Extended clinical safety profile of lovastatin.

Lovastatin has been available for prescription use in the United States for about 20 months (as of June 1989). Over 1 million patients have received the prescription drug, and approximately 14,000 patients have participated in clinical trials. It is estimated that 500,000 patients have received lovastatin continuously for at least 1 year. This report reviews the extended safety experience from all clinical trials and prescription use. At least 645 patients have received lovastatin for more than 3 years. There are new data from a recently completed 1 year, placebo-controlled trial in 8,245 patients (Expanded Clinical Evaluation of Lovastatin study) and 20 months of health professionals' reports on spontaneous adverse events associated with large prescription usage. Data from recent large clinical trials suggest that the risk of myopathy and asymptomatic sustained liver transaminase elevations is less than reported in prior studies. The early clinical trials enrolled very high risk patients receiving lovastatin at a usual dose of 80 mg/day and often receiving concomitant hypolipidemic agents including gemfibrozil and niacin. After more than 42 months' long-term clinical trial experience, data have not established adverse effects from lovastatin on the human lens. Possible new types of rare drug-related adverse events observed with large prescription use include hypersensitivity reactions such as arthralgia, thrombocytopenia, symptomatic hepatitis and interaction with warfarin. No new, unique adverse-event profile has emerged with extended clinical use, including use in a few patients who have received therapy for more than 5 years. The lovastatin extended safety profile is that of a generally well-tolerated drug.