      Document 0185
 DOCN  DRG0185
 UNIQUE IDENTIFIER        DRG-0062
 NAME OF SUBSTANCE        Erythropoietin [Merck Index 1989]
 REGISTRY NUMBER          113427-24-0
 STANDARD CHEMICAL NAME   1-165-Erythropoietin (human clone
                          lambdaHEPOFL13 protein moiety), glycoform
                          alpha [USAN 1996]
 SYNONYMS                 Eprex [FDA 004A-G]
 SYNONYMS                 EPO [FDA 004A-G]
 SYNONYMS                 r-HuEPO [FDA 004A-G]
 SYNONYMS                 Epogen [PDR 1995]
 SYNONYMS                 Procrit [PDR 1995]
 SYNONYMS                 Erythropoiesis stimulating factor [Merck
                          Index 1989]
 SYNONYMS                 ESF [Merck Index 1989]
 SYNONYMS                 Ep [Merck Index 1989]
 SYNONYMS                 Erypo [Merck Index 1989]
 SYNONYMS                 Marogen [Merck Index 1989]
 SYNONYMS                 Epoetin Alpha [USAN 1996]
 PROTOCOL ID NUMBERS      FDA 004A
 PROTOCOL ID NUMBERS      FDA 004B
 PROTOCOL ID NUMBERS      FDA 004C
 PROTOCOL ID NUMBERS      FDA 004D
 PROTOCOL ID NUMBERS      FDA 004E
 PROTOCOL ID NUMBERS      FDA 004F
 PROTOCOL ID NUMBERS      FDA 004G
 PROTOCOL ID NUMBERS      FDA 061A
 PROTOCOL ID NUMBERS      NCI 91 C-01
 PROTOCOL ID NUMBERS      FDA 077A
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Endogenous human
                          erythropoietin, a growth factor, is a
                          glycosylated protein hormone that appears to
                          be secreted principally by renal peritubular
                          interstitial cells. Secretion of the hormone
                          occurs principally in response to reduction
                          in arterial or venous oxygen tension and
                          tissue oxygenation in the kidneys.
                          Erythropoietin induces the production of
                          erythrocytes principally by stimulating the
                          proliferation and differentiation of
                          committed erythroid precursors (i.e.,
                          burst-forming unit erythroids and
                          colony-forming unit erythroids). In patients
                          with chronic renal failure (CRF), production
                          of erythropoietin is impaired and this
                          deficiency is the primary cause of their
                          anemia. Recombinant human erythropoietin has
                          been shown to stimulate erythropoiesis in
                          anemic patients with CRF. Because of the
                          length of time required for erythropoiesis -
                          several days for erythroid progenitors to
                          mature and be released into circulation - a
                          clinically significant increase in hematocrit
                          is usually not observed in less than two
                          weeks. Responsiveness to erythropoietin in
                          HIV-infected patients (receiving zidovudine)
                          is dependent upon the endogenous serum
                          erythropoietin level prior to treatment.
                          Patients with levels of less than or equal to
                          500 mU/ml (with a zidovudine of less than or
                          equal to 4200 mg/week) may respond to
                          erythropoietin therapy; patients with higher
                          levels do not seem to respond. [AHFS Drug
                          Information 1995] [PDR 1995]
 DISEASES STUDIED/TREATED Treatment of anemia in AZT treated
                          HIV-infected patients [PDR 1993]
 DISEASES STUDIED/TREATED FDA approved 1/2/91 for treatment of anemia
                          resulting from AZT therapy [PDR 1993]
 DISEASES STUDIED/TREATED While manufacturers state that erythropoietin
                          therapy is not indicated for treatment of
                          anemia in HIV patients other than that
                          associated with zidovudine therapy,
 DISEASES STUDIED/TREATED preliminary data suggests that anemia in HIV
                          patients not receiving zidovudine also may
                          respond to therapy with recombinant human
                          erythropoietin [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Red blood cell growth stimulator [PDR 1995]
 CLASSIFICATION CODE      Anti-anemic [USAN 1996]
 CLASSIFICATION CODE      Hematinic [USAN 1996]
 OTHER MAJOR USES         Treatment of anemia of chronic renal failure,
                          including patients on dialysis (end stage
                          renal disease) and patients not on dialysis.
                          Indicated for the treatment of anemia in
                          patients with non-myeloid malignancies where
                          anemia is due to the effect of concomitantly
                          administered chemotherapy [PDR 1995]
 SUBSTANCE INTERACTIONS   Systematic drug interaction studies have not
                          been performed. However erythropoietin
                          clinical trials with other drugs or
                          biologicals have shown no evidence of
                          clinically important interactions. Androgens
                          have been used as adjuncts to erythropoietin
                          therapy in a few patients to decrease the
                          total amount of erythropoietin needed to
                          ameliorate anemia. However, controlled
                          studies are needed to establish potential
                          benefits and risks of such combination
                          therapies. Probenecid has been shown to
                          inhibit the renal tubular secretion of
                          endogenous erythropoietin in animals. While
                          relevance of such an interaction to humans is
                          not known, it should be considered when these
                          two substances are given concomitantly. [AHFS
                          Drug Information 1995]
 ADVERSE EFFECTS          Adverse events reported in clinical trials
                          with erythropoietin in zidovudine-treated
                          HIV-infected patients were consistent with
                          progression of the HIV infection. Such events
                          were not very different from those in
                          placebo-treated patients. [PDR 1995]
 CONTRAINDICATIONS        Exacerbation of hypertension has not been
                          observed with zidovudine-treated HIV patients
                          on erythropoietin therapy. However,
                          erythropoietin should be withheld if
                          pre-existing hypertension is uncontrolled. To
                          prevent potential exacerbation of
                          thrombocytosis, some clinicians suggest that
                          erythropoietin therapy be used with caution
                          in patients with high baseline platelet count
                          (e.g., exceeding 500,000/cubic mm).
                          Erythropoietin therapy should be initiated
                          cautiously in patients with documented
                          unstable angina or a history of recent
                          myocardial infarction. Safety and efficacy of
                          erythropoietin have not been established in
                          patients with pre-existing seizure disorders.
                          Since erythropoietin is a growth factor, it
                          should be used with caution in patients with
                          a known neoplasm or leukemic disease.
                          However, in vitro tests indicate that the
                          risks of tumor growth enhancement in patients
                          may be minimal for nonmyeloid cell neoplasms.
                          Erythropoietin should be used with caution in
                          patients with a history of porphyria. [AHFS
                          Drug Information 1995] [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Erythropoietin is a
                          glycoprotein produced in the kidney that
                          stimulates red blood cell production and the
                          division and differentiation of committed
                          erythroid progenitors of the bone marrow [PDR
                          1995] [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Epoetin alfa is the proper
                          name for recombinant human erythropoietin, a
                          165 amino acid glycoprotein that has the same
                          effect as natural erythropoietin [PDR 1995]
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: It is produced by mammalian
                          cells (Chinese hamster ovary) into which the
                          human erythropoietin gene has been inserted
                          by recombinant DNA technology [PDR 1995]
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Urinary human
                          erythropoietin occurs as a mixture of two
                          forms, alpha and beta. Each form has the same
                          functional polypeptide portion and produces
                          the same in vivo response [PDR 1995] [AHFS
                          Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The distinguishing
                          characteristics between the two forms is the
                          overall carbohydrate composition [PDR 1995]
                          [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The alpha form appears to
                          have the greater percentage of
                          N-acetylneuraminic acid in its carbohydrate
                          portion [PDR 1995] [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: About 30,400 [AHFS Drug
                          Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Single polypeptide chain;
                          the molecule is very hydrophobic [EPREX -
                          Ortho Pharmaceutical]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C809H1301N229O240S5 [USAN
                          1996]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 2,000, 3,000, 4,000 and 10,000
                          u/ml ampules. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous injection,
                          subcutaneous injection. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 2 to 8 C (36 to 46 F). Do
                          not freeze or shake. [PDR 1995]
 MANUFACTURERS            Ortho Pharmaceutical
 MANUFACTURERS            Amgen Inc.
 REFERENCES               Bukowksi R, Glaspy J, Steinberg D, Taylor CW,
                          Vadhan-Raj S, Sarokhan B, Lonczak L. Phase IV
                          clinical evaluation of recombinant human
                          erythropoietin (r-HuEPO) in anemic cancer
                          patients recieving chemotherapy (Meeting
                          abstract). Proc Annu Meet Am Soc Clin Oncol.
                          1994;13:A1594.
 REFERENCES               Caselli D, Maccabruni A, Fundaro C, Portelli
                          E, De Santis U, Gabiano C, Forni GL. Human
                          recombinant erythropoietin (r-Hu EPO) for
                          treatment of anemia in HIV-infected children.
                          Int Conf AIDS. 1994 Aug 7-12;10(1):224
                          (abstract no. PBO324).
 REFERENCES               Revicki DA, Brown RE, Henry DH, Mcneill MV,
                          Rios A, Watson T. Recombinant human
                          erythropoietin and health-related quality of
                          life of AIDS patients with anemia. J Acquir
                          Immune Defic Syndr. 1994 May;7(5):474-84.
 REFERENCES               Ghirga P, De Longis P, Paglia MG. Effects of
                          treatment with erythropoietin on 25 patients
                          with HIV-correlated anemia. Int Conf AIDS.
                          1993 Jun 6-11;9(1):499 (abstract no.
                          PO-B29-2182).
 REFERENCES               Zuccotti GV, Flumine P, Locatelli V,
                          Banderali G, Riva E. Growth factors and
                          HIV-infection in children. J Int Med Res.
                          1993 Nov-Dec;21(6):342-5.
 REFERENCES               Phair JP, Abels RI, Mcneil MV, Sullivan DJ,
                          Recombinant human erythropoietin treatment:
                          investigational new drug protocol for the
                          anemia of the acquired immunodeficiency
                          syndrome. Arch Intern Med. 1993 Dec
                          13;153(23):2669-75.
 REFERENCES               Revicki D, Brown R, Corea J, Ables R. Impact
                          of recombinant human erythropoietin on health
                          status outcomes of persons with AIDS and
                          anemia. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B213 (abstract no. PoB 3736).
 REFERENCES               Henry DH, Beall GN, Benson CA, Carey J, Cone
                          LA, Eron LJ, Fiala M, Fischl MA, Gabin SJ,
                          Gottlieb MS, et al. Recombinant human
                          erythropoietin in the treatment of anemia
                          associated with human immunodeficiency virus
                          (HIV) infection and zidovudine therapy. Ann
                          Intern Med. 1992 Nov 1;117(9):739-48.
 REFERENCES               Phair J, Abels R. Recombinant human
                          erythropietin (r-HuEPO) treatment IND
                          protocol for the anemia of AIDS--overall
                          results and AZT subgroup analysis. Int Conf
                          AIDS. 1992 Jul 19-24;88(1):M06 (abstract no.
                          MoA 0008).
 REFERENCES               Herman P, De Wit S, Franchioly P, Bergmann P,
                          Sommereijns B, Clumeck N. R-HU erythropoietin
                          (EPO) in HIV/zidovudine (ZDV) associated
                          anemia. Int Conf AIDS. 1991 Jun
                          16-21;7(1):267 (abstract no. M.B.2341).
 ENTRY MONTH              8911
 LAST REVISION DATE       951107
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
