ZAFIRLUKAST - A REVIEW OF ITS PHARMACOLOGY AND THERAPEUTIC POTENTIAL IN THE MANAGEMENT OF ASTHMA

Zafirlukast is a competitive and selective leukotriene receptor antago nist indicated for the prophylaxis and treatment of chronic asthma. Th e rationale for the development of leukotriene antagonists was based o n in vitro and in vivo data demonstrating the extensive role of the cy steinyl leukotrienes C-4 (LTC4), D-4 (LTD4) and E-4 (LTE4) in the path ogenesis of asthma. Initial data have demonstrated an improvement in p ulmonary function and symptom control and a reduction in the use of sh ort-acting inhaled beta(2)-adrenoceptor agonist therapy in patients wi th mild to moderate asthma treated with oral zafirlukast at the recomm ended dosage of 20mg twice daily. Available data also suggest that zaf irlukast may significantly reduce the incidence of asthma exacerbation s. Data on the comparative efficacy of zafirlukast and existing antias thma medications are limited. Results from 2 double-blind randomised s tudies comparing zafirlukast 20mg twice daily with sodium cromoglycate aerosol or dry powder inhalation reported similar efficacy for both d rugs. In a comparison with inhaled beclomethasone dipropionate (0.2 to 0.25mg twice daily), improvements in morning peak expiratory flow rat e, forced expiratory volume in 1 second and daytime symptom score were significantly less with zafirlukast 20mg twice daily for 6 weeks. How ever, available data suggest that patient compliance and patient prefe rence may be greater with oral zafirlukast 20mg twice daily than with twice-daily inhaled corticosteroid therapy. Confounding results from 2 studies preclude any clear conclusions regarding the potential steroi d-sparing effect of zafirlukast at the recommended dosage of 20mg twic e daily. Furthermore, Churg-Strauss syndrome has been reported in 6 pa tients who were being withdrawn from oral corticosteroid therapy while receiving treatment with oral zafirlukast. It is, therefore, recommen ded that zafirlukast-treated patients who require a reduction in their oral corticosteroid therapy are closely monitored. Zafirlukast is gen erally well tolerated. Reports of elevated liver enzymes in patients r eceiving high dosages of zafirlukast (80mg twice daily) preclude the u se of dosages exceeding 40mg twice daily. Careful monitoring is necess ary in zafirlukast-treated patients receiving concomitant therapy with drugs such as warfarin, terfenadine and erythromycin because of the p otential for drug interactions. Thus, zafirlukast is a potentially use ful 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 ther apy as a result of poor inhaler technique. Further investigation of th e efficacy of zafirlukast is expected to more clearly define its posit ion in the management of asthma.