Ribavirin: How Does it Work and is it Still Needed?

Abstract

Ribavirin is a synthetic guanosine analogue, which acts against hepatitis C virus (HCV) through several mechanisms that include 1) immune modulation; 2) inhibition of inosine monophosphate dehydrogenase 3) inhibition of RNA-dependent RNA polymerase; 4) induction of HCV mutagenesis; and 5) modulation of interferonstimulated gene expression. Addition of ribavirin to peginterferon-α substantially improves sustained virologic response (SVR) and decreases relapse rates. Ribavirin can be associated with hemolytic anemia. However, recent data suggest that SVR is not negatively impacted by treatmentinduce anemia. Notably, optimal dosing strategy and the proper management of anemia are crucial to achieve the best treatment outcome. Several advances have been made in the areas relevant to ribavirin, such as the discovery of inosine triphosphatase gene as a promising pharmacogenetic marker and a predictor of anemia, and the role for erythropoiesis-stimulating agent in the management of anemia related to ribavirin use. Recent observations indicate that ribavirin will remain as a critical component of HCV therapy, even in the context of direct acting antivirals.

Management of patients with hepatitis C infection and renal disease

“…The route of RBV elimination is mainly by the kidney. Thus, body weight is also highly correlated with RBV clearance [47][48][49] . Notably, the optimal dosing strategy of RBV must be calculated according to the renal function, as measured by CrCl [47][48][49] .…”

“…Thus, body weight is also highly correlated with RBV clearance [47][48][49] . Notably, the optimal dosing strategy of RBV must be calculated according to the renal function, as measured by CrCl [47][48][49] . The AUC for RBV is increased by 2 folds in patients with CrCl 30-60 mL/min and by 3 folds in patients with CrCl 10-30 mL/min respectively, when compared to those with CrCl > 90 mL/min [50] .…”

“…Due to a short elimination half-life of IFN following subcutaneous injections (2-4 h), sustained plasma levels and subsequent oxidative stress within red blood cells (RBC) [51] . Ribavirin is actively transported into RBC and accumulates within RBC with the concentration greatly exceeding what is observed in plasma (up to 60-fold) [47,51,52] . Once inside RBC, RBV is phosphorylated to RBV-triphosphate, then it is eliminated slowly from RBC [47,51,52] .…”

“…It has extensive volume of distribution and the steady state is reached in 7-11 wk after multiple dosing and with a terminal half-life of 12 d [47][48][49] . The route of RBV elimination is mainly by the kidney.…”

Potential Liver Transplant Recipients with Hepatitis C: Should They Be Treated Before or After Transplantation?

“…68 RBV has extensive volume of distribution and is eliminated mainly through the kidneys. 85 There is increased risk of anemia in patients with cirrhosis due to associated hypersplenism, reduced output of erythropoietin, poorer bone marrow response, nutritional deficiencies and occult gastrointestinal blood loss. It is therefore, advisable to start with lower doses and gradually adjusted to weight based doses depending on hemoglobin and creatinine response.…”