[Experience in the management of immunosuppressant treatment with hepatitis C virus protease inhibitors]

Abstract

Introduction: Antiviral drugs for the treatment of hepatitis C virus (HCV) infections have a large number of interactions. The aim of this study was to describe the interactions of telaprevir, boceprevir and sofosbuvir with immunosuppressive drugs in liver transplant recipients.

Methods: A retrospective observational study was performed in liver transplant patients with HCV infection who started treatment with telaprevir, boceprevir or sofosbuvir. Dose, regimens and plasma levels of tacrolimus, cyclosporine and sirolimus before and after antiviral treatment initiation were collected. Average variations in dose, dosing interval and immunosuppressive plasma levels after the start of treatment were calculated.

Results: Thirty-five patients were included. In patients treated with telaprevir (n = 18), the cyclosporine dose was reduced by an average of 59.1% (SD = 14.6%), yielding an average reduction of 14.6% (18.8%) in plasma levels. The dose of tacrolimus was reduced by 34.3% (31.7%), increasing the dosing interval by a mean of 73.4 (38.2) hours. After this variation, tacrolimus levels were increased by an average of 59.7% (89.6%). In patients treated with boceprevir (n = 4), tacrolimus started with a reduction of 18.1% (9.8%) of the initial dose and an average increase in the dosing interval of 12.0 (16.9) hours, showing a mean reduction in plasma levels of 37.7% (21.8%). Sofosbuvir therapy (n = 13) showed no significant variations in immunosuppressive drug levels.

Conclusions: The interaction of telaprevir and boceprevir with immunosuppressive drugs requires a substantial dose reduction at the beginning of treatment and close monitoring of plasma levels.

Keywords: Drug interactions; Hepatitis C; Interacción medicamentosa; Liver transplantation; Trasplante hepático.