Pulmonary Infiltrates, Eosinophilia, and Cardiomyopathy Following Corticosteroid Withdrawal in Patients With Asthma Receiving Zafirlukast

Abstract

ZAFIRLUKAST (Accolate) is a novel, potent, orally administered, competitive cysteinyl leukotriene type 1 (CysLT1) receptor antagonist approved in September 1996 for the treatment of mild to moderate asthma. In the clinical trials leading to approval by the US Food and Drug Administration, 6243 patients encompassing 2479 person-years of exposure received zafirlukast; the drug was well tolerated, causing adverse clinical events (headaches, infection, and nausea) and laboratory abnormalities (elevated liver function test results) at rates similar to those with placebo.¹ However, since its approval, zafirlukast has been widely used by a diverse population of asthma patients; an estimated 40000 patient-years of use accrued in the first 6 months of the drug's availability by prescription.² As use of the drug increases, adverse events that occur at low frequency or in populations not examined in clinical trials may become manifest. We describe 8 patients (1 of whom we describe in detail) with steroid-dependent asthma who, in the setting of asthma treatment with zafirlukast, were able to discontinue or taper oral corticosteroid treatment but subsequently developed a clinical syndrome consisting of pulmonary infiltrates, peripheral blood eosinophilia, and cardiomyopathy.