Assessing adequacy of ribavirin therapy or potential drug-related toxicity
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
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