Naproxen Misoprostol

Naproxen is available as a free base, as sodium salt and in combination with misoprostol for the reduction of the gastrointestinal side-effects. 

In practice, a minority of patients are intolerant of aU NSAIDs. They may benefit from the co-administration of a proton pump inhibitor, a 112-receptor blocker or the prostaglandin analogue, misoprostol. To address this problem, some NSAIDs are presented in combination with misoprostol, e.g. diclofenac with misoprostol (Arthrotec) and naproxen with misoprostol (Napratec). Some patients experience abdominal pain and diarrhoea from the misoprostol component. 

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. 

A man with rheumatoid arthritis taking long-term naproxen developed ataxic symptoms a few hours after starting to take misoprostol. He said he felt like a drunk person, staggering about and vomiting. He rapidly improved when he stopped the misoprostol but the adverse symptoms recurred on two further occasions when he restarted misoprostol. ... 

Huq M. Neurological adverse effects of naproxen and misoprostol combination. BrJ Gen Pract (1990) 40,432. 

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