The utility of therapeutic drug monitoring for ribavirin in patients with chronic hepatitis C--a critical review.

OBJECTIVE

To evaluate the utility of therapeutic drug monitoring (TDM) for ribavirin in chronic hepatitis C.

DATA SOURCES

Literature searches were conducted through PubMed (1949-June 2009), EMBASE (1980-June 2009), BIOSIS Previews (1969-June 2009), International Pharmaceutical Abstracts (1970-June 2009), Google, and www.clinicaltrials.gov using the terms ribavirin, therapeutic monitoring, hepatitis C, and drug levels. In addition, pertinent reference citations from identified publications were reviewed. Studies were limited to English language, adult age, and human subjects.

STUDY SELECTION AND DATA EXTRACTION

All articles identified from the data sources were evaluated. Studies that measured ribavirin concentrations or dose and treatment response were included in the review.

DATA SYNTHESIS

While monitoring of ribavirin plasma concentrations to improve treatment response in patients with chronic hepatitis C has been described in the literature, the utility of TDM for ribavirin in this group of patients has not been systematically studied. Thus, a previously published 9-step decision-making algorithm was employed to help determine whether TDM is warranted, based on currently available evidence. Thirty articles involving patients with chronic hepatitis C mono-infection, 12 for hepatitis C-HIV coinfection, 5 for renal dysfunction, and 5 for post-liver transplant patients were reviewed. In all subpopulations, studies exist that either support or refute the usefulness of ribavirin TDM. Additionally, the majority of the included studies had methodologic limitations, such as small sample size, retrospective analyses, and lack of p value adjustment for multiple analyses. Large randomized controlled trials would help to definitively answer this question.

CONCLUSIONS

There is conflicting evidence about the existence of a correlation between ribavirin concentrations and virologic response or development of toxicity. This inconsistent evidence, coupled with the currently employed effective strategies that maximize sustained virologic response and minimize development of anemia, precludes the utility of TDM for ribavirin.