Drug Interactions between Olysio and phenobarbital

GENERALLY AVOID: Coadministration with potent and some moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of simeprevir, which is primarily metabolized by the isoenzyme. In 18 healthy study subjects administered simeprevir (200 mg once daily) in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily) for 7 days, mean simeprevir peak plasma concentration (Cmax) increased by 31% but systemic exposure (AUC) and trough plasma concentration (Cmin) decreased by 48% and 92%, respectively. Likewise, when simeprevir (150 mg once daily) was given with the moderate inducer efavirenz (600 mg once daily) to 23 healthy subjects for 14 days, mean simeprevir Cmax, AUC and Cmin decreased by 51%, 71% and 91%, respectively. Simeprevir had no significant effects on the pharmacokinetics of efavirenz or rifampin, but increased the AUC of metabolite 25-desacetyl-rifampin by 24%.

MANAGEMENT: The use of simeprevir in combination with potent and some moderate CYP450 3A4 inducers such as carbamazepine, dexamethasone, efavirenz, enzalutamide, eslicarbazepine, etravirine, nevirapine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifamycins, St. John's wort, and tipranavir should generally be avoided.