Zileuton has recently been approved by the U.S. Food and Drug Administration (FDA) for prophylaxis and maintenance treatment of chronic asthma. Zileuton acts as an inhibitor of leukotriene synthesis. Neither zileuton nor zafirlukast, a new leukotriene receptor antagonist recently approved by the FDA, are recommended for the treatment of acute asthma. Consultants from the Medical Letter on Drugs and Therapeutics review the clinical data on zileuton.
Because leukotrienes are among the many mediators of inflammation, they are marketed as leukotriene synthesis inhibitors. Taken with or without food, zileuton is rapidly absorbed and reaches peak plasma concentrations in one to three hours. In clinical trials, pulmonary function significantly improved within one to two hours after administration. In other double-blind trials in patients with mild to moderate asthma, zileuton, 600 mg four times a day, was more effective than placebo in relieving symptoms and improving airway function. Other studies demonstrated that zileuton was more effective than placebo in controlling asthma symptoms and in preventing exacerbations of asthma that required treatment with oral corticosteroids. In patients using beta agonists, zileuton reduced the frequency of inhaler use and decreased the number of patients who needed to take corticosteroids. Given prophylactically, zileuton decreased aspirin-induced bronchospasm in aspirin-sensitive asthmatic patients and airway hyperresponsiveness to cold and exercise.
Adverse effects include an increase of alanine aminotransferase (ALT) activity to three times normal or more in 2 to 5 percent of patients taking zileuton. Both ALT elevation and the presence of symptomatic hepatitis with jaundice resolved when the drug was stopped. The manufacturer recommends that aminotransferase activity be measured before initiation of treatment, once a month for three months, every two to three months for the remainder of the first year of treatment and periodically thereafter. Dyspepsia has also been reported. Laboratory animals developed tumors when the drug was given in high doses. When given concurrently, zileuton can decrease clearance and markedly increase serum concentrations of theophylline, and it can also cause clinically significant increases in serum concentrations of warfarin, propranolol and possibly terfenadine. The recommended dosage of zileuton is 600 mg, four times per day. The wholesale price of a 30-day supply is $75.
Consultants for the Medical Letter on Drugs and Therapeutics conclude that zileuton is modestly effective for maintenance treatment of chronic asthma. Patients taking zileuton must be monitored for hepatic toxicity.
COPYRIGHT 1997 American Academy of Family Physicians
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