Boceprevir versus Tacrolimus
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Study Design
Concomitant use of boceprevir (BOC) and tacrolimus (TAC) increased peak plasma concentration and exposure of TAC, but did not have a clinically important effect on BOC pharmacokinetics (PK).1,2 In a drug interaction study in healthy volunteers or patients with hepatitis C virus (HCV) positive genotype-1, coadministration of a single dose of TAC 0.5mg and BOC 800 mg three times daily for 11 days resulted in increased AUC and Cmax; the geometric mean ratios (GMRs; BOC + TAC / TAC) [90% CI] of AUC and Cmax for TAC were 17.1 [14.0, 20.8] and 9.90 [7.96, 12.3], respectively. However, PK of BOC was not significantly impacted when coadministered with TAC; GMRs (BOC+ TAC / BOC) [90% CIs] of AUC and Cmax were 1.00 [0.95, 1.06] and 0.97 [0.84, 1.13], respectively.
Study Results
PK study in liver transplant recipients also showed consistent result with the study done in healthy subjects or patients with HCV positive genotype-1.3 2 male liver transplant recipients, who were maintained on TAC with the target trough concentrations ranged from 5 to 10 ng/ml, received peg-IFN (1.5 µg/kg/week) + ribavirin (RBV; 800 to1400 mg/d) + BOC (800 mg three times daily) after coadministration of peg-IFN (1.5 µg/kg/week) and RBV (1000mg/day (<75Kg) or 100mg/day (>75Kg)) in 4-week lead-in phase. Concomitant administration with BOC reduced the estimated oral clearance of TAC by 80%, requiring reduced TAC dose. In a separate clinical study, TAC dose was empirically reduced in liver transplant recipient with recurrent HCV (n=1) who administered BOC concomitantly.4 An empiric decrease in TAC dose of 75% at BOC initiation resulted in an increase in TAC concentration of 18%.
Study Conclusions
ased on the study results, TAC dose should be reduced and/or the dosing interval should be increased based on close monitoring of TAC trough concentrations if BOC is used concomitantly with TAC.
References
Hulskotte E, Gupta S, Xuan F. Pharmacokinetic interaction between the hepatitis c virus protease inhibitor boceprevir and cyclosporine and tacrolimus in healthy volunteers. Hepatology. 2012; : 1622-1630.
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