Drug Interactions between darunavir and nevirapine

GENERALLY AVOID: Coadministration of darunavir-cobicistat with nevirapine may decrease the plasma concentrations of darunavir and/or cobicistat and increase the plasma concentrations of nevirapine. Reduced darunavir plasma levels may lead to diminished virologic response and possible resistance to darunavir. Increased nevirapine plasma concentrations may increase the risk of nevirapine-associated toxicity, including hepatotoxicity, fatal and non-fatal skin reactions (e.g., Stevens Johnson syndrome), and hypersensitivity reactions. The mechanism is nevirapine induction of the CYP450 3A4 isoenzyme and inhibition of CYP450 3A4 activity by darunavir and cobicistat. Pharmacokinetic data are not available for darunavir-cobicistat. However, when darunavir 400 mg-ritonavir 100 mg twice daily was used concomitantly with nevirapine 200 mg twice daily, there was increased systemic exposure (AUC) to nevirapine and darunavir of 27% and 24%, respectively. However, the trough plasma concentration (Cmin) of darunavir was unaffected. These changes are not considered to be clinically significant and do not warrant a dose adjustment to the standard recommended dose of darunavir-ritonavir.

MANAGEMENT: The concomitant use of darunavir-cobicistat with nevirapine is not recommended. As an alternative, darunavir boosted by low-dose ritonavir may be considered for use in combination with nevirapine.