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NSAIDsincluding mefenamic acidcan cause serious skin adverse reactions such as exfoliative dermatitisStevens-Johnson SyndromeSJSand toxic epidermal necrolysisTENwhich can be fatalThese serious events may occur without warningInform patients about the signs and symptoms of serious skin reactions and to discontinue the use of Ponstel at the first appearance of skin rash or any other sign of hypersensitivityPonstel is contraindicated in patients with previous serious skin reactions to NSAIDssee CONTRAINDICATIONS

NSAIDsincluding mefenamic acidcause serious gastrointestinalGIadverse events including inflammationbleedingulcerationand perforation of the esophagusstomachsmall intestineor large intestinewhich can be fatalThese serious adverse events can occur at any timewith or without warning symptomsin patients treated with NSAIDsOnly one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomaticUpper GI ulcersgross bleedingor perforation caused by NSAIDs occur in approximately 1of patients treated for 3-6 monthsand in about 2-4of patients treated for one yearHowevereven short-term NSAID therapy is not without risk.

Mefenamic acid is metabolized by cytochrome P450 enzyme CYP2C9 to 3-hydroxymethyl mefenamic acidMetabolite IFurther oxidation to a 3-carboxymefenamic acidMetabolite IImay occurThe activity of these metabolites has not been studiedThe metabolites may undergo glucuronidation and mefenamic acid is also glucuronidated directlyA peak plasma level approximating 20 mcg/mL was observed at 3 hours for the hydroxy metabolite and its glucuroniden=6after a single 1-gram doseSimilarlya peak plasma level of 8 mcg/mL was observed at 6-8 hours for the carboxy metabolite and its glucuronide.

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