Effect of posaconazole on the pharmacokinetics of fosamprenavir and vice versa in healthy volunteers

Objectives To manage the interaction between fosamprenavir/ritonavir and posaconazole, we hypothesized that ritonavir can be replaced by posaconazole as an alternative booster of fosamprenavir with no significant influence on posaconazole pharmacokinetics. Methods This was an open-label, randomized, three period, cross-over, single-centre trial in 24 healthy volunteers. All subjects received the following three treatments for 10 days, separated by washout periods of 17 days: posaconazole 400 mg twice daily; fosamprenavir/ritonavir 700/100 mg twice daily; posaconazole 400 mg twice daily with fosamprenavir 700 mg twice daily. Results Twenty subjects completed the trial. Geometric mean ratios (GMR; +90% confidence interval) of posaconazole AUC and Cmax when taken with fosamprenavir versus posaconazole alone were 0.77 (0.68–0.87) and 0.79 (0.71–0.89), respectively. The GMRs of amprenavir AUC and Cmax when taken as fosamprenavir and posaconazole versus fosamprenavir/ritonavir were 0.35 (0.32–0.39) and 0.64 (0.55–0.76), respectively. No serious adverse events were reported during the trial. Conclusion Unboosted fosamprenavir should not be used concomitantly with posaconazole.