Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

The international WAO/EAACI guideline for the management of hereditary angioedema-The 2017 revision and update.

Hereditary Angioedema (HAE) is a rare and disabling disease. Early diagnosis and appropriate therapy are essential. This update and revision of the global guideline for HAE provides up-to-date consensus recommendations for the management of HAE. In the development of this update and revision of the guideline, an international expert panel reviewed the existing evidence and developed 20 recommendations that were discussed, finalized and consented during the guideline consensus conference in June 2016 in Vienna. The final version of this update and revision of the guideline incorporates the contributions of a board of expert reviewers and the endorsing societies. The goal of this guideline update and revision is to provide clinicians and their patients with guidance that will assist them in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2). The key clinical questions covered by these recommendations are: (1) How should HAE-1/2 be defined and classified?, (2) How should HAE-1/2 be diagnosed?, (3) Should HAE-1/2 patients receive prophylactic and/or on-demand treatment and what treatment options should be used?, (4) Should HAE-1/2 management be different for special HAE-1/2 patient groups such as pregnant/lactating women or children?, and (5) Should HAE-1/2 management incorporate self-administration of therapies and patient support measures?

Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial.

Hereditary angioedema (HAE) is characterized by potentially life-threatening recurrent episodes of oedema. The open-label extension (OLE) phase of the For Angioedema Subcutaneous Treatment (FAST)-1 trial (NCT00097695) evaluated the efficacy and safety of repeated icatibant exposure in adults with multiple HAE attacks. Following completion of the randomized, controlled phase, patients could receive open-label icatibant (30 mg subcutaneously) for subsequent attacks. The primary end-point was time to onset of primary symptom relief, as assessed by visual analogue scale (VAS). Descriptive statistics were reported for cutaneous/abdominal attacks 1-10 treated in the OLE phase and individual laryngeal attacks. Post-hoc analyses were conducted in patients with ≥ 5 attacks across the controlled and OLE phases. Safety was evaluated throughout. During the OLE phase, 72 patients received icatibant for 340 attacks. For cutaneous/abdominal attacks 1-10, the median time to onset of primary symptom relief was 1·0-2·0 h. For laryngeal attacks 1-12, patient-assessed median time to initial symptom improvement was 0·3-1·2 h. Post-hoc analyses showed the time to onset of symptom relief based on composite VAS was consistent across repeated treatments with icatibant. One injection of icatibant was sufficient to treat 88·2% of attacks; rescue medication was required in 5·3% of attacks. No icatibant-related serious adverse events were reported. Icatibant provided consistent efficacy and was well tolerated for repeated treatment of HAE attacks.

Efficacy and safety of desloratadine/pseudoephedrine combination vs its components in seasonal allergic rhinitis.

BACKGROUND: Antihistamines are first-line therapy for the treatment of seasonal allergic rhinitis (AR); however, an oral decongestant is often added to improve control of nasal congestion. OBJECTIVE: To examine whether a tablet combining the nonsedating antihistamine desloratadine and the decongestant pseudoephedrine was more effective than either drug administered alone in reducing the symptoms of seasonal AR, including nasal congestion. PATIENTS AND METHODS: In this multicenter, double-blind study, participants (N = 598) with symptomatic seasonal AR were administered either a combination tablet of desloratadine 2.5 mg/pseudoephedrine 120 mg (DL/PSE) bid, a desloratadine 5.0 mg qd and a placebo tablet, or pseudoephedrine 120 mg bid. Participants assessed their symptom severity twice daily over the 2-week treatment period. RESULTS: The primary variable to assess the effects of the antihistamine component--mean change from baseline in average AM/PM reflective total symptom score (TSS), excluding nasal congestion--was significantly greater (-6.54) for DL/PSE than for desloratadine (-5.09) or pseudoephedrine (-5.07) monotherapy (P < .001 for both). The primary variable to assess the effects of the decongestant component--mean change from baseline in average AM/PM reflective nasal congestion score--was also significantly greater (-0.93) for DL/PSE than for desloratadine (-0.66) or pseudoephedrine (-0.75) (P < .001 vs desloratadine; P = .006 vs pseudoephedrine). CONCLUSION: This study demonstrated that DL/PSE therapy was more effective in reducing symptoms of seasonal AR, including nasal congestion, than the individual components when administered alone, thus supporting use of this combination in participants with symptomatic seasonal AR and prominent nasal congestion.

Once-daily budesonide via Turbuhaler improves symptoms in adults with persistent asthma.

BACKGROUND: Previous studies have demonstrated the efficacy and safety of twice-daily budesonide Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Wilmington, DE) for the treatment of mild to severe asthma. OBJECTIVE: To compare the efficacy and safety of budesonide Turbuhaler administered once daily each morning with placebo in inhaled corticosteroid-naive adults with persistent asthma. METHODS: In this randomized, double-blind, placebo-controlled, multicenter study, 177 adults (aged 18 to 70 years) received placebo or once-daily budesonide Turbuhaler (400 microg) for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1) and AM/PM peak expiratory flow rate (PEFR), and nighttime/daytime asthma symptom scores, patient discontinuations, use of breakthrough medication (albuterol), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), and quality of life assessments. Safety was evaluated based on adverse events, physical examinations, vital signs, and laboratory tests. RESULTS: Demographic and baseline characteristics were comparable between study groups. The mean percentages of predicted FEV1 at baseline were 71.9 +/- 9.8 in patients receiving budesonide Turbuhaler and 70.6 +/- 11.0 in patients receiving placebo. Mean changes from baseline over the 12-week treatment period in FEV1 were significantly (P = 0.007) improved in patients receiving once-daily budesonide Turbuhaler compared with placebo (0.31 L and 0.17 L, respectively). Significant (P < or = 0.037) improvements over placebo also were observed in AM PEFR, nighttime/daytime asthma symptoms, and albuterol use with budesonide Turbuhaler treatment. Adverse events were generally mild or moderate in intensity and similar between study groups. CONCLUSIONS: Budesonide Turbuhaler 400 microg administered once daily in the AM is efficacious and safe for inhaled corticosteroid-naive asthmatic adults.

Switching from Ventolin CFC to Ventolin HFA is well tolerated and effective in patients with asthma.

BACKGROUND: Environmental imperatives to eliminate the use of chlorofluorocarbon (CFC) propellants in metered-dose inhalers have led to the development of metered-dose inhalers with the hydrofluoroalkane (HFA-134a) propellants. OBJECTIVES: To evaluate the clinical effect of switching from Ventolin CFC to Ventolin HFA and to compare the efficacy and safety of Ventolin CFC, Ventolin HFA, and placebo in patients with asthma. METHODS: Multicenter, double-blind, randomized safety and efficacy trial comparing regular use of Ventolin CFC versus Ventolin HFA versus placebo for 12 weeks in 313 patients with asthma aged 12 years and older who received Ventolin CFC during a 3-week run-in period. RESULTS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained pulmonary function and other measures of asthma control at levels comparable with run-in baseline. Serial pulmonary function testing demonstrated that both Ventolin treatments had significantly greater mean improvement in FEV1 over baseline than the placebo group at treatment day 1 and weeks 6 and 12 (P < .001). Both Ventolin groups had comparable pulmonary function at every visit. Predose FEV1 values were maintained or improved over time with all treatments. Treatments were well-tolerated. The adverse event profile for both Ventolin treatments was comparable with placebo. No clinically relevant effects on ECG, vital signs, or clinical laboratory tests were noted. Asthma exacerbation rates were 4% to 5% in the Ventolin groups and slightly higher (8%) in the placebo group. CONCLUSIONS: Patients who were switched from Ventolin CFC to Ventolin HFA maintained comparable asthma control with a similar safety profile.

A randomized, 12-week, double-blind, placebo-controlled study comparing formoterol dry powder inhaler with albuterol metered-dose inhaler.

BACKGROUND: Formoterol is a beta2-adrenergic agent which, when inhaled, produces rapid and long-lasting bronchodilatation. OBJECTIVE: The aim of this study was to compare the efficacy, safety, and tolerability of formoterol powder for inhalation delivered via the Aerolizer device with placebo and with albuterol delivered via metered-dose inhaler in patients with mild to moderate persistent asthma. METHODS: In a multicenter, double-blind, parallel-group study, 541 patients were randomized at 26 trial sites to receive either formoterol, 12 microg twice daily; formoterol, 24 microg twice daily; albuterol, 180 microg four times daily; or a placebo for 12 weeks. The effects of each treatment on lung function, asthma symptoms, and frequency of rescue albuterol use were evaluated. Adverse effects and clinical laboratory parameters were also evaluated. RESULTS: The bronchodilatory effects of formoterol were rapid in onset and persisted for 12 hours. Both formoterol doses were more effective than placebo and albuterol for objective measures of lung function. Morning and evening peak expiratory flow rates were more improved with formoterol, and formoterol provided significantly greater improvements in asthma symptom scores compared with both albuterol and placebo. Overall, patients taking formoterol used significantly less rescue medication than did those taking albuterol or placebo. Nocturnal awakenings occurred less often with formoterol than with placebo or albuterol. The therapeutic effects of formoterol were maintained over the entire 12 weeks of treatment. Adverse events were similar for all treatment groups, and clinical laboratory data were unremarkable. CONCLUSIONS: Rapid-onset, long-acting formoterol, administered via the Aerolizer inhaler, is an effective and safe treatment for patients with mild to moderate persistent asthma.

Once-daily mometasone furoate dry powder inhaler in the treatment of patients with persistent asthma.

BACKGROUND: Although inhaled glucocorticoids are recommended for all stages of persistent asthma, compliance with long-term therapy is often poor, leading to significant morbidity and mortality. A simplified, once-daily dosing regimen may foster improved compliance. OBJECTIVE: To compare the efficacy and safety of once-daily (AM) administration of mometasone furoate dry powder inhaler (MF DPI) 200 microg and 400 microg with placebo in patients with asthma previously maintained only on short-acting inhaled beta-adrenergic receptor agonists. METHODS: This was a 12-week, double-blind, placebo-controlled, parallel group study. The mean change from baseline to endpoint (last treatment visit) for FEV1 was the primary efficacy variable. RESULTS: At endpoint, both doses of MF DPI were significantly more effective than placebo (P < or = .05) in improving FEV1. Based on morning peak expiratory flow rate, once-daily MF DPI 400 microg was more effective than placebo (P < or = .001) at endpoint. Both active treatments also demonstrated improvement at endpoint in asthma symptom scores, physician-evaluated response to therapy and use of rescue medication. Although both MF DPI dosages were efficacious, MF DPI 400 microg provided additional improvement in some measures of pulmonary function (eg, morning PEFR) when these agents were administered once daily in the morning. Both doses of MF DPI were well tolerated and treatment-related adverse events occurred at a similar incidence among the three treatment groups. CONCLUSIONS: The results of this study indicate that once-daily (AM) MF DPI provides a convenient and effective treatment option for patients with mild or moderate persistent asthma.

Combined salmeterol 50 microg and fluticasone propionate 250 microg in the diskus device for the treatment of asthma.

Three hundred forty-nine patients with asthma previously treated with medium doses of inhaled corticosteroids during a 2-wk, single-blind, run-in period were randomized to treatment with salmeterol 50 microg combined with fluticasone propionate (FP) 250 microg, salmeterol 50 microg, FP 250 microg, or placebo, each given twice daily through a Diskus device for 12 wk. Mean change in FEV(1) at endpoint was significantly (p

A review of the preclinical and clinical data of newer intranasal steroids used in the treatment of allergic rhinitis.

The anti-inflammatory activity of corticosteroids has prompted the exploration of their use in the treatment of allergic rhinitis. The development of intranasal steroids has resulted in several agents with quick actions, localized effects, and great efficacy in the treatment of seasonal allergic rhinitis and the prophylactic management of perennial rhinitis. This article presents a concise review of the preclinical and clinical evidence with these new agents and provides data-based guidance for the selection of optimal agents. The survey reveals that mometasone furoate, a new inhaled steroid with topical activity, has the greatest binding affinity for the glucocorticoid receptor, followed by fluticasone propionate, budesonide, triamcinolone acetonide, and dexamethasone. Mometasone furoate also has strong anti-inflammatory activity, with IL-4 and IL-5 inhibition activities equivalent to those of fluticasone propionate. Clinically, both mometasone furoate and fluticasone propionate appear to be well tolerated, to have quick onsets of action, and to be equivalent in efficacy in the treatment of seasonal allergic and perennial rhinitis. Of the intranasal steroids currently available, mometasone furoate has been shown to have the least systemic availability and, consequently, is expected to have the fewest systemic side effects. Some suppression of overnight cortisol levels has been reported with fluticasone propionate (indicative of hypothalamic-pituitary-adrenal axis suppression).

Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.

A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.

Efficacy, safety, and effects on quality of life of salmeterol versus albuterol in patients with mild to moderate persistent asthma.

BACKGROUND: Salmeterol xinafoate is a long-acting, highly selective, beta2-adrenergic agonist that produces bronchodilation and clinically significant improvement in pulmonary function for up to 12 hours in patients with asthma. OBJECTIVE: To evaluate the impact on asthma-specific quality of life, efficacy, and safety of salmeterol versus albuterol in adult patients with mild-to-moderate persistent asthma. METHODS: A randomized, double-blind, double-dummy, parallel-group, multicenter study was conducted in 539 adult asthma patients over 12 weeks. Patients were randomized to receive either salmeterol 42 microg via metered-dose inhaler twice daily or albuterol 180 microg four times daily. Upon entry into the study, 46% of patients were being treated with an inhaled corticosteroid and were allowed to continue treatment throughout the study. Pulmonary function and asthma symptoms were monitored daily, and patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Treatment with salmeterol twice daily produced significantly greater improvements from baseline in all quality of life domain ("Activity Limitation," "Asthma Symptoms," "Emotional Function," "Environmental Exposure") scores and in the global AQLQ score at 12 weeks (P < or = .038) compared with albuterol treatment four times daily. Pulmonary function and asthma symptoms were also significantly improved with salmeterol compared with albuterol. CONCLUSIONS: Salmeterol 42 microg administered twice daily is significantly more effective than albuterol 180 microg four times daily for improving asthma-specific quality of life, controlling asthma symptoms, and improving pulmonary function in patients with mild-to-moderate persistent asthma. Furthermore, those improvements were maintained over a 12-week period.

Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma.

BACKGROUND: Airway inflammation is a hallmark of asthma, therefore current treatment recommendations include the use of inhaled glucocorticosteroids (GCS). However, there is little evidence that the effects of inhaled GCS are dose dependent. OBJECTIVES: The objective of this study was to assess the efficacy and safety of a second-generation GCS, budesonide, delivered by Turbuhaler, in adults with chronic asthma. METHODS: In a 12-week, randomized, double-blind, multicenter, parallel-group study, 473 subjects 18 to 70 years of age received either placebo or budesonide (200, 400, 800, or 1600 microg total daily dose) administered twice daily. Primary efficacy end points were mean change from baseline for FEV1 and morning peak expiratory flow. Safety was assessed by reported adverse events and by a cosyntropin-stimulation test. RESULTS: The mean baseline FEV1 was 63% to 66% of predicted normal value between groups. All doses of budesonide were more effective than placebo (p < 0.001). The mean changes in morning peak expiratory flow were 12, 22, 27, and 30 L/min in the 200, 400, 800, and 1600 microg budesonide total daily dose groups, respectively, and -27 L/min for the placebo group. A statistically significant dose-response effect for the mean change from baseline over the 12-week study was seen for both morning peak expiratory flow and FEV1. Budesonide-treated subjects also demonstrated significant reduction in asthma symptoms and bronchodilator use compared with placebo. There were no clinically significant differences in treatment-related adverse experiences among groups. CONCLUSIONS: Budesonide administered by Turbuhaler exhibited a dose response and was effective at low doses. It was well tolerated and significantly more effective than placebo.

Tri-Nasal triamcinolone acetonide nasal spray 200 and 400 micrograms qd versus placebo and Nasacort triamcinolone acetonide nasal aerosol 440 micrograms qd in patients suffering from seasonal allergic rhinitis during the grass season.

Tri-Nasal Nasal Spray is an investigational solution of triamcinolone acetonide (TAA) currently being evaluated as a treatment for allergic rhinitis. The safety and efficacy of 200 and 400 micrograms once daily doses of Tri-Nasal Nasal Spray, an active control (440 micrograms once daily of Nasacort Nasal aerosol), and Tri-Nasal Nasal Spray placebo were compared over a 2-week treatment period in a double-blind (the Nasacort treatment was not blinded), parallel design trial. A total of 377 adult patients in 13 centers were enrolled during the grass pollen season. The primary efficacy variable was the weekly average of the SSI (Symptom Severity Index), the sum of daily nasal congestion, rhinorrhea, and sneezing severity scores from the patient diary. A total of 355 patients completed the study. All active treatments were significantly more effective than placebo in relieving nasal symptoms at each treatment week. The 400 micrograms Tri-Nasal Nasal Spray and Nasacort treatments had a rapid onset of action, demonstrating significant improvement in the SSI versus placebo by the second day of treatment. Results for the individual nasal symptoms and other secondary efficacy measures paralleled those of the primary efficacy variables. Tri-Nasal Nasal Spray and Nasacort were comparable in safety, and in treating the nonocular symptoms of seasonal allergic rhinitis.

Ipratropium bromide nasal spray 0.03% provides additional relief from rhinorrhea when combined with terfenadine in perennial rhinitis patients; a randomized, double-blind, active-controlled trial.

Medical treatment of perennial rhinitis is aimed at providing symptomatic relief of individual symptoms. Multiple agents are administered when no single agent provides complete relief. Studies assessing the benefit/risk of combined therapy are important, especially for newly available agents such as ipratropium bromide nasal spray, a topical anticholinergic agent approved for the treatment of rhinorrhea in allergic and nonallergic perennial rhinitis. The objective was to determine whether the combined use of ipratropium bromide nasal spray 0.03% (42 mcg per nostril) administered three times daily with a nonsedating antihistamine (terfenadine, 60 mg administered twice daily) is safe and provides greater clinical benefit than use of the placebo nasal spray plus terfenadine. Our method was a multicenter, 6-week, double-blind, randomized, active-controlled, crossover trial of 205 patients with perennial rhinitis (114 allergic and 91 nonallergic), 18 to 75 years of age, who had clinically significant rhinorrhea. After a 1-week run-in period, patients were treated for 2 weeks with one of the two treatment regimens, followed by a 1-week washout period, and then were treated for another 2 weeks with the other treatment regimen. Daily diary symptoms scores of rhinorrhea, congestion, and sneezing were obtained, as well as biweekly patient and physician global assessments of treatment effectiveness of each of the nasal symptoms. Ipratropium bromide nasal spray plus terfenadine was more effective than vehicle plus terfenadine in reducing the average severity (38% versus 28%) and duration (46% versus 30%) of rhinorrhea during the 2 weeks of treatment from baseline (p < 0.05). The advantage of ipratropium bromide nasal spray plus terfenadine was evident by the second day of treatment and continued throughout the 2-week treatment period. Of patients who responded more to one treatment than another, 69% responded to ipratropium bromide nasal spray plus terfenadine, compared to 31% to vehicle plus terfenadine (p < 0.05). Both physicians and patients rated control of rhinorrhea and sneezing by ipratropium bromide nasal spray plus terfenadine as superior to vehicle plus terfenadine (p < 0.05). The symptom of congestion was controlled equally well by both treatments. Combined active therapy was well tolerated with no increase in adverse events over that seen previously with ipratropium bromide nasal spray alone. The combination of ipratropium bromide nasal spray with terfenadine is more effective than vehicle plus terfenadine for the treatment of rhinorrhea, and does not result in a potentiation of adverse drug reactions.

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.

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.

Comparative study of cetirizine and terfenadine versus placebo in the symptomatic management of seasonal allergic rhinitis.

BACKGROUND: Cetirizine is a new antihistamine with greater selectivity for the histamine H1 receptor and a low rate of hepatic metabolism. Cetirizine once daily is effective in the symptomatic treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria. OBJECTIVE: The efficacy and safety of cetirizine 10 mg qd, terfenadine 60 mg bid, and placebo were compared in patients with seasonal allergic rhinitis. METHODS: A multicenter, prospective, double-blind, randomized, parallel study was conducted for 2 weeks during the ragweed pollen season in patients with documented allergic rhinitis. Total symptom complex and total symptom complex plus nasal congestion scores, global efficacy, overall satisfaction, and adverse events were assessed at baseline and after 1 and 2 weeks of treatment. RESULTS: Of the 311 patients randomized to treatment, 283 completed the study. Cetirizine produced a marked improvement in symptoms scores compared with placebo after 1 week of therapy (P = .001). By the end of week 1, total symptom complex scores were improved by 37% with cetirizine compared with 29% for terfenadine, and 23% for placebo. An overall treatment effect was evident at week 1 (P = .0019), with marked differences between cetirizine and both placebo (P = .0004) and terfenadine (P = .0464) but not between terfenadine and placebo (P = .1215). A more marked treatment effect was evident during the first week of the study; this appeared to be related to spontaneous resolution of symptoms, since mean pollen counts derived for each patient declined significantly each week of the study. Therapy was generally well tolerated. Headache was the most common side effect in each group. Four patients on cetirizine, one on terfenadine, and two on placebo withdrew because of side effects. Somnolence was reported in 12 patients on cetirizine (P < .05), 2 on terfenadine, and 3 on placebo. CONCLUSION: Cetirizine produced a greater improvement in symptoms of seasonal allergic rhinitis than terfenadine or placebo.