Combination therapy with ribavirin and amantadine in renal transplant patients with chronic hepatitis C virus infection is not superior to ribavirin alone

J Clin Virol. 2007 May;39(1):54-8. doi: 10.1016/j.jcv.2007.02.006. Epub 2007 Apr 3.

Abstract

Background: Standard treatment of chronic hepatitis C virus (HCV) infection based on interferon is not an option in renal transplant recipients due to the high risk of acute allograft rejection.

Objectives: To assess efficacy and tolerability of combined treatment with ribavirin and amantadine regarding viral clearance, normalization of liver enzymes, and improvement of HCV-related hepatopathy and graft nephropathy in HCV-RNA-positive renal transplant patients.

Study design: Prospective randomized controlled study comparing ribavirin, 1000 mg daily (n=7), versus ribavirin, 1000 mg, in combination with amantadine, 200 mg daily (n=8), for 12 months, versus no therapy (controls, n=26). Results were evaluated by intention-to-treat analysis.

Results: No relevant differences among treatment groups were found regarding liver enzymes, HCV viremia, liver histology and renal parameters. However, antiviral treatment was limited by anemia, resulting in premature withdrawal from therapy and requiring substitution with recombinant erythropoietin in most patients. The best predictor for tolerability of active treatment was a creatinine clearance rate>50 ml/min.

Conclusions: Addition of amantadine to ribavirin seems not to be superior to ribavirin monotherapy in renal transplant patients with chronic replicating HCV infection. However, this may be explained in part by the poor tolerability of both ribavirin and amantadine in patients with impaired renal function, resulting in drop-outs and subtherapeutic drug dosage.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amantadine / adverse effects
  • Amantadine / therapeutic use*
  • Anemia / chemically induced
  • Anemia / drug therapy
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Hepacivirus
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Ribavirin / adverse effects
  • Ribavirin / therapeutic use*

Substances

  • Antiviral Agents
  • Ribavirin
  • Amantadine