Drug interactions between Sustiva and Viracept

Coadministration with efavirenz may modestly increase the plasma concentrations of nelfinavir. The proposed mechanism is efavirenz inhibition of nelfinavir metabolism via CYP450 2C19 to its active metabolite M8, which is a secondary pathway to CYP450 3A4 metabolism that yields inactive metabolites. In 10 study subjects, coadministration of nelfinavir (750 mg every 8 hours) and efavirenz (600 mg once a day) for 7 days resulted in an approximately 20% increase in nelfinavir peak plasma concentration (Cmax) and area under the concentration-time curve (AUC). Efavirenz Cmax and AUC decreased by 12%, while M8 Cmax and AUC decreased by 40% and 37%, respectively. The effect of efavirenz on the pharmacokinetics of nelfinavir boosted by ritonavir, and vice versa, have also been studied. In 24 healthy subjects, coadministration of efavirenz (600 mg) in combination with ritonavir (200 mg) and nelfinavir (1875 mg) once a day in the evening with a snack for 10 days resulted in an increase in nelfinavir Cmax, AUC and C24 (plasma concentration at 24 hours postdose) by 29%, 30% and 48%, respectively, compared to administration of nelfinavir and ritonavir alone. No changes were observed for efavirenz or M8, presumably due to inhibition of CYP450 3A4 metabolism by ritonavir. Although ritonavir Cmax, AUC and C24 were decreased by 24%, 20% and 12%, respectively, its boosting effects apparently remained. No dosage adjustment should be necessary when efavirenz is prescribed with nelfinavir, with or without ritonavir.