Effect of glecaprevir/pibrentasvir on weight-adjusted tacrolimus trough/dose ratios in heart and kidney transplant recipients
© 2021 Wiley Periodicals LLC..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Transplant infectious disease : an official journal of the Transplantation Society - 23(2021), 5 vom: 13. Okt., Seite e13716 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nnani, Daryl U [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.11.2021 Date Revised 02.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/tid.13716 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329507842 |
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| 100 | 1 | |a Nnani, Daryl U |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of glecaprevir/pibrentasvir on weight-adjusted tacrolimus trough/dose ratios in heart and kidney transplant recipients |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 02.11.2021 | ||
| 500 | |a Date Revised 02.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Wiley Periodicals LLC. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a direct acting antivirals | |
| 650 | 4 | |a heart transplantation | |
| 650 | 4 | |a hepatitis C | |
| 650 | 4 | |a kidney transplantation | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a tacrolimus | |
| 650 | 7 | |a Aminoisobutyric Acids |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Benzimidazoles |2 NLM | |
| 650 | 7 | |a Cyclopropanes |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a Lactams, Macrocyclic |2 NLM | |
| 650 | 7 | |a Pyrrolidines |2 NLM | |
| 650 | 7 | |a Quinoxalines |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a pibrentasvir |2 NLM | |
| 650 | 7 | |a 2WU922TK3L |2 NLM | |
| 650 | 7 | |a Proline |2 NLM | |
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| 650 | 7 | |a Tacrolimus |2 NLM | |
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| 700 | 1 | |a Campbell, Alesa |e verfasserin |4 aut | |
| 700 | 1 | |a Ajaimy, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Saeed, Omar |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Snehal R |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed, Sana |e verfasserin |4 aut | |
| 700 | 1 | |a Graham, Jay A |e verfasserin |4 aut | |
| 700 | 1 | |a Jorde, Ulrich P |e verfasserin |4 aut | |
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