Review of the Safety of Diclofenac/Misoprostol

Summary

The safety of a fixed combination of diclofenac 50mg/misoprostol 200μg has been evaluated in clinical trials involving almost 2000 patients. Short term trials have been conducted in patients with Osteoarthritis (n = 1032) and rheumatoid arthritis (n = 685) over 1 or 3 months. Patients randomly received either diclofenac alone or diclofenac/misoprostol. In both groups, the most frequently reported adverse events were gastrointestinal in nature, with abdominal pain reported most frequently (in 22.6% of patients receiving diclofenac/misoprostol and 19.8% of patients receiving diclofenac), followed by diarrhoea (19.5 vs 11.3%), nausea (11.0 vs 6.5%) and dyspepsia (10.6 vs 7.8%). The most frequent nongastrointestinal adverse event was headache, which occurred in 7.9% of diclofenac/misoprostol recipients and 9.3% of diclofenac recipients. Although diclofenac/misoprostol was associated with a slightly higher prevalence of adverse events than diclofenac in these studies, the majority were of mild or moderate severity, and the treatment groups were similar as regards the number of patient withdrawals resulting from adverse events.

An interim analysis of the results of an ongoing trial of longer term administration of diclofenac/misoprostol (for up to 24 months) has been conducted. In this uncontrolled study, patients with rheumatoid arthritis, Osteoarthritis or ankylosing Spondylitis received diclofenac/misoprostol for up to 24 months; to date 1003 patients have been enrolled and treatment has been continued for 6, 12, 18 and 24 months in 640, 327, 108 and 13 patients, respectively. As in the short term trials, the adverse events reported most commonly in this study have been predominantly gastrointestinal. However, in this more prolonged study it is apparent that adverse events occur most frequently during the first 6 months of therapy, after which the rate of increase in the cumulative incidence of adverse events decreases with increasing duration of administration.

In addition, in both short and long term studies, the incidence of adverse events has been similar in elderly and younger patients and in patients with rheumatoid arthritis and Osteoarthritis who were receiving diclofenac/misoprostol.