Reason for posting: Health Canada has alerted health care professionals of a letter issued by Janssen-Ortho Inc. warning of serious postmarketing adverse events associated with the anemia drug epoetin alfa (Eprex).1 Seven cases of pure red cell aplasia (PRCA) have been reported in Canada after an estimated 80 000 patient-years of exposure to the drug. Affected patients had a worsening of anemia that was unresponsive to increasing doses of the drug months to years after initiation of the therapy and ultimately became transfusion dependent. PRCA was confirmed by means of bone marrow evaluation, and in many patients antibodies neutralizing the epoetin alfa were found.
The drug: Endogenous erythropoietin is a glycoprotein produced by the kidneys that stimulates the division and differentiation of erythroid precursors in the bone marrow. Epoetin alfa is a recombinant version of the hormone with an identical amino acid sequence. It is approved in Canada for the treatment of anemia associated with chronic renal failure, cancer, cancer chemotherapy and zidovudine-treated HIV infection, and for use in patients undergoing autologous blood donation and to reduce exposure to allogeneic blood for patients undergoing major elective surgery.
Previously recognized adverse events associated with epoetin alfa include hypertension, hypertensive crises (including headaches, confusion and generalized tonic-clonic seizures), thrombotic events and nonspecific “flu-like” symptoms.2 A complete list of adverse effects and contraindications is provided in the Compendium of Pharmaceuticals and Specialties.2
What to do: Physicians need to identify patients taking epoetin alfa who have a worsening of their anemia or do not respond to the drug. Relevant anemia workups should be performed, including assessments for blood loss, hemolysis, systemic infection or inflammation, aluminum toxicity and for deficiencies of iron, folate and vitamin B12 when appropriate. If PRCA is suspected, bone marrow evaluation and testing for erythropoietin autoantibodies are indicated. Other causes of PRCA should be excluded (see box) and the epoetin alfa therapy stopped immediately. Patients may become transfusion dependent.
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Pure red-cell aplasia (PRCA) is a selective failure of the erythroid elements in bone marrow. Affected patients have
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· normochromic, normocytic anemia
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· a severely restricted reticulocyte count
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· normal granulocyte and platelet counts
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· virtually no erythroid precursors in bone marrow aspirates
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Other conditions associated with PRCA include
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· thymomas
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· lymphoma
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· chronic T- or B-cell lymphocytic leukemia
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· acquired hypogammaglobulinemia
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· systemic lupus erythematosus
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· T-gamma lymphocytosis
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· AIDS
References
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