taribavirin and Anemia

The current standard therapy for chronic hepatitis C virus (HCV), combination therapy with pegylated interferon and ribavirin, is plagued by a number of side effects, most notably anemia. This anemia is typically managed with a reduction of ribavirin dosing, which may lead to reduced efficacy. Taribavirin, an oral prodrug of ribavirin, which has been shown to induce a lesser degree of anemia, is being investigated for the treatment of chronic HCV.. To summarize the clinical trials involving taribavirin and its potential role in the treatment of chronic HCV.. Information was obtained via searches for data related to taribavirin, as well as other current and investigational therapies for chronic HCV. Press releases discussing otherwise unpublished trial outcomes were obtained from the website of Valeant Pharmaceuticals, the producer of Viramidine (taribavirin).. Taribavirin may increase adherence to therapy for chronic HCV by reducing the need for dose reduction due to anemia. A recent Phase II trial investigating early and sustained virological response showed no statistically significant differences between ribavirin 1000/1200 mg and taribavirin at 800-, 1200-, or 1600-mg dosing, while illustrating a lesser degree of anemia in 800- and 1200-mg dosing of taribavirin. Ongoing studies will continue to examine the efficacy of combination therapy with taribavirin in the place of ribavirin.

Topics: Anemia; Animals; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Hepatitis C, Chronic; Humans; Prodrugs; Ribavirin; Treatment Outcome

Anemia is a common side effect that begins soon after the initiation of peginterferon/ribavirin in the treatment of hepatitis C virus (HCV) infection. It can cause symptoms that negatively impact quality of life (QOL) and is the most common reason for reducing the dose and temporarily or permanently discontinuing ribavirin. Such dose modifications have been shown to reduce the efficacy of treatment. Administering erythropoietin can improve anemia caused by peginterferon and ribavirin therapy and is more effective than dose reduction at improving QOL during treatment. However, erythropoietin, which is not approved by the U.S. Food and Drug Administration (FDA) for use in patients with HCV infection, adds another parenteral drug to the patient's treatment regimen, and is associated with additional costs, inconvenience, and potential side effects. A new ribavirin analog, viramidine, is expected to be associated with a lower incidence of anemia and, if proven effective, may eventually be substituted for ribavirin in combination with peginterferon to treat chronic hepatitis C. In the meantime, physicians must make the best possible use of the available options for managing anemia, especially in select patient groups who are most at risk for anemia and its complications.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Erythropoietin; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Quality of Life; Recombinant Proteins; Ribavirin

Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. The current best treatment for HCV infection is combination therapy with pegylated interferon and ribavirin. Although this regimen produces sustained virologic responses (SVRs) in approximately 50% of patients, it can be associated with a potentially dose-limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result of ribavirin-induced hemolysis, and this anemia can be problematic in patients with HCV infection, especially those who have comorbid renal or cardiovascular disorders. In general, anemia can increase the risk of morbidity and mortality, and may have negative effects on cerebral function and quality of life. Although ribavirin-associated anemia can be reversed by dose reduction or discontinuation, this approach compromises outcomes by significantly decreasing SVR rates. Recombinant human erythropoietin has been used to manage ribavirin-associated anemia but has other potential disadvantages. Viramidine, a liver-targeting prodrug of ribavirin, has the potential to maintain the virologic efficacy of ribavirin while decreasing the risk of hemolytic anemia in patients with chronic hepatitis C.

Topics: Anemia; Antiviral Agents; Cardiovascular System; Cognition Disorders; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hemoglobins; Hepacivirus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Polyethylene Glycols; Quality of Life; Recombinant Proteins; Ribavirin

Pegylated interferon (peg-IFN) plus ribavirin (standard of care for chronic hepatitis C virus [HCV]), can cause dose-limiting anemia in up to 22% of patients. Viramidine is associated with a lower incidence of anemia because of its liver-targeting properties.. The efficacy and safety of viramidine versus ribavirin plus peg-IFN alfa-2a was assessed in patients with HCV. Randomized patients received peg-IFN alfa-2a 180 mcg with viramidine 600 mg twice daily or weight-based doses of ribavirin 1000 or 1200 mg/day. Treatment duration was based on HCV ribonucleic acid (RNA) genotype: genotype 2/3 and non-2/3 patients were treated for 24 and 48 weeks, respectively. The primary efficacy end point was the non-inferiority of viramidine versus ribavirin (proportion of patients achieving sustained virologic response at week 24). The primary safety end point was the proportion of patients experiencing a hemoglobin event.. In total, 962 patients received peg-IFN alfa-2a with viramidine (n=644) or ribavirin (n=318). Sustained virologic response was achieved in 40% of viramidine-treated patients and 55% of ribavirin-treated patients (difference of proportions 0.150 [95% CI, 0.09, 0.21]). Improved efficacy was seen with higher viramidine exposure on a mg/kg basis. Viramidine was significantly superior to ribavirin in hemoglobin event rates (54% vs. 80%; p<0.001). Adverse event rates were similar between groups except for diarrhea (viramidine 29.5%; ribavirin 15.7%; p<0.0001).. Viramidine 600 mg BID did not meet the primary efficacy non-inferiority end point but met the safety end point. Determination of a viramidine dosage that would yield superior efficacy over ribavirin is needed.

Topics: Adult; Anemia; Antiviral Agents; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Endpoint Determination; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Incidence; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin; RNA, Viral; Treatment Outcome

Pegylated interferon plus ribavirin can cause dose-limiting anemia. Taribavirin, a ribavirin prodrug, has shown a lower incidence of anemia. We sought to determine the efficacy and safety of taribavirin vs. ribavirin combined with pegylated interferon in patients with chronic hepatitis C (CHC).. This phase 2 open-label study randomized 180 patients with CHC to receive pegylated interferon alfa-2a 180 microg/week plus taribavirin 800, 1200 or 1600 mg QD or ribavirin 1000 or 1200 mg QD. Efficacy variables included proportions of patients with undetectable serum HCV RNA levels at end of treatment and after a 24-week follow-up.. The proportions of patients with undetectable HCV RNA at 12 weeks did not differ significantly between taribavirin (38%, 42%, and 49% for the 800, 1200, and 1600 mg groups) and ribavirin (49%). The highest proportion of patients with undetectable HCV RNA at end of treatment and at follow-up occurred in both the taribavirin 1200mg QD (63% and 37%) and ribavirin groups (62% and 44%). SVR rates were 23%, 37% and 29% for taribavirin and 44% for ribavirin. Fewer patients on any dose of taribavirin had severe anemia (hemoglobin <10 g/dL) than on ribavirin (6/135 [4%] vs. 12/45 [27%]).. Given with interferon, taribavirin produced SVR rates comparable to those of ribavirin, with a lower occurrence of anemia.

Topics: Adult; Aged; Anemia; Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Incidence; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Ribavirin; RNA, Viral; Thrombocytopenia; Treatment Outcome

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Hepatitis C; Humans; Ribavirin; Treatment Outcome