coadministered with atazanavir/ ritonavir, decreases in telaprevir AUC and Cmin , were observed, while atazanavir AUC reased 17% and Cmin reased 85%. This combination is being evaluated in an ongoing study in HIV/HCV coinfected individuals . More significant dual negative drug interactions were noted between telaprevir and the remaining Diosmin boosted PI combinations. With the coadministration of darunavir/ritonavir, telaprevir AUC decreased 35% and Cmin decreased 32%, while darunavir AUC decreased 40% and Cmin decreased 42%. When combined with fosamprenavir/ritonavir, telaprevir AUC and Cmin decreased by 32% and 30% respectively, and amprenavir AUC and Cmin were reduced by 47% and 56%, respectively. Finally, when telaprevir was coadministered with lopinavir/ritonavir, telaprevir AUC and Cmin were reduced by 54% and 52%, respectively, while lopinavir exposure was not significantly altered.
The mechanism for these interactions has not yet been identified, but may lude decreased bioavailability RAF Signaling Pathway and/or effects on protein binding. Therefore, the manufacturer recommends that telaprevir should not be coadministered with ritonavir boosted darunavir, fosamprenavir, or lopinavir . In the final study in this series, 20 volunteers started telaprevir 750 mg every 8 h for 7 days followed by efavirenz and tenofovir at standard doses for 7 days after a washout. Subsequently, volunteers received either telaprevir 1,125 mg every 8 h plus efavirenz and tenofovir or telaprevir 1,500 mg every 12 h plus efavirenz and tenofovir for 7 days. Telaprevir was taken with food while efavirenz and tenofovir were taken on an empty stomach in the morning.
With the combination of telaprevir 1,500 mg every 12 h plus efavirenz and tenofovir, telaprevir AUC and Cmin decreased by 20% and 48%, respectively, efavirenz AUC and Cmin decreased by 15% and 11%, respectively, and tenofovir AUC and Cmin reased by 10% and 6%, respectively. fixative When telaprevir was dosed at 1,125 mg every 8 h with efavirenz and tenofovir, smaller reductions in telaprevir exposures were observed . This higher dose of telaprevir may partly offset the interaction with efavirenz, and is being evaluated in an ongoing study in HIV/HCV coinfected individuals . In a separate study, HIV negative subjects received telaprevir 750 mg every 8 h alone, or 250 mg or 750 mg twice daily with ritonavir 100 mg twice daily. Doses were given with food for 14 days.
Ritonavir did not exert a significant boosting effect on telaprevir exposures: when compared with telaprevir 750 mg every 8 h given alone , telaprevir pharmacokinetic parameters on Day 14 were 59%–75% lower when telaprevir 250 mg every 12 h was co administered with ritonavir 100 mg every 12 h and 15%–32% lower when telaprevir 750 mg every 12 h was co administered with ritonavir 100 mg every 12 h . Of note, ritonavir exposures were higher when co administered with telaprevir 750 mg every 12 h , compared with 250 every 12 h , suggesting that CYP3A inhibition by telaprevir was dosedependent . These studies illustrate the complexity of treating HIV and HCV co infection. Further research is needed in this area in order to identify optimal combinations of agents in Two recent publications involving voriconazole and posaconazole interactions are noteworthy.