      Document 0157
 DOCN  DRG0157
 UNIQUE IDENTIFIER        DRG-0090
 NAME OF SUBSTANCE        Interferon alfa-n3 [USAN 1996]
 STANDARD CHEMICAL NAME   Interferons, alfa [USAN 1993]
 SYNONYMS                 Alferon N [USAN 1996]
 SYNONYMS                 Leukocyte interferon [USAN 1996]
 SYNONYMS                 Alferon N Injection [USAN 1996]
 SYNONYMS                 Alferon [Merck Index 1989]
 SYNONYMS                 Veldona [NIAID DATRI 022]
 SYNONYMS                 Alferon LDO [NIAID DATRI 022]
 PROTOCOL ID NUMBERS      NIAID DATRI 022
 PROTOCOL ID NUMBERS      FDA 069A
 PROTOCOL ID NUMBERS      FDA 069B
 PROTOCOL ID NUMBERS      FDA 082A
 IND NUMBER               90-151ME
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   Interferons are naturally occurring proteins
                          with both antiviral and antiproliferative
                          properties.  They are produced and secreted
                          in response to viral infections and to a
                          variety of other synthetic and biological
                          inducers.  Three major families of
                          interferons have been identified:  alpha,
                          beta and gamma.  The interferon family
                          contains at least 15 different molecular
                          species.  Interferons bind to specific
                          membrane receptors on cell surfaces.
                          Interferon alfa-n3 binds to the same
                          receptors as interferon alfa-2b with high
                          species specificity.  Binding of interferon
                          to membrane receptors initiates a series of
                          events including induction of protein
                          synthesis.  These actions are followed by a
                          variety of cellular responses, including
                          inhibition of virus replication and
                          suppression of cell proliferation.
                          Immunomodulation, including enhancement of
                          phagocytosis by macrophages, augmentation of
                          the cytotoxicity of lymphocytes and
                          enhancement of human leukocyte antigen
                          expression occurs in response to exposure to
                          interferons.  Antiviral and antiproliferative
                          actions are thought to be related to
                          alterations in synthesis of RNA, DNA, and
                          cellular proteins, including oncogenes. To
                          date, no antibodies to interferon alfa-n3
                          have been detected in tested patients. Since
                          interferon alfa-n3 is manufactured using
                          human leukocytes, donors are screened to
                          minimize the risk that the leukocytes could
                          contain infectious agents including hepatitis
                          B antigen (HBsAG), antibodies to human
                          immunodeficiency virus (HIV-1) and human T
                          lymphotropic virus (HTLV-1). In addition, the
                          manufacturing process contains steps which
                          inactivate viruses, and there has been no
                          evidence of transmission to recipients in
                          clinical trials. [PDR 1995] [USP DI 1995]
 DISEASES STUDIED/TREATED Condylomata acuminata (genital warts) [USP DI
                          1995]
 DISEASES STUDIED/TREATED Kaposi's sarcoma [USP DI 1995]
 CLASSIFICATION CODE      Antiviral [USAN 1990]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 CLASSIFICATION CODE      Immunomodulator [FDA 069A]
 OTHER MAJOR USES         Bladder tumors; chronic myelogenous leukemia;
                          hairy cell leukemia; non-Hodgkin's lymphoma;
                          melanoma; multiple myeloma; renal carcinoma;
                          chronic non-A, non-B hepatitis; cutaneous
                          warts; laryngeal papillomatosis; and mycosis
                          fungoides [USP DI 1995]
 SUBSTANCE INTERACTIONS   Drug interactions and/or related problems may
                          be seen with alcohol or CNS
                          depression-producing medications (concurrent
                          use may enhance the CNS depressant effects of
                          either these medications or alfa interferon),
                          blood dyscrasia-causing medications
                          (leukopenic and/or thrombocytopenic effects
                          of interferon may be increased with
                          concurrent or recent therapy if these
                          medications cause the same effects), bone
                          marrow depressants, or radiation therapy
                          (additive bone marrow depression may occur).
                          [USP DI 1995].
 ADVERSE EFFECTS          May induce flu like symptoms (myalgias,
                          fever or headache), back pain, insomnia,
                          sensitivity to allergens, and neutropenia.
                          During dental work, bone marrow depressant
                          effects of interferons may result in an
                          increased incidence of microbial infection,
                          delayed healing and gingival bleeding. Other
                          side/adverse effects may include
                          cardiotoxicity, loss of appetite (with
                          continued treatment), unusual tiredness (with
                          continued treatment), nausea or vomiting,
                          weight loss, cold sores or stomatitis,
                          diarrhea, dizziness, dry mouth, dry skin or
                          itching, inability to have or keep an
                          erection, partial loss of hair. Adverse
                          reactions reported by 1 percent of patients
                          in clinical trials included left groin lymph
                          node swelling, tongue hyperesthesia, thirst,
                          tingling of legs/feet, hot sensation on
                          bottom of feet, strange taste in mouth,
                          increased salivation, heat intolerance,
                          visual disturbances, pharyngitis, muscle
                          cramps, nose bleed, throat tightness and
                          papular rash on neck, herpes labialis, hot
                          flashes, nervousness, decreased
                          concentration, dysuria, photosensitivity and
                          swollen lymph nodes. [AmFAR Tx Dir 1993;6(3)]
                          [Facts and Comparisons 1995] [USP DI 1995]
 CONTRAINDICATIONS        Due to the manufacturing process, strength
                          and type of interferon may vary for different
                          interferon formulations, and changing brands
                          may require a change in dosage. Caution
                          should be used in changing from one
                          interferon product to another.
                          Contraindicated in patients with
                          hypersensitivity to human interferon alpha or
                          any component of the product or those who
                          have anaphylactic sensitivity to mouse
                          immunoglobulin (IgG), egg protein or
                          neomycin. Use cautiously in patients with
                          debilitating medical conditions such as
                          cardiovascular disease (eg., unstable angina
                          and uncontrolled congestive heart failure),
                          severe pulmonary disease (eg., chronic
                          obstructive pulmonary disease), diabetes
                          mellitus with ketoacidosis, coagulation
                          disorders (eg., thrombophlebitis, pulmonary
                          embolism and hemophilia), severe
                          myelosupression or seizure disorders.
                          Interferon alpha affects the menstrual cycle
                          and decreases serum estradiol and
                          progesterone levels. Use with caution in
                          fertile men and women. Risk-benefit should be
                          considered with the following problems: bone
                          marrow depression, recent or existing
                          chickenpox (including recent exposure),
                          herpes zoster, hepatic disease, herpes
                          labialis, intolerance to alfa interferon,
                          severe renal disease and previous cytotoxic
                          drug therapy or radiation therapy. [USP DI
                          1995] [Facts and Comparisons 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Naturally occurring alpha
                          interferon [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Produced from pooled human
                          leukocytes which have been induced by
                          incomplete infection with an avian virus
                          (Sendai virus) to produce interferon alfa-n3
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 16,000-27,000 daltons [PDR
                          1995]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Water soluble [USP DI 1990]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Clear, colorless injectable
                          solution [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Sterile aqueous
                          formulation of purified, natural, human
                          interferon alpha proteins for use by
                          injection comprising 166 amino acids. Liquid
                          and solid forms for oral administration [PDR
                          1995] [NIAID DATRI 022]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Injection; oral. [USP DI
                          1995] [NIAID DATRI 022]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Injection: 5 mIU/vial in 1 ml
                          vials with 3.3 mg phenol and 1 mg albumin.
                          Oral: 500 IU/ml liquid in foil sachets and
                          150 IU lozenges. [USP DI 1995] [NIAID DATRI
                          022]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 2 to 8 C (36 to 46 F).  Do
                          not freeze.  Do not shake. [PDR 1995]
 MANUFACTURERS            Interferon Sciences Inc
 MANUFACTURERS            Purdue Frederick Company
 MANUFACTURERS            Amarillo Cell Culture
 REFERENCES               Friedman-Kein A. Management of condylomata
                          acuminata with Alferon N infection,
                          interferon alfa-n3 (human leukocyte derived).
                          Am J Obstet Gynecol. 1995 Apr;172(4 Pt
                          2):1359-68.
 REFERENCES               Fleshner PR, Freilich MI. Adjuvant interferon
                          for anal condyloma. A prospective, randomized
                          trial. Dis Colon Rectum. 1994
                          Dec;37(12):1255-9.
 REFERENCES               Beaulieu R, Shepard F, Murphy K, Gelmon K,
                          Thuot C, Sawka C, Singer J. A randomized
                          trial of 2 doses of alpha interferon (IFN)
                          added to AZT for the treatment of Kaposi's
                          sarcoma. Int Conf AIDS. 1994 Aug
                          7-12;10(1):174 (abstract no. PB0122).
 REFERENCES               Skillman DR, Wagner K, Malone JL, Decker C,
                          Paparello S, Meltzer MS. Phase 1 study of
                          interferon alfa-N3 in asymptomatic
                          HIV-infected persons. Int Conf AIDS. 1993 Jun
                          6-11;9(1):468 (abstract no. PO-B26-1998).
 REFERENCES               Hassett J, Mendelsohn L. Effect of low dose
                          oral interferon alfa-n3 (IFN) in ARC. Int
                          Conf AIDS. 1993 Jun 6-11;9(1):494 (abstract
                          no. PO-B28-2151).
 REFERENCES               Dupuy J, Price M, Lynch G, Bruce S, Schwartz
                          M. Intralesional interferon-alpha and
                          zidovudine in epidemic Kaposi's. J Am Acad
                          Dermatol. 1993 Jun;28(6):966-72.
 REFERENCES               Fan SX, Skillman DR, Liao MJ, Testa D,
                          Meltzer MS. Increased efficacy of human
                          natural interferon alpha (IFN-alpha n3)
                          versus human recombinant IFN-alpha 2 for
                          inhibition of HIV-1 replication in primary
                          human monocytes. AIDS Res Hum Retroviruses.
                          1993 Nov;9(11):1115-22.
 REFERENCES               Liao MJ, Axelrod HR, Kuchler M, Yip YK,
                          Kirkbright E, Testa D. Absence of
                          neutralizing antibodies to interferon in
                          condyloma acuminata and cancer patients
                          treated with natural human leukocyte
                          interferon. J Infect Dis. 1992
                          Apr;165(4):757-60.
 REFERENCES               Axelrod HR, Liao MJ, Kuchler M, Testa D.
                          Trace amounts of murine immunoglobulin in
                          affinity pruified leukocyte interferon alpha
                          are not immunogenic. Biotechnol Ther.
                          1992;3(1-2):35-49.
 REFERENCES               Davey RT Jr, Davey VJ, Metcalf JA, Zurlo JJ,
                          Kovacs JA, Falloon J, Polis MA, Zunich KM,
                          Masur H, Lane HC. A phase I/II trial of
                          zidovudine, interferon-alpha, and
                          granulocyte-macrophage colony-stimulating
                          factor in the treatment of human
                          immunodeficiency virus type 1 infection. J
                          Infect Dis. 1991 Jul;164(1):43-52.
 ENTRY MONTH              9007
 LAST REVISION DATE       960503
 

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