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Assessing adequacy of ribavirin therapy or potential drug-related toxicity
Ribavirin is a nucleoside analog with antiviral activity against a number of RNA and DNA viruses, including hepatitis C virus (HCV). In combination with interferon, ribavirin is a treatment of choice for chronic HCV infection. In this setting, higher serum concentrations of ribavirin appear to correlate with the likelihood of achieving virological response; however, the drug dose is limited by concentration-dependent hemolytic anemia. Although no consensus therapeutic targets or toxic thresholds have been established, ribavirin concentrations between 2,500 and 4,000 ng/mL have been suggested to improve virological response and minimize toxicity.
The half-life of ribavirin is very long, typically 5 days or more. For this reason, steady-state concentrations are not achieved until several weeks into therapy; most studies have performed initial therapeutic monitoring after at least 28 days of ribavirin treatment. Specimens should be drawn immediately prior to the next scheduled dose, or at minimum >12 hours after the last dose.
Elimination of ribavirin is also very slow, and due to incorporation of the drug into red blood cells, may take up to 6 months after the cessation of therapy. Ribavirin has shown teratogenic activity in animal models, thus patients are recommended to practice stringent birth control until at least 6 months after the end of treatment.
Ribavirin concentrations >2,500 ng/mL appear to correlate with greater likelihood of virological response in patients with chronic hepatitis C virus infection. Elevated concentrations in the setting of hemolytic anemia are consistent with ribavirin toxicity.
Therapeutic targets have not been well established; reference values are provided as a guide to interpretation but are not definitive.
Serum must be removed from cells within 2 hours. Delayed processing can result in decreased ribavirin concentration.
1. Jen JF, Glue P, Gupta S, et al: Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Ther Drug Monit 2000;22(5):555-65
2. Marquet P, Sauvage FL, Loustaud-Ratti V, et al: Stability of ribavirin concentrations depending on the type of blood collection tube and preanalytical conditions. Ther Drug Monit 2010;32:237-241
3. Pedersen C, Alsio A, Lagging M, et al: Ribavirin plasma concentration is a predictor of sustained virological response in patients treated for chronic hepatitis C virus genotype 2/3 infection. J Viral Hepatitis 2011;18(4):245-51