Pharmacokinetics of Tacrolimus and Cyclosporine in Liver Transplant Recipients Receiving 3 Direct-Acting Antivirals as Treatment for Hepatitis C Infection

Badri, Prajakta; Parikh, Apurvasena; Coakley, Eoin; Ding, Bifeng; Awni, Walid M.; Dutta, Sandeep; Menon, Rajeev

doi:10.1097/ftd.0000000000000315

Cited by 24 publications

(23 citation statements)

References 22 publications

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“…Assessment of drug–drug interactions is crucial as some medications are contraindicated or not recommended during DAA therapy (e.g., high‐dose proton pump inhibitors [twice daily dosing], amiodarone [contraindicated with sofosbuvir‐inclusive regimens], and certain statins [e.g., atorvastatin], among others). Importantly, complex interactions occur between DAAs and calcineurin inhibitors . Coadministration of elbasvir/grazoprevir and cyclosporine leads to a 15‐fold increase in grazoprevir and a 2‐fold increase in elbasvir area under the concentration–time curve; this DAA regimen and immunosuppressant combination should be avoided.…”

Section: Organ Transplantation From Hcv‐viremic Donors To Hcv‐negativmentioning

confidence: 99%

“…Importantly, complex interactions occur between DAAs and calcineurin inhibitors. (383)(384)(385)(386)(387)(388) Coadministration of elbasvir/grazoprevir and cyclosporine leads to a 15-fold increase in grazoprevir and a 2-fold increase in elbasvir area under the concentration-time curve (389) ; this DAA regimen and immunosuppressant combination should be avoided. A 40%-50% increase in tacrolimus level is predicted with coadministration of elbasvir/grazoprevir (389) ; no dosing adjustments are anticipated, but tacrolimus levels should be monitored.…”

Section: Recommendations For Daa Therapymentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

2020

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Section: Organ Transplantation From Hcv‐viremic Donors To Hcv‐negativmentioning

confidence: 99%

Section: Recommendations For Daa Therapymentioning

confidence: 99%

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

2020

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“…There is no indication for dose adjustment in chronic kidney disease (including end‐stage renal disease), whereas additional studies have shown no requirement for dose‐adjustment in mild hepatic disease, up to and including Child class A cirrhosis. ( 27 )…”

Section: Discussionmentioning

confidence: 99%

Use of Hepatitis C Nucleic Acid Test–Positive Liver Allografts in Hepatitis C Virus Seronegative Recipients

et al. 2020

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Because of underutilization of liver allografts, our center previously showed that hepatitis C virus (HCV) antibody-positive/ nucleic acid test (NAT)-negative livers when transplanted into HCV nonviremic recipients were safe with a 10% risk of HCV transmission. Herein, we present our single-center prospective experience of using HCV NAT+ liver allografts transplanted into HCV NAT-recipients. An institutional review board-approved matched cohort study was conducted examining postliver transplantation (LT) outcomes of HCV-patients who received HCV NAT+ organs (treatment group) compared with matched recipients with HCV NAT-organs (matched comparator group) between June 2018 to October 2019. The primary endpoint was success of HCV treatment and elimination of HCV infection. The secondary outcomes included the 30-day and 1-year graft and patient survival as well as perioperative complications. There were 32 recipients enrolled into each group. Because of 1 death in the index admission, 30/31 patients (97%) were given HCV treatment at a median starting time of 47 days (18-140 days) after LT. A total of 19 (63%) patients achieved sustained virological response at week 12 (SVR12). Another 6 patients achieved end-of-treatment response, while 5 remained on therapy and 1 is yet to start treatment. No HCV treatment failure has been noted. There were no differences in 30-day and 1-year graft and patient survival, length of hospital stay, biliary or vascular complications, or cytomegalovirus viremia between the 2 groups. In this interim analysis of a matched cohort study, which is the first and largest study to date, the patients who received the HCV NAT+ organs had similar outcomes regarding graft function, patient survival, and post-LT complications.Liver Transplantation 26 673-680 2020 AASLD.

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“…Very recently, Badri et al . reported on a pharmacokinetic study that examined the interactions between ombitasvir, paritaprevir/ritonavir, and dasabuvir (SD), plus the CNIs tacrolimus and cyclosporin. They concluded that the “observed data for tacrolimus and cyclosporin in liver transplant recipients confirm that the recommended dosing strategies are valid and therapeutic levels of immunosuppression can be maintained during 3D treatment.” Bearing this in mind, we recommend that calcineurin‐inhibitor levels are closely monitored during and within the weeks following DAA therapy.…”

Section: Treatment Of Hcv Infection After Kidney Transplantationmentioning

confidence: 99%

Use of direct-acting agents for hepatitis C virus-positive kidney transplant candidates and kidney transplant recipients

2016

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In some parts of the world, hepatitis C virus (HCV) infection remains a huge problem for kidney transplant candidates and kidney transplant (KT) recipients. Until 2 years ago, anti-HCV treatment for the general population relied on pegylated alpha-interferon plus ribavirin, but led to a sustained viral response (SVR) in <50% of cases. This treatment was contraindicated in KT patients because of acute-rejection issues and was poorly tolerated in patients with end-stage renal disease (ESRD). Over the last year, direct-acting antiviral agents (DAAs) have entered the market and are associated in the general population with a SVR of >90%, whatever the patient's HCV genotype. In KT patients, sofosbuvir-based therapy is associated with a SVR at nearly 100% in patients with a HCV genotype-1 infection, with almost no side effects and only mild interference with immunosuppressive drugs. Most HCV(+) patients with ESRD are genotype 1: in that setting, a recent study reported that the association of grazoprevir/elbasvir 100/50 mg/day led to a SVR of nearly 95% with very few side effects. Thus, it is concluded that DAAs can be safely used and lead to results in KT candidates and KT patients that are as good as those observed in the nonrenal population.

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Pharmacokinetics of Tacrolimus and Cyclosporine in Liver Transplant Recipients Receiving 3 Direct-Acting Antivirals as Treatment for Hepatitis C Infection

Abstract: Observed data for tacrolimus and CSA in liver transplant recipients confirm that the recommended dosing strategies are valid and therapeutic levels of immunosuppression can be maintained during 3D treatment.

Cited by 24 publications

References 22 publications

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

Use of Hepatitis C Nucleic Acid Test–Positive Liver Allografts in Hepatitis C Virus Seronegative Recipients

Use of direct-acting agents for hepatitis C virus-positive kidney transplant candidates and kidney transplant recipients

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