NSAIDs Valproate

Drugs that inhibit phenytoin metabolism (causing its plasma concentration to rise) include sodium valproate, cimetidine, co-trimoxazole, isoniazid, chloramphenicol, some NSAIDs, disulfiram. There is a considerable body of mediocre and contradictory data, the lesson of which is that possible interaction should be borne in mind wherever other drugs are prescribed to a patient taking phenytoin. 

Sodium valproate Aspirin Inhibition of valproate metabolism, increasing plasma concentration Avoid aspirin monitor plasma concentration if other NSAIDs are used... 

Slc21a4) taurocholate, thyroid hormones Drugs AZT, MTX Drugs NSAIDs, furosemide, valproate... 

Children given antipyretic doses of aspirin co-administered with valproate were found to exhibit a decrease in protein binding and an inhibition of the metabolism of valproate. The common use of aspirin should alert to the need for caution if these drugs are co-administered. Interaction with other non-steroidal anti-inflammatory drugs (NSAIDs) may not be so prominent. 

The clearance of a single oral dose of sodium valproate was reduced in 6 patients by 2 to 17% after a 4-week course of cimetidine, but was not affected by ranitidine. It seems doubtful if the interaction between valproate and cimetidine is of clinical importance. However, a case of fatal hyperammonaemia in a patient with systemic lupus erythematosus was speculated to have been induced by valproate, and the authors also considered that the concurrent use of cimetidine and aspirin (see Valproate + Aspirin or NSAIDs , p.575) may have contributed. The general importance of this case is unknown. 

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