Drug Interactions between fosphenytoin and Prezcobix

GENERALLY AVOID: Coadministration with carbamazepine, phenobarbital, phenytoin, or primidone may significantly reduce the plasma concentrations of darunavir. The proposed mechanism is induction of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of darunavir.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, darunavir should not be used in combination with carbamazepine, phenobarbital, phenytoin, or primidone.

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of cobicistat, which is primarily metabolized by the isoenzyme. In a study of 12 healthy volunteers, coadministration of the potent CYP450 3A4 inducer carbamazepine (200 mg twice daily) with cobicistat-elvitegravir (150 mg-150 mg once a day) reduced the cobicistat systemic exposure (AUC) and peak plasma concentration (Cmax) by 84% and 72%, respectively, and the elvitegravir AUC and Cmax by 69% and 45%, respectively. In addition, the AUC and Cmax of carbamazepine increased by 43% and 40%, respectively, due to inhibition of the CYP450 3A4-mediated metabolism by cobicistat.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic drug levels, concomitant use of antiretroviral regimens containing cobicistat with potent CYP450 3A4 inducers is considered contraindicated.