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Published in the Bulletin of Experimental Treatments for AIDS July 1998 issue, by the San Francisco AIDS Foundation. |
DRUG WATCH: Epoietin alfa (EPO) for AnemiaEpoietin alfa (EPO) is a genetically engineered version of a natural hormone, erythropoietin, which stimulates the bone marrow to produce red blood cells. The synthetic version of the hormone -- EPO -- is used to treat severe anemia. Brand names for the drug are Epogen, manufactured by Amgen, located in Thousand Oaks, CA, and Procrit, distributed by Ortho Biotech, a pharmaceutical company headquartered in Raritan, NJ. Development HistoryAmgen scientists first developed genetically engineered erythropoietin in 1983. They called the compound "epoietin alfa." In 1989, the drug was approved by the U.S. Food and Drug Administration (FDA) for treating anemia in people undergoing dialysis for chronic kidney failure, and clinical trials in people with HIV/AIDS and anemia were begun. Also in 1989, FDA approved a compassionate use program to distribute epoietin alfa free of charge to people with AIDS and severe anemia related to AZT (Retrovir) use. In January 1991, FDA approved EPO for the treatment of severe AZT-related anemia. Today, EPO is available for FDA-approved use to treat anemia that is caused by chronic kidney disease, AZT use and chemotherapy in people receiving cancer treatment and to decrease blood transfusions in surgery patients. The drug is also used (but not approved) for people with anemia that is caused by other drugs or chronic diseases. Indications and Use in People with HIVHIV infection itself can reduce the number of viable, oxygen-carrying red blood cells circulating in the bloodstream; people with HIV who use certain antiretroviral drugs, especially AZT, are at elevated risk for loss of red blood cells and consequent anemia. Anemia secondary to AZT use is much more common when higher doses of AZT are used, such as 1,200 mg/day. Now that the daily dose is nearly always 600 mg/day, the rate of anemia is much lower. The standard dose of EPO is 100 U/kg (ranging from 50-150) 3 times weekly, administered by subcutaneous or intravenous injection either at a doctor’s office or self-administered at home. People with HIV generally take the 100 U/kg dose 3 times per week for 8 weeks and are evaluated at 4-week intervals. Sometimes the dose is raised to 300 U/kg. In people with HIV, EPO is used to elevate or maintain the red blood cell level as reflected by measurements of hematocrit or hemoglobin (see Blood Cell Deficiencies, this issue), and to decrease the need for transfusions. EPO is intended for use in people who are receiving AZT at standard doses and who have low serum erythropoietin levels. EPO is not indicated for treating anemia that is related to iron or folate deficiencies or to gastrointestinal bleeding. Furthermore, EPO is not to be used by people who have uncontrolled hypertension (high blood pressure), known hypersensitivity to mammalian cell-derived products, or known hypersensitivity to human albumin (a blood protein). Because EPO can cause an increase in blood pressure, blood pressure should be monitored in people using the drug. In general, all persons using or administering EPO are cautioned to take proper precautions for injected products, in order to avoid allergic or other adverse reactions. Transient rashes have been reported in people using EPO, but neither anaphylaxis nor severe allergic reactions have been reported. There are no safety and efficacy data for people with underlying blood disorders (e.g., sickle cell anemia) or seizure disorders. Summary of Clinical Trial FindingsEPO was studied in 4 placebo-controlled trials with nearly 300 people with HIV and anemia. In clinical studies in people with HIV, EPO was shown to raise hematocrit and reduce or eliminate the need for transfusions in people with AZT-related anemia. People taking EPO were shown to require 40% less blood in transfusions than people taking placebo. Also, no adverse drug interactions were noted. HIV positive study participants taking EPO tolerated it well; the most common adverse events included fever, fatigue, headache, cough and reactions at the injection site (e.g., soreness), but participants taking placebo reported similar side effects. Since the drug is injected, not swallowed, its absorption is unaffected by food. EPO has not been studied in pregnant women. The FDA has assigned the drug to Pregnancy Category C; while some adverse effects were noticed when pregnant rats received doses equivalent to 5 times the human dose, no adequate studies have been conducted in humans. Therefore, EPO should be used during pregnancy only if the potential benefits have been deemed to equal or outweigh the potential risks to the fetus. Some post-menopausal women using EPO have reportedly experienced a resumption of menstruation; the possibility of pregnancy should be discussed and the need for contraception evaluated. There are no data from well controlled trials on the use of EPO in children. A cautionary note: the injection solution contains benzyl alcohol, which has been associated with death when given to some premature infants. ConclusionThe advent of EPO constituted a significant advance in the treatment of severe anemia. Before recombinant EPO, people with severe anemia, including people with HIV/AIDS, were treated by transfusion, an involved procedure that includes risk of secondary infection. With EPO, early treatment of mild-to-moderate anemia may prevent both the development of severe anemia and the need to resort to transfusions. More studies are needed in order to understand the usefulness of EPO for HIV positive persons with anemia who are not taking AZT and who have normal serum erythropoietin levels. Today, much controversy exists about the use of EPO in such persons; clinical trials might resolve questions about EPO’s role and efficacy. Often, the cost of the medicine precludes routine use in this population. Leslie Hanna is Associate Editor of BETA.
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