Procrit is appropriate in the anemias due to erytrhopoietin underproduction or deficiency. In Hepatitis C it is usually both as well as due to chronic illness.
Several studies have evaluated the use of recombinant human erythropoietin alfa (rHuEPO) (Procrit and Epogen) for the treatment of ribavirin/interferon-induced anemia in HCV-infected patients. In a letter to the editor of Hepatology, researchers in France reported the results of a study of 13 patients with HCV, one of whom was also HIV-infected, who developed anemia on interferon alfa-2b/ribavirin treatment and who were treated with rHuEPO.
In one of the first studies, 9 patients received high dose (6 million units 3 times a week) and 3 patients low-dose (3 million units 3 times a week) interferon alfa-2b and 1 patient received PEG-interferon alfa-2b at 80 µg per week. Ribavirin was given at 1 gram or 1.2 gram per day. When anemia developed, rHuEPO was given at a dose of 4,000 units 2 to 3 times weekly to 11 patients, 8,000 units 3 times weekly to 1 patient, and 10,000 units 3 times weekly to 2 patients.
The baseline median hemoglobin in the 13 patients was 13.3 g/dL and the median hemoglobin nadir on interferon/ribavirin was 10.2 g/dL. On rHuEPO, the hemoglobin increased to a median of 11.5 g/dL and none of the patients on rHuEPO stopped treatment due to anemia. It should be noted, however, that the ribavirin dose was also decreased to 800 mg in 3 patients, to 600 mg in 1 patient, and to 200 mg in 1 patient (who had cirrhosis and HIV). The authors reported that 10 patients had an initial response to interferon/ribavirin treatment, with 4 achieving a sustained response, 5 still under treatment or follow-up, and 1 patient relapsed.
The authors conclude, “in our cohort of patients with chronic hepatitis C treated with interferon/ribavirin combination therapy, rHuEPO was beneficial in the treatment of ribavirin-induced anemia and allowed for the maintenance of a generally efficient ribavirin dosage. “Well-designed clinical trials with larger numbers of patients would be useful to establish the benefit of rHuEPO in this clinical situation as well as the optimal dose and frequency of administration.” This report supports the use of rHuEPO in patients with interferon/ribavirin induced anemia. Further studies are underway to evaluate the questions raised by the authors in their conclusion.
A recent study examined the relationship between ribavirin administration and endogenous erythropoietin production. Adequate endogenous erythropoietin production was demonstrated in patients with compensated liver disease in response to ribavirin-induced hemolytic anemia. The response was maintained, although the anemia was not corrected because of ongoing hemolysis and the continuous intake of ribavirin. The authors challenged the 40,000-U/week subcutaneous dosage administered in clinical trials because it was 3 times higher than the physiologic increase in erythropoietin production in response to ribavirin-induced anemia.
In a study of 46 patients with HCV infection, monotherapy with standard or peginterferon caused hemoglobin levels to decline below baseline values in 7 days, with a compensatory 70-96% increase in endogenous erythropoietin levels.] Reticulocyte production did not increase over baseline values; this finding represented an inadequate response to increased erythropoietin level and contributed to the development of anemia. Therefore, despite increased erythropoietin levels, the compensatory response could not overcome the suppressive effects of interferon alfa on bone marrow.This suggests that erytrhopoietin is not useful in this situation. It remains investigational and more and larger studies remain to be done.
Samit Hirawat, Stuart M. Lichtman, Steven L. Allen : Recombinant human erythropoietin use in hemolytic anemia due to prosthetic heart valves: A promising treatment American Journal of Hematology: 66, 3, 224-226, 2001
A. Gergely and others. Treatment of ribavirin/interferon-induced anemia with erythropoietin in patients with hepatitis C. Hepatology 2002; 35:1281.
Dev A, Patel K, Muir A, McHutchison JG. Erythropoietin for ribavirin-induced anemia in hepatitis C: more answers but many more questions. Am J Gastroenterol 2003;98(11): 2344-7.
Durante Mangoni E, Marrone A, Saviano D, et al. Normal erythropoietin response in chronic hepatitis C patients with ribavirin-induced anaemia. Antivir Ther 2003;8(1):57-63.
Peck-Radosavljevic M, Wichlas M, Homoncik-Kraml M, et al. Rapid suppression of hematopoiesis by standard or pegylated interferon-alpha. Gastroenterology 2002;123(1):141-51.
Ortho Biotech Products, L.P. Procrit (epoetin alfa) full prescribing information. Raritan, NJ; 2004.