Efavirenz–indinavir pharmacokinetic interaction

The Efavirenz–indinavir pharmacokinetic interaction is a clinically significant drug-drug interaction (DDI) observed in the management of HIV-1 infection. Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), acts as a potent inducer of the Cytochrome P450 3A4 (CYP3A4) isoenzyme (Source: FDA Sustiva Label). Indinavir, a protease inhibitor, is a primary substrate for CYP3A4-mediated metabolism (Source: FDA Crixivan Label). When these drugs are co-administered, efavirenz-mediated induction of CYP3A4 leads to a substantial reduction in indinavir plasma concentrations, with studies showing a decrease in indinavir AUC by approximately 31-46% (Source: Haas et al., 1999, Journal of Infectious Diseases). This reduction poses a high risk of subtherapeutic drug levels, which can lead to virologic failure and the development of drug-resistant HIV strains. To mitigate this interaction, clinicians often increase the dose of indinavir or utilize ritonavir-boosting to inhibit CYP3A4 and maintain therapeutic indinavir levels (Source: NIH Clinical Info).

Other names

EFV-IDV interactionEfavirenz-indinavir drug interactionCYP3A4-mediated interaction between efavirenz and indinavir

Efavirenz induces the expression and activity of the CYP3A4 enzyme, which accelerates the oxidative metabolism of indinavir, thereby reducing its systemic exposure.