      Document 0230
 DOCN  DRG0230
 UNIQUE IDENTIFIER        DRG-0017
 NAME OF SUBSTANCE        Foscarnet sodium [USAN 1995]
 REGISTRY NUMBER          63585-09-1
 STANDARD CHEMICAL NAME   Phosphinecarboxylic acid, dihydroxy-, oxide,
                          trisodium salt [USAN 1995]
 SYNONYMS                 Foscarnet [NIAID ACTG 051]
 SYNONYMS                 Trisodium phosphonoformate [MERCK 1989]
 SYNONYMS                 Trisodium carboxyphosphate [Merck Index 1989]
 SYNONYMS                 Foscavir [Merck Index 1989]
 SYNONYMS                 Phosphonoformic acid, trisodium salt [USAN
                          1995]
 PROTOCOL ID NUMBERS      NIAID ACTG 015
 PROTOCOL ID NUMBERS      NIAID ACTG 028
 PROTOCOL ID NUMBERS      NIAID ACTG 053
 PROTOCOL ID NUMBERS      NIAID ACTG 092
 PROTOCOL ID NUMBERS      NIAID ACTG 093
 PROTOCOL ID NUMBERS      NIAID ACTG 095
 PROTOCOL ID NUMBERS      NIAID 88 EI-199
 PROTOCOL ID NUMBERS      NIAID 90 CC-118
 PROTOCOL ID NUMBERS      FDA 020A
 PROTOCOL ID NUMBERS      FDA 020B
 PROTOCOL ID NUMBERS      FDA 020E
 PROTOCOL ID NUMBERS      FDA 020F
 PROTOCOL ID NUMBERS      FDA 020G
 PROTOCOL ID NUMBERS      NIAID ACTG 129
 PROTOCOL ID NUMBERS      NIAID ACTG 151
 PROTOCOL ID NUMBERS      NIAID ACTG 136
 PROTOCOL ID NUMBERS      NIAID ACTG 228
 PROTOCOL ID NUMBERS      FDA 020H
 PROTOCOL ID NUMBERS      FDA 020I
 PROTOCOL ID NUMBERS      FDA 240A
 PROTOCOL ID NUMBERS      FDA 020J
 PROTOCOL ID NUMBERS      NIAID ACTG 266
 IND NUMBER               30,367
 SECONDARY SOURCE ID      A-29622 [Merck Index 1989]
 SECONDARY SOURCE ID      EHB 776 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: An organic analog of
                          inorganic pyrophosphate that inhibits
                          replication of all known herpesviruses in
                          vitro. Selectively inhibits the pyrophosphate
                          binding site on virus-specific DNA
                          polymerases and reverse transcriptase in
                          concentrations that do not affect cellular
                          DNA polymerase. Plasma concentrations in one
                          study were: after 57 mg/kg infusion, 78
                          (average min. conc.) to 573 (average max.
                          conc.). Clearance depends on renal function.
                          Both tubular secretion and glomerular
                          filtration account for urinary elimination of
                          foscarnet. In one study, drug plasma
                          half-lives of 0.45 (+/-0.32) hours were
                          determined following continuous infusion for
                          72 hours. Variable penetration--of
                          foscarnet--of cerebral spinal fluid has been
                          observed. [PDR 1995] Foscarnet lacks the
                          adverse myelosuppression effect of
                          ganciclovir. [PDR 1995]
 DISEASES STUDIED/TREATED FDA approved 9/27/91 for cytomegalovirus
                          retinitis in AIDS patients. [AHFS Drug
                          Information 1995] [FDA Press Release]
 CLASSIFICATION CODE      Antiviral [AHFS Drug Information 1995]
 OTHER MAJOR USES         Injection form for the treatment of
                          acyclovir-resistant herpes simplex virus in
                          immunocomprimised patients. [Astra USA; July
                          6, 1995]
 SUBSTANCE INTERACTIONS   A possible interaction with IV pentamidine
                          possibly causing hypocalcemia has been
                          described. Because foscarnet's tendency to
                          cause renal impairment, it should not be used
                          with potentially nephrotoxic drugs such as
                          aminoglycosides, amphotericin B and IV
                          pentamidine. Concomitant treatment wit
                          zidovudine is generally well tolerated; no
                          evidence of increased myelosuppressions was
                          seen. [PDR 1995]
 ADVERSE EFFECTS          The major toxicity is renal impariment. This
                          is manifested by a rise in serum creatinine
                          concentration to 2.0 mg/dL. This is usually,
                          but not uniformly, reversible by treatment
                          discontinuation. Foscarnet has been
                          associated with changes in serum electrolytes
                          including hypocalcemia (15% of patients in
                          controlled studies), hypophosphatemia (8%)
                          and hyperphosphatemia (6%), hypomagnesemia
                          (15%) and hypokalemia (16%). Foscarnet
                          treatment has been associated with seizures,
                          but rate of seizures did not increase with
                          duration of treatment. The most frequently
                          reported events in 5 foscarnet trials were:
                          fever (65%), nausea (47%), anemia (33%),
                          diarrhea (30%), abnormal renal function
                          (27%), vomiting (26%), headache (26%) and
                          seizures (10%). [PDR 1995]
 CONTRAINDICATIONS        Has a high toxicity profile and should only
                          be used when potential benefits outweigh the
                          possible risks. Must be used with caution in
                          patients with a history of renal impairment.
                          Dosage modification according to renal
                          function is essential. Because foscarnet has
                          a propensity to alter concentrations of
                          calcium and other electrolytes, it should be
                          used with caution in patients with altered
                          baseline serum concentrations of these
                          electrolytes, and especially in those with
                          neurologic or cardiac abnormalities. [AHSF
                          Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Phosphonoformic acid
                          trisodium salt [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: CNa3O5P [USAN 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 191.95 [USAN 1995]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C6.26%;
                          Na35.93%; O41.68%; P16.13% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: (hexahydrate): Greater than
                          250 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White crystalline solid
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Injection 40 mg/kg administered
                          BID or TID [Astra USA; July 6, 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Injection. [Astra USA; July
                          6, 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Should be stored at 15-30 C (59-86
                          F) and should be protected from excessive
                          heat and freezing. [PDR 1995]
 MANUFACTURERS            Astra Lakemedel
 REFERENCES               Fillet AM, Visse B, Caumes E, Dumont B,
                          Gentilini M, Huraux JM. Foscarnet-resistant
                          multidermatomal zoster in a patient with
                          AIDS. Clin Infect Dis. 1995 Nov;21(5):1348-9.
 REFERENCES               Sarasini A, Baldanti F, Furione M, Percivalle
                          E, Brerra R, Barbi M, Gerna G. Double
                          resistance to ganciclovir and foscarnet of
                          four human cytomegalovirus strains recovered
                          from AIDS patients. J Med Virol. 1995
                          Nov;47(3):237-44.
 REFERENCES               Arevalo JF, Gonzalez C, Capparelli EV, Kirsch
                          LS, Garcia RF, Quiceno JI, Connor JD,
                          Gambertoglio J, Bergeron-Lynn G, Freeman WR.
                          Intravitreous and plasma concentrations of
                          ganciclovir and foscarnet after intravenous
                          therapy in patients with AIDS and
                          cytomegalovirus retinitis. J Infect Dis. 1995
                          Oct;172(4):951-6.
 REFERENCES               Fisher M, Tomlinson DR, Coker RJ. Management
                          of cytomegalovirus infection. The Jefferiss
                          Wing Therapeutics and Protocols Group. Int J
                          STD AIDS. 1995 Sep-Oct;6(5):313-9.
 REFERENCES               Jabs DA. Controversies in the treatment of
                          cytomegalovirus retinitis: foscarnet versus
                          ganciclovir. Infect Agents Dis. 1995
                          Sep;4(3):131-42.
 REFERENCES               Tachedjian G, Hooker DJ, Gurusinghe AD, Bazmi
                          H, Deacon NJ, Mellors J, Birch C, Mills J.
                          Characterisation of foscarnet-resistant
                          strains of human immunodeficiency virus type
                          1. Virology. 1995 Sep 10;212(1):58-68.
 REFERENCES               Dusserre N, Lessard C, Paquette N, Perron S,
                          Poulin L, Tremblay M, Beauchamp D, Desormeaux
                          A, Bergeron MG. Encapsulation of foscarnet in
                          liposomes modifies drug intracellular
                          accumulation, in vitro anti-HIV-1 activity,
                          tissue distribution and pharmacokinetics.
                          AIDS. 1995 Aug;9(8):833-41.
 REFERENCES               Mellors JW, Bazmi HZ, Schinazi RF, Roy BM,
                          Hsiou Y, Arnold E, Weir J, Mayers DL. Novel
                          mutations in reverse transcriptase of human
                          immunodeficiency virus type 1 reduce
                          susceptibility to foscarnet in laboratory and
                          clinical isolates. Antimicrob Agents
                          Chemother. 1995 May;39(5):1087-92.
 REFERENCES               Morbidity and toxic effects associated with
                          ganciclovir or foscarnet therapy in a
                          randomized cytomegalovirus retinitis trial.
                          Arch Intern Med. 1995 Jan 9;155(1):65-74.
 ENTRY MONTH              8906
 LAST REVISION DATE       960529
 

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