Details of the Drug

General Information of Drug (ID: DM7EN8I)

• Drug Name: Diflunisal
• Synonyms: Adomal; Algobid; Citidol; Difludol; Diflunisalum; Dolisal; Dolobid; Dolobil; Dolobis; Dolocid; Flovacil; Fluniget; Fluodonil; Flustar; Noaldol; Reuflos; Unisal; Apotex Brand of Diflunisal; Cahill May Roberts Brand of Diflunisal; Diflunisal Novopharm Brand; Frosst SA Brand of Diflunisal; Merck Brand of Diflunisal; Novopharm Brand of Diflunisal; Nu Pharm Brand of Diflunisal; MK 647; MK647; Apo-Diflunisal; Diflunisalum [INN-Latin]; Dolobid (TN); MK-647; Merck Sharp & Dohme Brand of Diflunisal; Novo-Diflunisal; Nu-Diflunisal; Nu-Pharm Brand of Diflunisal; Diflunisal (JAN/USP/INN); Diflunisal [USAN:INN:BAN:JAN]; 2',4'-Difluoro-4-hydroxy-(1,1'-biphenyl)-3-carboxylic acid; 2',4'-Difluoro-4-hydroxy-3-biphenylcarboxylic acid; 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid; 2-(Hydroxy)-5-(2,4-difluorophenyl)benzoic acid; 5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID; 5-(2,4-Difluorophenyl)salicylic acid; 5-(2,4-difluorophenyl)-2-hydroxybenzoic acid; 5-[2,4-Difluorophenyl]salicylic acid

Indication

Disease Entry	ICD 11	Status	REF
Pain	MG30-MG3Z	Approved	[1], [2]

• Therapeutic Class: Analgesics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 250.2
  Topological Polar Surface Area (xlogp); 4.4
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Bioavailability: 85% of drug becomes completely available to its intended biological destination(s) [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.1 mL/min/kg [5]
  Elimination: 6% 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 8 - 12 hours [5]
  Metabolism: The drug is metabolized via the hepatic [6]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 99.91858 micromolar/kg/day [7]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.0016% [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.097 L/kg [5]
• Chemical Identifiers:
  Formula: C13H8F2O3
  IUPAC Name: 5-(2,4-difluorophenyl)-2-hydroxybenzoic acid
  Canonical SMILES: C1=CC(=C(C=C1C2=C(C=C(C=C2)F)F)C(=O)O)O
  InChI: InChI=1S/C13H8F2O3/c14-8-2-3-9(11(15)6-8)7-1-4-12(16)10(5-7)13(17)18/h1-6,16H,(H,17,18)
  InChIKey: HUPFGZXOMWLGNK-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 3059
  ChEBI ID: CHEBI:39669
  CAS Number: 22494-42-4
  DrugBank ID: DB00861
  TTD ID: D08LFZ
  VARIDT ID: DR00567
  INTEDE ID: DR0494
  ACDINA ID: D00197

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Inhibitor	[8]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME	DEYGVN4	UD11_HUMAN	Substrate	[9]

Molecular Expression Atlas of This Drug

• The Studied Disease: Pain
• ICD Disease Classification: MG30-MG3Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin G/H synthase 2 (COX-2)	DTT	PTGS2	7.93E-04	-0.29	-0.34
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DME	UGT1A1	1.10E-01	-5.91E-02	-3.60E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Diflunisal

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Aspirin	DM672AH	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Diflunisal and Aspirin.	Pain [MG30-MG3Z]	[29]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Repaglinide	DM5SXUV	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Repaglinide.	Acute diabete complication [5A2Y]	[30]
Glibenclamide	DM8JXPZ	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Glibenclamide.	Acute diabete complication [5A2Y]	[30]
Insulin-glulisine	DMQI0FU	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Insulin-glulisine.	Acute diabete complication [5A2Y]	[30]
Insulin-aspart	DMX7V28	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Insulin-aspart.	Acute diabete complication [5A2Y]	[31]
Glipizide	DMZA5PQ	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Glipizide.	Acute diabete complication [5A2Y]	[30]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Diflunisal caused by Arn-509 mediated induction of UGT.	Acute myeloid leukaemia [2A60]	[32]
Inotersen	DMJ93CT	Major	Increased risk of bleeding by the combination of Diflunisal and Inotersen.	Amyloidosis [5D00]	[32]
Cilostazol	DMZMSCT	Moderate	Increased risk of bleeding by the combination of Diflunisal and Cilostazol.	Arterial occlusive disease [BD40]	[33]
Budesonide	DMJIBAW	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Diflunisal and Budesonide.	Asthma [CA23]	[34]
Ofloxacin	DM0VQN3	Moderate	Additive CNS depression effects by the combination of Diflunisal and Ofloxacin.	Bacterial infection [1A00-1C4Z]	[35]
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Kanamycin.	Bacterial infection [1A00-1C4Z]	[36]
Sparfloxacin	DMB4HCT	Moderate	Additive CNS depression effects by the combination of Diflunisal and Sparfloxacin.	Bacterial infection [1A00-1C4Z]	[35]
Streptomycin	DME1LQN	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Streptomycin.	Bacterial infection [1A00-1C4Z]	[36]
Gemifloxacin	DMHT34O	Moderate	Additive CNS depression effects by the combination of Diflunisal and Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[35]
Norfloxacin	DMIZ6W2	Moderate	Additive CNS depression effects by the combination of Diflunisal and Norfloxacin.	Bacterial infection [1A00-1C4Z]	[35]
ABT-492	DMJFD2I	Moderate	Additive CNS depression effects by the combination of Diflunisal and ABT-492.	Bacterial infection [1A00-1C4Z]	[35]
Netilmicin	DMRD1QK	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Netilmicin.	Bacterial infection [1A00-1C4Z]	[36]
Levofloxacin	DMS60RB	Moderate	Additive CNS depression effects by the combination of Diflunisal and Levofloxacin.	Bacterial infection [1A00-1C4Z]	[35]
Lomefloxacin	DMVRH9C	Moderate	Additive CNS depression effects by the combination of Diflunisal and Lomefloxacin.	Bacterial infection [1A00-1C4Z]	[35]
Etidronic acid	DM1XHYJ	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Etidronic acid.	Bone paget disease [FB85]	[37]
Risedronate	DM5FLTY	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Risedronate.	Bone paget disease [FB85]	[37]
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of bleeding by the combination of Diflunisal and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[33]
Iodipamide	DMXIQYS	Major	Increased risk of nephrotoxicity by the combination of Diflunisal and Iodipamide.	Cholelithiasis [DC11]	[38]
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Diflunisal and Levomilnacipran.	Chronic pain [MG30]	[39]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Diflunisal and Regorafenib.	Colorectal cancer [2B91]	[32]
Drospirenone	DM1A9W3	Moderate	Increased risk of hyperkalemia by the combination of Diflunisal and Drospirenone.	Contraceptive management [QA21]	[40]
Mestranol	DMG3F94	Minor	Increased renal excretion of Diflunisal caused by Mestranol.	Contraceptive management [QA21]	[41]
Methoxyflurane	DML0RAE	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Methoxyflurane.	Corneal disease [9A76-9A78]	[32]
Ardeparin	DMYRX8B	Major	Increased risk of bleeding by the combination of Diflunisal and Ardeparin.	Coronary thrombosis [BA43]	[42]
Danaparoid	DM6CLBN	Major	Increased risk of bleeding by the combination of Diflunisal and Danaparoid.	Deep vein thrombosis [BD71]	[42]
Rivaroxaban	DMQMBZ1	Major	Increased risk of bleeding by the combination of Diflunisal and Rivaroxaban.	Deep vein thrombosis [BD71]	[43]
Sertraline	DM0FB1J	Moderate	Increased risk of bleeding by the combination of Diflunisal and Sertraline.	Depression [6A70-6A7Z]	[39]
Vilazodone	DM4LECQ	Moderate	Increased risk of bleeding by the combination of Diflunisal and Vilazodone.	Depression [6A70-6A7Z]	[39]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Diflunisal and Vortioxetine.	Depression [6A70-6A7Z]	[39]
Milnacipran	DMBFE74	Moderate	Increased risk of bleeding by the combination of Diflunisal and Milnacipran.	Depression [6A70-6A7Z]	[39]
Escitalopram	DMFK9HG	Moderate	Increased risk of bleeding by the combination of Diflunisal and Escitalopram.	Depression [6A70-6A7Z]	[39]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of bleeding by the combination of Diflunisal and Desvenlafaxine.	Depression [6A70-6A7Z]	[39]
Clomipramine	DMINRKW	Moderate	Increased risk of bleeding by the combination of Diflunisal and Clomipramine.	Depression [6A70-6A7Z]	[39]
Ethacrynic acid	DM60QMR	Moderate	Antagonize the effect of Diflunisal when combined with Ethacrynic acid.	Essential hypertension [BA00]	[44]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Diflunisal and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[32]
Dorzolamide	DMA17D0	Major	Increased risk of metabolic acidosis by the combination of Diflunisal and Dorzolamide.	Glaucoma [9C61]	[45]
Brinzolamide	DMBAPFG	Major	Increased risk of metabolic acidosis by the combination of Diflunisal and Brinzolamide.	Glaucoma [9C61]	[45]
Chlorothiazide	DMLHESP	Moderate	Antagonize the effect of Diflunisal when combined with Chlorothiazide.	Heart failure [BD10-BD1Z]	[44]
Bumetanide	DMRV7H0	Moderate	Antagonize the effect of Diflunisal when combined with Bumetanide.	Heart failure [BD10-BD1Z]	[44]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Diflunisal and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[46]
Trichlormethiazide	DMHAQCO	Moderate	Antagonize the effect of Diflunisal when combined with Trichlormethiazide.	Hypertension [BA00-BA04]	[44]
Dipyridamole	DMXY30O	Moderate	Increased risk of bleeding by the combination of Diflunisal and Dipyridamole.	Hypertension [BA00-BA04]	[33]
Probenecid	DMMFWOJ	Minor	Increased plasma concentration of Diflunisal and Probenecid due to competitive binding of plasma proteins.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[47]
Balsalazide	DMO091F	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Balsalazide.	Indeterminate colitis [DD72]	[48]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Diflunisal caused by PF-06463922 mediated induction of UGT.	Lung cancer [2C25]	[49]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of bleeding by the combination of Diflunisal and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[50]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Diflunisal and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[51]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Diflunisal and Ibrutinib.	Mature B-cell lymphoma [2A85]	[52]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Diflunisal and Ponatinib.	Mature B-cell lymphoma [2A85]	[53]
Ethinyl estradiol	DMODJ40	Minor	Increased renal excretion of Diflunisal caused by Ethinyl estradiol.	Menopausal disorder [GA30]	[41]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Diflunisal and Exjade.	Mineral absorption/transport disorder [5C64]	[54]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Diflunisal and Panobinostat.	Multiple myeloma [2A83]	[49]
Deflazacort	DMV0RNS	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Diflunisal and Deflazacort.	Muscular dystrophy [8C70]	[34]
Ruxolitinib	DM7Q98D	Moderate	Increased risk of bleeding by the combination of Diflunisal and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[33]
Dasatinib	DMJV2EK	Major	Increased risk of bleeding by the combination of Diflunisal and Dasatinib.	Myeloproliferative neoplasm [2A20]	[55]
Omacetaxine mepesuccinate	DMPU2WX	Major	Increased risk of bleeding by the combination of Diflunisal and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[56]
Prasugrel	DM7MT6E	Major	Increased risk of bleeding by the combination of Diflunisal and Prasugrel.	Myocardial infarction [BA41-BA43]	[32]
Vorapaxar	DMA16BR	Major	Increased risk of bleeding by the combination of Diflunisal and Vorapaxar.	Myocardial infarction [BA41-BA43]	[57]
Sibutramine	DMFJTDI	Moderate	Increased risk of bleeding by the combination of Diflunisal and Sibutramine.	Obesity [5B80-5B81]	[39]
Dexfenfluramine	DMJ7YDS	Moderate	Increased risk of bleeding by the combination of Diflunisal and Dexfenfluramine.	Obesity [5B80-5B81]	[39]
Polythiazide	DMCH80F	Moderate	Antagonize the effect of Diflunisal when combined with Polythiazide.	Oedema [MG29]	[44]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Diflunisal and MK-4827.	Ovarian cancer [2C73]	[32]
Epoprostenol	DMUTYR2	Moderate	Increased risk of bleeding by the combination of Diflunisal and Epoprostenol.	Pulmonary hypertension [BB01]	[58]
Iloprost	DMVPZBE	Moderate	Increased risk of bleeding by the combination of Diflunisal and Iloprost.	Pulmonary hypertension [BB01]	[58]
Everolimus	DM8X2EH	Major	Increased risk of nephrotoxicity by the combination of Diflunisal and Everolimus.	Renal cell carcinoma [2C90]	[59]
Temsirolimus	DMS104F	Major	Increased risk of nephrotoxicity by the combination of Diflunisal and Temsirolimus.	Renal cell carcinoma [2C90]	[59]
Gatifloxacin	DMSL679	Moderate	Additive CNS depression effects by the combination of Diflunisal and Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[35]
Dexamethasone	DMMWZET	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Diflunisal and Dexamethasone.	Rheumatoid arthritis [FA20]	[34]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Diflunisal and Leflunomide.	Rheumatoid arthritis [FA20]	[46]
Methylprednisolone	DM4BDON	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Diflunisal and Methylprednisolone.	Solid tumour/cancer [2A00-2F9Z]	[34]
Pitolisant	DM8RFNJ	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Diflunisal and Pitolisant.	Somnolence [MG42]	[32]
Plicamycin	DM7C8YV	Moderate	Increased risk of bleeding by the combination of Diflunisal and Plicamycin.	Testicular cancer [2C80]	[33]
Caplacizumab	DMPUKA7	Moderate	Increased risk of bleeding by the combination of Diflunisal and Caplacizumab.	Thrombocytopenia [3B64]	[33]
Apixaban	DM89JLN	Major	Increased risk of bleeding by the combination of Diflunisal and Apixaban.	Thrombosis [DB61-GB90]	[32]
Cangrelor	DM8JRH0	Moderate	Increased risk of bleeding by the combination of Diflunisal and Cangrelor.	Thrombosis [DB61-GB90]	[33]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Diflunisal and Brilinta.	Thrombosis [DB61-GB90]	[32]
Cabozantinib	DMIYDT4	Major	Increased risk of bleeding by the combination of Diflunisal and Cabozantinib.	Thyroid cancer [2D10]	[60]
Sirolimus	DMGW1ID	Major	Increased risk of nephrotoxicity by the combination of Diflunisal and Sirolimus.	Transplant rejection [NE84]	[59]
Tacrolimus	DMZ7XNQ	Major	Increased risk of nephrotoxicity by the combination of Diflunisal and Tacrolimus.	Transplant rejection [NE84]	[59]
Tolbutamide	DM02AWV	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Tolbutamide.	Type 2 diabetes mellitus [5A11]	[30]
Insulin-detemir	DMOA4VW	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Insulin-detemir.	Type-1/2 diabete [5A10-5A11]	[30]
Insulin degludec	DMPL395	Moderate	Increased risk of hypoglycemia by the combination of Diflunisal and Insulin degludec.	Type-1/2 diabete [5A10-5A11]	[30]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Olsalazine.	Ulcerative colitis [DD71]	[48]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Diflunisal and Plazomicin.	Urinary tract infection [GC08]	[36]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Diflunisal and Betrixaban.	Venous thromboembolism [BD72]	[61]

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
FD&C blue no. 2	E00446	2723854	Colorant
Sodium stearyl fumarate	E00545	23665634	lubricant
Sunset yellow FCF	E00255	17730	Colorant
Carmellose sodium	E00625	Not Available	Disintegrant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Diflunisal 500 mg tablet	500 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

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