Overview of clinical safety with misoprostol

Abstract

The number of subjects who had participated in completed clinical trials of misoprostol as of 1 May 1984 was 2272. Of this number 1549 subjects were exposed to misoprostol doses as high as 400 μg q.i.d. and for periods up to eight weeks. In ongoing trials subjects are receiving as much as 300 μg q.i.d. for up to 12 weeks, or 400 μg daily for up to one year. Five large controlled multicenter multicountry clinical trials have been conducted with misoprostol, including double-blind placebo-controlled comparisons of misoprostol in two duodenal ulcer studies and one gastric ulcer study, and double-blind comparisons of two doses of misoprostol and cimetidine in duodenal ulcer and gastric ulcer studies. In the placebo-controlled trials the only complaint clearly associated with misoprostol therapy in a meaningful number of patients was diarrhea, defined as any change in bowel habits whether or not this included true watery diarrhea, The incidence of diarrhea was higher with misoprostol 200 μg (13.1% of 107 subjects) and misoprostol 100 μg (9.5% of 199 subjects) than with placebo (3.8% of 314 subjects). This relatively high incidence of diarrhea is offset by the fact that only four subjects had withdrawn from studies worldwide because of diarrhea. It appears that compliance was excellent. In the cimetidine-controlled studies, diarrhea and related complaints were greater with misoprostol 200 μg (5.6% of 337 subjects) than with misoprostol 50 μg (3.0% of 328 subjects) or with cimetidine 300 μg q.i.d. (1.8% of 327 subjects). There were no unusual differences in the results of laboratory analyses, including tests of liver function, between misoprostol and placebo groups. Cimetidine caused an increase in serum creatinine in many cases, but this has been reported in the literature. Misoprostol has proven to be an extremely safe and well tolerated drug for the treatment of peptic ulcer disease.