Leukotriene Receptor Antagonists

Marzena E. Krawiec, MD, Nizar J. Jarjour, MD

Disclosures

Semin Respir Crit Care Med. 2002;23(4) 

In This Article

Safety

The LTRAs are generally safe and well-tolerated agents. The majority of clinical trials in both adults and children have consistently demonstrated a low incidence of mild adverse effects compared with placebo. Because zafirlukast is hepatically metabolized through the p450 system, this drug may interfere with the metabolism of certain drugs such as warfarin. Other drugs with similar metabolism may require serum monitoring. Mild gastrointestinal discomfort has been primarily reported with zafirlukast compared with montelukast. Based on its metabolism, liver transaminases should be measured at the start and monthly for the first 3 months during zafirlukast therapy, and then quarterly.

An association between the LTRAs and Churg-Strauss syndrome, a disorder first describe in 1951 by Jacob Churg and Lotte Strauss consisting of a constellation of symptoms and clinical findings including pulmonary infiltrates, eosinophilia, and cardiomyopathy, has been reported in several isolated adult case studies. There are no reports in children. Wechsler and colleagues reported a total of eight cases in difficult-to-control asthmatics with zafirlukast[102] and four with montelukast,[103] all of which were concurrent with withdrawal from frequent IV, oral, or high-dose ICS. Similar reports have been generated concerning pranlukast in Japan.[104] Of note, several cases have also been reported with various ICS therapies.[105,106] This disorder appears to often be associated with the unmasking of underlying eosinophilic disorders following corticosteroid tapering and/or withdrawal, but it remains unclear whether LTRAs can also have a primary effect. In general, Wechsler and colleagues estimate that the incidence of Churg-Strauss syndrome in association with LT modifiers was approximately 60 cases per million patient-years. Because of the potential association, the use of cysLTRAs in more severe, steroid-dependent patients should be accompanied by intermittent evaluation of blood eosinophils.

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