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Churg-Strauss syndrome has been reported in 6 patients who were being withdrawn from oral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.