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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Zafirlukast. A review of its pharmacology and therapeutic potential in the management of asthma.

Zafirlukast is a competitive and selective leukotriene receptor antagonist indicated for the prophylaxis and treatment of chronic asthma. The rationale for the development of leukotriene antagonists was based on in vitro and in vivo data demonstrating the extensive role of the cysteinyl leukotrienes C4 (LTC4), D4 (LTD4) and E4 (LTE4) in the pathogenesis of asthma. Initial data have demonstrated an improvement in pulmonary function and symptom control and a reduction in the use of short-acting inhaled beta 2-adrenoceptor agonist therapy in patients with mild to moderate asthma treated with oral zafirlukast at the recommended dosage of 20 mg twice daily. Available data also suggest that zafirlukast may significantly reduce the incidence of asthma exacerbations. Data on the comparative efficacy of zafirlukast and existing antiasthma medications are limited. Results from 2 double-blind randomised studies comparing zafirlukast 20 mg twice daily with sodium cromoglycate aerosol or dry powder inhalation reported similar efficacy for both drugs. In a comparison with inhaled beclomethasone dipropionate (0.2 to 0.25 mg twice daily), improvements in morning peak expiratory flow rate, forced expiratory volume in 1 second and daytime symptom score were significantly less with zafirlukast 20 mg twice daily for 6 weeks. However, available data suggest that patient compliance and patient preference may be greater with oral zafirlukast 20 mg twice daily than with twice-daily inhaled corticosteroid therapy. Confounding results from 2 studies preclude any clear conclusions regarding the potential steroid-sparing effect of zafirlukast at the recommended dosage of 20 mg twice daily. Furthermore, Churg-Strauss syndrome has been reported in 6 patients who were being withdrawn from oral corticosteroid therapy while receiving treatment with oral zafirlukast. It is, therefore, recommended that zafirlukast-treated patients who require a reduction in their oral corticosteroid therapy are closely monitored. Zafirlukast is generally well tolerated. Reports of elevated liver enzymes in patients receiving high dosages of zafirlukast (80 mg twice daily) preclude the use of dosages exceeding 40 mg twice daily. Careful monitoring is necessary in zafirlukast-treated patients receiving concomitant therapy with drugs such as warfarin, terfenadine and erythromycin because of the potential for drug interactions. Thus, zafirlukast is a potentially useful addition to current antiasthma therapies in patients with mild to moderate asthma. Because zafirlukast is administered orally, it may be particularly beneficial in patients poorly compliant with asthma therapy as a result of poor inhaler technique. Further investigation of the efficacy of zafirlukast is expected to more clearly define its position in the management of asthma.[1]


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