Concomitant use of sirolimus with boceprevir is not recommended due to significantly increased sirolimus exposure. The magnitude of the potential interaction between these agents in organ transplant patients is not known. If concomitant use is unavoidable, dose reduction of sirolimus and/or prolonged dosing interval should be anticipated, guided by close monitoring of sirolimus concentrations and frequent assessmeants of renal function and sirolimus-related side effects.
Sirolimus vs boceprevir
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Study Design
In an open-label, 3-period, fixed-sequence trial, 12 healthy subjects were given a single-dose sirolimus 2 mg on Day 1. After 14-day washout, subjects received boceprevir 800 mg three times a day for 6 days, followed by coadministration of boceprevir (BOC) 800 mg three times a day plus a single dose of sirolimus 2 mg. Then, subjects received boceprevir 800mg three times a day for 8 days. Blood samples were collected for the pharmacokinetic (PK) assessment of sirolimus and boceprevir.
Study Results
Coadministration of sirolimus and BOC resulted in significant increase of AUC and Cmax for sirolimus; geometric mean ratios (GMRs; sirolimus+BOC/sirolimus) [90% CI] of AUC and Cmax were 8.1 [7.08, 9.32] and 4.8 [3.99, 5.88], respectively. However, PK of BOC was not significantly impacted when coadministered with sirolimus; GMRs (BOC+sirolimus / BOC) [90% CIs] of AUC and Cmax were 1.0 [0.89, 1.01] and 0.9 [0.82, 1.07], respectively.
References
Hulskotte EGJ, Feng HP, F Xuan, et al. Pharmacokinetic interactions between the hcv protease inhibitor boceprevir and sirolimus in healthy subjects [abstract 463]. 48th Annual Meeting Of The European Association For The Study Of The Liver (easl). Amsterdam. ; 2013.
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