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

Daryl U. Nnani, Alesa Campbell, Maria Ajaimy, Omar Saeed, Snehal R. Patel, Sana Ahmed, Jay A. Graham, Ulrich P. Jorde

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: 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. Material and methods: This was a single-center, retrospective analysis of hepatitis C virus (HCV) viremic donors to HCV negative heart or kidney transplant recipients who received 12 weeks 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. Results: 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. Conclusion: 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.

Original languageEnglish (US)
Article numbere13716
JournalTransplant Infectious Disease
Volume23
Issue number5
DOIs
StatePublished - Oct 2021

Keywords

  • direct acting antivirals
  • heart transplantation
  • hepatitis C
  • kidney transplantation
  • pharmacokinetics
  • tacrolimus

ASJC Scopus subject areas

  • Infectious Diseases
  • Transplantation

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