Levels of tacrolimus after treatment for chronic hepatitis C with direct antiviral agents in solid organ transplant recipients

Int J Clin Pharm. 2021 Jun;43(3):731-736. doi: 10.1007/s11096-020-01162-6. Epub 2020 Oct 9.

Abstract

Background and objective The main objective was to evaluate the impact of Hepatitis C Virus treatment with direct-acting antiviral agents on tacrolimus blood levels in recipients of kidney and heart allografts. Method We analysed Hepatitis C Virus infected adult patients who received tacrolimus as immunosuppressive maintenance therapy and received direct-acting antiviral agents treatment in a tertiary hospital with solid transplant multidisciplinary program in Madrid, Spain. Liver and renal function, tacrolimus dose and blood levels were analysed before and 12 weeks after the end of treatment. Results We identified 7 kidney and 2 heart transplant recipients. All patients achieved sustained virologic response at 24 weeks. At week 12 after treatment, all liver functionality tests improved significantly with no significant changes in renal function. A decrease in the tacrolimus blood level/dose ratio for every patient was observed (370.04 ± 253.93 vs. 186.44 ± 123.74 ng/mL per mg/kg; p < 0.05). The requirements of tacrolimus dose increased after Hepatitis C Virus treatment (0.03 ± 0.04 vs. 0.04 ± 0.03 mg/kg/day, p < 0.05) to reach lower blood levels than before treatment (6 ± 2.25 vs. 4.67 ± 1.51 ng/mL, p < 0.05). Conclusion Caution is advised to clinicians; close monitoring of tacrolimus levels after direct-acting antiviral agents is recommended in order to avoid infradosification that could pose a risk of graft rejection.

Keywords: Direct-acting antiviral; Hepatitis C virus; Organ transplantation; Tacrolimus.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Hepatitis C* / drug therapy
  • Hepatitis C, Chronic* / drug therapy
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation*
  • Tacrolimus
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Immunosuppressive Agents
  • Tacrolimus