Decreased tacrolimus plasma concentrations during HCV therapy: a drug–drug interaction or is there an alternative explanation?

Smolders, Elise J; Pape, Simon; Kanter, Clara T. M. M. de; Berg, A. P. van den; Drenth, Joost P.H.; Burger, David M.

doi:10.1016/j.ijantimicag.2016.12.004

Cited by 20 publications

(22 citation statements)

References 18 publications

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“…Such findings are in line with single case reports and case series of LT and KT recipients , and demand explanations other than direct drug‐to‐drug interactions. It has been proposed a role for the repression of certain drug‐metabolizing enzymes, such as CYP3A4, due to the sustained inflammatory stimulus associated with chronic HCV infection . For instance, plasma levels of midazolam or HCV or HIV protease inhibitors (all of them CYP3A4 subtracts) have been shown to be higher in HCV patients than healthy volunteers .…”

Section: Discussionsupporting

confidence: 87%

Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid-term follow-up in a single-center cohort study

et al. 2018

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The medium-term impact on graft function and immunosuppressive drug pharmacokinetics of direct antiviral agents (DAAs) among hepatitis C virus (HCV)-infected kidney transplant (KT) recipients remain unclear. We compared pre- and post-treatment 12-month trajectories of estimated glomerular filtration rate (ΔeGFR) and 24-h proteinuria (Δ24-h proteinuria) in 49 recipients treated with DAAs (mostly sofosbuvir plus ledipasvir). Among evaluable patients, 66.7% and 100.0% had undetectable viral load by week 4 and end of therapy (EoT). The sustained virologic response rate at 12 weeks was 95.8%. Overall, 80.6% of patients receiving tacrolimus required dose escalation while on DAA-based therapy (median increase of 66.7%) to maintain target levels. Tacrolimus levels resulted to be higher at 12 months compared to EoT (7.8 ± 2.1 vs. 6.7 ± 2.0 ng/ml; P-value = 0.002). No changes in graft function during the course of therapy were observed. However, eGFR significantly decreased (P-value <0.001) throughout the first 12 months after EoT. Median ΔeGFR and Δ24-h over pre- and post-treatment periods were 3.9% and -6.1% (P-value = 0.002) and -5.3% and 26.2% (P-value = 0.057). Caution should be exercised when adjusting immunosuppression in HCV-infected KT recipients upon initiation of DAAs, followed by mid-term monitoring of immunosuppressive drug levels and graft function.

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Section: Discussionsupporting

confidence: 87%

Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid-term follow-up in a single-center cohort study

et al. 2018

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“…The similar changes were also observed in our study. However, the underlying mechanism could be connected with the dysfunction of hepatocyte enzymatic systems during active HCV infection or/and lower intestinal absorption/metabolism induced by HCV or CYP3A4 enzyme inhibition by pro‐inflammatory cytokines . During anti‐HCV therapy, while the inflammation subsides, CNI metabolism can increase, resulting in decreased CNI blood levels.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of sofosbuvir‐based therapy against chronic hepatitis C infection after successful kidney transplantation

Musialik

Kolonko

Kościelska‐Kasprzak

et al. 2019

Transplant Infectious Dis

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Background Direct‐acting antivirals (DAAs), including sofosbuvir (SOF), are recommended for treatment of chronic hepatitis C virus (HCV) infection. However, few studies have investigated the effectiveness and safety of new DAAs in kidney transplant recipients (KTRs). Objectives To assess the effectiveness and safety of SOF‐based therapy in stable KTRs. Patients and methods Forty KTRs were treated with SOF‐based regimens. Rapid, end‐therapeutic, and sustained virologic responses were assessed, as was liver stiffness by elastometry. Safety was monitored by measuring the estimated glomerular filtration rate (eGFR), blood hemoglobin (Hb) concentration, proteinuria, and blood trough levels of calcineurin inhibitors (CNIs). Other side effects were also recorded. Results The effectiveness of DAAs was 100% at all time points. The therapy did not significantly influence eGFR or proteinuria, but significantly decreased mean blood Hb levels (13.5 ± 2.0 vs 11.6 ± 1.9, respectively, P < 0.001), which required a dose reduction or cessation of ribavirin (RBV) in 50% of patients. A profound, significant decrease in initial CNI concentrations was also observed during treatment in the majority of patients within the first month of therapy. Conclusions In this cohort of KTRs, the new SOF‐based therapies were characterized by 100% effectiveness and good safety profiles. However, in patients co‐treated with RBV, close blood Hb monitoring and early RBV dose reduction are necessary. In the majority of KTRs, antiviral therapy leads to a substantial and early decrease in CNIs levels, thus frequent measurement of CNI levels is necessary during SOF‐based therapy.

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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%

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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Decreased tacrolimus plasma concentrations during HCV therapy: a drug–drug interaction or is there an alternative explanation?

Cited by 20 publications

References 18 publications

Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid-term follow-up in a single-center cohort study

Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid-term follow-up in a single-center cohort study

Effectiveness and safety of sofosbuvir‐based therapy against chronic hepatitis C infection after successful kidney transplantation

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

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