhinitis in children vied levocabastine has less side effects.",1998.0,0,0
300,9722799,"A comparison of the efficacy of fluticasone propionate aqueous nasal spray and loratadine, alone and in combination, for the treatment of seasonal allergic rhinitis.",P H Ratner; J H van Bavel; B G Martin; F C Hampel; W C Howland; P R Rogenes; R E Westlund; B W Bowers; C K Cook,"Intranasal corticosteroids and oral antihistamines are both effective in the treatment of seasonal allergic rhinitis, although the therapeutic value of administering the two types of agents concurrently has rarely been evaluated. This study was designed to compared the efficacy, safety, and impact on quality of life of fluticasone propionate aqueous nasal spray (FP ANS), loratadine, FP ANS plus loratadine, and placebo (an aqueous nasal spray plus tablet) in the treatment of seasonal allergic rhinitis during the mountain cedar allergy season in south central Texas. Six hundred patients with seasonal allergic rhinitis were treated for 2 weeks with either FP ANS 200 microgram once daily, loratadine 10 mg once daily, the FP ANS and loratadine regimens combined, or placebo in a multicenter, randomized, double-blind, double-dummy, parallel-group study. Clinician- and patient-rated total and individual nasal symptom scores after 7 and 14 days of therapy and overall evaluations were significantly lower (P < .001) in the FP ANS and FP ANS plus loratadine groups compared with the loratadine only and placebo groups. Loratadine was not statistically different from placebo in clinician and patient symptom score ratings nor in overall clinician and patient evaluations. FP ANS plus loratadine and FP ANS monotherapy were comparable in efficacy in almost all evaluations; for some patient-rated symptoms the combination was found superior. Mean score changes in the Rhinoconjunctivitis Quality of Life Questionnaire from baseline to day 14 showed significantly greater improvement (P < .001) in quality of life in the FP ANS group than in the group of patients receiving loratadine only or placebo and no significant benefit was demonstrated in the FP ANS plus loratadine group over the FP ANS monotherapy group. No serious or unusual drug-related adverse events were reported. Combining loratadine with FP ANS did not alter the adverse events profile or frequency.",2001.0,0,0
301,9725552,Atorvastatin does not produce a clinically significant effect on the pharmacokinetics of terfenadine.,R H Stern; J A Smithers; S C Olson,"The effect of atorvastatin, a CYP3A4 substrate, on the pharmacokinetics of terfenadine and its carboxylic acid metabolite, fexofenadine, were evaluated. Single 120-mg doses of terfenadine were given 2 weeks apart to healthy volunteers with 80-mg daily doses of atorvastatin administered from 7 days before through 2 days after the second terfenadine dose. Concentrations of terfenadine and fexofenadine were measured for 72 hours after each terfenadine dose. Administration of terfenadine alone or in combination with atorvastatin produced no alterations in the QTc interval. For terfenadine, atorvastatin coadministration produced an 8% decrease in maximum concentration (Cmax), a 35% increase in area under the concentration-time curve extrapolated to infinity (AUC0-infinity), and a 2% decrease in elimination half-life (t1/2). For fexofenadine, atorvastatin coadministration produced a 16% decrease in Cmax, a 2% decrease in AUC0-infinity and a 51 % increase in t1/2. None of these changes achieved statistical significance. Coadministration of atorvastatin with terfenadine does not result in a clinically significant drug interaction. Because 80 mg is the highest atorvastatin dose used clinically, drug interactions mediated by CYP3A4 inhibition are unlikely in clinical practice.",1998.0,0,0
302,9732164,Comparison of the effects of cetirizine and ebastine on the skin response to histamine iontophoresis monitored with laser Doppler flowmetry.,T Leroy; C Tasset; B Valentin; D Van Neste,"The administration of histamine with iontophoresis is an alternative method to skin prick tests or intradermal injections. Skin reactions obtained with this method can be recorded with laser Doppler flowmetry (LDF) and previous studies with this method have shown histamine-induced laser Doppler changes in the wheal area. In order to compare the influence of two H1 receptor antagonists (cetirizine 10 mg vs. ebastine 10 mg) on the skin vascular responses to histamine introduced by iontophoresis, we designed a double-blind, randomized, two-period crossover trial in which 18 volunteers were randomized. Before and 2, 5 and 7 h after drug administration, iontophoresis (30 s, 1.4 mA/cm2) of histamine 10% was performed and followed by (1) monitoring of skin vascular responses with LDF at the administration site and at 1 cm from it, and (2) wheal and flare area measurements. 2, 5 and 7 h after intake of the antihistaminic drug, there were significant differences between both drugs. Concerning LDF recordings, we noted at the histamine administration site an increase in perfusion unit (PU) values which is an effect known to be in proportion to the degree of inhibition of wheal reaction, and at 1 cm distal to the histamine administration site, there was a decrease in PU values. These changes were more marked under cetirizine. A greater suppressive effect of cetirizine on the wheal and flare reaction was consistently observed at all time points during the study, demonstrating its superior efficacy. We conclude that (1) cetirizine demonstrated a stronger antihistaminic effect compared to ebastine at all time points; (2) iontophoresis appears to be an appropriate method to study specific microvascular changes at the delivery site of histamine and hence to detect the earliest changes occurring at the site of agonist-antagonist competition in the skin.",2000.0,0,1
303,9764958,Prescription-event monitoring--recent progress and future horizons.,R D Mann,,1998.0,0,0
304,9786037,[Accidental cetirizine poisoning in a four-year-old boy].,J J Hansen; N H Feilberg Jørgensen,"Cetirizine is a commonly used non-sedating antihistamine for the symptomatic relief of allergic reactions. Few reports exist on the result of overdose in children. We would like to report the result of a 12 fold overdose of cetirizine in a four-year-old-boy (weight 20 kg) who accidentally ingested 60 mg. Vomiting was induced 1 1/2 hour after ingestion in the out-patient clinic at the local hospital because of severe drowsiness. Due to continued lethargy he was transferred to the referral paediatric department for further observation. He was fully recovered after five to six hours without any treatment. Electrocardiographic monitoring was normal. Five incidents of cetirizine overdose in children have been reported previously. Drowsiness and sedation were observed, but no other side effects. The risk of cardiac events related to an overdose of cetirizine is extremely small. A certain degree of sedation is to be expected.",1998.0,0,0
305,9788685,Efficacy and safety relative to placebo of an oral formulation of cetirizine and sustained-release pseudoephedrine in the management of nasal congestion.,F Horak; J Toth; B Marks; U P Stübner; U E Berger; S Jäger; B Burtin; C Duby,"The aim of this study was to assess the clinical efficacy of an oral formulation of cetirizine 5 mg with sustained-release pseudoephedrine (PSE) 120 mg relative to placebo in patients with nasal congestion. Twenty-four patients with perennial rhinitis due to house-dust-mite (HDM) allergy were recruited in this crossover study. A treatment period of 1 week, in which cetirizine/PSE was administered twice daily, was followed by a washout period of at least 2 weeks and a further period of 1 week in which the alternative treatment was given to each patient. Immediately after the first dose of each medication (day 1), nasal congestion and related symptoms were assessed during a 7-h challenge with HDM feces, with the Vienna Challenge Chamber (VCC), to investigate onset of action of the preparation. A second challenge of 3-h duration, carried out at least 12 h after the final dose, was undertaken after 1 week (mean) of twice-daily treatment to assess residual effects of the formulation after achievement of steady state. The oral formulation of cetirizine/PSE was significantly (P<0.001) superior to placebo in improving nasal obstruction during both challenges. The improvement in nasal airflow and nasal patency was significantly greater with cetirizine/PSE than with placebo (P<0.02). In addition, subjective assessment of nasal symptoms showed that cetirizine/PSE was significantly superior to placebo in both challenges for the sum of nasal obstruction scores (P<0.01). Both medications were well tolerated, and no serious adverse events occurred during the study. In this study, cetirizine/PSE relieved nasal congestion and other objective and subjective symptoms to a significantly greater extent than placebo. No serious adverse events occurred, and both regimens were equally well tolerated.",1998.0,0,0
306,9806113,Mometasone furoate. A review of its intranasal use in allergic rhinitis.,S V Onrust; H M Lamb,"Mometasone furoate is a synthetic corticosteroid which has been evaluated for intranasal use in the treatment of adults and children with allergic rhinitis. In several large, well-controlled clinical trials, mometasone furoate 200 micrograms administered once daily as an aqueous intranasal spray was significantly more effective than placebo in controlling the symptoms associated with moderate to severe seasonal or perennial allergic rhinitis. Mometasone furoate was as effective as twice-daily beclomethasone dipropionate or once-daily fluticasone propionate in the treatment of perennial allergic rhinitis, and was as effective as twice-daily beclomethasone dipropionate and slightly more effective than once-daily oral loratadine in the treatment of seasonal allergic rhinitis. Mometasone furoate was also as effective as twice-daily beclomethasone dipropionate or once-daily budesonide, and significantly more effective than placebo in the prophylaxis of seasonal allergic rhinitis. The onset of action of mometasone furoate was approximately 7 hours in patients with seasonal allergic rhinitis. Mometasone furoate was as well tolerated as beclomethasone dipropionate, fluticasone propionate and budesonide in clinical trials, with an overall incidence of adverse events similar to placebo. Adverse events were generally mild to moderate and of limited duration. The most common adverse events associated with mometasone furoate therapy were nasal irritation and/or burning, headache, epistaxis and pharyngitis. Intranasal or oral mometasone furoate had no detectable effect on hypothalamic-pituitary-adrenal axis function in studies of < or = 1 year in duration. Mometasone furoate is a well tolerated intranasal corticosteroid with minimal systemic activity and an onset of action of < or = 7 hours. It is effective in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in patients with moderate to severe symptoms.",1998.0,0,0
307,9818712,Dose proportionality and comparison of single and multiple dose pharmacokinetics of fexofenadine (MDL 16455) and its enantiomers in healthy male volunteers.,D K Robbins; M A Castles; D J Pack; V O Bhargava; S J Weir,"The pharmacokinetics and dose proportionality of fexofenadine, a new non-sedating antihistamine, and its enantiomers were characterized after single and multiple-dose administration of its hydrochloride salt. A total of 24 healthy male volunteers (31 +/- 8 years) received oral doses of 20, 60, 120 and 240 mg fexofenadine HCl in a randomized, complete four-period cross-over design. Subjects received a single oral dose on day 1, and multiple oral doses every 12 h on day 3 through the morning on day 7. Treatments were separated by a 14-day washout period. Serial blood and urine samples were collected for up to 48 h following the first and last doses of fexofenadine HCl. Fexofenadine and its R(+) and S(-) enantiomers were analysed in plasma and urine by validated HPLC methods. Fexofenadine pharmacokinetics were linear across the 20-120 mg dose range, but a small disproportionate increase in area under the plasma concentration-time curve (AUC) (< 25%) was observed following the 240 mg dose. Single-dose pharmacokinetics of fexofenadine were predictive of steady-state pharmacokinetics. Urinary elimination of fexofenadine played a minor role (10%) in the disposition of this drug. A 63:37 steady-state ratio of R(+) and S(-) fexofenadine was observed in plasma. This ratio was essentially constant across time and dose. R(+) and S(-) fexofenadine were eliminated into urine in equal rates and quantities. All doses of fexofenadine HCl were well tolerated after single and multiple-dose administration.",2000.0,0,0
308,9930595,In vivo and ex vivo inhibitory effects of loratadine on histamine release in patients with allergic rhinitis.,A Miadonna; M Cottini; N Milazzo; D Tosi; M Danzig; A Tedeschi,"The aim of this study was to evaluate the in vivo and ex vivo effects of the H1-antagonist loratadine on histamine release. The study was designed as a double-blind, crossover trial. Ten patients with allergic rhinitis due to Dermatophagoides pteronyssinus were treated with loratadine (10 mg daily p.o.) and with placebo for 1 week, with a 2-week interval between the two treatments. Nasal lavages with saline solution were done before and after challenge with the relevant allergen at the end of treatments with loratadine and placebo. Venous blood was taken after treatments, and basophil histamine release induced by anti-IgE (10 microg/ml), N-formyl-methionyl-leucyl-phenylalanine (fMLP, 1 microM), and Ca2+ ionophore A23187 (1 microM) was evaluated by an automated fluorometric method. Treatment with loratadine attenuated early antigen-induced nasal obstruction, rhinorrhea, and itching. Nasal symptoms were accompanied by a significant histamine release in the nasal lavages collected 5 min after stimulation when the patients received placebo (median 4 ng/ml, range 1-28; P < 0.05). After treatment with loratadine, histamine release in the 5-min postchallenge lavages was almost abrogated (median 0.5 ng/ml, range 0-3; P < 0.01 vs placebo). Median anti-IgE-induced histamine release from basophils was 41.9% (range 27.8-79.2) after placebo and 30.0% (range 1.7-73.3, P < 0.05) after loratadine. Active treatment exerted an inhibitory effect also on basophil histamine release induced by fMLP and Ca2+ ionophore A23187. Treatment for 1 week with loratadine reduces allergen-induced nasal symptoms and inhibits in vivo and ex vivo histamine release in patients with allergic rhinitis.",1999.0,0,1
309,9934406,Comparative study between fluticasone propionate and cetirizine in the treatment of allergic rhinitis.,F P D'Ambrosio; S Gangemi; R A Merendino; A Arena; L Ricciardi; G F Bagnato,"Among the most frequently used drugs in the treatment of allergic rhinitis we have to mention topical nasal corticosteroids and H1 antihistamines used both systemically and topically. The present study focused the effectiveness and tolerability of cetirizine and fluticasone propionate in seasonal allergic rhinitis. 54 patients, divided into three homogeneous groups, underwent the following different treatments: Group 1: Placebo of fluticasone (2 puff per nostril once daily by aerosol) + cetirizine (10 mg/die per os) for 60 days. Group 2: Fluticasone (100 mg per nostril once daily by aerosol) + placebo of cetirizine (per os) for 60 days. Group 3: Cetirizine (10 mg/die per os) for 60 days + fluticasone (100 mg per nostril once daily by aerosol) for 20 days. The patients reported nasal symptoms (sneezing, obstruction, itching, rhinorrea) on a clinical diary. ECP levels in nasal secretions were investigated in all patients to determine the anti-inflammatory activity of both treatments. Cetirizine resulted very effective in the treatment of sneezing, itching and acqueous rhinorrea whereas not much effective on nasal obstruction. On the contrary, fluticasone, which acted effectively on nasal obstruction, resulted inefficacious on the other symptoms. The third group of patients achieved the best results on all four symptoms, including obstruction, which continued even after interrupting the treatment with fluticasone. The ECP levels were significantly reduced by both treatments. The side effects in all 3 groups were rare and not serious. From these results we can assert that the synergic action of the two drugs, achieves the best effectiveness, that the fluticasone treatment can be limited to 20 days cycles and finally that both molecules are well tolerated.",1999.0,0,0
310,9951950,Second-generation antihistamines: a comparative review.,J W Slater; A D Zechnich; D G Haxby,"Second-generation histamine H1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adverse effects that occur with older H1 receptor antagonists. This article evaluates second-generation antihistamines, including acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mizolastine and terfenadine, for significant features that affect choice. In addition to their primary mechanism of antagonising histamine at the H1 receptor, these agents may act on other mediators of the allergic reaction. However, the clinical significance of activity beyond that mediated by histamine H1 receptor antagonism has yet to be demonstrated. Most of the agents reviewed are metabolised by the liver to active metabolites that play a significant role in their effect. Conditions that result in accumulation of astemizole, ebastine and terfenadine may prolong the QT interval and result in torsade de pointes. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis, all agents are effective and the choice should be based on other factors. For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare at the dosages recommended by the manufacturer. For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although current evidence does not suggest a primary role for these agents in the management of asthma, it does support their use for asthmatic patients when there is coexisting allergic rhinitis, dermatitis or urticaria.",1999.0,0,1