Drug Interactions between aspirin / pravastatin and nevirapine

MONITOR: Coadministration with efavirenz may decrease the plasma concentrations and pharmacologic effects of certain HMG-CoA reductase inhibitors (i.e., statins) and/or their active metabolites. The proposed mechanism is efavirenz induction of CYP450 3A4 metabolism. In 14 healthy, HIV-negative adult volunteers, coadministration of efavirenz (600 mg once daily for 15 days) and simvastatin (40 mg once daily on the last 4 days of efavirenz administration) resulted in a 58% median decrease in the systemic exposure (AUC) of simvastatin acid and a 60% median decrease in active HMG-CoA reductase inhibitory activity compared to administration of simvastatin alone. For atorvastatin (10 mg once daily in the same study), the systemic exposure was reduced by 43% and the total active atorvastatin exposure by 34% with efavirenz. Similarly, pravastatin (40 mg once daily in the same study) systemic exposure was reduced 40% by efavirenz. The median LDL cholesterol decrease associated with simvastatin was 11 mg/dL smaller with efavirenz coadministration than with simvastatin alone. For atorvastatin, the median LDL decrease was 6.5 mg/dL smaller with efavirenz, but the difference exhibited only a trend toward statistical significance. There was no significant difference in LDL decrease for pravastatin with or without efavirenz. Neither simvastatin, atorvastatin, nor pravastatin had any effect on the pharmacokinetics of efavirenz.

MANAGEMENT: Coadministration of simvastatin, atorvastatin, or other statins that are primarily metabolized by CYP450 3A4 (e.g., lovastatin) with efavirenz may result in diminished hypolipidemic efficacy. Although pravastatin is not significantly metabolized by CYP450 3A4, it has also been implicated. Dosage adjustment of these statins may be necessary if they are prescribed with efavirenz. The same precaution may be applicable during therapy with nevirapine, another nonnucleoside reverse transcriptase inhibitor that induces CYP450 3A4.