Ritonavir corrects drug interaction between efavirenz and saquinavir

Saquinavir levels are significantly reduced when given with efavirenz. In previous studies, efavirenz was found to reduce the area under the curve (AUC) of saquinavir by 62%, and the combination of saquinavir and efavirenz are not recommended unless ritonavir is given concomitantly to boost saquinavir levels.

In a trial presented as a late breaker poster at the 8th ECCATHI, the safety of once daily dosing of efavirenz and saquinavir-sgc (Fortovase), when given with “boosting” doses of ritonavir, was evaluated.

In the study, 24 healthy volunteers received either (1) efavirenz 600 mg daily for 14 days and on the 15th day added saquinavir-sgc 1600 mg and ritonavir 200mg to the daily regimen, or (2) saquinavir-sgc and ritonavir therapy alone for 14 days and on day 15 added efavirenz for 2 weeks.

The investigators found that the addition of efavirenz to the saquinavir and ritonavir (1) reduced the saquinavir area under the curve by 18.9%, (2) reduced the saquinavir Cmax from 2340 ng/ml to 2130 ng/ml, (3) did not alter the trough levels of saquinavir. These alterations in saquinavir levels are unlikely to be of any clinical significance. The authors further reported that efavirenz levels were “not significantly influenced by SQV.”

The authors conclude: “the [saquinavir] trough levels remained unaffected in this trial when combined with [efavirenz]. The observed small differences of the AUC [area under the curve] and the Cmax for [saquinavir] are not expected to limit the clinical use of this triple combination.”

M Kurowski and others. Minor interaction between efavirenz and saquinavir when combined with small doses of ritonavir in a QD regimen. 8th ECCATH, Athens, Greece, October 2001. LB/P9.