      Document 0227
 DOCN  DRG0227
 UNIQUE IDENTIFIER        DRG-0020
 NAME OF SUBSTANCE        Interferon gamma [Merck Index 1989]
 REGISTRY NUMBER          82115-62-6
 STANDARD CHEMICAL NAME   N2-L-methionyl-1-139-interferon gamma (human
                          lymphocyte protein moiety reduced)
                          (Interferon gamma-1b) [USAN 1996]
 SYNONYMS                 Recombinant Human Interferon-Gamma [NIAID
                          ACTG 025]
 SYNONYMS                 rIFN-gamma [NIAID ACTG 025]
 SYNONYMS                 Immune IFN [Merck Index 1989]
 SYNONYMS                 Type II Interferon [Merck Index 1989]
 SYNONYMS                 Immuneron [Drug Evaluations Annual 1992]
 SYNONYMS                 Actimmune [PDR 1995]
 SYNONYMS                 IFN-gamma [Merck Index 1989]
 SYNONYMS                 Polyferon [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 025
 PROTOCOL ID NUMBERS      NIAID ACTG 072
 PROTOCOL ID NUMBERS      NHLBI 88 H-78A
 PROTOCOL ID NUMBERS      FDA 062A
 PROTOCOL ID NUMBERS      FDA 062B
 PROTOCOL ID NUMBERS      ACTG 211
 IND NUMBER               BB3048
 IND NUMBER               BB2679
 SECONDARY SOURCE ID      S-6819 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Interferons are a family of
                          functionally related, species-specific
                          proteins, synthesized by eukaryotic cells in
                          response to viruses and a variety of natural
                          and synthetic stimuli. Interferon gamma has
                          potent phagocyte-activating effects not seen
                          with other interferons. In patients, drug has
                          broad range of biological activities
                          including enhancement of oxidative metabolism
                          of tissue macrophages, enhancement of
                          antibody-dependent cellular cytotoxicity and
                          natural killer cell activity. Interferon
                          gamma interacts functionally with other
                          interleukin molecules such as interleukin-2.
                          Interferon gamma treatment of patients with
                          chronic granulomatous disease showed
                          enhancement of phagocyte function. The drug
                          is slowly absorbed after IM or subcutaneous
                          injection; the fraction of dose absorbed was
                          greater than 89%. The mean elimination
                          half-life in healthy male subjects after IV
                          administration of 100 mcg/square meter was 38
                          minutes. After IM and subcutaneous injections
                          of the same dose, elimination half-lives were
                          2.9 and 5.9 hours respectively. The drug was
                          not detected in the urine of volunteers
                          following administration by any of those
                          routes. Treatment with the drug is indicated
                          for reducing the frequency and severity of
                          serious infections associated with chronic
                          granulomatous disease. [PDR 1995]
 DISEASES STUDIED/TREATED Under investigation for treatment of
                          Mycobacterium tuberculosis infection in
                          HIV-positive people [AmFar Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Antineoplastic [Merck Index 1989]
 CLASSIFICATION CODE      Antiviral [Merck Index 1989]
 CLASSIFICATION CODE      Immunomodulator [Merck Index 1989]
 OTHER MAJOR USES         FDA approved for treatment of chronic
                          granulomatous disease. Used to reduce the
                          frequency and severity of infections
                          associated with chronic granulomatous disease
                          [PDR 1995; USP DI 1995]
 SUBSTANCE INTERACTIONS   Interaction with other drugs have not been
                          fully evaluated. Caution should be used in
                          concomitant administration with other
                          myelosuppressive agents. [PDR 1995]
 ADVERSE EFFECTS          The most common adverse experiences occurring
                          with interferon gamma therapy are flu-like
                          symptoms which may be ameliorated with
                          acetaminophen. May cause fever, headache,
                          rash, chills, injection site erythema,
                          fatigue, diarrhea, nausea, or vomiting.
                          Rarely seen effects when used in higher
                          dosages in cases other than chronic,
                          granulomatous disease were cardiovascular
                          effects, CNS effects, gastrointestinal
                          effects and hematologic effects. No
                          significant differences between treated and
                          placebo-receiving patients were observed in
                          laboratory studies of hematologic,
                          coagulation, hepatic and renal functions.
                          [PDR 1995]
 CONTRAINDICATIONS        Should be used during pregnancy only if
                          potential benefits justify the potential risk
                          to the fetus. In nursing mothers, a decision
                          should be made whether to discontinue nursing
                          or the drug, depending on importance of the
                          drug to the mother. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Production of Actimmune
                          (Genentech, Inc. tradename for interferon
                          gamma-1b) is through fermentation of
                          genetically engineered Escherichia coli with
                          DNA that encodes for human protein. [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Interferon gamma is
                          structurally unrelated to interferons alfa
                          and beta. [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Acid-labile [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Powder [NIAID ACTG 025]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C734H1166N204O216S5 [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 16,000-25,000 daltons
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Interferon gamma-1b is a
                          single-chain polypeptide containing 140 amino
                          acids. [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Actimmune (Genentech, Inc.
                          preparation of interferon gamma-1b) is a
                          sterile, clear solution in a single vial for
                          subcutaneous injection.
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Each 0.5 ml contains 100 mcg (3
                          million U) of interferon gamma-1b with 20 mg
                          mannitol. 0.36 mg sodium succinate, and 0.05
                          mg polysorbate 20 in sterile water. [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Subcutaneous injection.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Vials must be placed in a 2-8C
                          (36-46F) refrigerator immediately upon
                          receipt. Freezing and/or vigorous agitation
                          must be avoided.
 SUBSTANCE DELIVERY DATA  STORAGE: Vials should not left at room
                          temperature longer than 12 hours before
                          usage. [PDR 1995]
 MANUFACTURERS            Genentech
 REFERENCES               Holland SM, Eisenstein EM, Kuhns DB, Turner
                          ML, Fleisher TA, Strober W, Gallin JI.
                          Treatment of refractory disseminated
                          nontuberculous mycobacterial infection with
                          interferon gamma. A preliminary report. N
                          Engl J Med. 1994 May 12;330(19):1348-55.
 REFERENCES               Murray HW. Interferon-gamma and host
                          antimicrobial defense: current and future
                          clinical applications. Am J Med. 1994
                          Nov;97(5):459-67.
 REFERENCES               Weiss G, Zangerle R, Wachter H, Fuchs D.
                          Interferon-gamma and coronary lesions in HIV
                          infection [letter]. Lancet. 1993
                          Feb;341(8841):383.
 REFERENCES               Thoma-Greber E, Froschl M, Stolz W,
                          Landthaler M, Plewig G. [Interferon-gamma.
                          Therapy of recurrent furunculosis in HIV
                          infections]. Hautarzt. 1993 Sep;44(9):587-9.
 REFERENCES               Agosti JM, Coombs RW, Collier AC, Paradise
                          MA, Benedetti JK, Jaffe HS, Corey L. A
                          randomized, double-blind, phase I/II trial of
                          tumor necrosis factor and interferon-gamma
                          for treatment of AIDS-related complex
                          (Protocol 025 from the AIDS Clinical Trials
                          Group). AIDS Res Hum Retroviruses. 1992
                          May;8(5):581-7.
 REFERENCES               Parkin J, Underhill J, Eales J, Pinching A.
                          The use of recombinant human gamma interferon
                          (IFN-gamma) in AIDS patients: dose-related
                          immunomodulation and prolonged survival. Int
                          Conf AIDS. 1992 Jul 19-24;8(2):B162 (abstract
                          no. PoB 3450).
 REFERENCES               Reichel RP, Fitz R, Neumann R, Pohl-Markl H,
                          Pichel E, Hoffer Z, Budiman R. Clinical study
                          with recombinant interferon gamma versus
                          interferon alpha-2c in patients with
                          condylomata acuminata. Int J STD AIDS. 1992
                          Sep-Oct;3(5):350-4.
 REFERENCES               Squires KE, Brown ST, Armstrong D, Murphy WF,
                          Murray HW. Interferon-gamma treatment for
                          Mycobacterium avium-intracellular complex
                          bacillemia in patients with AIDS [letter]. J
                          Infect Dis. 1992 Sep;166(3):686-7.
 REFERENCES               Heagy W, Groopman J, Schindler J, Finberg R.
                          Use of IFN-gamma in patients with AIDS. J
                          Acquir Immune Defic Syndr. 1990;3(6):584-90.
 REFERENCES               Kaplan LD, Abrams DI, Sherwin SA, Kahn J,
                          Volberding PA. A phase I/II study of
                          recombinant tumor necrosis factor and
                          recombinant interferon gamma in patients with
                          AIDS-related complex. Biotechnol Ther.
                          1989-90;1(3):229-36.
 ENTRY MONTH              8906
 LAST REVISION DATE       960604
 

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