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 language | English (US) |
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Article number | e13716 |
Journal | Transplant Infectious Disease |
Volume | 23 |
Issue number | 5 |
DOIs | |
State | Published - Oct 2021 |
Keywords
- direct acting antivirals
- heart transplantation
- hepatitis C
- kidney transplantation
- pharmacokinetics
- tacrolimus
ASJC Scopus subject areas
- Infectious Diseases
- Transplantation