Details of the Drug

General Information of Drug (ID: DM3P5DA)

• Drug Name: Rofecoxib
• Synonyms: Ceoxx; Refecoxib; Vioxx; Cahill May Roberts brand of rofecoxib; MSD brand of rofecoxib; Merck Frosst brandof rofecoxib; Merck brand of rofecoxib; Vioxx Dolor; MK 0966; MK 0996; MK 966; MK0966; Ceeoxx (TN); Ceoxx (TN); KS-1107; MK-0966; MK-966; Merck Sharp & Dhome brand of rofecoxib; Vioxx (TN); Vioxx (trademark); Rofecoxib (JAN/USAN/INN); 3-(4-methylsulfonylphenyl)-4-phenyl-2H-furan-5-one; 3-Phenyl-4-(4-(methylsulfonyl)phenyl))-2(5H)-furanone; 3-phenyl-4-[4-(methylsulfonyl)phenyl]-2(5H)-furanone; 4-(4-(Methylsulfonyl)phenyl)-3-phenyl-2(5H)-furanone; 4-(4-methylsulfonylphenyl)-3-phenyl-5H-furan-2-one; 4-(p-(Methylsulfonyl)phenyl)-3-phenyl-2(5H)-furanone; 4-[4-(methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone; 4-[4-(methylsulfonyl)phenyl]-3-phenylfuran-2(5H)-one

Indication

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[1]

• Therapeutic Class: Antiinflammatory Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 314.4
  Logarithm of the Partition Coefficient (xlogp); 2.3
  Rotatable Bond Count (rotbonds); 3
  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 [2]
  Bioavailability: The bioavailability of drug is 93% []
  Clearance: The drug present in the plasma can be removed from the body at the rate of 2 mL/min/kg [3]
  Elimination: 1% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 17 hours [3]
  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 2.64981 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.13% [3]
  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 1.3 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.1 mg/mL [2]
• Chemical Identifiers:
  Formula: C17H14O4S
  IUPAC Name: 3-(4-methylsulfonylphenyl)-4-phenyl-2H-furan-5-one
  Canonical SMILES: CS(=O)(=O)C1=CC=C(C=C1)C2=C(C(=O)OC2)C3=CC=CC=C3
  InChI: InChI=1S/C17H14O4S/c1-22(19,20)14-9-7-12(8-10-14)15-11-21-17(18)16(15)13-5-3-2-4-6-13/h2-10H,11H2,1H3
  InChIKey: RZJQGNCSTQAWON-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5090
  ChEBI ID: CHEBI:8887
  CAS Number: 162011-90-7
  DrugBank ID: DB00533
  TTD ID: D05VLS
  VARIDT ID: DR00753
  INTEDE ID: DR1433

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	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Substrate	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[9]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Substrate	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
15-hydroxyprostaglandin dehydrogenase (HPGD)	OTYZI6JB	PGDH_HUMAN	Gene/Protein Processing	[10]
A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8)	OT2KFY1S	ATS8_HUMAN	Gene/Protein Processing	[10]
Adhesion G-protein coupled receptor F1 (ADGRF1)	OTRAOBYH	AGRF1_HUMAN	Gene/Protein Processing	[10]
Adhesion G-protein coupled receptor G6 (ADGRG6)	OTY2UBXO	AGRG6_HUMAN	Gene/Protein Processing	[10]
Afadin (AFDN)	OTTRU341	AFAD_HUMAN	Gene/Protein Processing	[10]
Aldehyde oxidase (AOX1)	OT2FZP6H	AOXA_HUMAN	Gene/Protein Processing	[10]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Gene/Protein Processing	[10]
Angiopoietin-1 (ANGPT1)	OTVZ1NG3	ANGP1_HUMAN	Gene/Protein Processing	[10]
Angiopoietin-related protein 1 (ANGPTL1)	OTXIN6V5	ANGL1_HUMAN	Gene/Protein Processing	[10]
Annexin A1 (ANXA1)	OT5OFDJC	ANXA1_HUMAN	Gene/Protein Processing	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Osteoarthritis
• ICD Disease Classification: FA00-FA05

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
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	1.82E-04	-1.35E-01	-5.84E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	7.36E-01	1.62E-02	1.08E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	1.90E-01	-9.81E-03	-5.96E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01
Prostaglandin G/H synthase 1 (COX-1)	DME	PTGS1	3.97E-03	1.56E-01	4.33E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Rofecoxib

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Diclofenac	DMPIHLS	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Diclofenac.	Osteoarthritis [FA00-FA05]	[11]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[12]
Repaglinide	DM5SXUV	Moderate	Increased risk of hypoglycemia by the combination of Rofecoxib and Repaglinide.	Acute diabete complication [5A2Y]	[13]
Glibenclamide	DM8JXPZ	Moderate	Increased risk of hypoglycemia by the combination of Rofecoxib and Glibenclamide.	Acute diabete complication [5A2Y]	[13]
Tolazamide	DMIHRNA	Moderate	Increased risk of hypoglycemia by the combination of Rofecoxib and Tolazamide.	Acute diabete complication [5A2Y]	[14]
Nateglinide	DMLK2QH	Moderate	Increased risk of hypoglycemia by the combination of Rofecoxib and Nateglinide.	Acute diabete complication [5A2Y]	[13]
Glipizide	DMZA5PQ	Moderate	Increased risk of hypoglycemia by the combination of Rofecoxib and Glipizide.	Acute diabete complication [5A2Y]	[13]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Rofecoxib and Inotersen.	Amyloidosis [5D00]	[15]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[16]
Budesonide	DMJIBAW	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Budesonide.	Asthma [CA23]	[17]
Aminophylline	DML2NIB	Moderate	Decreased metabolism of Rofecoxib caused by Aminophylline mediated inhibition of CYP450 enzyme.	Asthma [CA23]	[18]
Ofloxacin	DM0VQN3	Moderate	Additive CNS stimulant effects by the combination of Rofecoxib and Ofloxacin.	Bacterial infection [1A00-1C4Z]	[19]
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Kanamycin.	Bacterial infection [1A00-1C4Z]	[20]
Ciprofloxacin XR	DM2NLS9	Moderate	Additive CNS depression effects by the combination of Rofecoxib and Ciprofloxacin XR.	Bacterial infection [1A00-1C4Z]	[19]
Trovafloxacin	DM6AN32	Moderate	Additive CNS stimulant effects by the combination of Rofecoxib and Trovafloxacin.	Bacterial infection [1A00-1C4Z]	[21]
Streptomycin	DME1LQN	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Streptomycin.	Bacterial infection [1A00-1C4Z]	[20]
Gemifloxacin	DMHT34O	Moderate	Additive CNS depression effects by the combination of Rofecoxib and Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[19]
Norfloxacin	DMIZ6W2	Moderate	Additive CNS stimulant effects by the combination of Rofecoxib and Norfloxacin.	Bacterial infection [1A00-1C4Z]	[21]
ABT-492	DMJFD2I	Moderate	Additive CNS depression effects by the combination of Rofecoxib and ABT-492.	Bacterial infection [1A00-1C4Z]	[19]
Gentamicin	DMKINJO	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Gentamicin.	Bacterial infection [1A00-1C4Z]	[20]
Levofloxacin	DMS60RB	Moderate	Additive CNS stimulant effects by the combination of Rofecoxib and Levofloxacin.	Bacterial infection [1A00-1C4Z]	[19]
Tobramycin	DMUI0CH	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Tobramycin.	Bacterial infection [1A00-1C4Z]	[20]
Etidronic acid	DM1XHYJ	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Etidronic acid.	Bone paget disease [FB85]	[22]
Risedronate	DM5FLTY	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Risedronate.	Bone paget disease [FB85]	[22]
Alendronate	DMY2KX9	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Alendronate.	Bone paget disease [FB85]	[22]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Rofecoxib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[23]
Drospirenone	DM1A9W3	Moderate	Increased risk of hyperkalemia by the combination of Rofecoxib and Drospirenone.	Contraceptive management [QA21]	[24]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Cannabidiol.	Epileptic encephalopathy [8A62]	[15]
Ethacrynic acid	DM60QMR	Moderate	Antagonize the effect of Rofecoxib when combined with Ethacrynic acid.	Essential hypertension [BA00]	[25]
Eplerenone	DMF0NQR	Moderate	Antagonize the effect of Rofecoxib when combined with Eplerenone.	Heart failure [BD10-BD1Z]	[26]
Chlorothiazide	DMLHESP	Moderate	Antagonize the effect of Rofecoxib when combined with Chlorothiazide.	Heart failure [BD10-BD1Z]	[25]
Furosemide	DMMQ8ZG	Moderate	Antagonize the effect of Rofecoxib when combined with Furosemide.	Heart failure [BD10-BD1Z]	[25]
Amiloride	DMRTSGP	Moderate	Antagonize the effect of Rofecoxib when combined with Amiloride.	Heart failure [BD10-BD1Z]	[25]
Bumetanide	DMRV7H0	Moderate	Antagonize the effect of Rofecoxib when combined with Bumetanide.	Heart failure [BD10-BD1Z]	[25]
Hydroflumethiazide	DMVPUQI	Moderate	Antagonize the effect of Rofecoxib when combined with Hydroflumethiazide.	Heart failure [BD10-BD1Z]	[25]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Rofecoxib caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[27]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[28]
Efavirenz	DMC0GSJ	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Efavirenz.	Human immunodeficiency virus disease [1C60-1C62]	[29]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Rofecoxib and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[30]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Rofecoxib and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[31]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Rofecoxib and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[32]
Captopril	DM458UM	Moderate	Antagonize the effect of Rofecoxib when combined with Captopril.	Hypertension [BA00-BA04]	[26]
Indapamide	DMGN1PW	Moderate	Antagonize the effect of Rofecoxib when combined with Indapamide.	Hypertension [BA00-BA04]	[25]
Hydrochlorothiazide	DMUSZHD	Moderate	Antagonize the effect of Rofecoxib when combined with Hydrochlorothiazide.	Hypertension [BA00-BA04]	[33]
Fludrocortisone	DMUDIR8	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Fludrocortisone.	Hypo-osmolality/hyponatraemia [5C72]	[17]
Ramelteon	DM7IW9J	Moderate	Decreased metabolism of Rofecoxib caused by Ramelteon mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[34]
Tasimelteon	DMLOQ1V	Moderate	Decreased metabolism of Rofecoxib caused by Tasimelteon mediated inhibition of CYP450 enzyme.	Insomnia [7A00-7A0Z]	[35]
Alosetron	DML2A03	Moderate	Decreased metabolism of Rofecoxib caused by Alosetron mediated inhibition of CYP450 enzyme.	Irritable bowel syndrome [DD91]	[36]
Methotrexate	DM2TEOL	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Methotrexate.	Leukaemia [2A60-2B33]	[15]
Lurbinectedin	DMEFRTZ	Moderate	Decreased metabolism of Rofecoxib caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[37]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[38]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Idelalisib.	Mature B-cell leukaemia [2A82]	[39]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Clofarabine.	Mature B-cell lymphoma [2A85]	[15]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Rofecoxib and Exjade.	Mineral absorption/transport disorder [5C64]	[40]
Deflazacort	DMV0RNS	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Deflazacort.	Muscular dystrophy [8C70]	[17]
Polythiazide	DMCH80F	Moderate	Antagonize the effect of Rofecoxib when combined with Polythiazide.	Oedema [MG29]	[25]
Aspirin	DM672AH	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Aspirin.	Pain [MG30-MG3Z]	[41]
Rasagiline	DM3WKQ4	Moderate	Decreased metabolism of Rofecoxib caused by Rasagiline mediated inhibition of CYP450 enzyme.	Parkinsonism [8A00]	[12]
Prednisone	DM2HG4X	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Prednisone.	Postoperative inflammation [1A00-CA43]	[17]
Hydrocortisone	DMGEMB7	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Hydrocortisone.	Postoperative inflammation [1A00-CA43]	[17]
Everolimus	DM8X2EH	Major	Increased risk of nephrotoxicity by the combination of Rofecoxib and Everolimus.	Renal cell carcinoma [2C90]	[42]
Temsirolimus	DMS104F	Major	Increased risk of nephrotoxicity by the combination of Rofecoxib and Temsirolimus.	Renal cell carcinoma [2C90]	[42]
Gatifloxacin	DMSL679	Moderate	Additive CNS stimulant effects by the combination of Rofecoxib and Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[21]
Sulfasalazine	DMICA9H	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Sulfasalazine.	Rheumatoid arthritis [FA20]	[43]
Dexamethasone	DMMWZET	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Dexamethasone.	Rheumatoid arthritis [FA20]	[17]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Rofecoxib and Leflunomide.	Rheumatoid arthritis [FA20]	[31]
Asenapine	DMSQZE2	Moderate	Decreased metabolism of Rofecoxib caused by Asenapine mediated inhibition of CYP450 enzyme.	Schizophrenia [6A20]	[44]
Pimozide	DMW83TP	Moderate	Decreased metabolism of Rofecoxib caused by Pimozide mediated inhibition of CYP450 enzyme.	Schizophrenia [6A20]	[45]
Methylprednisolone	DM4BDON	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Methylprednisolone.	Solid tumour/cancer [2A00-2F9Z]	[17]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[15]
Prednisolone	DMQ8FR2	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Prednisolone.	Solid tumour/cancer [2A00-2F9Z]	[17]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Rofecoxib and Naltrexone.	Substance abuse [6C40]	[46]
Tizanidine	DMR2IQ4	Major	Decreased metabolism of Rofecoxib caused by Tizanidine mediated inhibition of CYP450 enzyme.	Tonus and reflex abnormality [MB47]	[47]
Sirolimus	DMGW1ID	Major	Increased risk of nephrotoxicity by the combination of Rofecoxib and Sirolimus.	Transplant rejection [NE84]	[42]
Tacrolimus	DMZ7XNQ	Major	Increased risk of nephrotoxicity by the combination of Rofecoxib and Tacrolimus.	Transplant rejection [NE84]	[42]
Tolbutamide	DM02AWV	Moderate	Increased risk of hypoglycemia by the combination of Rofecoxib and Tolbutamide.	Type 2 diabetes mellitus [5A11]	[14]
Chlorpropamide	DMPHZQE	Moderate	Increased risk of hypoglycemia by the combination of Rofecoxib and Chlorpropamide.	Type 2 diabetes mellitus [5A11]	[14]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Olsalazine.	Ulcerative colitis [DD71]	[43]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Rofecoxib and Plazomicin.	Urinary tract infection [GC08]	[48]
Triamcinolone	DM98IXF	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Rofecoxib and Triamcinolone.	Vasomotor/allergic rhinitis [CA08]	[17]

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