Details of the Drug

General Information of Drug (ID: DMAY7H4)

• Drug Name: Valdecoxib
• Synonyms: Bextra; COX; Kudeq; Valdyn; Pfizer brand of valdecoxib; Valdecoxib [USAN]; SC 65872; ND-0214; SC-65872; YM-974; Valdecoxib (USAN/INN); P-(5-Methyl-3-phenyl-4-isoxazolyl)benzenesulfonamide; Benzenesulfonamide, 4-(5-methyl-3-phenyl-4-isoxazolyl)-(9CI); 4-(5-Methyl-3-phenyl-4-isoxazolyl)benzenesulfonamide; 4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)benzenesulfonamide; 4-(5-methyl-3-phenyl-4-isoxazolyl) benzenesulfonamide; 4-(5-methyl-3-phenyl-isoxazol-4-yl)benzenesulfonamide; 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide; 4-(Methyl-3-phenyl-isoxazol-4-yl)-benzenesulfonamide

Indication

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

• Therapeutic Class: Antiinflammatory Agents
• Affected Organisms: Humans and other mammals
• ATC Code:
  M01AH03: Valdecoxib
  M01AH: Coxibs
  M01A: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
  M01: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
  M: MUSCULO-SKELETAL SYSTEM
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 314.4
  Logarithm of the Partition Coefficient (xlogp); 2.6
  Rotatable Bond Count (rotbonds); 3
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [2]
  Bioavailability: The bioavailability of drug is 83% []
  Clearance: The apparent oral clearance of drug is 6 L/h []
  Half-life: The concentration or amount of drug in body reduced by one-half in 8 - 11 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 2.12173 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.02% [3]
  Vd: The volume of distribution (Vd) of drug is 86 L []
• Chemical Identifiers:
  Formula: C16H14N2O3S
  IUPAC Name: 4-(5-methyl-3-phenyl-1,2-oxazol-4-yl)benzenesulfonamide
  Canonical SMILES: CC1=C(C(=NO1)C2=CC=CC=C2)C3=CC=C(C=C3)S(=O)(=O)N
  InChI: InChI=1S/C16H14N2O3S/c1-11-15(12-7-9-14(10-8-12)22(17,19)20)16(18-21-11)13-5-3-2-4-6-13/h2-10H,1H3,(H2,17,19,20)
  InChIKey: LNPDTQAFDNKSHK-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 119607
  ChEBI ID: CHEMBL865
  CAS Number: 181695-72-7
  UNII: 2919279Q3W
  DrugBank ID: DB00580
  TTD ID: D0L6DA
  VARIDT ID: DR01196
  INTEDE ID: DR1666
• Drug-Molecule Activity Atlas (DMA)NEW: Click to Jump to the Detailed DMA Information of This Drug
• Drug Pharmacogenomic Perturbation (DPP)NEW: Click to Jump to the Detailed DPP Information of This Drug
• Drug ADMET Endpoint Profile (DAE)NEW: Click to Jump to the Detailed DAE Information of This Drug

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) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[6]
Cytochrome P450 2C9 (CYP2C9) Main DME	DE5IED8	CP2C9_HUMAN	Substrate	[7]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Substrate	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
HLA class II histocompatibility antigen, DM beta chain (HLA-DMB)	OT17HGXJ	DMB_HUMAN	Gene/Protein Processing	[9]
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Gene/Protein Processing	[9]
Vascular endothelial growth factor A, long form	OTIM9MZ3	VEGFA_HUMAN	Protein Interaction/Cellular Processes	[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 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

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Valdecoxib

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

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[12]
Repaglinide	DM5SXUV	Moderate	Increased risk of hypoglycemia by the combination of Valdecoxib and Repaglinide.	Acute diabete complication [5A2Y]	[13]
Glibenclamide	DM8JXPZ	Moderate	Increased risk of hypoglycemia by the combination of Valdecoxib and Glibenclamide.	Acute diabete complication [5A2Y]	[13]
Tolazamide	DMIHRNA	Moderate	Increased risk of hypoglycemia by the combination of Valdecoxib and Tolazamide.	Acute diabete complication [5A2Y]	[14]
Nateglinide	DMLK2QH	Moderate	Increased risk of hypoglycemia by the combination of Valdecoxib and Nateglinide.	Acute diabete complication [5A2Y]	[13]
Glipizide	DMZA5PQ	Moderate	Increased risk of hypoglycemia by the combination of Valdecoxib and Glipizide.	Acute diabete complication [5A2Y]	[13]
Arn-509	DMT81LZ	Moderate	Increased metabolism of Valdecoxib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[15]
Metronidazole	DMTIVEN	Moderate	Decreased metabolism of Valdecoxib caused by Metronidazole mediated inhibition of CYP450 enzyme.	Amoebiasis [1A36]	[16]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Valdecoxib and Inotersen.	Amyloidosis [5D00]	[15]
Dronedarone	DMA8FS5	Moderate	Decreased metabolism of Valdecoxib caused by Dronedarone mediated inhibition of CYP450 enzyme.	Angina pectoris [BA40]	[17]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[18]
Voriconazole	DMAOL2S	Moderate	Decreased metabolism of Valdecoxib caused by Voriconazole mediated inhibition of CYP450 enzyme.	Aspergillosis [1F20]	[12]
Budesonide	DMJIBAW	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Budesonide.	Asthma [CA23]	[19]
Ofloxacin	DM0VQN3	Moderate	Additive CNS stimulant effects by the combination of Valdecoxib and Ofloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Kanamycin.	Bacterial infection [1A00-1C4Z]	[21]
Dalfopristin	DM4LTKV	Moderate	Decreased metabolism of Valdecoxib caused by Dalfopristin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[16]
Clarithromycin	DM4M1SG	Moderate	Decreased metabolism of Valdecoxib caused by Clarithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[16]
Trovafloxacin	DM6AN32	Moderate	Additive CNS stimulant effects by the combination of Valdecoxib and Trovafloxacin.	Bacterial infection [1A00-1C4Z]	[22]
Sulfamethoxazole	DMB08GE	Moderate	Decreased metabolism of Valdecoxib caused by Sulfamethoxazole mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[16]
Streptomycin	DME1LQN	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Streptomycin.	Bacterial infection [1A00-1C4Z]	[21]
Gemifloxacin	DMHT34O	Moderate	Additive CNS depression effects by the combination of Valdecoxib and Gemifloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Norfloxacin	DMIZ6W2	Moderate	Additive CNS stimulant effects by the combination of Valdecoxib and Norfloxacin.	Bacterial infection [1A00-1C4Z]	[22]
ABT-492	DMJFD2I	Moderate	Additive CNS depression effects by the combination of Valdecoxib and ABT-492.	Bacterial infection [1A00-1C4Z]	[20]
Gentamicin	DMKINJO	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Gentamicin.	Bacterial infection [1A00-1C4Z]	[21]
Levofloxacin	DMS60RB	Moderate	Additive CNS stimulant effects by the combination of Valdecoxib and Levofloxacin.	Bacterial infection [1A00-1C4Z]	[20]
Tobramycin	DMUI0CH	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Tobramycin.	Bacterial infection [1A00-1C4Z]	[21]
Telithromycin	DMZ4P3A	Moderate	Decreased metabolism of Valdecoxib caused by Telithromycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[23]
Etidronic acid	DM1XHYJ	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Etidronic acid.	Bone paget disease [FB85]	[24]
Risedronate	DM5FLTY	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Risedronate.	Bone paget disease [FB85]	[24]
Alendronate	DMY2KX9	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Alendronate.	Bone paget disease [FB85]	[24]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Valdecoxib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[25]
Alpelisib	DMEXMYK	Moderate	Increased metabolism of Valdecoxib caused by Alpelisib mediated induction of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[26]
Drospirenone	DM1A9W3	Moderate	Increased risk of hyperkalemia by the combination of Valdecoxib and Drospirenone.	Contraceptive management [QA21]	[27]
Mifepristone	DMGZQEF	Moderate	Decreased metabolism of Valdecoxib caused by Mifepristone mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[28]
Ivacaftor	DMZC1HS	Moderate	Decreased metabolism of Valdecoxib caused by Ivacaftor mediated inhibition of CYP450 enzyme.	Cystic fibrosis [CA25]	[29]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Valdecoxib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[30]
Aprepitant	DM053KT	Moderate	Increased metabolism of Valdecoxib caused by Aprepitant mediated induction of CYP450 enzyme.	Depression [6A70-6A7Z]	[31]
Nefazodone	DM4ZS8M	Moderate	Decreased metabolism of Valdecoxib caused by Nefazodone mediated inhibition of CYP450 enzyme.	Depression [6A70-6A7Z]	[16]
Diazepam	DM08E9O	Moderate	Decreased metabolism of Valdecoxib caused by Diazepam mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Primidone	DM0WX6I	Moderate	Increased metabolism of Valdecoxib caused by Primidone mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Oxcarbazepine	DM5PU6O	Moderate	Increased metabolism of Valdecoxib caused by Oxcarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Fosphenytoin	DMOX3LB	Moderate	Increased metabolism of Valdecoxib caused by Fosphenytoin mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Rufinamide	DMWE60C	Moderate	Increased metabolism of Valdecoxib caused by Rufinamide mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[15]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Valdecoxib caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[16]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Cannabidiol.	Epileptic encephalopathy [8A62]	[15]
Ethacrynic acid	DM60QMR	Moderate	Antagonize the effect of Valdecoxib when combined with Ethacrynic acid.	Essential hypertension [BA00]	[32]
Itraconazole	DMCR1MV	Moderate	Decreased metabolism of Valdecoxib caused by Itraconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[16]
Miconazole	DMPMYE8	Moderate	Decreased metabolism of Valdecoxib caused by Miconazole mediated inhibition of CYP450 enzyme.	Fungal infection [1F29-1F2F]	[16]
Eplerenone	DMF0NQR	Moderate	Increased risk of hyperkalemia by the combination of Valdecoxib and Eplerenone.	Heart failure [BD10-BD1Z]	[33]
Chlorothiazide	DMLHESP	Moderate	Antagonize the effect of Valdecoxib when combined with Chlorothiazide.	Heart failure [BD10-BD1Z]	[32]
Furosemide	DMMQ8ZG	Moderate	Antagonize the effect of Valdecoxib when combined with Furosemide.	Heart failure [BD10-BD1Z]	[32]
Amiloride	DMRTSGP	Moderate	Antagonize the effect of Valdecoxib when combined with Amiloride.	Heart failure [BD10-BD1Z]	[32]
Bumetanide	DMRV7H0	Moderate	Antagonize the effect of Valdecoxib when combined with Bumetanide.	Heart failure [BD10-BD1Z]	[32]
Hydroflumethiazide	DMVPUQI	Moderate	Antagonize the effect of Valdecoxib when combined with Hydroflumethiazide.	Heart failure [BD10-BD1Z]	[32]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Valdecoxib caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[34]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[35]
Delavirdine	DM3NF5G	Moderate	Decreased metabolism of Valdecoxib caused by Delavirdine mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Efavirenz	DMC0GSJ	Moderate	Increased metabolism of Valdecoxib caused by Efavirenz mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[36]
Saquinavir	DMG814N	Moderate	Decreased metabolism of Valdecoxib caused by Saquinavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Amprenavir	DMLMXE0	Moderate	Decreased metabolism of Valdecoxib caused by Amprenavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Darunavir	DMN3GCH	Moderate	Decreased metabolism of Valdecoxib caused by Darunavir mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[37]
Fluvastatin	DM4MDJY	Moderate	Decreased metabolism of Valdecoxib caused by Fluvastatin mediated inhibition of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[16]
Fenofibrate	DMFKXDY	Moderate	Decreased metabolism of Valdecoxib caused by Fenofibrate mediated inhibition of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[12]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Valdecoxib and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[38]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Valdecoxib and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[39]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Valdecoxib and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[40]
Verapamil	DMA7PEW	Moderate	Decreased metabolism of Valdecoxib caused by Verapamil mediated inhibition of CYP450 enzyme.	Hypertension [BA00-BA04]	[16]
Indapamide	DMGN1PW	Moderate	Antagonize the effect of Valdecoxib when combined with Indapamide.	Hypertension [BA00-BA04]	[32]
Hydrochlorothiazide	DMUSZHD	Moderate	Antagonize the effect of Valdecoxib when combined with Hydrochlorothiazide.	Hypertension [BA00-BA04]	[41]
Conivaptan	DM1V329	Moderate	Decreased metabolism of Valdecoxib caused by Conivaptan mediated inhibition of CYP450 enzyme.	Hypo-osmolality/hyponatraemia [5C72]	[42]
Fludrocortisone	DMUDIR8	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Fludrocortisone.	Hypo-osmolality/hyponatraemia [5C72]	[19]
Balsalazide	DM7I1T9	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Balsalazide.	Indeterminate colitis [DD72]	[43]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Valdecoxib caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[44]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Valdecoxib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[45]
Selpercatinib	DMZR15V	Moderate	Decreased metabolism of Valdecoxib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[46]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[47]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Idelalisib.	Mature B-cell leukaemia [2A82]	[48]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Valdecoxib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[49]
Clofarabine	DMCVJ86	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Clofarabine.	Mature B-cell lymphoma [2A85]	[15]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Valdecoxib caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[15]
Ethinyl estradiol	DMODJ40	Moderate	Decreased metabolism of Valdecoxib caused by Ethinyl estradiol mediated inhibition of CYP450 enzyme.	Menopausal disorder [GA30]	[50]
Danazol	DML8KTN	Moderate	Decreased metabolism of Valdecoxib caused by Danazol mediated inhibition of CYP450 enzyme.	Menstrual cycle bleeding disorder [GA20]	[16]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Valdecoxib and Exjade.	Mineral absorption/transport disorder [5C64]	[51]
Deflazacort	DMV0RNS	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Deflazacort.	Muscular dystrophy [8C70]	[19]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Valdecoxib caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[15]
Nilotinib	DM7HXWT	Moderate	Decreased metabolism of Valdecoxib caused by Nilotinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[52]
Imatinib	DM7RJXL	Moderate	Decreased metabolism of Valdecoxib caused by Imatinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[16]
Dasatinib	DMJV2EK	Moderate	Decreased metabolism of Valdecoxib caused by Dasatinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[53]
Modafinil	DMYILBE	Minor	Increased metabolism of Valdecoxib caused by Modafinil mediated induction of CYP450 enzyme.	Narcolepsy [7A20]	[54]
Polythiazide	DMCH80F	Moderate	Antagonize the effect of Valdecoxib when combined with Polythiazide.	Oedema [MG29]	[32]
Rucaparib	DM9PVX8	Moderate	Decreased metabolism of Valdecoxib caused by Rucaparib mediated inhibition of CYP450 enzyme.	Ovarian cancer [2C73]	[55]
Aspirin	DM672AH	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Aspirin.	Pain [MG30-MG3Z]	[56]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Valdecoxib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[57]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Valdecoxib caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[58]
Prednisone	DM2HG4X	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Prednisone.	Postoperative inflammation [1A00-CA43]	[19]
Hydrocortisone	DMGEMB7	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Hydrocortisone.	Postoperative inflammation [1A00-CA43]	[19]
Lonafarnib	DMGM2Z6	Moderate	Decreased metabolism of Valdecoxib caused by Lonafarnib mediated inhibition of CYP450 enzyme.	Premature ageing appearance [LD2B]	[59]
Enzalutamide	DMGL19D	Moderate	Increased metabolism of Valdecoxib caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[60]
Everolimus	DM8X2EH	Major	Increased risk of nephrotoxicity by the combination of Valdecoxib and Everolimus.	Renal cell carcinoma [2C90]	[61]
Temsirolimus	DMS104F	Major	Increased risk of nephrotoxicity by the combination of Valdecoxib and Temsirolimus.	Renal cell carcinoma [2C90]	[61]
Gatifloxacin	DMSL679	Moderate	Additive CNS stimulant effects by the combination of Valdecoxib and Gatifloxacin.	Respiratory infection [CA07-CA4Z]	[22]
Sulfasalazine	DMICA9H	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Sulfasalazine.	Rheumatoid arthritis [FA20]	[43]
Dexamethasone	DMMWZET	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Dexamethasone.	Rheumatoid arthritis [FA20]	[19]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Valdecoxib and Leflunomide.	Rheumatoid arthritis [FA20]	[39]
Telotristat ethyl	DMDIYFZ	Moderate	Increased metabolism of Valdecoxib caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[15]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Valdecoxib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[12]
Methylprednisolone	DM4BDON	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Methylprednisolone.	Solid tumour/cancer [2A00-2F9Z]	[19]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[15]
Armodafinil	DMGB035	Minor	Increased metabolism of Valdecoxib caused by Armodafinil mediated induction of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[54]
LEE011	DMMX75K	Moderate	Decreased metabolism of Valdecoxib caused by LEE011 mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[62]
Prednisolone	DMQ8FR2	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Prednisolone.	Solid tumour/cancer [2A00-2F9Z]	[19]
Disulfiram	DMCL2OK	Moderate	Decreased metabolism of Valdecoxib caused by Disulfiram mediated inhibition of CYP450 enzyme.	Substance abuse [6C40]	[16]
Naltrexone	DMUL45H	Moderate	Increased risk of hepatotoxicity by the combination of Valdecoxib and Naltrexone.	Substance abuse [6C40]	[63]
Warfarin	DMJYCVW	Moderate	Decreased metabolism of Valdecoxib caused by Warfarin mediated inhibition of CYP450 enzyme.	Supraventricular tachyarrhythmia [BC81]	[16]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Valdecoxib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[64]
Sirolimus	DMGW1ID	Major	Increased risk of nephrotoxicity by the combination of Valdecoxib and Sirolimus.	Transplant rejection [NE84]	[61]
Tacrolimus	DMZ7XNQ	Major	Increased risk of nephrotoxicity by the combination of Valdecoxib and Tacrolimus.	Transplant rejection [NE84]	[61]
Tolbutamide	DM02AWV	Moderate	Increased risk of hypoglycemia by the combination of Valdecoxib and Tolbutamide.	Type 2 diabetes mellitus [5A11]	[14]
Chlorpropamide	DMPHZQE	Moderate	Increased risk of hypoglycemia by the combination of Valdecoxib and Chlorpropamide.	Type 2 diabetes mellitus [5A11]	[14]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Olsalazine.	Ulcerative colitis [DD71]	[43]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Valdecoxib and Plazomicin.	Urinary tract infection [GC08]	[65]
Triamcinolone	DM98IXF	Moderate	Increased risk of GI mucosal injury/bleeding risk by the combination of Valdecoxib and Triamcinolone.	Vasomotor/allergic rhinitis [CA08]	[19]
Amiodarone	DMUTEX3	Moderate	Decreased metabolism of Valdecoxib caused by Amiodarone mediated inhibition of CYP450 enzyme.	Ventricular tachyarrhythmia [BC71]	[16]

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: 2894).
• [2] BDDCS applied to over 900 drugs
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] 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
• [5] Biochemical mechanisms of New Molecular Entities (NMEs) approved by United States FDA during 2001-2004: mechanisms leading to optimal efficacy and ... Curr Top Med Chem. 2006;6(5):461-78.
• [6] Simultaneous assessment of drug interactions with low- and high-extraction opioids: application to parecoxib effects on the pharmacokinetics and pharmacodynamics of fentanyl and alfentanil. Anesthesiology. 2003 Apr;98(4):853-61.
• [7] Genetically based impairment in CYP2C8- and CYP2C9-dependent NSAID metabolism as a risk factor for gastrointestinal bleeding: is a combination of pharmacogenomics and metabolomics required to improve personalized medicine? Expert Opin Drug Metab Toxicol. 2009 Jun;5(6):607-20.
• [8] 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.
• [9] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [10] The effect of valdecoxib on the production of growth factors evoked by hypoxia and bacterial lipopolysaccharide in HMEC-1 cells. Adv Clin Exp Med. 2013 Nov-Dec;22(6):795-800.
• [11] Product Information. Solaraze (diclofenac topical). Doak Dermatologics Division, Fairfield, NJ.
• [12] Cerner Multum, Inc. "Australian Product Information.".
• [13] 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]
• [14] Christensen LK, Hansen JM, Kristensen M "Sulphaphenazole-induced hypoglycemic attacks in tolbutamide-treated diabetics." Lancet 2 (1963): 1298-301. [PMID: 14071924]
• [15] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [16] Product Information. Bextra (valdecoxib). Pharmacia Corporation, Peapack, NJ.
• [17] Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
• [18] Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
• [19] Buchman AL, Schwartz MR "Colonic ulceration associated with the systemic use of nonsteroidal antiinflammatory medication." J Clin Gastroenterol 22 (1996): 224-6. [PMID: 8724264]
• [20] Product Information. Factive (gemifloxacin). GeneSoft Inc, San Francisco, CA.
• [21] Assael BM, Chiabrando C, Gagliardi L, Noseda A, Bamonte F, Salmona M "Prostaglandins and aminoglycoside nephrotoxicity." Toxicol Appl Pharmacol 78 (1985): 386-94. [PMID: 4049389]
• [22] Davey PG "Overview of drug interactions with the quinolones." J Antimicrob Chemother 22(suppl c) (1988): 97-107. [PMID: 3053579]
• [23] Product Information. Ketek (telithromycin). Aventis Pharmaceuticals, Bridgewater, NJ.
• [24] Product Information. Actonel (risedronate). Procter and Gamble Pharmaceuticals, Cincinnati, OH.
• [25] Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
• [26] Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32. [PMID: 9562227]
• [27] Product Information. Yasmin (drospirenone-ethinyl estradiol) Berlex Laboratories, Richmond, CA.
• [28] Product Information. Korlym (mifepristone). Corcept Therapeutics Incorporated, Menlo Park, CA.
• [29] Product Information. Kalydeco (ivacaftor). Vertex Pharmaceuticals, Cambridge, MA.
• [30] Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
• [31] Product Information. Emend (aprepitant). Merck & Company Inc, West Point, PA.
• [32] Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV "Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers." Eur J Clin Pharmacol 48 (1995): 247-51. [PMID: 7589049]
• [33] Abdel-Haq B, Magagna A, Favilla S, Salvetti A "Hemodynamic and humoral interactions between perindopril and indomethacin in essential hypertensive subjects." J Cardiovasc Pharmacol 18 (1991): s33-6. [PMID: 1725198]
• [34] Product Information. Priftin (rifapentine). Hoechst Marion-Roussel Inc, Kansas City, MO.
• [35] Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
• [36] Product Information. Sustiva (efavirenz). DuPont Pharmaceuticals, Wilmington, DE.
• [37] Product Information. Prezista (darunavir). Ortho Biotech Inc, Bridgewater, NJ.
• [38] Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
• [39] EMEA "EMEA public statement on leflunomide (ARAVA) - severe and serious hepatic reactions.".
• [40] Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
• [41] McCarthy JT, Torres VE, Romero JC, et al "Acute intrinsic renal failure induced by indomethacin." Mayo Clin Proc 57 (1982): 289-96. [PMID: 6952058]
• [42] Product Information. Vaprisol (conivaptan). Cumberland Pharmaceuticals Inc, Nashville, TN.
• [43] Novis BH, Korzets Z, Chen P, Bernheim J "Nephrotic syndrome after treatment with 5-aminosalicylic acid." Br Med J (Clin Res Ed) 296 (1988): 1442. [PMID: 3132281]
• [44] Product Information. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
• [45] Product Information. Lorbrena (lorlatinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
• [46] Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
• [47] 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]
• [48] Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
• [49] Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
• [50] Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]
• [51] Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
• [52] Product Information. Tasigna (nilotinib). Novartis Pharmaceuticals, East Hanover, NJ.
• [53] Product Information. Sprycel (dasatinib). Bristol-Myers Squibb, Princeton, NJ.
• [54] Doherty MM, Charman WN "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet 41 (2002): 235-53. [PMID: 11978143]
• [55] EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
• [56] Abdel-Rahman MS, Reddi AS, Curro FA, Turkall RM, Kadry AM, Hansrote JA "Bioavailability of aspirin and salicylamide following oral co-administration in human volunteers." Can J Physiol Pharmacol 69 (1991): 1436-42. [PMID: 1777842]
• [57] Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
• [58] Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
• [59] Product Information. Zokinvy (lonafarnib). Eiger BioPharmaceuticals, Palo Alto, CA.
• [60] Benoist G, van Oort I, et al "Drug-drug interaction potential in men treated with enzalutamide: Mind the gap." Br J Clin Pharmacol 0 (2017): epub. [PMID: 28881501]
• [61] Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
• [62] DSouza DL, Levasseur LM, Nezamis J, Robbins DK, Simms L, Koch KM "Effect of alosetron on the pharmacokinetics of alprazolam." J Clin Pharmacol 41 (2001): 452-4. [PMID: 11304902]
• [63] Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.
• [64] Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.
• [65] Farag MM, Mikhail MR, Abdel-Meguid E, Abdel-Tawab S "Assessment of gentamicin-induced nephrotoxicity in rats treated with low doses of ibuprofen and diclofenac sodium." Clin Sci 91 (1996): 187-91. [PMID: 8795442]