      Document 0246
 DOCN  DRG0246
 UNIQUE IDENTIFIER        DRG-0001
 NAME OF SUBSTANCE        Ampligen [Merck Index 1989]
 REGISTRY NUMBER          38640-92-5
 RELATED REGISTRY NUMBER  125570-55-0
 STANDARD CHEMICAL NAME   5'-Inosinic acid, homopolymer, complex with
                          5'-cytidylic acid polymer with 5'-uridylic
                          acid [CHEMLINE]
 SYNONYMS                 Atvogen [NIAID ACTG 054]
 SYNONYMS                 Poly I - poly C (C12,U) [Merck Index 1989]
 SYNONYMS                 Poly rI(n)-r(C12U)n [Merck Index 1989]
 SYNONYMS                 Poly (rI)-poly[r(C12U)n] [Merck Index 1989]
 SYNONYMS                 Polyribonucleotide [USP DI 1995]
 SYNONYMS                 Poly I: Poly C12U [USP DI 1995]
 SYNONYMS                 Polyriboinosinic:
                          polyribocytidylic-polyribouridilic acid [USP
                          DI 1995]
 SYNONYMS                 Mismatched double-stranded RNA [CHEMLINE]
 SYNONYMS                 (rI(n).r(C(12)U)n) [CHEMLINE]
 PROTOCOL ID NUMBERS      NIAID ACTG 038
 PROTOCOL ID NUMBERS      NIAID ACTG 054
 PROTOCOL ID NUMBERS      NIAID ACTG 056
 PROTOCOL ID NUMBERS      FDA 073A
 IND NUMBER               BB2775
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: May have a dual mechanism of
                          action: direct antiviral action and various
                          indirect, immunomodulatory actions. Acts
                          through a number of pathways to stimulate
                          intracellular antiviral activity and to
                          increase the effective cellular and other
                          activities of the immune system. Stimulates
                          interferon production, activates the 2'-5'
                          oligoadenylate synthetase (2-5A) RNase L
                          pathway, stimulates natural killer cell
                          activity, and, in general, acts as a
                          nonmitogenic stimulator of the immune system.
                          Ampligen inhibits replication of HIV in
                          vitro. After intravenous injection of 200 mg
                          of Ampligen in humans, its plasma half-life
                          was estimated at 23 minutes. [NIAID ACTG 054]
 DISEASES STUDIED/TREATED Primary HIV infection (stimulation of immune
                          system) [NIAID ACTG 054]
 CLASSIFICATION CODE      Antiretroviral [USP DI 1995]
 CLASSIFICATION CODE      Immunomodulator [USP DI 1995]
 OTHER MAJOR USES         Treatment of renal carcinoma; chronic fatigue
                          syndrome; invasive metastatic melanoma [USP
                          DI 1995]
 SUBSTANCE INTERACTIONS   May act synergistically with zidovudine
                          (AZT). [J Infect Dis 1992 Oct;166(4)]
 ADVERSE EFFECTS          May cause mild flu-like symptoms; mild
                          fatigue; fever; hypersensitivity skin
                          reactions. A flushing reaction, characterized
                          by at least one occurrence of reddening of
                          the face and chest, has been observed in
                          about 10% of patients when the drug was
                          prepared in plastic IV bags. This flushing
                          reaction was not observed when glass IV
                          bottles were used. Other less frequently
                          occurring adverse effects include nausea,
                          diarrhea, photophobia, rash and transient
                          visual disturbances. [USP DI 1995; NIAID ACTG
                          054]
 CONTRAINDICATIONS        Should not be used by pregnant or lactating
                          women or by patients requiring antineoplastic
                          therapy. [NIAID ACTG 054]
 CHEMICAL/PHYSICAL DATA   DESCRIPTION: Polynucleotide derivative of
                          poly I - poly C with occasional uracil
                          residues in the polypyrimidine strand; a
                          synthetic mismatched, double-stranded RNA
                          molecule [NIAID ACTG 054]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Disperses in water [NIAID ACTG
                          054]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Freeze-dried powder
                          [NIAID ACTG 054]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Indication of partial
                          denaturation when formulated in plastic bags
                          [Intl Conf AIDS 1990 Jun 20-23 6(2); Abstract
                          no. SB 490]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules (30 mg); sterile
                          aqueous solution. [NIAID ACTG 054]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous infusion; oral.
                          [NIAID ACTG 054]
 SUBSTANCE DELIVERY DATA  STORAGE: Do not store in solution for more
                          than 3 hours. [NIAID ACTG 054]
 MANUFACTURERS            HEM Research
 REFERENCES               Gillespie D, Hubbell HR, Carter WA, Midgette
                          PM, Elsasser W, Mullaney R, Strayer DR.
                          Synergistic inhibition of AZT-resistant HIV
                          by AZT combined with poly(I):poly(C12U),
                          without synergistic toxicity to bone marrow
                          progenitor cell elements. In Vivo. 1994
                          May-Jun;8(3):375-81.
 REFERENCES               Pazin GJ, Armstrong JA, Rinaldo CR, McMahon
                          DK, Huang XL, Gupta P, Winkelstein A, Ho M. A
                          synthetic double stranded RNA (rIn:r(C12U)n)
                          stabilizes CD4+ lymphocyte counts in
                          volunteers with early HIV disease. Int Conf
                          AIDS. 1994 Jun 16-21(2):216 (abstract no.
                          W.B.2136).
 REFERENCES               Schroder HC, Kelve M, Schacke H, Pfleiderer
                          W, Charubala R, Suhadolnik RJ, Muller WE.
                          Inhibition of DNA topoisomerase I activity by
                          2',5'-oligoadenylates and mismatched
                          double-stranded RNA in uninfected and
                          HIV-1-infected H9 cells. Chem Biol Interact.
                          1994 Feb;90(2):169-83.
 REFERENCES               Strayer DR, Carter WA, Brodsky I, Cheney P,
                          Peterson D, Salvato P, Thompson C, Loveless
                          M, Shapiro DE, Elsasser W, et al. A
                          controlled clinical trial with a specifically
                          configured RNA drug, poly(I).poly(C12U) in
                          chronic fatigue syndrome. Clin Infect Dis.
                          1994 Jan;18 Suppl 1:S88-95.
 REFERENCES               Ushijima H, Rytik PG, Schacke H, Scheffer U,
                          Muller WE, Schroder HC. Mode of action of the
                          anti-AIDS compound poly(I).poly(C12U)
                          (Ampligen):activator of 2',5'-oligoadenylate
                          synthetase and double-stranded RNA-dependent
                          kinase. J Interferon Res. 1993
                          Apr;13(2):161-71.
 REFERENCES               Hendrix CW, Margolick JB, Petty BG, Markham
                          RB, Nerhood L, Farzadegan H, Ts'o PO, Lietman
                          PS. Biologic effects after a single dose of
                          poly(I):poly (C12U) in healthy volunteers.
                          Antimicrob Agents Chemother. 1993
                          Mar;37(3):429-35.
 REFERENCES               Armstrong JA, McMahon D, Huang XL, Pazin GJ,
                          Gupta P, Rinaldo CR Jr, Schoenfeld DA,
                          Gaccione P, Tripoli CA, Bensasi S, et al. A
                          phase I study of ampligen in human
                          immunodeficiency virus-infected subjects. J
                          Infect Dis. 1992 Oct;166(4):717-22.
 REFERENCES               McMahon D, Winkelstein A, Huang XL, Armstrong
                          J, Pazin G, Rinaldo CM, Tripoli C, Ho M.
                          Acute reactions associated with infusion of
                          ampligen [letter]. AIDS. 1992 Feb;6(2):235-6.
 REFERENCES               Gillespie D, Carter WA. An hypothesis
                          concerning optimal therapy in HIV disease.
                          Med Hypotheses. 1992 Jan;37(1):1-5.
 REFERENCES               Carter WA, Ventura D, Shapiro DE, Strayer DR,
                          Gillespie DH, Hubbell HR. Mismatched
                          double-stranded RNA, Ampligen (poly(I):
                          poly(C12U), demonstrates antiviral and
                          immunostimulatory activities in HIV disease.
                          Int J Immunopharmacol. 1991;13 Suppl 1:69-76.
 ENTRY MONTH              8906
 LAST REVISION DATE       960424
 

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