Diclofenac/misoprostol. A review of its pharmacology and therapeutic efficacy in painful inflammatory conditions.

Diclofenac is a well established nonsteroidal anti-inflammatory drug (NSAID) used in the treatment of a variety of painful inflammatory conditions. Although generally well tolerated, diclofenac, like other NSAIDs, is associated with gastrointestinal adverse effects which infrequently can be serious and/or life-threatening. Misoprostol, a prostaglandin E1 analogue, reduces the incidence of NSAID related ulcers, both gastric and duodenal. The lack of conclusive pharmacoeconomic data for misoprostol and the widespread use of NSAIDs makes routine administration of misoprostol difficult to justify for all NSAID users. However, it appears to be an economically warranted approach in the elderly, who are at particularly high risk for NSAID-related gastrointestinal complications. The fixed combination of diclofenac 50mg and misoprostol 200 micrograms administered 2 to 3 times daily for 4 to 12 weeks has shown equivalent therapeutic efficacy to diclofenac (alone or combined with placebo), piroxicam and naproxen, and was slightly more effective than ibuprofen in clinical studies in patients with a variety of painful inflammatory conditions. No significant differences in therapeutic efficacy were noted between elderly (aged > or = 65 years) and younger patients in these studies. Gastrointestinal adverse events are common with diclofenac and misoprostol, administered alone or in combination. Diarrhoea (presumably attributable to the misoprostol component) appears to be more frequent in diclofenac/misoprostol recipients than in those receiving diclofenac alone or combined with placebo. However, diclofenac/misoprostol recipients had significantly fewer gastroduodenal ulcers at the end of treatment relative to patients receiving comparators in clinical trials. In addition, the types and incidences of adverse events are similar in elderly and younger patients. Routine ulcer prophylaxis with misoprostol in all NSAID users is not warranted from a pharmacoeconomic viewpoint. In common with other fixed combination products, dosage flexibility is somewhat compromised with diclofenac/misoprostol. However, once drug dosages are determined in the individual patient, the fixed combination of diclofenac and misoprostol offers the potential for increased patient convenience and possibly patient compliance, and lower drug acquisition costs than those of the individual drugs used together. Thus, it should be considered a useful treatment option in appropriately selected patients with a high risk for serious NSAID-related gastrointestinal complications who require NSAID therapy.