Misoprostol Indometacin

NSAIDs (nonsteroidal antiinflammatory drugs) Isolated cases of adverse neurological side effects have been seen with naproxen or phenylbutazone given with misoprostol. Misoprostol also increases the abdominal pain and other side effects of diclofenac and indometacin (indomethacin). Paracetamol (acetaminophen) intensifies pain if given with mifepristone and sulprostone used to induce abortion. 

Misoprostol increases the incidence of abdominal pain and diarrhoea when used with diclofenac or indometacin. Isolated cases of neurological adverse effects have been seen with naproxen or phenylbutazone given with misoprostol. However, no important pharmacokinetic interactions seem to occur between aspirin, diclofenac, ibuprofen or indometacin and misoprostol. NSAIDs are reported not to affect the abortive effects of intravaginal misoprostol. 

A higher incidence of abdominal pain, diarrhoea, nausea and dyspepsia occurred when diclofenac was combined with misoprostol. Concurrent use of indometacin and misoprostol also resulted in an increase in frequency and severity of abdominal symptoms, frequency of bowel movements and a decrease in faecal consistency. The most frequent adverse effect of misoprostol alone is diarrhoea, and this may limit the dose tolerated. When using misoprostol with NSAIDs, warn patients about the possibility of increased stomach pain and diarrhoea. Preparations combining diclofenac or naproxen with misoprostol are available. 

No clinically important pharmacokinetic interactions have been found to occur between aspirin 975 mg and misoprostol 200 micrograms, or between ibuprofen and misoprostol. One study found that misoprostol 800 micrograms daily decreased the AUC of a single 100-mg dose of diclofenac by a modest 20%. However, other studies have found that misoprostol had no effect on steady-state diclofenac pharmacokinetics. One study found that misoprostol 200 micrograms raised the steady-state levels of indometacin 50 mg three times daily by about 30%, whereas another found that misoprostol 400 micrograms twice daily reduced the AUC of indometacin 50 mg twice daily by 13% after one dose and reduced the maximum steady-state plasma concentration by 24%. These modest changes in serum indometacin levels are unlikely to be clinically important. 

Indometacin (Amuno ) provides a representative example ofthe fenac class. The search for better-tolerated drugs led inl974to diclofenac (Voltaren ). [ 184] This is weU-tolerated and nowadays available in a variety of application forms. For the prevention of gastrointestinal ulceration, a combination product with the prostaglandin misoprostol (Cytotec ) (cf. section 5.6, prostaglandins) has been developed. 

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