MOCLOBEMIDE SAFETY - MONITORING A NEWLY DEVELOPED PRODUCT IN THE 1990S

Moclobemide is a reversible and selective inhibitor of monoamine oxida se subtype A with a wide spectrum of antidepressant activity. To fully evaluate product safety, Roche Drug Safety has collected data on adve rse events (AEs), regardless of causality, from ah sources worldwide t hrough the product development phase and after launch. This effort has included analyses of reports from clinical trials, regulatory authori ties, the literature, observational studies, and the marketplace. Roch e 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 wo rld markets. In clinical trials, moclobemide appeared only slightly le ss well tolerated than placebo. In comparative trials, moclobemide was largely devoid of the anticholinergic effects associated with tricycl ic 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. T he most frequently reported AEs were psychiatric, neurologic, and gast rointestinal disorders. Hepatobiliary AEs were rare, suggesting that m oclobemide is largely devoid of hepatotoxic potential. Cardiovascular AEs reflected the prevalence of cardiovascular disease in the populati on treated. This safety profile is largely unchanged from those observ ed at 1 and 2 years postlaunch, when the estimated exposed populations were 168,000 and 328,000, respectively. It is of great significance t hat the fatal toxicity index of moclobemide is zero. A review of singl e-drug intoxications with moclobemide at doses of up to 20.55 g reveal ed no deaths due solely to moclobemide overdose. All patients recovere d fully within 1 to 7 days without residual hepatic or cardiovascular toxicity. There is no evidence of an increased risk of suicidal behavi or in users of moclobemide. Close compound monitoring through developm ent and after launch has confirmed the safety of moclobemide in therap eutic doses and in overdose.