Coadministration of efavirenz (600 mg once daily) with simvastatin (40 mg once daily) decreased the steady-state AUC and Cmax of simvastatin by 69% and 76%, respectively; of simvastatin acid by 58% and 51%, respectively; and of total HMG-CoA reductase inhibitors by 60% and 70%, respectively, compared to simvastatin administered alone (CYP3A4). Coadministration did not affect efavirenz AUC or Cmax values. Cholesterol levels should be periodically monitored. Dosage adjustments of simvastatin may be required (refer to the SmPC for simvastatin). No dosage adjustment is necessary for efavirenz. 

Coadministration of simvastatin (40 mg once daily for 4 days) and efavirenz (600 mg for 15 days) was studied in 14 subjects. There were decreases in simvastatin Cmax, AUC and Cmin of 72%, 68% and 45%, respectively. Total active drug (including metabolites) decreased by 68% (Cmax) and 60% (AUC). Efavirenz Cmax and Cmin both decreased by 12% with no change in AUC. Consult the complete prescribing information for simvastatin for guidance on individualising the dose.

Coadministration of efavirenz (600 mg once daily) and simvastatin (40 mg once daily) was studied in 14 HIV-negative subjects. Efavirenz reduced simvastatin AUC0-24 h by 58% (P=0.003) and active HMG-CoA reductase inhibitory activity by 60% (P<0.001). Simvastatin had no effect on non-steady-state efavirenz concentrations. The reduced inhibition of HMG-CoA reductase activity may result in diminished antilipid efficacy at usual doses of simvastatin.