Drug Interactions between atazanavir and nevirapine

CONTRAINDICATED: Coadministration with nevirapine may decrease the plasma concentrations of atazanavir, with or without cobicistat or low-dose ritonavir as a pharmacokinetic booster, while the plasma concentrations of nevirapine may be increased. The plasma concentrations of cobicistat may also be reduced. Reduced plasma concentrations of atazanavir may lead to a loss of therapeutic effect and development of resistance to atazanavir. 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 proposed mechanisms are induction of the CYP450 3A4 isoenzyme by nevirapine and the inhibition of CYP450 3A4 by atazanavir and cobicistat. No clinically significant interaction has been reported between nevirapine and ritonavir. When atazanavir-ritonavir (300 mg-100 mg once daily) was given in combination with nevirapine (200 mg twice daily) in HIV-infected patients, there was a reduction in atazanavir mean systemic exposure (AUC), peak plasma concentration (Cmax) and trough plasma concentration (Cmin) of 42%, 28%, and 72%, respectively. In contrast, the mean AUC, Cmax, and Cmin of nevirapine increased by 25%, 17%, and 32%, respectively. Data are not available for atazanavir-cobicistat.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, along with the increased risk of nevirapine-associated toxicity, it is not recommended to prescribe unboosted atazanavir or atazanavir-boosted with cobicistat or low-dose ritonavir in combination with nevirapine. Some authorities consider concomitant use of nevirapine with unboosted atazanavir or atazanavir boosted with cobicistat contraindicated (US).