Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects.
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Study Design
Luber, et al studied the pharmacokinetics of maraviroc and fosamprenavir when given concomitantly in three different dosing schedules1. Co-administration of maraviroc (MVC) 300 mg twice daily with unboosted fosamprenavir (FVP) 1400 mg twice daily decreased MVC AUC, Cmax, and Cmin by 13%, 11% and 29%, respectively. Amprenavir AUC, Cmax, and Cmin decreased by 44%, 51% and 2%, respectively. When given with once daily, ritonavir boosted fosamprenavir (1400 mg/100 mg), the maraviroc AUC, Cmax and Cmin decreased by 2%, 7%, and 23%, respectively, while amprenavir AUC, Cmax and Cmin decreased by 21%, 32% and 36%, respectively. Twice twice daily, boosted fosamprenavir was given with maraviroc, MVC AUC, Cmax and Cmin decreased by 66%, 70%, and 54%, while amprenavir AUC, Cmax and Cmin decreased by 26%, 31% and 24% respectively. The authors stated that the mechanism of this interaction is currently unknown, but may involve induction of MDR1 transport proteins.
Study Results
Vourvahis, et al, also studied the pharmacokinetics of maraviroc and fosamprenavir when given simultaneously, and found conflicting results2. Co-administration of 300 mg of MVC twice daily plus ritonavir boosted fosamprenavir 700 mg / 100 mg twice daily appeared to increase MVC AUC, Cmax and Cmin 2.49, 1.52, and 4.74 fold, respectively. Amprenavir AUC, Cmax and Cmin decreased by 35%, 34% and 36%, respectively. When maraviroc 300 mg daily was given with boosted fosamprenavir 1400 mg / 100 mg daily, MVC AUC, Cmax and Cmin were increased 2.26, 1.45, and 1.8 fold, whereas amprenavir AUC, Cmax, and Cmin decreased 30%, 29% and 15% respectively. This study also compared maraviroc plasma concentrations when given once or twice daily with boosted fosamprenavir, and found similar concentrations (235 ng/ml vs 217 ng/ml, for 300 mg once daily and 300 mg twice daily, respectively).
Study Conclusions
Given the conflicting data, the concomitant use of maraviroc and fosamprenavir should be done with caution. If these agents must be given together, DHHS guidelines recommend maraviroc be dosed at 150 mg twice daily. Ritonavir boosted fosamprenavir twice daily, or use of an alternative ritonavir boosted protease inhibitor may be warranted.
References
Vourvahis M, Plotka A, da Costa LM, Fang A, Heera J. Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an open-label, fixed-sequence study in healthy subjects. Antimicrobial Agents And Chemotherapy . 2013; 12: 6158-6164.
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