Drug Interactions between fosphenytoin and posaconazole

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GENERALLY AVOID: Phenytoin and other enzyme-inducing anticonvulsants may decrease the plasma concentration of posaconazole. The mechanism is induction of posaconazole clearance via the UDP-glucuronosyltransferase glucuronidation and P-glycoprotein efflux pathways. According to product labeling, coadministration of posaconazole (200 mg tablets once a day) with phenytoin (200 mg once a day) for 10 days resulted in reduced posaconazole mean peak plasma concentration (Cmax) by 41% and systemic exposure (AUC) by 50%. Treatment failure could result. Conversely, posaconazole is an inhibitor of CYP450 3A4 and can increase the plasma levels of phenytoin, which is thought to be partially metabolized by the isoenzyme. Phenytoin Cmax and AUC increased by 16% during coadministration of posaconazole.

MANAGEMENT: Use of posaconazole in combination with enzyme-inducing anticonvulsants should generally be avoided unless the potential benefit outweighs the risk. If coadministration is considered necessary, patient response to the antifungal should be closely monitored. In addition, pharmacologic response and serum phenytoin levels should be closely monitored following initiation or discontinuation of posaconazole, and the phenytoin dosage adjusted, as necessary.