      Document 0212
 DOCN  DRG0212
 UNIQUE IDENTIFIER        DRG-0035
 NAME OF SUBSTANCE        Interferon Alfa-2b [USAN 1995]
 REGISTRY NUMBER          99210-65-8
 STANDARD CHEMICAL NAME   Interferon alpha-2b [human leukocyte clone
                          Hif-SN206 protein moiety reduced] [USAN 1995]
 SYNONYMS                 Intron A [USAN 1995]
 SYNONYMS                 Intron A interferon alfa-2b, recombinant [PDR
                          1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 090
 PROTOCOL ID NUMBERS      NIAID 88 I-170
 PROTOCOL ID NUMBERS      NIAID 88 I-172
 PROTOCOL ID NUMBERS      NIAID 88 I-181
 PROTOCOL ID NUMBERS      NIAID 90 CC-110
 PROTOCOL ID NUMBERS      FDA 074A
 PROTOCOL ID NUMBERS      NIAID ACTG 206
 PROTOCOL ID NUMBERS      NIAID ACTG 203P
 SECONDARY SOURCE ID      Sch 30500 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: The pharmacokinetics of
                          interferon alfa-2b were studied in 12 healthy
                          male volunteers following single dose of 5
                          million IU/m2 administered intramuscularly,
                          subcutaneously, and as a 30-minute
                          intravenous infusion in a cross-over design.
                          The maximum serum concentrations obtained via
                          these routes were approximately 18 to 116
                          IU/ml and occurred 3 to 12 hours after
                          administration. The elimination half-lives
                          were approximately 2 to 3 hours. Interferon
                          alfa-2b has exhibited antiproliferative
                          effects in preclinical studies employing both
                          cell culture systems and human tumor
                          xenografts in animals, and has demonstrated
                          significant immunomodulatory activity in
                          vitro. Results of clinical trials in patients
                          with AIDS-related Kaposi's sarcoma showed
                          objective responses related to improvement in
                          the level of T4(CD4) count. [PDR 1993]
 DISEASES STUDIED/TREATED Kaposi's sarcoma [PDR 1995]
 DISEASES STUDIED/TREATED FDA approved 11/21/88 for adult Kaposi's
                          sarcoma [PDR 1995]
 DISEASES STUDIED/TREATED FDA approved 2/25/91 for chronic Non-A, Non-B
                          hepatitis [PDR 1995]
 CLASSIFICATION CODE      Immunomodulator [PDR 1995]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 CLASSIFICATION CODE      Antiviral [PDR 1995]
 OTHER MAJOR USES         Selected cases of condyloma acuminata
                          involving external surfaces of the genital
                          and perianal areas; treatment of hairy cell
                          leukemia [PDR 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. [USP DI 1995]
 ADVERSE EFFECTS          AIDS-related Kaposi's sarcoma: The incidence
                          and severity of adverse reactions is similar
                          to those reported in patients with other
                          malignancies. The most frequently reported
                          adverse reactions were flu-like symptoms with
                          fatigue, dizziness, fever, anorexia, myalgia,
                          headache, rigors, dry mouth, increased
                          sweating, chest pain, and asthenia. More
                          severe side effects were observed at higher
                          doses (35 million IU per day) and included:
                          dyspnea, pharyngitis, ataxia, confusion,
                          dysphagia, GI hemorrhage, cardiomyopathy,
                          face edema, depression, emotional lability,
                          suicide attempt, chest pain, and coughing.
                          Abnormal laboratory test values included
                          thrombocytopenia, granulocytopenia,
                          leukopenia, and increased liver function
                          tests. [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with a history of
                          hypersensitivity to interferon alfa-2b or any
                          component of its injection formulation.
                          Should not be used by pregnant or nursing
                          mothers. It should be used with caution in
                          patients with a history of significant
                          cardiac disease (myocardial infarction,
                          arrhythmias), pulmonary disease (COPD), or
                          diabetes mellitus patients prone to
                          ketoacidosis. Caution should be observed in
                          patients with coagulation disorders. Should
                          not be used for patients with rapidly
                          progressive visceral Kaposi's sarcoma or in
                          patients with preexisting thyroid
                          abnormalities whose thyroid function cannot
                          be maintained in the normal range with
                          medication. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A synthetic 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 an arginine
                          group at position 23 in the 165 amino acid
                          chain [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C860H1353N229O255S9 [USAN
                          1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 19,271 [PDR 1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Water soluble [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Lyophilized Intron A
                          Interferon alfa-2b, recombinant for injection
                          is a white to cream colored powder [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: The solution for
                          injection is colorless to light yellow [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: The powder for reconstitution is
                          stable for up to 7 days at 45 C. After
                          reconstitution with bacteriostatic water for
                          injection the solution is stable for one
                          month at 2 C to 8 C [PDR 1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Reconstituted solutions for
                          injection prepared with sterile water for
                          injection are stable for 24 hours when stored
                          between 2 C and 8 C [USP DI 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Injectable solution in vials
                          containing 3, 5, 18, 25 and 50 million IU/ml.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Subcutaneous,
                          intramuscular, or intralesional injection.
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store (both before and after
                          reconstitution) between 2 and 8 C (36 and 46
                          F). [PDR 1995]
 MANUFACTURERS            Schering
 REFERENCES               Soriano V, Garcia-Samaniego J, Bravo R,
                          Castro A, Gonzalez J, Mtnez-Odriozola P,
                          Colmenero J, Carballo E, Del Romero J,
                          Pedreira J, et al. Efficacy of interferon for
                          chronic hepatitis C in HIV+ patients. Int
                          Conf AIDS. 1994 Aug 7-12;10(1):220 (abstract
                          no. PB0310).
 REFERENCES               Szlavik J, Banhegyi D, Miskovits E, Gerlei Z.
                          Recombinant interferon-alfa treatment in
                          advanced KS and chronic HBV hepatitis
                          associated with HIV infection. Int Conf AIDS.
                          1993 Jun 6-11;9(1):401 (abstract no.
                          PO-B12-1595).
 REFERENCES               Dhiver C, Drogoul MP, Poizot-Martin I,
                          Bouabdallah R, Gastaut JA. Long term therapy
                          of HIV related thrombocytopenia with alpha
                          interferon. Int Conf AIDS. 1993 Jun
                          6-11;9(1):453 (abstract no. PO-B21-1910).
 REFERENCES               Cital JL, Villarreal C, Robles M, Torres R,
                          Cano C. Interferon alfa 2-b in 20 patients
                          with HIV+ and concomitant chronic hepatitis B
                          or C. Int Conf AIDS. 1993 Jun 6-11;9(1):353
                          (abstract no. PO-B08-1306).
 REFERENCES               Podzamczer D, Bolao F, Clotet B, Garcia P,
                          Casanova A, Pagerols X, Gudiol F. Low-dose
                          interferon alpha combined with zidovudine in
                          patients with AIDS-associated Kaposi's
                          sarcoma. J Intern Med. 1993
                          Mar;233(3):247-53.
 REFERENCES               Vianelli N, Catani L, Gugliotta L, Belmonte
                          MM, Cascione L, Colangeli V, Ricchi E, Mazza
                          P, Mazzucconi MG, Chistolini A, et al.
                          Recombinant alpha-interferon 2b in the
                          treatment of HIV-related thrombocytopenia.
                          AIDS. 1993 Jun;7(6):823-7.
 REFERENCES               Orlando R, D'Abbraccio M, Abrescia N, Foggia
                          M, Tosone G, Piazza M. Alpha-2b IFN in
                          HIV-infected patients with chronic C
                          hepatitis. Int Conf AIDS. 1993 Jun
                          6-11;9(1);447 (abstract no. PO-B19-1870).
 REFERENCES               Ocana I, Ruiz I, Ribera E, Bellmunt J,
                          Albanell J, Capdevila JA, Martinez Vazquez M.
                          Interferon A 2b (IFNa 2b) versus
                          monochemotherapy in AIDS-related Kaposi
                          sarcoma (KS). Int Conf AIDS. 1992 Jul
                          19-24;8(2):B107 (abstract no. PoB 3121).
 REFERENCES               Henrivaux P, Fairon Y, Baijot P. Addition of
                          interferon alpha-2B to previous long-term
                          zidovudine therapy. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B184 (abstract no. PoB 3584).
 REFERENCES               Rozenbaum W, Tabah I, Garakhanian S, Cardon
                          B, Bideault H. Randomized study of 3
                          different dosages of interferon (IFN) alpha 2
                          B for well responding AIDS-related Kaposi's
                          Sarcoma (KS). Int Conf AIDS. 1991 Jun
                          16-21;7(2):275 (abstract no. W.B.2374).
 ENTRY MONTH              8906
 LAST REVISION DATE       960310
 

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