      Document 0228
 DOCN  DRG0228
 UNIQUE IDENTIFIER        DRG-0019
 NAME OF SUBSTANCE        Interferon alfa-n1 [USAN 1995]
 SYNONYMS                 Wellferon [USAN 1995]
 SYNONYMS                 Sumiferon [Merck Index 1989]
 SYNONYMS                 Ferimmune [Pharma Pacific Product Information
                          5/96]
 PROTOCOL ID NUMBERS      NIAID DATRI 022
 PROTOCOL ID NUMBERS      FDA 052C
 PROTOCOL ID NUMBERS      NIAID ACTG 013
 PROTOCOL ID NUMBERS      NIAID ACTG 014
 PROTOCOL ID NUMBERS      NIAID IRP 011
 SECONDARY SOURCE ID      NSC 339140 [Merck Index 1989]
 SECONDARY SOURCE ID      CL-884 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION:  Precise mechanism of action
                          of interferons have not been fully elucidated
                          but appear to be substantially interrelated.
                          The antiviral and antineoplastic properties
                          of interferons appear to result from a
                          complex cascade of biological effects rather
                          than from direct virucidal or cytocidal
                          effects. The drugs affect many cell functions
                          producing restoration, augmentation and/or
                          modulation of the host's immune system,
                          direct antiproliferative and antineoplastic
                          activities, modulation of cell
                          differentiation, and modulation of cellular
                          transciption and translation. Alfa
                          interferons are totally filtered through the
                          glomeruli and undergo rapid proteolytic
                          degradation during tubular reabsorption.
                          Following an intravenous infusion interferon
                          alfa-n1 has a half-life of about 8 hours.
                          Interferons alfa-2a, -2b, -n1, and -n3 are
                          not interchangeable. [AHFS Drug Information
                          1995] [USP DI 1995]
 DISEASES STUDIED/TREATED Kaposi's sarcoma in selected patients, 18
                          years of age or older [USP DI 1995]
 CLASSIFICATION CODE      Antiviral [Merck Index 1989]
 CLASSIFICATION CODE      Antineoplastic [USAN 1995]
 CLASSIFICATION CODE      Immunomodulator [USAN 1995]
 OTHER MAJOR USES         Hairy cell leukemia; genital and anal warts;
                          chronic non-A, non-B hepatitis; chronic
                          myelogenous leukemia; recurrent respiratory
                          papillomatosis; non-Hodgkin's and cutaneous
                          T-cell lymphomas; renal cell and bladder
                          carcinoma; skin cancers; melanoma; and
                          multiple myeloma [USP DI 1995]
 SUBSTANCE INTERACTIONS   Use of alpha interferons with zidovudine in a
                          limited number of patients with Kaposi's
                          sarcoma seems to enhance antiretroviral
                          effects and improve tumor response rates.
                          There may be increased risks of hematologic
                          and hepatic toxicities. Interferons should be
                          used with caution in patients receiving drugs
                          that are potentially myelosuppressive. [AHFS
                          Drug Information 1995]
 ADVERSE EFFECTS          The following adverse reactions have been
                          reported with various alpha interferon
                          products. Almost all patients experience
                          adverse effects during courses of interferon
                          alfa theapy. These include flu-like symptoms
                          (fever, fatigue/malaise, myalgia, chills,
                          headache, arthralgia, abdominal cramps,
                          diarrhea). Fever frequently reaching 38-40 C
                          can be ameliorated with non-steroidal
                          anti-inflammatory agents. Anorexia and
                          associated weight loss are common in patients
                          during continued therapy. Adverse CNS effects
                          ranging from anxiety, fatigue and headache to
                          delirium and global dysfunctions have been
                          reported. Reversible EEG abnormalities have
                          been reported. Adverse hematologic effects,
                          e.g., mild, transient myelosuppression, occur
                          frequently in patients on interferon alpha
                          therapy. hepatic effects that seem to be
                          dose-related also have been reported.
                          Respiratory effects such dyspnea, cough and
                          drying of the oropharynx have been reported
                          in 34% of patients and may be severe. There
                          may be rashes and transient alopecia.
                          Proteinuria is the most common adverse renal
                          effect (15-20% of patients). Cardiovascular
                          effects such as edema and hypotension occur
                          in up to 9% of patients. Adverse effects seen
                          with Ferimmune include mild nausea, anorexia
                          or appetite stimulation, malaise, fatigue,
                          headache, myalgia, nasal congestion, fever,
                          and viral oral lesions. [AHFS Drug
                          Information 1995] [Pharma Pacific Product
                          Information 5/96]
 CONTRAINDICATIONS        Should be used with caution in patients with
                          hepatic disease, renal disease, CNS
                          disorders, thyroid abnormalities, and with
                          myelosupression. Safety and efficacy in
                          children younger than 18 years have not been
                          established. Should be used during pregnancy
                          only when potential benefits justify possible
                          risk to the fetus. It is not known whether
                          the drug distributes into milk, but because
                          of potential serious adverse effects (to the
                          infant) if it were so distributed, a decision
                          should be made whether or not to continue
                          nursing. [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Interferon alfa-n1 is a
                          highly purified blend of natural human alpha
                          interferons, obtained from human
                          lymphoblastoid cells following induction with
                          Sendai virus [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: It is a mixture of natural
                          alpha interferon subtypes, but in different
                          proportions than in human leukocyte
                          interferon [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 18,000-20,000 daltons
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Off-white tablets
                          [Pharma Pacific Product Information 5/96]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Injection: Vials containing 3
                          and 10 million units respectively of
                          injectable solution. Oral: 200 IU tablets.
                          [USP DI 1995] [Pharma Pacific Product
                          Information 5/96]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular or
                          subcutaneous injection; oral. [USP DI 1995]
                          [Pharma Pacific Product Information 5/96]
 SUBSTANCE DELIVERY DATA  STORAGE: Injection: Store between 2 and 8 C
                          (36 and 46 F), unless otherwise specified by
                          the manufacturer. Protect from light. [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Oral: Store below 25 C and protect
                          from light. [Pharma Pacific Product
                          Information 5/96]
 MANUFACTURERS            Schering-Plough Corporation
 MANUFACTURERS            Glaxo Wellcome
 MANUFACTURERS            Pharma Pacific
 REFERENCES               Wenner CA, Guler ML, Macatonia SE, O'Garra A,
                          Murphy KM. Roles of IFN-gamma and IFN-alpha
                          in IL-12-induced T helper cell-1 development.
                          J Immunol. 1996 Feb 15;156(4):1442-7.
 REFERENCES               Agy MB, Acker RL, Sherbert CH, Katze MG.
                          Interferon treatment inhibits virus
                          replication in HIV-1-and SIV-infected CD4+
                          T-cells lines by distinct mechanisms:
                          evidence for decreased stability and aberrant
                          processing of HIV-1 proteins. Virology. 1995
                          Dec 20;214(2):379-86.
 REFERENCES               Nelson MR, Chard S, Barton SE. Intralesional
                          interferon for the treatment of recalcitrant
                          molluscum contagiosum in HIV antibody
                          positive individuals--a preliminary report.
                          Int J STD AIDS. 1995 Sep-Oct;6(5):351-2.
 REFERENCES               Toraldo R, D'Avanzo M, Tolone C, Canino G,
                          Iafusco F, Notarangelo LD, Ugazio A, Cirillo
                          C. Effect of interferon-alpha therapy in a
                          patient with common variable immunodeficiency
                          and chronic Epstein-Barr virus infection.
                          Pediatr Hematol Oncol. 1995
                          Sep-Oct;12(5):489-93.
 REFERENCES               Fernandez-Cruz E, Lang JM, Frissen J, Furner
                          V, Chateauvert M, Boucher CA, Dowd P, Stevens
                          J. Zidovudine plus interferon-alpha versus
                          zidovudine alone in HIV-infected symptomatic
                          or asymptomatic persons with CD4+ cell counts
                          > 150 x 10(6)/L: results of the Zidon trial.
                          Zidon Study Group. AIDS. 1995
                          Sep;9(9):1025-35.
 REFERENCES               Soriano V, Garcia-Samaniego J, Bravo R,
                          Castro A, Odriozola PM, Gonzalez J, Colmenero
                          M, Carballo E, Suarez D, Llibre JM, et al.
                          Efficacy and safety of alpha-interferon
                          treatment for chronic hepatitis C in
                          HIV-infected patients. HIV-Hepatitis Spanish
                          Study Group. J Infect. 1995 Jul;31(1):9-13.
 REFERENCES               Ebbesen P, Hager H, Norskov-Lauritsen N,
                          Aboagye-Mathiesen G, Zdravkovic M, Villaden
                          J, Liu X, Peterson PM, Bambra C, Nyongo A, et
                          al. Concurrence of high levels of interferons
                          alpha and beta in cord and maternal blood and
                          simultaneous presence of interferon in
                          trophoblast in an African population. J
                          Interferon Cytokine Res. 1995
                          Feb;15(2):123-8.
 REFERENCES               Valentine AD, Meyers CA, Talpaz M. Treatment
                          of neurotoxic side effects of
                          interferon-alpha with naltrexone. Cancer
                          Invest; VOL 133, ISS 6, 1995, P561-6.
 REFERENCES               Tavio M, Colomba A, Izzo E, Pintus A, Puppoa
                          F, Serraino D, Traina C, Tirelli U.
                          Preliminary results of a phase II study on
                          the efficacy and tolerability of AZT plus
                          alfa-interferon in patients with asymptomatic
                          HIV infection and CD4 between 200 and 500.
                          Int Conf AIDS. 1994 Aug 7-12;10(1):210
                          (abstract no. PB0270).
 REFERENCES               Acone N, Bill'Aquila G, Maglicocca M, Nigro
                          FS, Pacifico P, Imparato L. [IFN in the
                          treatment of chronic viral hepatitis.
                          Efficacy and tolerance of lymphoblastoid
                          alpha interferon in HIV-negative drug addicts
                          and associated chronic active hepatitis C].
                          Clin Ter. 1994 Nov;145(11):369-72.
 ENTRY MONTH              8906
 LAST REVISION DATE       960612
 

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