Details of the Drug

General Information of Drug (ID: DMGCHDS)

• Drug Name: Sulfamethizole
• Synonyms: Ayerlucil; Famet; Lucosil; Methazol; Microsul; Proklar; Renasul; Rufol; SULFAMETHIAZOLE; Salimol; Solfametizolo; Sulamethizole; Sulfamethazole; Sulfamethizol; Sulfamethizolum; Sulfamethylthiadiazole; Sulfametizol; Sulfapyelon; Sulfstat; Sulfurine; Sulphamethizole; Sulphamethyltiadiazole; Tetracid; Thidicur;Thiosulfil; Ultrasul; Urocydal; Urodiaton; Urolucosil; Urosulfin; Uroz; Solfametizolo [DCIT]; Sulfa gram; Thiosulfil Forte; RP 2145; VK 53; Sulfamethizolum [INN-Latin]; Sulfametizol [INN-Spanish]; Thiosulfil (TN); Sulfamethizole [USAN:INN:JAN]; Thiosulfil-A-Forte; Sulfamethizole (JP15/USP/INN); N1-(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanilamide; N(1)-(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanilamide; N(sup 1)-(5-Methyl-1,3,4-thiadiazol-2-yl)sulfanilamide; N(sup 1)-(5-Methyl-1,3,4-thiadiazol-2-yl)-sulfanilamide; 2-(p-Aminobenzenesulfonamido)-5-methylthiadiazole; 2-Methyl-5-sulfanilamido-1,3,4-thiadiazole; 2-Sulfanilamido-5-methyl-1,3,4-thiadiazole; 4-Amino-N-(5-Methyl-1,3,4-Thiadiazol-2-Yl)Benzene-1-Sulfonamide; 4-Amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide; 4-Amino-N-[5-methyl-1,3,4-thiadiazol-2-yl]benzenesulfonamide; 5-Methyl-2-sulfanilamido-1,3,4-thiadiazole

Indication

Disease Entry	ICD 11	Status	REF
Acute otitis media	AB00	Approved	[1]
Bacillary dysentery	1A02	Approved	[1]
Urinary tract infection	GC08	Approved	[2]

• Therapeutic Class: Antiinfective Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 270.3
  Logarithm of the Partition Coefficient (xlogp); 0.5
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 7
• ADMET Property:
  Absorption: The drug is rapidly absorbed []
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
  Elimination: 86% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 3 - 8 hours [4]
  Metabolism: The drug is metabolized via the hepatic []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 211.38 micromolar/kg/day [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.25 mg/mL [3]
• Chemical Identifiers:
  Formula: C9H10N4O2S2
  IUPAC Name: 4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide
  Canonical SMILES: CC1=NN=C(S1)NS(=O)(=O)C2=CC=C(C=C2)N
  InChI: InChI=1S/C9H10N4O2S2/c1-6-11-12-9(16-6)13-17(14,15)8-4-2-7(10)3-5-8/h2-5H,10H2,1H3,(H,12,13)
  InChIKey: VACCAVUAMIDAGB-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5328
  ChEBI ID: CHEBI:9331
  CAS Number: 144-82-1
  DrugBank ID: DB00576
  TTD ID: D07JJS
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Dihydropteroate synthetase (Bact folP)	TT4ILYC	DHPS_ECOLI	Inhibitor	[6]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Sulfamethizole (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[7]
Repaglinide	DM5SXUV	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Repaglinide.	Acute diabete complication [5A2Y]	[8]
Glibenclamide	DM8JXPZ	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Glibenclamide.	Acute diabete complication [5A2Y]	[8]
Tolazamide	DMIHRNA	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Tolazamide.	Acute diabete complication [5A2Y]	[9]
Nateglinide	DMLK2QH	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Nateglinide.	Acute diabete complication [5A2Y]	[8]
Insulin-glulisine	DMQI0FU	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Insulin-glulisine.	Acute diabete complication [5A2Y]	[8]
Insulin-aspart	DMX7V28	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Insulin-aspart.	Acute diabete complication [5A2Y]	[10]
Glipizide	DMZA5PQ	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Glipizide.	Acute diabete complication [5A2Y]	[8]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[11]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[12]
Mycophenolic acid	DMRBMAU	Moderate	Altered absorption of Sulfamethizole due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[13]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Cannabidiol.	Epileptic encephalopathy [8A62]	[14]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[15]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[17]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Sulfamethizole and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[18]
Lesinurad	DMUR64T	Moderate	Decreased metabolism of Sulfamethizole caused by Lesinurad mediated inhibition of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[19]
Porfimer Sodium	DM7ZWNY	Moderate	Increased risk of photosensitivity reactions by the combination of Sulfamethizole and Porfimer Sodium.	Lung cancer [2C25]	[20]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[21]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Idelalisib.	Mature B-cell leukaemia [2A82]	[22]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Clofarabine.	Mature B-cell lymphoma [2A85]	[23]
Prilocaine	DMI7DZ2	Major	Increased risk of methemoglobinemia by the combination of Sulfamethizole and Prilocaine.	Pain [MG30-MG3Z]	[24]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Sulfamethizole caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[25]
Vardenafil	DMTBGW8	Moderate	Decreased metabolism of Sulfamethizole caused by Vardenafil mediated inhibition of CYP450 enzyme.	Sexual dysfunction [HA00-HA01]	[26]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[14]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Sulfamethizole and Naltrexone.	Substance abuse [6C40]	[27]
Warfarin	DMJYCVW	Major	Increased plasma concentration of Sulfamethizole and Warfarin due to competitive binding of plasma proteins.	Supraventricular tachyarrhythmia [BC81]	[28]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Sulfamethizole due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[13]
Tolbutamide	DM02AWV	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Tolbutamide.	Type 2 diabetes mellitus [5A11]	[9]
Chlorpropamide	DMPHZQE	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Chlorpropamide.	Type 2 diabetes mellitus [5A11]	[9]
Insulin-detemir	DMOA4VW	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Insulin-detemir.	Type-1/2 diabete [5A10-5A11]	[8]
Insulin degludec	DMPL395	Moderate	Increased risk of hypoglycemia by the combination of Sulfamethizole and Insulin degludec.	Type-1/2 diabete [5A10-5A11]	[8]

References

• [1] Sulfamethizole FDA Label
• [2] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [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] Inhibition of bioluminescence in Photobacterium phosphoreum by sulfamethizole and its stimulation by thymine. Biochim Biophys Acta. 1990 Jun 26;1017(3):229-34.
• [7] Cerner Multum, Inc. "Australian Product Information.".
• [8] Abad S, Moachon L, Blanche P, Bavoux F, Sicard D, Salmon-Ceron D "Possible interaction between glicazide, fluconazole and sulfamethoxazole resulting in severe hypoglycaemia." Br J Clin Pharmacol 52 (2001): 456-7. [PMID: 11678792]
• [9] Christensen LK, Hansen JM, Kristensen M "Sulphaphenazole-induced hypoglycemic attacks in tolbutamide-treated diabetics." Lancet 2 (1963): 1298-301. [PMID: 14071924]
• [10] Asplund K, Wiholm BE, Lithner F "Glibenclamide-associated hypoglycaemia: a report on 57 cases." Diabetologia 24 (1983): 412-7. [PMID: 6411511]
• [11] Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
• [12] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [13] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [14] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [15] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
• [16] Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3. [PMID: 23763943]
• [17] Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
• [18] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
• [19] Product Information. Accolate (zafirlukast). Zeneca Pharmaceuticals, Wilmington, DE.
• [20] Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
• [21] 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]
• [22] Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
• [23] Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
• [24] Canadian Pharmacists Association.
• [25] Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
• [26] Product Information. Levitra (vardenafil). Bayer, West Haven, CT.
• [27] Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.
• [28] Cook DE, Ponte CD "Suspected trimethoprim sulfamethoxazole induced hypoprothrombinemia." J Fam Pract 39 (1994): 589-91. [PMID: 7798864]