      Document 0193
 DOCN  DRG0193
 UNIQUE IDENTIFIER        DRG-0054
 NAME OF SUBSTANCE        Interferon beta [AHFS Drug Information 1995]
 REGISTRY NUMBER          74899-71-1
 STANDARD CHEMICAL NAME   Interferon beta [human fibroblast protein
                          moiety reduced] [CAS Registry Handbook
                          1965-1971]
 SYNONYMS                 Fibroblast interferon [Merck Index 1989]
 SYNONYMS                 IFN-beta [Merck Index 1989]
 SYNONYMS                 FIF [Merck Index 1989]
 SYNONYMS                 FIFN [Merck Index 1983]
 SYNONYMS                 Beta interferon [AmFAR Tx Dir Dec 1988]
 SYNONYMS                 Recombinant interferon beta [AmFAR Tx Dir Dec
                          1988]
 SYNONYMS                 IFN-Bser [AmFAR Tx Dir Dec 1988]
 SYNONYMS                 Betaseron [USAN 1996]
 SYNONYMS                 IFN-beta1 [Merck Index 1989]
 SYNONYMS                 Feron [Merck Index 1989]
 SYNONYMS                 Fiblaferon [Merck Index 1989]
 SYNONYMS                 Frone [Merck Index 1989]
 SYNONYMS                 Naferon [Merck Index 1989]
 SYNONYMS                 Interferon beta, reconbinant human [USP DI
                          1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 057
 PROTOCOL ID NUMBERS      FDA 002A
 PROTOCOL ID NUMBERS      FDA 017A
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The exact mechanism by which
                          interferon beta induces cellular resistance
                          to viral infection is incompletely
                          understood, whether the interferon is
                          endogenously produced or exogenously
                          administered.  A prevalent view of interferon
                          action is that, following binding, there is
                          synthesis of new cellular RNA's and proteins,
                          which mediate the antiviral effect. Inteferon
                          beta-1b receptor binding is 5 to 10 times
                          that of the alpha interferons. Chromosome 21
                          is required to develop the antiviral state in
                          humans no matter which species of IFN (alpha,
                          beta, or gamma) is employed. At least three
                          of the newly synthesized proteins in
                          interferon-treated cells appear to be
                          associated with the development of the
                          antiviral state: (1) a 2',5' oligoadenylate
                          (2-5A) synthetase, (2) a protein kinase, and
                          (3) an endonuclease. The antiviral state is
                          not fully expressed until these primed cells
                          are infected with virus. Double stranded RNA,
                          which is produced during the replication of
                          many viruses, activates 2-5A synthetase and
                          protein kinase. The activated synthetase
                          catalyzes the polymerization of ATP into
                          2'-5' oligonucleotides that in turn activate
                          endogenous cellular endoribonuclease, which
                          degrades viral RNA. The activated protein
                          kinase phosphorylates the alpha subunit of
                          eukaryotic initiation factor 2 resulting in
                          inhibition of viral protein synthesis. The
                          combined effects of protein kinase and
                          endonuclease are thought to result in
                          inhibition of virus protein synthesis and
                          virus replication. Interferon, in
                          retroviruses, appears not to act by
                          inhibiting virus-specific RNA or protein
                          synthesis in all virus systems. In
                          retroviruses interferon appears to inhibit
                          the final maturation of retroviruses in
                          infected cells so that they are not released
                          into the medium but instead accumulate on the
                          cell surface. [Drug Evaluations Annual 1992]
                          [Drug Evaluations Annual 1995]
 DISEASES STUDIED/TREATED Kaposi's sarcoma [Int Conf AIDS. 1992 Jul
                          19-24;8(2):(abstract no. PoB 3126)]
 DISEASES STUDIED/TREATED Primary HIV infection [Ann Int Med 1990 Apr
                          15;112]
 DISEASES STUDIED/TREATED Cytomegalovirus retinitis (CMV retinitis)
                          [FDA 017A]
 DISEASES STUDIED/TREATED Received licensure on July 23, 1993 [Ann Int
                          Med 1990 Apr 15;112; Betaferon Patient
                          Information Line, last updated July 30, 1993]
 CLASSIFICATION CODE      Antineoplastic [Merck Index 1989]
 CLASSIFICATION CODE      Antiviral [Merck Index 1989]
 CLASSIFICATION CODE      Immunomodulator [USAN 1996]
 CLASSIFICATION CODE      Antiretroviral [USP DI 1995]
 OTHER MAJOR USES         Interferon beta-1b is being investigated in
                          hairy cell leukemia, renal cell carcinoma,
                          recurrent glioma and other malignant brain
                          tumors. It is approved for use in multiple
                          sclerosis therapy. [Drug Evaulations Annual
                          1995]
 SUBSTANCE INTERACTIONS   Interferon beta has been shown to be
                          synergistic with zidovudine (AZT) in
                          suppressing HIV expression in human
                          peripheral blood lymphocytes in vitro. [Int
                          Conf AIDS Jun 12-16;2 (Abstract no. 3633)]
 ADVERSE EFFECTS          The most common side effects are injection
                          site reactions which occur in 85% of the
                          patients and flu-like symptoms which occur in
                          75% of the patients. Possible adverse effects
                          from parenteral administration may include:
                          fever, headache, chills, rigors, arthralgias,
                          myalgias, dizziness, paresthesias,
                          diaphoresis, nausea, fatigue, proteinuria,
                          leukopenia, thrombocytopenia, pain at
                          injection site, anorexia, diarrhea, emesis,
                          elevation of serum liver enzyme levels,
                          transient visual disturbances, seizures,
                          confusion, and formation of antibodies to
                          interferon. [Drug Evaluations Annual 1992]
                          [Int Conf AIDS 1988 Jun 12-16;2 (Abstract no.
                          3633)] [Drug Evaulations Annual 1995]
 CONTRAINDICATIONS        Should not be used by pregnant or lactating
                          women or by patients with evidence of
                          clinically significant cardiac dysfunction.
                          [NIAID ACTG 057]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Interferon beta is a
                          cytokine that is one of three classes of
                          interferons identified.  The native molecule
                          can be readily induced in cultured human
                          foreskin fibroblasts by synthetic
                          double-stranded RNA. [Proc AACR 1987;28(460)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Recombinant interferon beta
                          is produced in Escherichia coli and has
                          specific activity comparable to that of the
                          native molecule. [Proc AACR 1987;28(460)]
 CHEMICAL/PHYSICAL DATA   STABILITY: Generally stable at pH 2 [Merck
                          Index 1983]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: about 20,000 [Merck Index
                          1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Vial (5 ml) with 0.3 mg as a
                          sterile lyophilized powder, reconstituted in
                          1.2 ml sterile water to obtain a sol of 0.25
                          mg/ml (45 MU) of interferon beta. [NIAID ACTG
                          057]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Subcutaneous injection as a
                          bolus. [NIAID ACTG 057]
 SUBSTANCE DELIVERY DATA  STORAGE: Refrigerate vials containing
                          lyophilized powder at 2-8 C (stability up to
                          36 months); [NIAID ACTG 057]
 SUBSTANCE DELIVERY DATA  STORAGE: Reconstituted interferon beta
                          solution should be used immediately or held
                          at 2-8 C for no more than 3 hours to ensure
                          stability. [NIAID ACTG 057]
 MANUFACTURERS            Triton Biosciences
 REFERENCES               Olmos L, Vilata J, Rodriguez Pichardo A,
                          Lloret A, Ojeda A, Calderon MD. Double-blind,
                          randomized clinical trial on the effect of
                          interferion-beta in the treatment of
                          condylomata acuminata. Int J STD AIDS. 1994
                          May-Jun;5(3):182-5.
 REFERENCES               Semprini AE, Stillo A, Marcozzi S, Castagna
                          C, Fiore S, Radaelli U. Treatment with
                          interferon for genital HPV in HIV-positive
                          and HIV-negative women. Eur J Obstet Gynecol
                          Reprod Biol. 1994 Feb;53(2):135-7.
 REFERENCES               Frega A, di Renzi F, Stentella P, Pachi A.
                          Management of human papilloma virus
                          vulvo-perineal infection with systemic
                          beta-interferon and thymostimulin in
                          HIV-positive patients. Int J Gynaecol Obstet.
                          1994 Mar;44(3):255-8.
 REFERENCES               Izzo CM, Buonocore S, De Sena R, Manzillo E,
                          Maio G, Manzillo G. Treatment of chronic
                          hepatitis by HCV with association of
                          beta-interferon and zidovudine in patients
                          (pts) HIV positive. Int Conf AIDS 1993 Jun
                          6-11;9(1):174 (abstract no. PO-A13-0238).
 REFERENCES               Brockmeyer NH, Keller A, Seemann U, Mock M,
                          Martins L, Goos M. Two year double blind
                          randomized trial of zidovudine alone or
                          combination with low dose interferon alpha or
                          interferon beta. Int Conf AIDS. 1993 Jun
                          6-11;9(1):466 (abstract no. PO-B26-1987).
 REFERENCES               Stadler R, Ruszczak Z. Interferons. New
                          additions and indications for use. Dermatol
                          Clin. 1993 Jan;11(1):187-99.
 REFERENCES               Stuart-Harris RC, Lauchlan R, Day R. The
                          clinical application of the interferons: a
                          review. Med J Aust. 1992 Jun
                          15;156(12):869-72.
 REFERENCES               Orani AM, Fossati M, Bolis D, Nigro M, Fideli
                          D. Efficacy and safety evaluation on
                          combination therapy with systemic inteferon
                          beta and electrocautery in the anogenital
                          warts treatment of HIV-seropositive patients.
                          Int Conf AIDS. 1993 Jun 6-11;9(1):356
                          (abstract no. PO-B08-1326).
 REFERENCES               Stavermann T, Hubner P, Ruess A. Recombinant
                          interferon-beta in the therapy of advanced
                          AIDS-related Kaposi's sarcoma. Int Conf AIDS.
                          1992 Jul 19-24;8(2):B108 (abstract no. PoB
                          3126).
 REFERENCES               Main J, Handley J. Interferon: current and
                          future clinical uses in infectious disease
                          practice. Int J STD AIDS. 1992
                          Jan-Feb;3(1):4-9.
 ENTRY MONTH              8909
 LAST REVISION DATE       960310
 

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