Interactions between invirase(saquinavir) and Aptivus (tipranavir)
saquinavir and tipranavir (Major Drug-Drug)
GENERALLY AVOID: Coadministration with tipranavir plus low-dose ritonavir may significantly decrease the plasma concentrations of other protease inhibitors. The mechanism of interaction has not been described. Data are available for amprenavir, atazanavir, lopinavir, and saquinavir. In 16 HIV-positive subjects, administration of amprenavir (600 mg plus ritonavir 100 mg) in combination with tipranavir/ritonavir (500 mg/200 mg) twice a day for 14 days decreased the mean steady-state peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) of amprenavir by 39%, 44% and 55%, respectively, compared to administration without tipranavir/ritonavir. In 21 HIV-positive subjects, mean steady-state Cmax, AUC and Cmin of lopinavir (400 mg plus ritonavir 100 mg) decreased by 47%, 55% and 70%, respectively, while those of saquinavir (600 mg plus ritonavir 100 mg) decreased by 70%, 76% and 82%, respectively, during coadministration with tipranavir/ritonavir twice a day for 14 days. Likewise, mean steady-state Cmax, AUC and Cmin of atazanavir decreased by 57%, 68% and 81%, respectively, when atazanavir (300 mg plus ritonavir 100 mg once a day) was coadministered with tipranavir/ritonavir (500 mg/100 mg twice a day) for nine days in 13 subjects with unspecified HIV status. Atazanavir plus ritonavir increased tipranavir AUC by 20% and Cmin by 75%.
MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, use of other protease inhibitors in combination with tipranavir/ritonavir is not recommended.
