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Identification
NameRofecoxib
Accession NumberDB00533  (APRD00151)
TypeSmall Molecule
GroupsInvestigational, Withdrawn
DescriptionRofecoxib is used for the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras. Rofecoxib is a solid. This compound belongs to the stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids. Rofecoxib has a half-life of 17 hours and its mean oral bioavailability at therapeutically recommended doses of 125, 25, and 50 mg is approximately 93%. The proteins that rofecoxib target include elastin and prostaglandin G/H synthase 2. Cytochrome P450 1A2, Cytochrome P450 3A4, Cytochrome P450 2C9, Cytochrome P450 2C8, and Prostaglandin G/H synthase 1 are known to metabolize rofecoxib. On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.
Structure
Thumb
SynonymsNot Available
External Identifiers
  • MK 966
  • MK 996
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vioxx Suspension 12.5mg/5mlsuspension12.5 mgoralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.2000-05-082004-09-30Canada
Vioxx Tab 12.5mgtablet12.5 mgoralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1999-11-082004-09-30Canada
Vioxx Tab 25mgtablet25 mgoralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1999-11-082004-09-30Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
VioxxNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII0QTW8Z7MCR
CAS number162011-90-7
WeightAverage: 314.356
Monoisotopic: 314.061279626
Chemical FormulaC17H14O4S
InChI KeyInChIKey=RZJQGNCSTQAWON-UHFFFAOYSA-N
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
IUPAC Name
4-(4-methanesulfonylphenyl)-3-phenyl-2,5-dihydrofuran-2-one
SMILES
CS(=O)(=O)C1=CC=C(C=C1)C1=C(C(=O)OC1)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassStilbenes
Sub ClassNot Available
Direct ParentStilbenes
Alternative Parents
Substituents
  • Stilbene
  • Benzenoid
  • 2-furanone
  • Monocyclic benzene moiety
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Sulfonyl
  • Sulfone
  • Dihydrofuran
  • Lactone
  • Carboxylic acid ester
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras.
PharmacodynamicsRofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.
Mechanism of actionThe anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX-2 isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-1.
Related Articles
AbsorptionThe mean oral bioavailability of rofecoxib at therapeutically recommended doses of 12.5, 25, and 50 mg is approximately 93%.
Volume of distributionNot Available
Protein binding87%
Metabolism

Hepatic. Metabolism of rofecoxib is primarily mediated through reduction by cytosolic enzymes. The principal metabolic products are the cis-dihydro and trans-dihydro derivatives of rofecoxib, which account for nearly 56% of recovered radioactivity in the urine. An additional 8.8% of the dose was recovered as the glucuronide of the hydroxy derivative, a product of oxidative metabolism. The biotransformation of rofecoxib and this metabolite is reversible in humans to a limited extent (< 5%). These metabolites are inactive as COX-1 or COX-2 inhibitors. Cytochrome P450 plays a minor role in metabolism of rofecoxib.

SubstrateEnzymesProduct
Rofecoxib
5-HydroxyrofecoxibDetails
Rofecoxib
Dihydro-5-hydroxyrofecoxibDetails
Rofecoxib
Rofecoxib-threo-3,4-dihydrohydroxy acidDetails
Rofecoxib
Rofecoxib-erythro-3,4-dihydrohydroxy acidDetails
Rofecoxib-erythro-3,4-dihydrohydroxy acid
Not Available
cis-DihydrorofecoxibDetails
Rofecoxib-threo-3,4-dihydrohydroxy acid
Not Available
trans-DihydrorofecoxibDetails
Dihydro-5-hydroxyrofecoxib
Not Available
Rofecoxib-threo-3,4-dihydrohydroxy acidDetails
5-Hydroxyrofecoxib
5-Hydroxyrofecoxib O-glucuronideDetails
Route of eliminationNot Available
Half life17 hours
ClearanceNot Available
ToxicityNo overdoses of rofecoxib were reported during clinical trials. Administration of single doses of rofecoxib 1000 mg to 6 healthy volunteers and multiple doses of 250 mg/day for 14 days to 75 healthy volunteers did not result in serious toxicity.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Rofecoxib Action PathwayDrug actionSMP00087
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9938
Blood Brain Barrier+0.6296
Caco-2 permeable-0.5696
P-glycoprotein substrateNon-substrate0.7186
P-glycoprotein inhibitor INon-inhibitor0.5401
P-glycoprotein inhibitor IINon-inhibitor0.922
Renal organic cation transporterNon-inhibitor0.7846
CYP450 2C9 substrateNon-substrate0.5807
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5941
CYP450 1A2 substrateInhibitor0.5426
CYP450 2C9 inhibitorInhibitor0.6668
CYP450 2D6 inhibitorNon-inhibitor0.889
CYP450 2C19 inhibitorInhibitor0.6214
CYP450 3A4 inhibitorNon-inhibitor0.8508
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7596
Ames testNon AMES toxic0.6152
CarcinogenicityNon-carcinogens0.5754
BiodegradationNot ready biodegradable0.7716
Rat acute toxicity2.4527 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9848
hERG inhibition (predictor II)Non-inhibitor0.8932
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Merck research laboratories div merck co inc
Packagers
Dosage forms
FormRouteStrength
Suspensionoral12.5 mg
Tabletoral12.5 mg
Tabletoral25 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5474995 No1993-06-242013-06-24Us
US5691374 Yes1995-11-182015-11-18Us
US6063811 Yes1997-11-062017-11-06Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0106 mg/mLALOGPS
logP2.32ALOGPS
logP2.56ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)14.84ChemAxon
pKa (Strongest Basic)-7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area60.44 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity84.08 m3·mol-1ChemAxon
Polarizability31.74 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med. 2000 Nov 23;343(21):1520-8, 2 p following 1528. [PubMed:11087881 ]
  2. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 2005 Mar 17;352(11):1092-102. Epub 2005 Feb 15. [PubMed:15713943 ]
  3. Curfman GD, Morrissey S, Drazen JM: Expression of concern reaffirmed. N Engl J Med. 2006 Mar 16;354(11):1193. Epub 2006 Feb 22. [PubMed:16495386 ]
  4. Fitzgerald GA: Coxibs and cardiovascular disease. N Engl J Med. 2004 Oct 21;351(17):1709-11. Epub 2004 Oct 6. [PubMed:15470192 ]
  5. Karha J, Topol EJ: The sad story of Vioxx, and what we should learn from it. Cleve Clin J Med. 2004 Dec;71(12):933-4, 936, 938-9. [PubMed:15641522 ]
  6. Baron JA, Sandler RS, Bresalier RS, Lanas A, Morton DG, Riddell R, Iverson ER, Demets DL: Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet. 2008 Nov 15;372(9651):1756-64. doi: 10.1016/S0140-6736(08)61490-7. Epub 2008 Oct 14. [PubMed:18922570 ]
  7. Matheson AJ, Figgitt DP: Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs. 2001;61(6):833-65. [PubMed:11398914 ]
  8. Hillson JL, Furst DE: Rofecoxib. Expert Opin Pharmacother. 2000 Jul;1(5):1053-66. [PubMed:11249495 ]
External Links
ATC CodesM01AH02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (291 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabRofecoxib may increase the anticoagulant activities of Abciximab.
AbirateroneThe serum concentration of Rofecoxib can be increased when it is combined with Abiraterone.
AcebutololRofecoxib may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Aceclofenac.
AcenocoumarolRofecoxib may increase the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Acetylsalicylic acid.
AdapaleneThe risk or severity of adverse effects can be increased when Adapalene is combined with Rofecoxib.
Alendronic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Alendronic acid.
AliskirenRofecoxib may decrease the antihypertensive activities of Aliskiren.
AlprenololRofecoxib may decrease the antihypertensive activities of Alprenolol.
AlprostadilThe therapeutic efficacy of Alprostadil can be decreased when used in combination with Rofecoxib.
AmikacinRofecoxib may decrease the excretion rate of Amikacin which could result in a lower serum level and potentially a reduction in efficacy.
AmilorideRofecoxib may decrease the antihypertensive activities of Amiloride.
AmiodaroneThe metabolism of Rofecoxib can be decreased when combined with Amiodarone.
AncrodRofecoxib may increase the anticoagulant activities of Ancrod.
AntipyrineThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Antipyrine.
Antithrombin III humanRofecoxib may increase the anticoagulant activities of Antithrombin III human.
ApixabanRofecoxib may increase the anticoagulant activities of Apixaban.
ApremilastThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Apremilast.
AprepitantThe serum concentration of Rofecoxib can be increased when it is combined with Aprepitant.
ArdeparinRofecoxib may increase the anticoagulant activities of Ardeparin.
ArgatrobanRofecoxib may increase the anticoagulant activities of Argatroban.
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Rofecoxib.
ArotinololRofecoxib may decrease the antihypertensive activities of Arotinolol.
AtazanavirThe metabolism of Rofecoxib can be decreased when combined with Atazanavir.
AtenololRofecoxib may decrease the antihypertensive activities of Atenolol.
AtomoxetineThe metabolism of Rofecoxib can be decreased when combined with Atomoxetine.
AzapropazoneThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Azapropazone.
AzelastineThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Azelastine.
Azilsartan medoxomilThe risk or severity of adverse effects can be increased when Azilsartan medoxomil is combined with Rofecoxib.
AzithromycinThe metabolism of Rofecoxib can be decreased when combined with Azithromycin.
BalsalazideRofecoxib may increase the nephrotoxic activities of Balsalazide.
BalsalazideThe risk or severity of adverse effects can be increased when Balsalazide is combined with Rofecoxib.
BecaplerminRofecoxib may increase the anticoagulant activities of Becaplermin.
BefunololRofecoxib may decrease the antihypertensive activities of Befunolol.
BenazeprilThe risk or severity of adverse effects can be increased when Benazepril is combined with Rofecoxib.
BendroflumethiazideThe therapeutic efficacy of Bendroflumethiazide can be decreased when used in combination with Rofecoxib.
BenoxaprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Benoxaprofen.
BetaxololRofecoxib may decrease the antihypertensive activities of Betaxolol.
BevantololRofecoxib may decrease the antihypertensive activities of Bevantolol.
BexaroteneThe serum concentration of Rofecoxib can be decreased when it is combined with Bexarotene.
BimatoprostThe therapeutic efficacy of Bimatoprost can be decreased when used in combination with Rofecoxib.
BisoprololRofecoxib may decrease the antihypertensive activities of Bisoprolol.
BivalirudinRofecoxib may increase the anticoagulant activities of Bivalirudin.
BoceprevirThe metabolism of Rofecoxib can be decreased when combined with Boceprevir.
BopindololRofecoxib may decrease the antihypertensive activities of Bopindolol.
BortezomibThe metabolism of Rofecoxib can be decreased when combined with Bortezomib.
BosentanThe serum concentration of Rofecoxib can be decreased when it is combined with Bosentan.
BromfenacThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Bromfenac.
BufuralolRofecoxib may decrease the antihypertensive activities of Bufuralol.
BumetanideRofecoxib may decrease the diuretic activities of Bumetanide.
BupranololRofecoxib may decrease the antihypertensive activities of Bupranolol.
CaffeineThe metabolism of Rofecoxib can be decreased when combined with Caffeine.
CandesartanThe risk or severity of adverse effects can be increased when Candesartan is combined with Rofecoxib.
CandoxatrilThe risk or severity of adverse effects can be increased when Candoxatril is combined with Rofecoxib.
CapecitabineThe metabolism of Rofecoxib can be decreased when combined with Capecitabine.
CaptoprilThe risk or severity of adverse effects can be increased when Captopril is combined with Rofecoxib.
CarbamazepineThe metabolism of Rofecoxib can be increased when combined with Carbamazepine.
Carboprost TromethamineThe therapeutic efficacy of Carboprost Tromethamine can be decreased when used in combination with Rofecoxib.
CarprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Carprofen.
CarteololRofecoxib may decrease the antihypertensive activities of Carteolol.
CarvedilolRofecoxib may decrease the antihypertensive activities of Carvedilol.
CastanospermineThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Castanospermine.
CelecoxibThe risk or severity of adverse effects can be increased when Celecoxib is combined with Rofecoxib.
CeliprololRofecoxib may decrease the antihypertensive activities of Celiprolol.
CeritinibThe serum concentration of Rofecoxib can be increased when it is combined with Ceritinib.
CertoparinRofecoxib may increase the anticoagulant activities of Certoparin.
ChloroquineThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Chloroquine.
ChlorothiazideThe therapeutic efficacy of Chlorothiazide can be decreased when used in combination with Rofecoxib.
ChlorthalidoneThe therapeutic efficacy of Chlorthalidone can be decreased when used in combination with Rofecoxib.
CholecalciferolThe metabolism of Rofecoxib can be decreased when combined with Cholecalciferol.
CholestyramineCholestyramine can cause a decrease in the absorption of Rofecoxib resulting in a reduced serum concentration and potentially a decrease in efficacy.
CilazaprilThe risk or severity of adverse effects can be increased when Cilazapril is combined with Rofecoxib.
CitalopramThe metabolism of Rofecoxib can be decreased when combined with Citalopram.
Citric AcidRofecoxib may increase the anticoagulant activities of Citric Acid.
ClarithromycinThe metabolism of Rofecoxib can be decreased when combined with Clarithromycin.
ClemastineThe metabolism of Rofecoxib can be decreased when combined with Clemastine.
ClodronateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Clodronate.
ClonixinThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Clonixin.
ClopidogrelThe metabolism of Rofecoxib can be decreased when combined with Clopidogrel.
CloprostenolThe therapeutic efficacy of Cloprostenol can be decreased when used in combination with Rofecoxib.
ClotrimazoleThe metabolism of Rofecoxib can be decreased when combined with Clotrimazole.
CobicistatThe metabolism of Rofecoxib can be decreased when combined with Cobicistat.
ColesevelamColesevelam can cause a decrease in the absorption of Rofecoxib resulting in a reduced serum concentration and potentially a decrease in efficacy.
ColestipolColestipol can cause a decrease in the absorption of Rofecoxib resulting in a reduced serum concentration and potentially a decrease in efficacy.
ConivaptanThe serum concentration of Rofecoxib can be increased when it is combined with Conivaptan.
CrizotinibThe metabolism of Rofecoxib can be decreased when combined with Crizotinib.
CyclosporineRofecoxib may increase the nephrotoxic activities of Cyclosporine.
CyclosporineThe metabolism of Rofecoxib can be decreased when combined with Cyclosporine.
Cyproterone acetateThe serum concentration of Rofecoxib can be decreased when it is combined with Cyproterone acetate.
D-LimoneneThe risk or severity of adverse effects can be increased when Rofecoxib is combined with D-Limonene.
Dabigatran etexilateRofecoxib may increase the anticoagulant activities of Dabigatran etexilate.
DabrafenibThe serum concentration of Rofecoxib can be decreased when it is combined with Dabrafenib.
DalteparinRofecoxib may increase the anticoagulant activities of Dalteparin.
DanaparoidRofecoxib may increase the anticoagulant activities of Danaparoid.
DarunavirThe metabolism of Rofecoxib can be decreased when combined with Darunavir.
DasatinibThe serum concentration of Rofecoxib can be increased when it is combined with Dasatinib.
DaunorubicinRofecoxib may decrease the excretion rate of Daunorubicin which could result in a lower serum level and potentially a reduction in efficacy.
DeferasiroxThe serum concentration of Rofecoxib can be decreased when it is combined with Deferasirox.
DeferasiroxThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Deferasirox.
DelavirdineThe metabolism of Rofecoxib can be decreased when combined with Delavirdine.
DesirudinRofecoxib may increase the anticoagulant activities of Desirudin.
DesmopressinThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Desmopressin.
DexamethasoneThe serum concentration of Rofecoxib can be decreased when it is combined with Dexamethasone.
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Rofecoxib.
DextranRofecoxib may increase the anticoagulant activities of Dextran.
Dextran 40Rofecoxib may increase the anticoagulant activities of Dextran 40.
Dextran 70Rofecoxib may increase the anticoagulant activities of Dextran 70.
Dextran 75Rofecoxib may increase the anticoagulant activities of Dextran 75.
DiclofenacThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Diclofenac.
DicoumarolRofecoxib may increase the anticoagulant activities of Dicoumarol.
DiflunisalThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Diflunisal.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Rofecoxib.
DihydroergotamineThe metabolism of Rofecoxib can be decreased when combined with Dihydroergotamine.
DihydrostreptomycinRofecoxib may decrease the excretion rate of Dihydrostreptomycin which could result in a lower serum level and potentially a reduction in efficacy.
DiltiazemThe metabolism of Rofecoxib can be decreased when combined with Diltiazem.
DinoprostoneThe therapeutic efficacy of Dinoprostone can be decreased when used in combination with Rofecoxib.
DoxorubicinRofecoxib may decrease the excretion rate of Doxorubicin which could result in a lower serum level and potentially a reduction in efficacy.
DoxycyclineThe metabolism of Rofecoxib can be decreased when combined with Doxycycline.
DronedaroneThe metabolism of Rofecoxib can be decreased when combined with Dronedarone.
DrospirenoneRofecoxib may increase the hyperkalemic activities of Drospirenone.
DroxicamThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Droxicam.
Edetic AcidRofecoxib may increase the anticoagulant activities of Edetic Acid.
EdoxabanRofecoxib may increase the anticoagulant activities of Edoxaban.
EfavirenzThe serum concentration of Rofecoxib can be decreased when it is combined with Efavirenz.
EnalaprilThe risk or severity of adverse effects can be increased when Enalapril is combined with Rofecoxib.
EnalaprilatThe risk or severity of adverse effects can be increased when Enalaprilat is combined with Rofecoxib.
EnoxaparinRofecoxib may increase the anticoagulant activities of Enoxaparin.
EnzalutamideThe serum concentration of Rofecoxib can be decreased when it is combined with Enzalutamide.
EpirizoleThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Epirizole.
EpirubicinRofecoxib may decrease the excretion rate of Epirubicin which could result in a lower serum level and potentially a reduction in efficacy.
EplerenoneRofecoxib may decrease the antihypertensive activities of Eplerenone.
EpoprostenolThe therapeutic efficacy of Epoprostenol can be decreased when used in combination with Rofecoxib.
EprosartanThe risk or severity of adverse effects can be increased when Eprosartan is combined with Rofecoxib.
ErythromycinThe metabolism of Rofecoxib can be decreased when combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Rofecoxib can be decreased when it is combined with Eslicarbazepine acetate.
EsmololRofecoxib may decrease the antihypertensive activities of Esmolol.
Etacrynic acidRofecoxib may decrease the diuretic activities of Etacrynic acid.
EtanerceptThe risk or severity of adverse effects can be increased when Etanercept is combined with Rofecoxib.
Ethyl biscoumacetateRofecoxib may increase the anticoagulant activities of Ethyl biscoumacetate.
Etidronic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Etidronic acid.
EtodolacThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Etodolac.
EtofenamateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Etofenamate.
EtoricoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Etoricoxib.
EtravirineThe serum concentration of Rofecoxib can be decreased when it is combined with Etravirine.
Evening primrose oilThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Evening primrose oil.
exisulindThe risk or severity of adverse effects can be increased when Rofecoxib is combined with exisulind.
FelodipineThe metabolism of Rofecoxib can be decreased when combined with Felodipine.
FenbufenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Fenbufen.
FenoprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Fenoprofen.
FloctafenineThe risk or severity of adverse effects can be increased when Floctafenine is combined with Rofecoxib.
FloxuridineThe metabolism of Rofecoxib can be decreased when combined with Floxuridine.
FluconazoleThe metabolism of Rofecoxib can be decreased when combined with Fluconazole.
FlunixinThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Flunixin.
FluorouracilThe metabolism of Rofecoxib can be decreased when combined with Fluorouracil.
FlurbiprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Flurbiprofen.
FluvastatinThe metabolism of Rofecoxib can be decreased when combined with Fluvastatin.
FluvoxamineThe metabolism of Rofecoxib can be decreased when combined with Fluvoxamine.
Folic AcidThe therapeutic efficacy of Folic Acid can be decreased when used in combination with Rofecoxib.
Fondaparinux sodiumRofecoxib may increase the anticoagulant activities of Fondaparinux sodium.
ForasartanThe risk or severity of adverse effects can be increased when Forasartan is combined with Rofecoxib.
FosamprenavirThe metabolism of Rofecoxib can be decreased when combined with Fosamprenavir.
FosaprepitantThe serum concentration of Rofecoxib can be increased when it is combined with Fosaprepitant.
FosinoprilThe risk or severity of adverse effects can be increased when Fosinopril is combined with Rofecoxib.
FosphenytoinThe metabolism of Rofecoxib can be increased when combined with Fosphenytoin.
FramycetinRofecoxib may decrease the excretion rate of Framycetin which could result in a lower serum level and potentially a reduction in efficacy.
FurosemideRofecoxib may decrease the diuretic activities of Furosemide.
Fusidic AcidThe serum concentration of Rofecoxib can be increased when it is combined with Fusidic Acid.
GemeprostThe therapeutic efficacy of Gemeprost can be decreased when used in combination with Rofecoxib.
GemfibrozilThe metabolism of Rofecoxib can be decreased when combined with Gemfibrozil.
GentamicinRofecoxib may decrease the excretion rate of Gentamicin which could result in a lower serum level and potentially a reduction in efficacy.
HaloperidolThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Haloperidol.
HeparinRofecoxib may increase the anticoagulant activities of Heparin.
HirulogRofecoxib may increase the anticoagulant activities of Hirulog.
HMPL-004The risk or severity of adverse effects can be increased when Rofecoxib is combined with HMPL-004.
HydralazineRofecoxib may decrease the antihypertensive activities of Hydralazine.
HydrochlorothiazideThe therapeutic efficacy of Hydrochlorothiazide can be decreased when used in combination with Rofecoxib.
HydroflumethiazideThe therapeutic efficacy of Hydroflumethiazide can be decreased when used in combination with Rofecoxib.
Hygromycin BRofecoxib may decrease the excretion rate of Hygromycin B which could result in a lower serum level and potentially a reduction in efficacy.
IbandronateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Ibandronate.
IbuprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Ibuprofen.
IbuproxamThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Ibuproxam.
IcatibantThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Icatibant.
IdarubicinRofecoxib may decrease the excretion rate of Idarubicin which could result in a lower serum level and potentially a reduction in efficacy.
IdelalisibThe serum concentration of Rofecoxib can be increased when it is combined with Idelalisib.
IloprostThe therapeutic efficacy of Iloprost can be decreased when used in combination with Rofecoxib.
ImatinibThe metabolism of Rofecoxib can be decreased when combined with Imatinib.
IndapamideThe therapeutic efficacy of Indapamide can be decreased when used in combination with Rofecoxib.
IndenololRofecoxib may decrease the antihypertensive activities of Indenolol.
IndinavirThe metabolism of Rofecoxib can be decreased when combined with Indinavir.
IndomethacinThe risk or severity of adverse effects can be increased when Indomethacin is combined with Rofecoxib.
IndoprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Indoprofen.
IrbesartanThe risk or severity of adverse effects can be increased when Irbesartan is combined with Rofecoxib.
IsavuconazoniumThe metabolism of Rofecoxib can be decreased when combined with Isavuconazonium.
IsoxicamThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Isoxicam.
IsradipineThe metabolism of Rofecoxib can be decreased when combined with Isradipine.
ItraconazoleThe metabolism of Rofecoxib can be decreased when combined with Itraconazole.
IvacaftorThe serum concentration of Rofecoxib can be increased when it is combined with Ivacaftor.
KanamycinRofecoxib may decrease the excretion rate of Kanamycin which could result in a lower serum level and potentially a reduction in efficacy.
KebuzoneThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Kebuzone.
KetoconazoleThe metabolism of Rofecoxib can be decreased when combined with Ketoconazole.
KetoprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Ketoprofen.
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Rofecoxib.
LabetalolRofecoxib may decrease the antihypertensive activities of Labetalol.
LapatinibThe metabolism of Rofecoxib can be decreased when combined with Lapatinib.
LeflunomideThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Leflunomide.
LepirudinRofecoxib may increase the anticoagulant activities of Lepirudin.
LevobunololRofecoxib may decrease the antihypertensive activities of Levobunolol.
LidocaineThe metabolism of Rofecoxib can be decreased when combined with Lidocaine.
LisinoprilThe risk or severity of adverse effects can be increased when Lisinopril is combined with Rofecoxib.
LithiumThe serum concentration of Lithium can be increased when it is combined with Rofecoxib.
LopinavirThe metabolism of Rofecoxib can be decreased when combined with Lopinavir.
LornoxicamThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Lornoxicam.
LosartanThe risk or severity of adverse effects can be increased when Losartan is combined with Rofecoxib.
LovastatinThe metabolism of Rofecoxib can be decreased when combined with Lovastatin.
LoxoprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Loxoprofen.
LubiprostoneThe therapeutic efficacy of Lubiprostone can be decreased when used in combination with Rofecoxib.
LuliconazoleThe serum concentration of Rofecoxib can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Rofecoxib can be decreased when it is combined with Lumacaftor.
LumiracoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Lumiracoxib.
Magnesium salicylateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Magnesium salicylate.
MasoprocolThe risk or severity of adverse effects can be increased when Masoprocol is combined with Rofecoxib.
Meclofenamic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Meclofenamic acid.
Mefenamic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Mefenamic acid.
MeloxicamThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Meloxicam.
MesalazineRofecoxib may increase the nephrotoxic activities of Mesalazine.
MesalazineThe risk or severity of adverse effects can be increased when Mesalazine is combined with Rofecoxib.
MetamizoleThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Metamizole.
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Rofecoxib.
MethyclothiazideThe therapeutic efficacy of Methyclothiazide can be decreased when used in combination with Rofecoxib.
MetipranololRofecoxib may decrease the antihypertensive activities of Metipranolol.
MetolazoneThe therapeutic efficacy of Metolazone can be decreased when used in combination with Rofecoxib.
MetoprololRofecoxib may decrease the antihypertensive activities of Metoprolol.
MetrizamideRofecoxib may decrease the excretion rate of Metrizamide which could result in a lower serum level and potentially a reduction in efficacy.
MexiletineThe metabolism of Rofecoxib can be decreased when combined with Mexiletine.
MifepristoneThe metabolism of Rofecoxib can be decreased when combined with Mifepristone.
MisoprostolThe therapeutic efficacy of Misoprostol can be decreased when used in combination with Rofecoxib.
MitotaneThe serum concentration of Rofecoxib can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Rofecoxib can be decreased when it is combined with Modafinil.
MoexiprilThe risk or severity of adverse effects can be increased when Moexipril is combined with Rofecoxib.
MorniflumateThe risk or severity of adverse effects can be increased when Morniflumate is combined with Rofecoxib.
Mycophenolate mofetilThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Mycophenolate mofetil.
Mycophenolic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Mycophenolic acid.
NabumetoneThe risk or severity of adverse effects can be increased when Nabumetone is combined with Rofecoxib.
NadololRofecoxib may decrease the antihypertensive activities of Nadolol.
NadroparinRofecoxib may increase the anticoagulant activities of Nadroparin.
NafcillinThe serum concentration of Rofecoxib can be decreased when it is combined with Nafcillin.
NaftifineThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Naftifine.
NaproxenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Naproxen.
NCX 4016The risk or severity of adverse effects can be increased when Rofecoxib is combined with NCX 4016.
NefazodoneThe metabolism of Rofecoxib can be decreased when combined with Nefazodone.
NelfinavirThe metabolism of Rofecoxib can be decreased when combined with Nelfinavir.
NeomycinRofecoxib may decrease the excretion rate of Neomycin which could result in a lower serum level and potentially a reduction in efficacy.
NepafenacThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Nepafenac.
NetilmicinRofecoxib may decrease the excretion rate of Netilmicin which could result in a lower serum level and potentially a reduction in efficacy.
NetupitantThe serum concentration of Rofecoxib can be increased when it is combined with Netupitant.
NevirapineThe metabolism of Rofecoxib can be decreased when combined with Nevirapine.
NicardipineThe metabolism of Rofecoxib can be decreased when combined with Nicardipine.
Niflumic AcidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Niflumic Acid.
NilotinibThe metabolism of Rofecoxib can be decreased when combined with Nilotinib.
NimesulideThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Nimesulide.
NintedanibThe serum concentration of Nintedanib can be decreased when it is combined with Rofecoxib.
OlaparibThe metabolism of Rofecoxib can be decreased when combined with Olaparib.
OlmesartanThe risk or severity of adverse effects can be increased when Olmesartan is combined with Rofecoxib.
OlopatadineThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Olopatadine.
OlsalazineRofecoxib may increase the nephrotoxic activities of Olsalazine.
OlsalazineThe risk or severity of adverse effects can be increased when Olsalazine is combined with Rofecoxib.
Omacetaxine mepesuccinateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Omacetaxine mepesuccinate.
OmapatrilatThe risk or severity of adverse effects can be increased when Omapatrilat is combined with Rofecoxib.
OmeprazoleThe metabolism of Rofecoxib can be decreased when combined with Omeprazole.
OrgoteinThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Orgotein.
OsimertinibThe serum concentration of Rofecoxib can be increased when it is combined with Osimertinib.
OtamixabanRofecoxib may increase the anticoagulant activities of Otamixaban.
OxaprozinThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Oxaprozin.
OxprenololRofecoxib may decrease the antihypertensive activities of Oxprenolol.
OxyphenbutazoneThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Oxyphenbutazone.
PalbociclibThe serum concentration of Rofecoxib can be increased when it is combined with Palbociclib.
PamidronateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Pamidronate.
ParecoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Parecoxib.
ParomomycinRofecoxib may decrease the excretion rate of Paromomycin which could result in a lower serum level and potentially a reduction in efficacy.
Peginterferon alfa-2bThe serum concentration of Rofecoxib can be increased when it is combined with Peginterferon alfa-2b.
PenbutololRofecoxib may decrease the antihypertensive activities of Penbutolol.
PentobarbitalThe metabolism of Rofecoxib can be increased when combined with Pentobarbital.
Pentosan PolysulfateRofecoxib may increase the anticoagulant activities of Pentosan Polysulfate.
PerindoprilThe risk or severity of adverse effects can be increased when Perindopril is combined with Rofecoxib.
PhenindioneRofecoxib may increase the anticoagulant activities of Phenindione.
PhenobarbitalThe metabolism of Rofecoxib can be increased when combined with Phenobarbital.
PhenprocoumonRofecoxib may increase the anticoagulant activities of Phenprocoumon.
PhenylbutazoneThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Phenylbutazone.
PhenytoinThe metabolism of Rofecoxib can be increased when combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Rofecoxib.
PindololRofecoxib may decrease the antihypertensive activities of Pindolol.
PioglitazoneThe metabolism of Rofecoxib can be decreased when combined with Pioglitazone.
PiretanideRofecoxib may decrease the diuretic activities of Piretanide.
PirfenidoneThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Pirfenidone.
PiroxicamThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Piroxicam.
PlicamycinRofecoxib may decrease the excretion rate of Plicamycin which could result in a lower serum level and potentially a reduction in efficacy.
PolythiazideThe therapeutic efficacy of Polythiazide can be decreased when used in combination with Rofecoxib.
PosaconazoleThe metabolism of Rofecoxib can be decreased when combined with Posaconazole.
PractololRofecoxib may decrease the antihypertensive activities of Practolol.
PralatrexateThe serum concentration of Pralatrexate can be increased when it is combined with Rofecoxib.
PrimidoneThe metabolism of Rofecoxib can be increased when combined with Primidone.
ProbenecidThe serum concentration of Rofecoxib can be increased when it is combined with Probenecid.
PropacetamolThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Propacetamol.
PropranololRofecoxib may decrease the antihypertensive activities of Propranolol.
Prostaglandin D2The therapeutic efficacy of Prostaglandin D2 can be decreased when used in combination with Rofecoxib.
Protein CRofecoxib may increase the anticoagulant activities of Protein C.
ProtocatechualdehydeRofecoxib may increase the anticoagulant activities of Protocatechualdehyde.
PTC299The risk or severity of adverse effects can be increased when Rofecoxib is combined with PTC299.
PuromycinRofecoxib may decrease the excretion rate of Puromycin which could result in a lower serum level and potentially a reduction in efficacy.
PyrimethamineThe metabolism of Rofecoxib can be decreased when combined with Pyrimethamine.
QuinaprilThe risk or severity of adverse effects can be increased when Quinapril is combined with Rofecoxib.
QuinethazoneThe therapeutic efficacy of Quinethazone can be decreased when used in combination with Rofecoxib.
QuinineThe metabolism of Rofecoxib can be decreased when combined with Quinine.
RabeprazoleThe metabolism of Rofecoxib can be decreased when combined with Rabeprazole.
RamiprilThe risk or severity of adverse effects can be increased when Ramipril is combined with Rofecoxib.
RanolazineThe metabolism of Rofecoxib can be decreased when combined with Ranolazine.
RescinnamineThe risk or severity of adverse effects can be increased when Rescinnamine is combined with Rofecoxib.
ResveratrolThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Resveratrol.
ReviparinRofecoxib may increase the anticoagulant activities of Reviparin.
RibostamycinRofecoxib may decrease the excretion rate of Ribostamycin which could result in a lower serum level and potentially a reduction in efficacy.
RifabutinThe metabolism of Rofecoxib can be increased when combined with Rifabutin.
RifampicinThe metabolism of Rofecoxib can be increased when combined with Rifampicin.
RifapentineThe metabolism of Rofecoxib can be increased when combined with Rifapentine.
RisedronateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Risedronate.
RitonavirThe metabolism of Rofecoxib can be decreased when combined with Ritonavir.
RivaroxabanRofecoxib may increase the anticoagulant activities of Rivaroxaban.
RopiniroleThe metabolism of Rofecoxib can be decreased when combined with Ropinirole.
RosiglitazoneThe metabolism of Rofecoxib can be decreased when combined with Rosiglitazone.
SalicylamideThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Salicylamide.
Salicylic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Salicylic acid.
SalsalateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Salsalate.
SaprisartanThe risk or severity of adverse effects can be increased when Saprisartan is combined with Rofecoxib.
SaquinavirThe metabolism of Rofecoxib can be decreased when combined with Saquinavir.
SaralasinThe risk or severity of adverse effects can be increased when Saralasin is combined with Rofecoxib.
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Rofecoxib.
SecobarbitalThe metabolism of Rofecoxib can be increased when combined with Secobarbital.
SeratrodastThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Seratrodast.
SildenafilThe metabolism of Rofecoxib can be decreased when combined with Sildenafil.
SiltuximabThe serum concentration of Rofecoxib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Rofecoxib can be increased when it is combined with Simeprevir.
SorafenibThe metabolism of Rofecoxib can be decreased when combined with Sorafenib.
SotalolRofecoxib may decrease the antihypertensive activities of Sotalol.
SpectinomycinRofecoxib may decrease the excretion rate of Spectinomycin which could result in a lower serum level and potentially a reduction in efficacy.
SpiraprilThe risk or severity of adverse effects can be increased when Spirapril is combined with Rofecoxib.
SpironolactoneRofecoxib may decrease the antihypertensive activities of Spironolactone.
SRT501The risk or severity of adverse effects can be increased when Rofecoxib is combined with SRT501.
St. John's WortThe serum concentration of Rofecoxib can be decreased when it is combined with St. John&#39;s Wort.
StiripentolThe serum concentration of Rofecoxib can be increased when it is combined with Stiripentol.
StreptomycinRofecoxib may decrease the excretion rate of Streptomycin which could result in a lower serum level and potentially a reduction in efficacy.
StreptozocinRofecoxib may decrease the excretion rate of Streptozocin which could result in a lower serum level and potentially a reduction in efficacy.
SulfadiazineThe metabolism of Rofecoxib can be decreased when combined with Sulfadiazine.
SulfamethoxazoleThe metabolism of Rofecoxib can be decreased when combined with Sulfamethoxazole.
SulfasalazineRofecoxib may increase the nephrotoxic activities of Sulfasalazine.
SulfasalazineThe risk or severity of adverse effects can be increased when Sulfasalazine is combined with Rofecoxib.
SulfisoxazoleThe metabolism of Rofecoxib can be decreased when combined with Sulfisoxazole.
SulindacThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Sulindac.
SulodexideRofecoxib may increase the anticoagulant activities of Sulodexide.
SuprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Suprofen.
TacrolimusRofecoxib may increase the nephrotoxic activities of Tacrolimus.
TalniflumateThe risk or severity of adverse effects can be increased when Talniflumate is combined with Rofecoxib.
TamoxifenThe metabolism of Rofecoxib can be decreased when combined with Tamoxifen.
TasosartanThe risk or severity of adverse effects can be increased when Tasosartan is combined with Rofecoxib.
Technetium Tc-99m MedronateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Technetium Tc-99m Medronate.
TelaprevirThe metabolism of Rofecoxib can be decreased when combined with Telaprevir.
TelithromycinThe metabolism of Rofecoxib can be decreased when combined with Telithromycin.
TelmisartanThe risk or severity of adverse effects can be increased when Telmisartan is combined with Rofecoxib.
TemocaprilThe risk or severity of adverse effects can be increased when Temocapril is combined with Rofecoxib.
TenofovirThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tenofovir.
TenofovirThe metabolism of Rofecoxib can be decreased when combined with Tenofovir.
TenoxicamThe risk or severity of adverse effects can be increased when Tenoxicam is combined with Rofecoxib.
TepoxalinThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tepoxalin.
TeriflunomideThe serum concentration of Rofecoxib can be decreased when it is combined with Teriflunomide.
TeriflunomideThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Teriflunomide.
TheophyllineThe metabolism of Rofecoxib can be decreased when combined with Theophylline.
Tiaprofenic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tiaprofenic acid.
TicagrelorThe metabolism of Rofecoxib can be decreased when combined with Ticagrelor.
TiclopidineThe metabolism of Rofecoxib can be decreased when combined with Ticlopidine.
TiludronateThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tiludronate.
TimololRofecoxib may decrease the antihypertensive activities of Timolol.
TobramycinRofecoxib may decrease the excretion rate of Tobramycin which could result in a lower serum level and potentially a reduction in efficacy.
TocilizumabThe serum concentration of Rofecoxib can be decreased when it is combined with Tocilizumab.
TolbutamideThe metabolism of Rofecoxib can be decreased when combined with Tolbutamide.
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tolfenamic Acid.
TolmetinThe risk or severity of adverse effects can be increased when Tolmetin is combined with Rofecoxib.
TorasemideRofecoxib may decrease the diuretic activities of Torasemide.
TrandolaprilThe risk or severity of adverse effects can be increased when Trandolapril is combined with Rofecoxib.
TranilastThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Tranilast.
TravoprostThe therapeutic efficacy of Travoprost can be decreased when used in combination with Rofecoxib.
TreprostinilThe risk or severity of adverse effects can be increased when Treprostinil is combined with Rofecoxib.
TriamtereneRofecoxib may decrease the antihypertensive activities of Triamterene.
TrichlormethiazideThe therapeutic efficacy of Trichlormethiazide can be decreased when used in combination with Rofecoxib.
TrimethoprimThe metabolism of Rofecoxib can be decreased when combined with Trimethoprim.
Trisalicylate-cholineThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Trisalicylate-choline.
ValdecoxibThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Valdecoxib.
Valproic AcidThe metabolism of Rofecoxib can be decreased when combined with Valproic Acid.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Rofecoxib.
VancomycinThe serum concentration of Vancomycin can be increased when it is combined with Rofecoxib.
VemurafenibThe serum concentration of Rofecoxib can be increased when it is combined with Vemurafenib.
VenlafaxineThe metabolism of Rofecoxib can be decreased when combined with Venlafaxine.
VerapamilThe metabolism of Rofecoxib can be decreased when combined with Verapamil.
VoriconazoleThe metabolism of Rofecoxib can be decreased when combined with Voriconazole.
WarfarinRofecoxib may increase the anticoagulant activities of Warfarin.
XimelagatranRofecoxib may increase the anticoagulant activities of Ximelagatran.
ZafirlukastThe metabolism of Rofecoxib can be decreased when combined with Zafirlukast.
ZaltoprofenThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Zaltoprofen.
ZileutonThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Zileuton.
ZiprasidoneThe metabolism of Rofecoxib can be decreased when combined with Ziprasidone.
Zoledronic acidThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Zoledronic acid.
ZomepiracThe risk or severity of adverse effects can be increased when Rofecoxib is combined with Zomepirac.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, p...
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular Weight:
68995.625 Da
References
  1. Ehrich EW, Schnitzer TJ, McIlwain H, Levy R, Wolfe F, Weisman M, Zeng Q, Morrison B, Bolognese J, Seidenberg B, Gertz BJ: Effect of specific COX-2 inhibition in osteoarthritis of the knee: a 6 week double blind, placebo controlled pilot study of rofecoxib. Rofecoxib Osteoarthritis Pilot Study Group. J Rheumatol. 1999 Nov;26(11):2438-47. [PubMed:10555907 ]
  2. Malmstrom K, Daniels S, Kotey P, Seidenberg BC, Desjardins PJ: Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial. Clin Ther. 1999 Oct;21(10):1653-63. [PubMed:10566562 ]
  3. Langman MJ, Jensen DM, Watson DJ, Harper SE, Zhao PL, Quan H, Bolognese JA, Simon TJ: Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA. 1999 Nov 24;282(20):1929-33. [PubMed:10580458 ]
  4. Pascucci RA: COX-2-specific inhibition: implications for clinical practice. J Am Osteopath Assoc. 1999 Nov;99(11 Suppl):S18-22. [PubMed:10643177 ]
  5. Hawkey C, Laine L, Simon T, Beaulieu A, Maldonado-Cocco J, Acevedo E, Shahane A, Quan H, Bolognese J, Mortensen E: Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group. Arthritis Rheum. 2000 Feb;43(2):370-7. [PubMed:10693877 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Ashok V, Dash C, Rohan TE, Sprafka JM, Terry PD: Selective cyclooxygenase-2 (COX-2) inhibitors and breast cancer risk. Breast. 2011 Feb;20(1):66-70. doi: 10.1016/j.breast.2010.07.004. Epub 2010 Aug 17. [PubMed:20724158 ]
  8. Baron JA, Sandler RS, Bresalier RS, Lanas A, Morton DG, Riddell R, Iverson ER, Demets DL: Cardiovascular events associated with rofecoxib: final analysis of the APPROVe trial. Lancet. 2008 Nov 15;372(9651):1756-64. doi: 10.1016/S0140-6736(08)61490-7. Epub 2008 Oct 14. [PubMed:18922570 ]
  9. Chakraborti AK, Garg SK, Kumar R, Motiwala HF, Jadhavar PS: Progress in COX-2 inhibitors: a journey so far. Curr Med Chem. 2010;17(15):1563-93. [PubMed:20166930 ]
  10. Matheson AJ, Figgitt DP: Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis. Drugs. 2001;61(6):833-65. [PubMed:11398914 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Extracellular matrix structural constituent
Specific Function:
Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial structure by regulating proliferation and organization of vascular smooth muscle (By similarity).
Gene Name:
ELN
Uniprot ID:
P15502
Molecular Weight:
68468.375 Da
References
  1. Oitate M, Hirota T, Koyama K, Inoue S, Kawai K, Ikeda T: Covalent binding of radioactivity from [14C]rofecoxib, but not [14C]celecoxib or [14C]CS-706, to the arterial elastin of rats. Drug Metab Dispos. 2006 Aug;34(8):1417-22. Epub 2006 May 5. [PubMed:16679386 ]
  2. Oitate M, Hirota T, Takahashi M, Murai T, Miura S, Senoo A, Hosokawa T, Oonishi T, Ikeda T: Mechanism for covalent binding of rofecoxib to elastin of rat aorta. J Pharmacol Exp Ther. 2007 Mar;320(3):1195-203. Epub 2006 Dec 12. [PubMed:17164475 ]
  3. Oitate M, Hirota T, Murai T, Miura S, Ikeda T: Covalent binding of rofecoxib, but not other cyclooxygenase-2 inhibitors, to allysine aldehyde in elastin of human aorta. Drug Metab Dispos. 2007 Oct;35(10):1846-52. Epub 2007 Jul 9. [PubMed:17620346 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinducer
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423 ]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014 ]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: 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. Epub 2009 Sep 1. [PubMed:19515014 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
May be an organic anion pump relevant to cellular detoxification.
Gene Name:
ABCC4
Uniprot ID:
O15439
Molecular Weight:
149525.33 Da
References
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. [PubMed:12835412 ]
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Drug created on June 13, 2005 07:24 / Updated on September 25, 2016 03:31