Side Effects of Leukotriene Modifiers
Modulation of leukotrienes is a novel path of pharmacologic intervention in asthma. The exact role of leukotriene modulation is in a state of evolution. Zafirlukast (ZFK) is an orally active leukotriene modulator with a favorable side effect profile as demonstrated in premarketing data. Larger population exposure post-marketing has disclosed previously unreported consequences, such as a syndrome of pulmonary infiltrates, eosinophilia, and cardiomyopathy in patients whose steroid dose was reduced or discontinued after the favorable steroid-sparing effects of ZFK. The authors review eight such cases.
Consistent among all cases was a marked level of eosinophilia (19-71%); indeed, the authors posit that the described syndrome may be one of disordered (exaggerated) eosinophil recruitment. Patients had been previously taking steroids, which would likely mask the toxic effects of eosinophils until the steroids were tapered or discontinued. Why the eosinophil derangement occurs is speculative, but the authors suggest mechanisms to include a vasculitis-like allergic reaction to ZFK, initially masked by concomitant steroid administration. Atypias from Churg-Strauss syndrome call into question an earlier hypothesis that steroid reduction was unmasking previously controlled Churg-Strauss. The authors acknowledge ZFK as a safe and effective medication for mild-moderate asthma, suggesting clinicians heighten their vigilance for untoward effects and monitor for rising eosinophil counts, pulmonary infiltrates, and cardiomyopathy in patients who have previously required oral corticosteroids.
Wechsler ME, et al. JAMA 1998;279: 455-457.
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