Cysteinyl-
leukotrienes are important mediators in the pathogenesis of
asthma.
Zafirlukast is a selective and competitive
leukotriene receptor antagonist that has been developed for the treatment of
asthma. It inhibits
exercise-induced asthma, both the early- and late-phase response after
allergen challenge in asthmatic subjects, and
aspirin-induced asthma in
aspirin-sensitive asthmatic patients. Published data indicate that
zafirlukast 20 mg twice daily causes an improvement in lung function (FEV(1) and peak expiratory flow measurements) and symptom control, together with a reduction in the use of short-acting beta-agonist inhaled
therapy in patients with mild to moderate
asthma. Studies presented in abstract form have shown that
zafirlukast 20 mg twice daily had similar efficacy as
sodium cromoglycate aerosol or dry
powder inhalation; in one of the studies, no advantage of the active drugs was reported over placebo. Compared to inhaled
beclomethasone dipropionate therapy (200-250 microg b.i.d.), improvements in morning peak flow, FEV(1) and daytime symptom score were significantly less with
zafirlukast 20 mg twice daily than with inhaled
steroids. A
steroid-sparing effect of
zafirlukast (20 mg b.i.d.) was not observed in studies of 12-20 weeks duration in patients on inhaled
steroid therapy. A significant improvement in lung function and symptom control was observed on addition of
zafirlukast 80 mg twice daily in symptomatic patients maintained on high-dose inhaled
steroid therapy. Meta-analysis of 5 large studies indicate that there is a significant reduction in the number of
asthma exacerbations compared to placebo.
Zafirlukast at 20 mg twice daily dosage appears to be well-tolerated comparable to placebo. High doses of 80 mg twice daily have been associated with reports of elevated liver
enzymes.
Zafirlukast is a useful addition to existing antiasthma
therapies. It may be used in combination with inhaled or oral
corticosteroid therapy. Further investigation of its efficacy and antiinflammatory effects will clarify its use as a first-line
antiinflammatory agent in mild
asthma.
Zafirlukast is administered orally and may therefore be useful in patients poorly compliant with inhaled
steroid therapy and with a poor
inhaler technique.