Dosage Adjustment of Ribavirin Based on Renal Function in Japanese Patients with Chronic Hepatitis C

Abstract

The daily dose of ribavirin is currently determined based on body weight. In the present study, the authors examined factors influencing total plasma clearance (CL(total)) and the toxic level on red blood cells of ribavirin in such body weight-based dosage adjustment in Japanese chronic hepatitis C patients (13 male and 6 female). Patients received ribavirin (600 or 800 mg/d) orally, depending on their body weights, together with interferon alpha-2b (6 million units) intramuscularly. A steady-state trough plasma concentration (C(pss)) was achieved approximately 4 weeks after the initiation of treatment, but the value was scattered among patients in a range from 1100 to 4200 ng/mL. The high C(pss) of ribavirin of approximately 4000 ng/mL decreased hemoglobin concentrations to less than 8.5 g/dL. The individual CL(total), estimated by dividing dose normalized by body weight by C(pss), of ribavirin correlated significantly with the patient's creatinine clearance. In contrast, no relationship was observed with other parameters such as age, body weight, serum creatinine concentration, alanine aminotransferase (ALT) concentration, or aspartate aminotransferase (AST) concentration, though ALT and AST concentrations decreased with ribavirin treatment in most patients. These results indicate that CL(total) of ribavirin is dependent on renal function (creatinine clearance), and hemolysis is induced by high ribavirin concentrations in plasma. Dosage adjustment of ribavirin based on renal function and body weight would provide effective and safer treatment without causing hemolysis.

Ribavirin Levels and Haemoglobin Decline in Early Virological Responders and Non-Responders to Hepatitis C Virus Combination Therapy

“…While renal function was normal in all patients investigated in the present study, this confi rms previous fi ndings that ribavirin clearance is highly dependent on GFR [10,12] .…”

“…This might indirectly affect the antioxidant defence mechanism leading to haemolytic anaemia, although the exact underlying mechanism is unknown [6] . Whatever the responsible factor, anaemia as well as impaired renal function may necessitate dose reductions for ribavirin [4,12] .…”

A Practical Guide to the Management of HCV Infection Following Liver Transplantation

“…Watt et al Figure 2) (25). In the nontransplant setting, higher doses and longer duration of therapy can both increase SVR rates.…”

Safety, Tolerability, and Pharmacokinetics of Ribavirin in Hepatitis C Virus-Infected Patients with Various Degrees of Renal Impairment

“…RBV exposure has been shown to influence both clinical response and toxicity to therapy (9)(10)(11)(12)(13)(14). Current treatment guidelines recommend RBV doses ranging from 200 to 800 mg/day in patients with moderate to severe kidney disease not undergoing hemodialysis and markedly reduced RBV daily doses in patients on dialysis (5).…”