Moclobemide safety: monitoring a newly developed product in the 1990s

Moclobemide is a reversible and selective inhibitor of monoamine oxidase subtype A with a wide spectrum of antidepressant activity. To fully evaluate product safety, Roche Drug Safety has collected data on adverse events (AEs), regardless of causality, from all sources worldwide through the product development phase and after launch. This effort has included analyses of reports from clinical trials, regulatory authorities, the literature, observational studies, and the marketplace. Roche Drug Safety has also carefully examined all cases where moclobemide was taken in overdose, whether with or without other substances. This article presents the safety profile of the product after 3 years on world markets. In clinical trials, moclobemide appeared only slightly less well tolerated than placebo. In comparative trials, moclobemide was largely devoid of the anticholinergic effects associated with tricyclic antidepressants. To the end of June 1993, with an estimated 780,000 subjects exposed, AEs had been reported by less than 0.2% of users. The most frequently reported AEs were psychiatric, neurologic, and gastrointestinal disorders. Hepatobiliary AEs were rare, suggesting that moclobemide is largely devoid of hepatotoxic potential. Cardiovascular AEs reflected the prevalence of cardiovascular disease in the population treated. This safety profile is largely unchanged from those observed at 1 and 2 years postlaunch, when the estimated exposed populations were 168,000 and 328,000, respectively. It is of great significance that the fatal toxicity index of moclobemide is zero. A review of single-drug intoxications with moclobemide at doses of up to 20.55 g revealed no deaths due solely to moclobemide overdose. All patients recovered fully within 1 to 7 days without residual hepatic or cardiovascular toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)