Probenecid Indometacin

NS AIDs ANTIGOUT DRUGS-PROBENECID T levels of indometacin, ketorolac and possibly dexketoprolien, ketoprofen, naproxen, tenoxicam and tiaprofenic acid Probenecid competitively inhibits renal metabolism of these NSAIDs Watch for signs of toxicity of these NSAIDs. Consider using an alternative NSAID. The manufacturers of ketorolac advise avoiding co-adminis-tration of ketorolac and probenecid... 

Probenecid inhibits the tubular secretion of indometacin (SEDA-4, 66). 

Interactions with indometacin have been documented through inhibition of renal tubular excretion (26,27). In 17 patients with rheumatoid arthritis, probenecid 500 mg bd improved the therapeutic response to indometacin 25 mg tds over 3 weeks (28). There were changes in the pharmacokinetics of indometacin, which the authors attributed to a reduction in the non-renal clearance of indome-tacin, possibly because of reduced biliary clearance. 

A study in 28 patients with osteoarthritis, taking indometacin 50 to 150 mg daily orally or rectally, showed that probenecid 500 mg to 1 g daily roughly doubled their indometacin plasma levels and this paralleled the increased effectiveness (relief of morning stiffness, joint tenderness and raised grip strength indices). However, 4 patients developed indometacin toxicity. ... 

Other studies have also demonstrated the marked rise in plasma indometacin levels caused by probenecid. " Clear signs of indometacin toxicity (nausea, headache, tinnitus, confusion and a rise in blood urea) occurred when a woman with stable mild renal impairment was given probenecid. The uricosuric effects of probenecid were not altered. ... 

The interaction between indometacin and probenecid is established and adequately documented. Concurrent use should be well monitored because, while clinical improvement can undoubtedly occur, some patients may develop indometacin toxicity (headache, dizziness, light-headedness, nausea, etc.). This is particularly likely in those with some renal impairment. Reduce the indometacin dosage as necessary. Information about other NSAIDs is limited, but these interactions also appear to be established. The clinical importance of most of them is uncertain, but probably small. Reports of adverse effects seem to be lacking, but it would still be prudent to be alert for any evidence of increased adverse effects. Reduce the NSAID dosage if necessary. The exception is ketorolac, which its manufacturers contraindicate with probenecid because of the marked increases seen in its plasma levels. 

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See also in sourсe #XX -- [ ]

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