Adverse Effects Drug Interactions and Contraindications

Dyspepsia is the most common side effect of zileuton. Liver transaminase levels are elevated in a small percentage of patients taking zileuton. Serum liver transaminase levels should be monitored and treatment halted if significant elevations occur. Zileuton inhibits the metabolism of theophylline. Thus, when these agents are used concomitantly, the dose of theophylline should be reduced by approximately one-half, and plasma concentrations of theophylline should be monitored closely. Caution should also be exercised when using zileuton concomitantly with warfarin, terfenadine, or propranolol, as zileuton inhibits the metabolism of these agents. Zileuton is contraindicated in patients with acute liver disease and should be used with caution in patients who consume substantial quantities of alcohol or have a history of liver disease.

Zafirlukast and montelukast are well tolerated. Zafirlukast increases plasma concentrations of warfarin and decreases the concentrations of theophylline and erythromycin. In rare cases, treatment of patients with CysLT receptor antagonists is associated with the development of Churg-Strauss syndrome, a condition marked by acute vasculitis, eosinophilia, and a worsening of pulmonary symptoms. Because these symptoms often appear when patients are given the leukotriene receptor antagonists when they are being weaned from oral corticosteroid therapy, it is not clear whether they are related to the action of the antagonists or are due to a sudden reduction in corticosteroid therapy.

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