      Document 0213
 DOCN  DRG0213
 UNIQUE IDENTIFIER        DRG-0034
 NAME OF SUBSTANCE        Interferon alfa-2a [USAN 1995]
 REGISTRY NUMBER          76543-88-9
 STANDARD CHEMICAL NAME   Interferon alpha-A [human leukocyte protein
                          moiety reduced] [USAN 1995]
 SYNONYMS                 Interferon alfa-2a, recombinant [PDR 1995]
 SYNONYMS                 Roferon-A [USAN 1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 013
 PROTOCOL ID NUMBERS      NIAID ACTG 014
 PROTOCOL ID NUMBERS      NIAID ACTG 068
 PROTOCOL ID NUMBERS      NIAID ACTG 096
 PROTOCOL ID NUMBERS      NIAID ACTG 197
 PROTOCOL ID NUMBERS      NIAID ACTG 216
 PROTOCOL ID NUMBERS      NIAID ACTG 153
 PROTOCOL ID NUMBERS      NCI 95 C-144
 IND NUMBER               30,001
 IND NUMBER               BB3038
 IND NUMBER               BB3043
 SECONDARY SOURCE ID      Ro 22-8181 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Alterations in the synthesis
                          of DNA, RNA and cellular proteins are
                          proposed mechanisms for the antiviral
                          antiproliferative activities of interferons.
                          The mechanism of antineoplastic activity is
                          unknown. Interferon alfa-2a is totally
                          filtered through the glomeruli and undergoes
                          rapid proteolytic degradation during tubular
                          reabsorption, rendering a negligible
                          reappearance of intact alpha interferon in
                          the systemic circulation. Minor pathways of
                          elimination for alpha interferon are liver
                          metabolism and biliary excretion. It has an
                          elimination half-life of 3.7 to 8.5 hours
                          (mean 5.1 hours); a volume of distribution at
                          steady-state of 0.223 to 0.748 l/kg (mean of
                          0.400 l/kg) and a total body clearance of
                          2.14 to 3.62 ml/min/kg (mean 2.79 ml/min/kg)
                          after a 36 million IU intravenous infusion.
                          After intramuscular and subcutaneous
                          administrations of 36 million IU, peak serum
                          concentration ranged from 1500 to 2580 pg/ml
                          (mean 2020 pg/ml) at a mean time to peak of
                          3.8 hours and from 1250 to 2320 pg/ml (mean
                          1730 pg/ml) of a mean time to peak of 7.3
                          hours, respectively. [PDR 1995]
 DISEASES STUDIED/TREATED Treatment of AIDS-related Kaposi's sarcoma
                          [PDR 1995]
 DISEASES STUDIED/TREATED FDA approved 11/21/88 for Kaposi's sarcoma
                          [PDR 1995]
 CLASSIFICATION CODE      Antineoplastic [USAN 1995]
 CLASSIFICATION CODE      Antiviral [USAN 1990]
 CLASSIFICATION CODE      Immunomodulator [USAN 1995]
 OTHER MAJOR USES         Hairy cell leukemia; condylomata acuminata;
                          chronic active hepatitis; bladder, cervical
                          and renal carcinoma; chronic myelocytic
                          leukemia; laryngeal papillomatosis;
                          non-Hodgkin's lymphoma; malignant melanoma;
                          multiple myeloma; and mycosis fungoides [USP
                          DI 1995]
 SUBSTANCE INTERACTIONS   Potential interactions which may be
                          beneficial or toxic can occur with the
                          following drugs: zidovudine can increase
                          antiviral efficacy or increase risk of
                          toxicity; vidarabine may produce
                          neurotoxicity; acyclovir increases antiviral
                          activity; antineoplastic agents and other
                          myelosuppressive drugs can potentiate
                          interferon activity or increase toxicity.
                          Theophylline and barbiturate metabolism may
                          be inhibited and CNS depressant activity may
                          be enhanced. Severe toxicity has followed
                          radiation therapy. [AHFS Drug Information
                          1995]
 ADVERSE EFFECTS          In patients with AIDS-related Kaposi's
                          sarcoma the following symptoms were observed:
                          Flu-like symptoms with fatigue, fever,
                          myalgia, chills, headache, and arthralgias.
                          Gastrointestinal: Anorexia, nausea, diarrhea,
                          emesis and abdominal pain. Central and
                          peripheral nervous system: Dizziness,
                          decreased mental status, depression,
                          paresthesia, confusion, diaphoresis, visual
                          disturbances and numbness. Pulmonary and
                          cardiovascular: Coughing, dyspnea, edema,
                          chest pain, and hypotension. Skin: Partial
                          alopecia, rash, dry skin, or pruritis. Other:
                          Weight loss, change in taste, dryness or
                          inflammation of oropharynx, night sweats and
                          rhinorrhea. Occasionally: Anxiety,
                          nervousness, emotional lability, vertigo,
                          forgetfulness, cardiac adverse effects
                          including palpitations and arrhythmias.
                          Abnormal laboratory test values, leukopenia,
                          neutropenia, thrombocytopenia, decreased
                          hemoglobin, increased SGOT, LDH, alkaline
                          phosphatase, bilirubin, BUN, and serum
                          creatinine. In other investigational studies
                          of interferon alfa-2a other adverse
                          experiences that occurred included: abdominal
                          fullness, hypermotility, hepatitis, gait
                          disturbance, hallucinations, encephalopathy,
                          psychomotor retardation, coma, stroke,
                          transient ischemia attacks, dysphagia,
                          sedation, apathy, irritability,
                          hyperactivity, claustrophobia, loss of
                          libido, congestive heart failure, myocardial
                          infarction, Raynaud's phenomenon, hot
                          flushes, tachypnea, and excessive salivation.
                          [PDR 1995]
 CONTRAINDICATIONS        Should be used with caution in patients with
                          severe preexisting cardiac disease, severe
                          renal or hepatic disease, seizure disorders
                          and/or compromised central nervous system
                          function, or myelosuppression. Should be used
                          during pregnancy only if potential benefit
                          outweighs the risk to the fetus. Should not
                          be used by breastfeeding women.
                          Contraindicated in patients with known
                          hypersensitivity to alpha interferon, mouse
                          immunoglobulin, or any component of Roferon.
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A synthetic recombinant
                          interferon manufactured by recombinant DNA
                          technology employing a genetically engineered
                          E. coli bacterium which codes for the human
                          protein [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Contains only a single
                          alpha interferon subtype and has a lysine
                          group at position 23 in the 165 amino acid
                          chain [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C860H1353N227O255S9 [USAN
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 19,241.28 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Water soluble [USP DI 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to beige powder
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Highly purified protein
                          containing 165 amino acids. Amino acid
                          sequence has been established [USP DI 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vials containing solution of
                          injectable saline formulation of 3, 9, 18, or
                          36 million units of interferon alfa-2a per
                          ml. [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vials containing 18 million IU
                          sterile powder for reconstitution
                          (reconstituted solution contains 6 million
                          units per ml). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Subcutaneous or
                          intramuscular injection. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store the injectable solution and
                          the sterile powder, its accompanying diluent,
                          and the reconstituted solution at 2-8 C
                          (36-46 F); do not freeze or shake. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Use reconstituted powder within
                          thirty days. [PDR 1995]
 MANUFACTURERS            Hoffmann-La Roche
 REFERENCES               Opravil M, Hodapp K, Luthy R. Interferon
                          alpha-2a+zidovudine vs. bleomycin+zidovudine
                          for HIV-associated Kaposi's sarcoma. Int Conf
                          AIDS. 1994 Aug 7-12;10(1):179 (abstract no.
                          PB0141).
 REFERENCES               Mouton Y, Goujard C, Raffi F, Seigneurin JM,
                          Bilbault P. A phase I/II open label
                          combination study of the tolerability and
                          activity of ddC and interferon alpha in
                          patients with early symptomatic HIV-infection
                          (ANRS protocol 016). Int Conf AIDS. 1994 Aug
                          7-12;10(1):211 (abstract no. PB0274).
 REFERENCES               Christeff N, Garakhanian S, Thobie N, Wirbel
                          E, Rozenbaum W, Nunez EA. Effects of
                          interferon alpha 2A on serum androgen in HIV+
                          men with Kaposi's sarcoma. Int Conf AIDS.
                          1994 Aug 7-12;10(1):173 (abstract no.
                          PB0120).
 REFERENCES               Rosenthal E, Pesce A, Vinti H, Reboulot B,
                          Hoffman P, Cassuto JP. Isotretinoin plus
                          interferon alph-2a in AIDS-related Kaposi's
                          sarcoma. Int Conf AIDS. 1993 Jun
                          6-11;9(1):403 (abstract no. PO-B12-1607)
 REFERENCES               Gornitsky M, Srolovitz H, Miller BA.
                          Intralesional interferon alfa 2A in the
                          treatment of oral lesions of Kaposi's sarcoma
                          in homosexual AIDS patients. Int Conf AIDS.
                          1992 Jul 19-24;8(2):B147 (abstract no. PoB
                          3361).
 REFERENCES               Mildvan D, Bassiakos Y. Zidovudine (ZDV) and
                          interferon-alpha 2a (IFN): ongoing assessment
                          of synergy and tolerance in early ARC
                          patients, ACTG 068. Int Cont AIDS. 1992 Jul
                          19-24;8(2):B184 (abstract no. PoB 3586).
 REFERENCES               Giovannini M, Zuccotti GV, Biasucci G,
                          Locatelli V, Riva E. Combined zidovudine and
                          interferon-alpha 2a therapy in children with
                          acquired immune deficiency syndrome. J Int
                          Med Res. 1992 Jun;20(93): 295-301.
 REFERENCES               Mezzaroma I, Avella A, Paganelli  R, Ensoli
                          B, d'Offizi G, Sirianni MC, Luzi G, Valdarchi
                          C, Aiuti F. Recombinant alpha-2a interferon
                          treatment in patients with acquired
                          immunodeficiency syndrome (AIDS) and
                          AIDS-related complex (ARC): clinical and
                          immunological evaluation. Allergol
                          Immunopathol (Madr) 1991 Sep-Oct;19(5):201-7.
 REFERENCES               Evans LM, Itri LM, Campion M, Wyler-Plaut R,
                          Krown SE, Groopman JE, Goldsweig H,
                          Volberding PA, West SB, Mitsuyasu RT, et al.
                          Interferon-alpha 2a in the treatment of
                          acquired immunodeficiency syndrome-related
                          Kaposi's sarcoma. J Immunother. 1991
                          Feb;10(1):39-50.
 REFERENCES               Fischl MA, Uttamchandani RB, Resnick L,
                          Agarwal R, Fletcher MA, Patrone-Reese J,
                          Dearmas L, Chidekel J, McCann M, Myers M. A
                          phase I study of recombinant human
                          interferon-alpha 2a or human lymphoblastoid
                          interferon-alpha n1 and concomitant
                          zidovudine in patients with AIDS-related
                          Kaposi's sarcoma. J Acquir Immune Defic
                          Syndr. 1991;4(1):1-10.
 ENTRY MONTH              8906
 LAST REVISION DATE       960514
 

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