Feb 25, 2009
Optimizing the Current Therapy for Chronic Hepatitis C Virus:
Peginterferon and Ribavirin Dosing and the Utility of Growth Factors
Clin Liver Dis 12 (2008) 487–505
Mitchell L. Shiffman, MD
Impact of adverse events and dose reduction
As opposed to interrupting or prematurely stopping ribavirin, which enhances breakthrough and relapse, recent data suggest that merely reducing the dose of ribavirin in response to adverse events does not significantly affect these milestones, and therefore has little impact on the SVR.
A more recent analysis has evaluated the impact of stepwise ribavirin dosing, from greater than 97% to less than 60% of the total expected cumulative dose, on virologic response and SVR .
It is important to note that this study included only those patients who remained on full-dose peginterferon for 48 weeks, and therefore evaluated the impact of reducing only the ribavirin dose. No significant impact of ribavirin dose on virologic response was observed.
A significant decline in SVR (from 57% to 67% to only 34%) did occur but only when the total cumulative ribavirin dose declined to less than 60%.
In fact, the medical and nursing staff at the author’s institution frequently perform a one-step (200 mg) ribavirin reduction in a patient who has developed severe fatigue even if the hemoglobin has not declined to less than 10 mg/dL. This small reduction in the ribavirin dose does not have a significant impact on the total cumulative ribavirin exposure (see Fig. 6) and, in many cases, yields significant symptomatic improvement and allows the patient to be more enthusiastic about continuing therapy.
The goal of dose reduction is to prevent the hemoglobin from decreasing so much that the patient must interrupt ribavirin dosing, which clearly increases the risks of breakthrough and relapse.
(Thanks to CockSparrow for finding this)