General Information of Drug (ID: DMCL2OK)

Drug Name
Disulfiram
Synonyms
Abstenisil; Abstinil; Abstinyl; Alcophobin; Antabus; Antabuse; Antadix; Antaenyl; Antaethan; Antaethyl; Antaetil; Antalcol; Antetan; Antethyl; Antetil; Anteyl; Anthethyl; Antiaethan; Anticol; Antietanol; Antiethanol; Antietil; Antikol; Antivitium; Aversan; Averzan; Bonibal; Contralin; Contrapot; Cronetal; Dicupral; Disetil; Disulfan; Disulfirame; Disulfiramo; Disulfiramum; Disulfirm; Disulfram; Disulfuram; Disulphuram; Ephorran; Espenal; Esperal; Etabus; Ethyldithiourame; Ethyldithiurame; Exhoran; Exhorran; Gababentin; Hoca; Krotenal; Nocbin; Nocceler; Noxal; Refusal; Stopaethyl; Stopethyl; Stopety; Stopetyl; TATD; TETD; THIOCID; TTD; TTS; Tenurid; Tenutex; Tetidis; Tetradin; Tetradine; Tetraethylthiuram; Tetraetil; Teturam; Teturamin; Thireranide; Thiuranide; Tillram; Tiuram; Accel TET; Akrochem TETD; Ancazide ET; Antab use; Disulfirame [DCIT]; Ekagom DTET; Ekagom TEDS; Ekagom TETDS; Ekaland TETD; Esperal [France]; Eta bus; Ethyl Thiram; Ethyl Thiudad; Ethyl Thiurad; Ethyl Tuads Rodform; Ethyl Tuex; Ethyl tuads; Etyl Tuex; Nocceler TET; Perkacit TETD; Perkait TETD; Robac TET; Sanceler TET; Soxinol TET; TTS x; Tet raethylthiuram; Thiuram E; Dupon 4472; T 1132; Accel TET-R; Alk-aubs; Antabus (TN); Antabuse (TN); Anti-ethyl; Antivitium (Spain); ENT 27,340; Nocceler TET-G; Noxal (VAN); Ro-sulfiram; Sanceler TET-G; Tuads, ethyl; Usaf B-33; Ro-Sulfram-500 (USA)
Indication
Disease Entry ICD 11 Status REF
Alcohol dependence 6C40.2 Approved [1], [2]
Therapeutic Class
Alcohol Deterrents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 296.5
Topological Polar Surface Area (xlogp) 3.9
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 4
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Bioavailability
80% of drug becomes completely available to its intended biological destination(s) [4]
Elimination
0% of drug is excreted from urine in the unchanged form [3]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 24.0873 micromolar/kg/day [5]
Water Solubility
The ability of drug to dissolve in water is measured as 0.2 mg/mL [3]
Chemical Identifiers
Formula
C10H20N2S4
IUPAC Name
diethylcarbamothioylsulfanyl N,N-diethylcarbamodithioate
Canonical SMILES
CCN(CC)C(=S)SSC(=S)N(CC)CC
InChI
InChI=1S/C10H20N2S4/c1-5-11(6-2)9(13)15-16-10(14)12(7-3)8-4/h5-8H2,1-4H3
InChIKey
AUZONCFQVSMFAP-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
3117
ChEBI ID
CHEBI:4659
CAS Number
97-77-8
DrugBank ID
DB00822
TTD ID
D0X5SD
VARIDT ID
DR00310
INTEDE ID
DR0519
ACDINA ID
D00206

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Fatty aldehyde dehydrogenase (ALDH3A2) TTB6UM0 AL3A2_HUMAN Inhibitor [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2E1 (CYP2E1) DEVDYN7 CP2E1_HUMAN Substrate [8]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Disulfiram (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Disulfiram and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [42]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Disulfiram and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [43]
Aminophylline DML2NIB Moderate Decreased metabolism of Disulfiram caused by Aminophylline mediated inhibition of CYP450 enzyme. Asthma [CA23] [44]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Disulfiram and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [45]
Oxtriphylline DMLHSE3 Moderate Decreased metabolism of Disulfiram caused by Oxtriphylline mediated inhibition of CYP450 enzyme. Cough [MD12] [44]
Sertraline DM0FB1J Major Decreased metabolism of Disulfiram caused by Sertraline mediated inhibition of non-CYP450 enzyme. Depression [6A70-6A7Z] [46]
Fosphenytoin DMOX3LB Moderate Decreased metabolism of Disulfiram caused by Fosphenytoin mediated inhibition of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [47]
Isoniazid DM5JVS3 Moderate Additive dopaminergic effects by the combination of Disulfiram and Isoniazid. HIV-infected patients with tuberculosis [1B10-1B14] [48]
Brentuximab vedotin DMWLC57 Moderate Increased risk of peripheral neuropathy by the combination of Disulfiram and Brentuximab vedotin. Hodgkin lymphoma [2B30] [49]
Tipranavir DM8HJX6 Major Decreased metabolism of Disulfiram caused by Tipranavir mediated inhibition of non-CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [50]
Zalcitabine DMH7MUV Moderate Increased risk of peripheral neuropathy by the combination of Disulfiram and Zalcitabine. Human immunodeficiency virus disease [1C60-1C62] [51]
Abacavir DMMN36E Minor Increased plasma concentrations of Disulfiram and Abacavir due to competitive inhibition of the same metabolic pathway. Human immunodeficiency virus disease [1C60-1C62] [52]
Mipomersen DMGSRN1 Major Increased risk of hepatotoxicity by the combination of Disulfiram and Mipomersen. Hyper-lipoproteinaemia [5C80] [53]
Teriflunomide DMQ2FKJ Major Increased risk of hepatotoxicity by the combination of Disulfiram and Teriflunomide. Hyper-lipoproteinaemia [5C80] [54]
BMS-201038 DMQTAGO Major Increased risk of hepatotoxicity by the combination of Disulfiram and BMS-201038. Hyper-lipoproteinaemia [5C80] [55]
Pirfenidone DM6VZFQ Moderate Decreased metabolism of Disulfiram caused by Pirfenidone mediated inhibition of CYP450 enzyme. Idiopathic interstitial pneumonitis [CB03] [56]
Paraldehyde DMOC1BX Major Decreased metabolism of Disulfiram caused by Paraldehyde mediated inhibition of non-CYP450 enzyme. Insomnia [7A00-7A0Z] [42]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Disulfiram and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [57]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Disulfiram and Idelalisib. Mature B-cell leukaemia [2A82] [58]
Vemurafenib DM62UG5 Moderate Decreased metabolism of Disulfiram caused by Vemurafenib mediated inhibition of CYP450 enzyme. Melanoma [2C30] [42]
Thalidomide DM70BU5 Moderate Increased risk of peripheral neuropathy by the combination of Disulfiram and Thalidomide. Multiple myeloma [2A83] [51]
Leflunomide DMR8ONJ Major Increased risk of hepatotoxicity by the combination of Disulfiram and Leflunomide. Rheumatoid arthritis [FA20] [54]
Vardenafil DMTBGW8 Moderate Decreased metabolism of Disulfiram caused by Vardenafil mediated inhibition of CYP450 enzyme. Sexual dysfunction [HA00-HA01] [59]
⏷ Show the Full List of 23 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Stearic acid E00079 5281 Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Beta-D-lactose E00099 6134 Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium E00625 Not Available Disintegrant
Crospovidone E00626 Not Available Disintegrant
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Poloxamer 188 E00645 Not Available Emulsifying agent; Solubilizing agent; Surfactant
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
⏷ Show the Full List of 9 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Disulfiram 250 mg tablet 250 mg Oral Tablet Oral
Disulfiram 500 mg tablet 500 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7168).
2 Choosing the right medication for the treatment of alcoholism. Curr Psychiatry Rep. 2006 Oct;8(5):383-8.
3 BDDCS applied to over 900 drugs
4 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
5 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6 Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76.
7 Interaction of disulfiram with antiretroviral medications: efavirenz increases while atazanavir decreases disulfiram effect on enzymes of alcohol metabolism. Am J Addict. 2014 Mar-Apr;23(2):137-44.
8 Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans. J Pharmacol Exp Ther. 1999 Oct;291(1):213-9.
9 Identification of the human P-450 enzymes responsible for the sulfoxidation and thiono-oxidation of diethyldithiocarbamate methyl ester: role of P-450 enzymes in disulfiram bioactivation. Alcohol Clin Exp Res. 1998 Sep;22(6):1212-9.
10 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
11 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
12 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
13 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
14 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
15 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
16 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
17 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
18 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
19 Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
20 Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
21 Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
22 Drug Interactions Flockhart Table
23 Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
24 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
25 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
26 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
27 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
28 Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs. Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G54-63.
29 Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int. 2003 May;63(5):1687-96.
30 Genotoxicity of tamoxifen, tamoxifen epoxide and toremifene in human lymphoblastoid cells containing human cytochrome P450s. Carcinogenesis. 1994 Jan;15(1):5-9.
31 Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 2010 Mar;44(3):340-55.
32 A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther. 1998 Sep;286(3):1294-300.
33 The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
34 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
35 Novel metabolic pathway of estrone and 17beta-estradiol catalyzed by cytochrome P-450. Drug Metab Dispos. 2000 Feb;28(2):110-2.
36 Inhibition of cytochrome P450 2E1 by propofol in human and porcine liver microsomes. Biochem Pharmacol. 2002 Oct 1;64(7):1151-6.
37 CYP2E1 and clinical features in alcoholics. Neuropsychobiology. 2003;47(2):86-9.
38 Diverse Mechanisms of Antiepileptic Drugs in the Development Pipeline. Epilepsy Res. 2006 June; 69(3): 273-294.
39 Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast... J Med Chem. 2010 Apr 8;53(7):2757-65.
40 Elgonica-Dimers A and B, Two Potent Alcohol Metabolism Inhibitory Constituents of Aloe arborescens J. Nat. Prod. 60(11):1180-1182 (1997).
41 Aldehyde dehydrogenase inhibitors: alpha,beta-acetylenic N-substituted aminothiolesters are reversible growth inhibitors of normal epithelial but i... Eur J Med Chem. 2008 May;43(5):906-16.
42 Cerner Multum, Inc. "Australian Product Information.".
43 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
44 Loi CM, Day JD, Jue SG, et al "Dose-dependent inhibition of theophylline metabolism by disulfiram in recovering alcoholics." Clin Pharmacol Ther 45 (1989): 476-86. [PMID: 2721103]
45 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
46 Product Information. Antabuse (disulfiram). Wyeth-Ayerst Laboratories, Philadelphia, PA.
47 Brown CG, Kaminsky MJ, Feroli ER, Gurley HT "Delirium with phenytoin and disulfiram administration." Ann Emerg Med 12 (1983): 310-3. [PMID: 6625283]
48 Whittington HG, Grey L "Possible interaction between disulfiram and isoniazid." Am J Psychiatry 125 (1969): 1725-9. [PMID: 5770196]
49 Carrion C, Espinosa E, Herrero A, Garcia B "Possible vincristine-isoniazid interaction." Ann Pharmacother 29 (1995): 201. [PMID: 7756727]
50 Elenbaas RM "Drug therapy reviews: management of the disulfiram-alcohol reaction." Am J Hosp Pharm 34 (1977): 827-31. [PMID: 331944]
51 Argov Z, Mastaglia FL "Drug-induced peripheral neuropathies." Br Med J 1 (1979): 663-6. [PMID: 219931]
52 Product Information. Ziagen (abacavir). Glaxo Wellcome, Research Triangle Pk, NC.
53 Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
54 Canadian Pharmacists Association.
55 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
56 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
57 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
58 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
59 Product Information. Levitra (vardenafil). Bayer, West Haven, CT.