      Document 0179
 DOCN  DRG0179
 UNIQUE IDENTIFIER        DRG-0068
 NAME OF SUBSTANCE        Disulfiram [USAN 1996]
 REGISTRY NUMBER          97-77-8
 RELATED REGISTRY NUMBER  11078-22-1
 STANDARD CHEMICAL NAME   Thioperoxydicarbonic diamide [(H2N)C(S)]2S2,
                          tetraethyl- [USAN 1996]
 SYNONYMS                 Abstensil [Merck Index 1989]
 SYNONYMS                 Abstinyl [Merck Index 1989]
 SYNONYMS                 Accel TET [CHEMLINE]
 SYNONYMS                 Alcophobin [CHEMLINE]
 SYNONYMS                 ALK-AUBS [CHEMLINE]
 SYNONYMS                 Antabuse [USAN 1996]
 SYNONYMS                 Antadix [Merck Index 1989]
 SYNONYMS                 Antaenyl [CHEMLINE]
 SYNONYMS                 Antaethan [CHEMLINE]
 SYNONYMS                 Antaethyl [CHEMLINE]
 SYNONYMS                 Antalcol [CHEMLINE]
 SYNONYMS                 Antetan [CHEMLINE]
 SYNONYMS                 Antetil [CHEMLINE]
 SYNONYMS                 Anteyl [CHEMLINE]
 SYNONYMS                 Anticol [CHEMLINE]
 SYNONYMS                 Antietanol [Merck Index 1989]
 SYNONYMS                 Antietil [CHEMLINE]
 SYNONYMS                 Antivitium [CHEMLINE]
 SYNONYMS                 Aversan [CHEMLINE]
 SYNONYMS                 Averzan [CHEMLINE]
 SYNONYMS                 Bonibal [CHEMLINE]
 SYNONYMS                 Contralin [Merck Index 1989]
 SYNONYMS                 Contrapot [CHEMLINE]
 SYNONYMS                 Cronetal [Merck Index 1989]
 SYNONYMS                 Dicupral [CHEMLINE]
 SYNONYMS                 Disetil [CHEMLINE]
 SYNONYMS                 Ekagom DTET [CHEMLINE]
 SYNONYMS                 Ekagom TEDS [CHEMLINE]
 SYNONYMS                 Espenal [CHEMLINE]
 SYNONYMS                 Esperal [Merck Index 1989]
 SYNONYMS                 Etabus [Merck Index 1989]
 SYNONYMS                 Ethyl thiram [CHEMLINE]
 SYNONYMS                 Ethyl thiudad [CHEMLINE]
 SYNONYMS                 Ethyl thiurad [Merck Index 1989]
 SYNONYMS                 Ethyl tuads [CHEMLINE]
 SYNONYMS                 Ethyl tuex [CHEMLINE]
 SYNONYMS                 Ethyldithiourame [CHEMLINE]
 SYNONYMS                 Ethyldithiurame [CHEMLINE]
 SYNONYMS                 Exhoran [Merck Index 1989]
 SYNONYMS                 Exhorran [CHEMLINE]
 SYNONYMS                 HOCA [CHEMLINE]
 SYNONYMS                 Krotenal [CHEMLINE]
 SYNONYMS                 Nocbin [CHEMLINE]
 SYNONYMS                 Nocceler [CHEMLINE]
 SYNONYMS                 Noxal [Merck Index 1989]
 SYNONYMS                 Refusal [CHEMLINE]
 SYNONYMS                 Ro-Sulfiram [Merck Index 1989]
 SYNONYMS                 Stopaethyl [CHEMLINE]
 SYNONYMS                 Stopethyl [CHEMLINE]
 SYNONYMS                 Stopetyl [Merck Index 1989]
 SYNONYMS                 Tenurid [CHEMLINE]
 SYNONYMS                 Tenutex [CHEMLINE]
 SYNONYMS                 Tetraethylthiuram disulfide [AHFS Drug
                          Information 1995]
 SYNONYMS                 Tetraetil [Merck Index 1989]
 SYNONYMS                 Thiuranide [Merck Index 1989]
 PROTOCOL ID NUMBERS      FDA 024A
 SECONDARY SOURCE ID      A13-27340 [CHEMLINE]
 SECONDARY SOURCE ID      HSDB 3317 [CHEMLINE]
 SECONDARY SOURCE ID      NCI-C02959 [CHEMLINE]
 SECONDARY SOURCE ID      CCRIS 582 [CHEMLINE]
 SECONDARY SOURCE ID      NSC 190940 [CHEMLINE]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Produces irreversible
                          inhibition of the enzyme responsible for
                          oxidation of the ethanol metabolite
                          acetaldehyde resulting in accumulation of
                          acetaldehyde which may be responsible for
                          most of the signs and symptoms occurring
                          after ethanol ingestion in disulfiram-treated
                          patients. During alcohol metabolism following
                          disulfiram intake, the level of acetaldehyde
                          occurring in the blood may be 5-10 times
                          higher than that found during metabolism of
                          the same amount of alcohol alone. Disulfiram
                          does not seem to influence the rate of
                          alcohol elimination from the body. The
                          observed hypotensive response may be due to
                          inhibition of norepinephrine synthesis by the
                          major disulfiram metabolite
                          diethyldithiocarbamate. Disulfiram is
                          absorbed slowly and incompletely from the
                          gastrointestinal tract and is eliminated
                          slowly from the body. Its biotransformation
                          occurs in the liver. Prolonged administration
                          of disulfiram does not produce tolerance; the
                          longer a patient remains on therapy, the more
                          sensitive the patient becomes to alcohol.
                          Initial onset of action may be delayed for up
                          to 12 hours since disulfiram is initially
                          localized in body fat. Reaction from alcohol
                          ingestion during disulfiram maintenance
                          usually occurs within 5-10 minutes. The
                          duration of disulfiram action is up to 14
                          days following the last dose. Disulfiram
                          elimination is primarily renal, as
                          metabolites, although about 5-20 percent of a
                          dose is eliminated unchanged in the feces and
                          some of the medication is exhaled as carbon
                          disulfide; up to 20 percent of a dose may
                          remain in the body for 1 week or longer. [PDR
                          1995] [USP DI 1995]
 DISEASES STUDIED/TREATED Primary HIV infection [Int Conf AIDS 1989 Jun
                          4-9;5: (abstract no. WBP 307)]
 CLASSIFICATION CODE      Alcohol-abuse deterrent [USAN 1996]
 CLASSIFICATION CODE      Immunomodulator [FDA 024A]
 CLASSIFICATION CODE      Antiretroviral [FDA 024A]
 OTHER MAJOR USES         Used to help maintain sobriety in treating
                          chronic alcoholism and as an adjunct to
                          supportive and psychotherapeutic measures
                          [PDR 1995]
 SUBSTANCE INTERACTIONS   May decrease plasma clearance and prolong
                          duration of action of alfentanil. May
                          increase anticoagulant effect of
                          anticoagulants due to inhibition of enzymatic
                          metabolism of the anticoagulant; disulfiram
                          also may act directly in the liver to
                          increase the hypoprothrombinemia-inducing
                          activity of coumarin derivatives;
                          anticoagulant dosage adjustments based on
                          prothrombin time may be necessary. May
                          increase serum levels of hydantoins,
                          especially phenytoin, possibly leading to
                          hydantoin toxicity. Concurrent use of
                          disulfiram with tricyclic antidepressants
                          (especially amitriptyline) may cause
                          transient delirium. Ascorbic acid may
                          interfere with the disulfiram-alcohol
                          reaction, especially with chronic use or high
                          doses of ascorbic acid. Concurrent use of
                          disulfiram and the following drugs may
                          enhance or potentiate toxic effects:
                          metronidazole, midazolam, paraldehyde,
                          neurotoxic medications, hepatic enzyme
                          inhibitors, central nervous system (CNS)
                          depression-producing medications, and
                          isoniazid. [PDR 1995] [USP DI 1995]
 ADVERSE EFFECTS          May cause eye pain, optic neuritis,
                          cholestatic and fulminant hepatitis,
                          psychotic reactions, peripheral neuritis and
                          polyneuritis in hands or feet, drowsiness,
                          headache, skin eruptions, impotence,
                          dermatitis, metallic/garlic-like aftertaste.
                          [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients receiving or
                          having recently received metronidazole,
                          paraldehyde, alcohol, or alcohol-containing
                          preparations, e.g., cough syrups, tonics.
                          Disulfiram medications should never be
                          administered to patients who are in a state
                          of alcohol intoxication or without knowledge
                          on the part of the patient. Contraindicated
                          in patients with severe myocardial disease or
                          coronary occlusion, psychoses, and
                          hypersensitivity to disulfiram or other
                          thiuram derivatives used in pesticides and
                          rubber vulcanization. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Alkyl thiocarbamoyl
                          derivative [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C10H20N2S4 [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   PERCENT ELEMENTAL COMPOSITION: C40.50%,
                          H6.80%, N9.45%, S43.25% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 296.55 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 70 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Practically insoluble in water
                          (0.02 g/100 ml); soluble in alcohol (3.82
                          g/100 ml) and ether (7.14 g/100 ml); also
                          soluble in acetone, benzene, chloroform,
                          carbon disulfide [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Aqueous suspensions prepared from
                          disulfiram powder or tablets are stable up to
                          295 days when stored at room temperature and
                          protected from light. [Facts and Comparisons
                          1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white,
                          odorless, almost tasteless crystalline powder
                          [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Tablets (250 mg or 500 mg). [PDR
                          1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store below 40 C (104 F), preferably
                          between 15-30 C (59-86 F), in tight,
                          light-resistant container. [USP DI 1995]
 MANUFACTURERS            Wyeth-Ayerst Research
 MANUFACTURERS            Danbury Pharmacal
 MANUFACTURERS            Par Pharmaceutical
 REFERENCES               Forns X, Caballeria J, Bruguera M, Salmeron
                          JM, Vilella A, Mas A, Pares A, Rodes J.
                          Disulfiram-induced hepatitis. Report of four
                          cases and review of the literature. J
                          Hepatol. 1994 Nov;21(5):853-7.
 REFERENCES               Gessner PK, Gessner T. Disulfiram and its
                          metabolite diethyldithiocarbamate:
                          pharmacology and status in the treatment of
                          alcoholism, HIV infections, AIDS and heavy
                          metal toxicity. London; New York: Chapman &
                          Hall, 1992 xix, 452 p.: ill.
 REFERENCES               Gallant DM, Head-Dunham R. Antabuse
                          (disulfiram) and AIDS. Alcohol Clin Exp Res.
                          1991 Oct;15(5):900-1.
 REFERENCES               Hording M, Gotzsche PC, Bygbjerg IC,
                          Christensen LD, Faber V. Lack of
                          immunomodulating effect of disulfiram on HIV
                          positive patients. Int J Immunopharmacol.
                          1990;12(2):145-7.
 REFERENCES               Kahn S, Farnum JB, Thomas E.
                          Disulfiram-induced hepatitis. South Med J.
                          1990 Jul;83(7):833-6.
 REFERENCES               Bihari B, Fleischer T, Devine J, Seaman JD.
                          Disulfiram as an immunomodulating agent -
                          follow up. Int Conf AIDS. 1989 Jun 4-9;5:661
                          (abstract no. C.619).
 REFERENCES               Davis I, Leibel J, Paroski P, Morgan A,
                          Norris B. Case report of disulfiram as first
                          line therapy in seropositive patients
                          attending a community clinic. Int Conf AIDS.
                          1989 Jun 4-9;5:403 (abstract no. W.B.P.307).
 ENTRY MONTH              8911
 LAST REVISION DATE       960313
 

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