Drug interactions with nimesulide.

Nimesulide is a recently developed analgesic, antipyretic and anti-inflammatory agent that differs from conventional nonsteroidal anti-inflammatory drugs both in structure and pharmacological profile. Since nimesulide may be prescribed for patients receiving concomitant medication, the propensity for drug interactions exists. Investigations have been conducted to assess the potential for pharmacokinetic and pharmacodynamic interaction. With regard to absorption, there is some evidence that nimesulide may decrease the oral bioavailability of furosemide (frusemide). Nimesulide is extensively bound to plasma proteins and may be displaced from binding sites by concurrently administered drugs such as fenofibrate, salicylic acid and tolbutamide. In addition, nimesulide may displace salicylic acid and furosemide (but not warfarin) from plasma proteins. Major interactions involving interference with drug metabolism have not been described with nimesulide. A marginal decrease in plasma theophylline levels (without changes in respiratory function tests) has been described after addition of nimesulide to chronic theophylline therapy. Despite earlier suggestions that nimesulide may increase the hypoglycaemic effect of glibenclamide, a formal study excluded any influence of the drug on fasting blood sugar and glucose tolerance in diabetic patients treated with various sulfonylureas. Although nimesulide does not usually affect the response to warfarin, a few patients may show some increase in anticoagulant effect; therefore, it would seem prudent to monitor coagulation status when the 2 drugs are administered together. Finally, nimesulide may reduce the natriuretic response to furosemide and potentiate the furosemide-induced reduction in glomerular filtration rate and renal blood flow, through a pharmacodynamic interaction which is likely to involve inhibition of renal cyclo-oxygenase. These results suggest that caution should be exercised when nimesulide is used in combination with drugs that are known to adversely affect renal haemodynamics.