Effect of glecaprevir/pibrentasvir on weight-adjusted tacrolimus trough/dose ratios in heart and kidney transplant recipients.

Abstract

The pharmacokinetic implications of direct-acting antiviral (DAA) use on tacrolimus posttransplant are unknown. This study sought to investigate the effects of glecaprevir/pibrentasvir (G/P), a CYP3A4 substrate and inhibitor, on weight-adjusted tacrolimus (FK) trough/dose ratio (T/D) following heart or kidney transplantation. This was a single-center, retrospective analysis of hepatitis C virus (HCV) viremic donors to HCV negative heart or kidney transplant recipients who received 12weeks of G/P therapy. Weight-adjusted T/D was assessed while patients were at steady-state before, during, and after G/P treatment. Forty-one HCV negative recipients (three heart, 38 kidney) were evaluated. The weight-adjusted T/D significantly increased during G/P treatment (119.31, IQR 88-173.8) compared to before G/P treatment (67.4, IQR 53.4-115.9) (p<0.01), but decreased after completion of treatment (90.1, IQR 52.9-122.7) (p<0.01). There was no difference in weight-adjusted T/D before and after G/P treatment (p=0.42). Four patients experienced acute rejection. Initiation of G/P in heart or kidney transplant recipients induces a reversible change in tacrolimus metabolism. A 33%-50% tacrolimus dose reduction may be considered at the time of G/P initiation. Regardless of tacrolimus dose adjustment, tacrolimus trough levels should be monitored 3 days after initiation of G/P. No clear relationship between HCV viremic organ transplantation and rejection risk was found. Larger studies are warranted to validate these findings.