U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

Details

Stereochemistry ACHIRAL
Molecular Formula C17H14O4S
Molecular Weight 314.356
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ROFECOXIB

SMILES

CS(=O)(=O)C1=CC=C(C=C1)C2=C(C(=O)OC2)C3=CC=CC=C3

InChI

InChIKey=RZJQGNCSTQAWON-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C17H14O4S
Molecular Weight 314.356
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Rofecoxib is a nonsteroidal anti-inflammatory drug which selectively inhibits COX-2 and subsequent prostaglandin synthesis. The drug was developed by Merk and approved by FDA in 1999 for relief of signs and symptoms of arthritis, acute pain in adults, and painful menstrual cycles under the name Vioxx. Later on Merck voluntarily withdrawn Vioxx from the market due to safety concerns (high risk of heart attack and stroke).

CNS Activity

Curator's Comment: Rofecoxib has been shown to cross the blood-brain barrier in rats.

Originator

Curator's Comment: # Merck

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.02 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Palliative
VIOXX

Approved Use

For relief of the signs and symptoms of osteoarthritis, rheumatoid arthritis in adults, pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older and who weigh 10 kg (22 lbs) or more, for the management of acute pain in adults, for the treatment of primary dysmenorrhea, for the acute treatment of migraine attacks with or without aura in adults.

Launch Date

1999
Palliative
VIOXX

Approved Use

For relief of the signs and symptoms of osteoarthritis, rheumatoid arthritis in adults, pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older and who weigh 10 kg (22 lbs) or more, for the management of acute pain in adults, for the treatment of primary dysmenorrhea, for the acute treatment of migraine attacks with or without aura in adults.

Launch Date

1999
Primary
VIOXX

Approved Use

For relief of the signs and symptoms of osteoarthritis, rheumatoid arthritis in adults, pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older and who weigh 10 kg (22 lbs) or more, for the management of acute pain in adults, for the treatment of primary dysmenorrhea, for the acute treatment of migraine attacks with or without aura in adults.

Launch Date

1999
Primary
VIOXX

Approved Use

For relief of the signs and symptoms of osteoarthritis, rheumatoid arthritis in adults, pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older and who weigh 10 kg (22 lbs) or more, for the management of acute pain in adults, for the treatment of primary dysmenorrhea, for the acute treatment of migraine attacks with or without aura in adults.

Launch Date

1999
Primary
VIOXX

Approved Use

For relief of the signs and symptoms of osteoarthritis, rheumatoid arthritis in adults, pauciarticular or polyarticular course Juvenile Rheumatoid Arthritis (JRA) in patients 2 years and older and who weigh 10 kg (22 lbs) or more, for the management of acute pain in adults, for the treatment of primary dysmenorrhea, for the acute treatment of migraine attacks with or without aura in adults.

Launch Date

1999
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
321 ng/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ROFECOXIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4018 ng × h/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ROFECOXIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
17 h
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ROFECOXIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
13%
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ROFECOXIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
12.5 mg 1 times / day steady, oral
Recommended
Dose: 12.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 12.5 mg, 1 times / day
Sources:
unhealthy, 44-76 years
Health Status: unhealthy
Age Group: 44-76 years
Sex: M+F
Sources:
Disc. AE: Renal impairment...
AEs leading to
discontinuation/dose reduction:
Renal impairment (grade 1, 1 patient)
Sources:
50 mg 1 times / day steady, oral
Studied dose
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy, 44-76 years
Health Status: unhealthy
Age Group: 44-76 years
Sex: M+F
Sources:
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources:
unhealthy, 58–71years
Health Status: unhealthy
Age Group: 58–71years
Sex: M+F
Sources:
Disc. AE: Cardiac thrombosis...
Other AEs: Cardiac thrombosis...
AEs leading to
discontinuation/dose reduction:
Cardiac thrombosis (grade 5, 4 patients)
Other AEs:
Cardiac thrombosis (16 patients)
Sources:
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, 66.8 years
Health Status: unhealthy
Age Group: 66.8 years
Sex: M+F
Sources:
Disc. AE: Dyspepsia, Nausea...
AEs leading to
discontinuation/dose reduction:
Dyspepsia (4.4%)
Nausea (2.4%)
Dizziness (2.1%)
Sources:
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Disc. AE: Death...
Other AEs: Hemorrhage, Edema...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 1653 patients)
Other AEs:
Hemorrhage (3915 patients)
Edema (3677 patients)
Thrombosis (1917 patients)
Embolism (233 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Renal impairment grade 1, 1 patient
Disc. AE
12.5 mg 1 times / day steady, oral
Recommended
Dose: 12.5 mg, 1 times / day
Route: oral
Route: steady
Dose: 12.5 mg, 1 times / day
Sources:
unhealthy, 44-76 years
Health Status: unhealthy
Age Group: 44-76 years
Sex: M+F
Sources:
Cardiac thrombosis 16 patients
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources:
unhealthy, 58–71years
Health Status: unhealthy
Age Group: 58–71years
Sex: M+F
Sources:
Cardiac thrombosis grade 5, 4 patients
Disc. AE
25 mg 1 times / day steady, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: steady
Dose: 25 mg, 1 times / day
Sources:
unhealthy, 58–71years
Health Status: unhealthy
Age Group: 58–71years
Sex: M+F
Sources:
Dizziness 2.1%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, 66.8 years
Health Status: unhealthy
Age Group: 66.8 years
Sex: M+F
Sources:
Nausea 2.4%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, 66.8 years
Health Status: unhealthy
Age Group: 66.8 years
Sex: M+F
Sources:
Dyspepsia 4.4%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, 66.8 years
Health Status: unhealthy
Age Group: 66.8 years
Sex: M+F
Sources:
Thrombosis 1917 patients
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Embolism 233 patients
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Edema 3677 patients
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Hemorrhage 3915 patients
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Death grade 5, 1653 patients
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely
weak (co-administration study)
Comment: A 30% interactions, additional studies would be necessary reduction of the AUC of the CYP3A4 substrate to more completely elucidate the drug interaction midazolam was observed with rofecoxib 25mg profile of rofecoxib and determine the clinical rele- daily. This reduction is most probably due to in- vance of any possible interactions. creased first-pass metabolism through induction of intestinal CYP3A4 by rofecoxib
Page: 4.0
no
no
no
no
yes [IC50 1.17 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia-reperfusion-induced gastric lesions.
1999 Nov 26
Rofecoxib.
2000 Jul
Alzheimer's disease, inflammation and non-steroidal anti-inflammatory drugs.
2001
Rofecoxib: a review of its use in the management of osteoarthritis, acute pain and rheumatoid arthritis.
2001
Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis.
2001
A multicenter, randomized, controlled trial to evaluate the safety profile, tolerability, and efficacy of rofecoxib in advanced elderly patients with osteoarthritis.
2001 Apr
Gastrointestinal damage induced by celecoxib and rofecoxib in rats.
2001 Apr
Selective COX-2 inhibitors.
2001 Apr
Cyclo-oxygenase and lipoxygenase pathways in mast cell dependent-neurogenic inflammation induced by electrical stimulation of the rat saphenous nerve.
2001 Apr
Effects of specific inhibition of cyclo-oxygenase-1 and cyclo-oxygenase-2 in the rat stomach with normal mucosa and after acid challenge.
2001 Apr
COX-2 inhibitors and the gastrointestinal tract.
2001 Apr
Rofecoxib (Vioxx): a year in review.
2001 Apr 3
Rofecoxib as an alternative in aspirin hypersensitivity.
2001 Aug
Effects of COX-2 inhibitors on aortic prostacyclin production in cholesterol-fed rabbits.
2001 Aug
Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2.
2001 Feb
FDA refuses companies' request to drop ulcer warning.
2001 Feb 17
Efficacy of cyclooxygenase-2-specific inhibitors.
2001 Feb 19
Anti-inflammatory drugs, cyclooxygenases and other factors.
2001 Jan
Effect of rofecoxib on the pharmacokinetics of digoxin in healthy volunteers.
2001 Jan
Cyclooxygenase inhibitors: any reservations?
2001 Jan-Feb
Renal effects of COX-2-selective inhibitors.
2001 Jan-Feb
Gastric preconditioning induced by short ischemia: the role of prostaglandins, nitric oxide and adenosine.
2001 Jul-Aug
[Selective COX-2 inhibitor. Stomach protection--but not always].
2001 Jun 21
Cyclooxygenase-2 inhibition and renal function.
2001 Jun 5
Preoperative oral rofecoxib does not decrease postoperative pain or morphine consumption in patients after radical prostatectomy: a prospective, randomized, double-blinded, placebo-controlled trial.
2001 Mar
Osteoarthritis management: the role of cyclooxygenase-2-selective inhibitors.
2001 Mar
[Therapy with preferential and specific COX-2 inhibitors].
2001 Mar
Is rofecoxib safer than naproxen?
2001 Mar
Where is the evidence that cyclooxygenase inhibition is the primary cause of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal injury? Topical injury revisited.
2001 Mar 15
[Cyclooxygenase inhibitors].
2001 Mar 17
Cyclooxygenase-2--specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients.
2001 Mar-Apr
Cardiovascular and renal effects of COX-2-specific inhibitors: recent insights and evolving clinical implications.
2001 Mar-Apr
Current concepts regarding pharmacologic treatment of rheumatoid and osteoarthritis.
2001 May
Upper gastrointestinal toxicity of rofecoxib and naproxen.
2001 May 3
[The coxibs, third generation of non-steroidal anti-inflammatory agents].
2001 May-Jun
LC determination of rofecoxib in bulk and pharmaceutical formulations.
2001 Nov
COX-1 and COX-2 inhibitors.
2001 Oct
Tolerability to new COX-2 inhibitors in NSAID-sensitive patients with cutaneous reactions.
2001 Sep
Ischemic preconditioning, the most effective gastroprotective intervention: involvement of prostaglandins, nitric oxide, adenosine and sensory nerves.
2001 Sep 21
Patents

Sample Use Guides

Osteoarthritis: the recommended starting dose of rofecoxib (VIOXX) is 12.5 mg once daily. Rheumatoid Arthritis: the recommended dose is 50 mg once daily. Management of Acute Pain and Treatment of Primary Dysmenorrhea: the recommended dose is 50 mg once daily. Acute Treatment of Migraine Attacks with or without aura: the recommended dose is 25 mg once daily.
Route of Administration: Oral
THP-1 human macrophages and peripheral blood mononuclear cells were incubated with rofecoxib (at 5, 10, 25 uM). The presence of rofecoxib (at high concentrations) significantly decreased expression of 27-hydroxylase and ABCA1, interfering with normal cholesterol outflow from macrophages.
Substance Class Chemical
Created
by admin
on Wed Apr 02 07:55:36 GMT 2025
Edited
by admin
on Wed Apr 02 07:55:36 GMT 2025
Record UNII
0QTW8Z7MCR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
M01AH02
Preferred Name English
ROFECOXIB
HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
NSC-758705
Code English
rofecoxib [INN]
Common Name English
MK-966
Code English
TRM-201
Code English
VIOXX
Brand Name English
ROFECOXIB [MI]
Common Name English
NSC-720256
Code English
ROFECOXIB [MART.]
Common Name English
ROFECOXIB [USAN]
Common Name English
MK-0966
Code English
MK0966
Code English
TRM201
Code English
ROFECOXIB [VANDF]
Common Name English
Rofecoxib [WHO-DD]
Common Name English
4-[4-(Methylsulfonyl)phenyl]-3-phenyl-2(5H)-furanone
Systematic Name English
ROFECOXIB [ORANGE BOOK]
Common Name English
ROFECOXIB [JAN]
Common Name English
4-(P-(METHYLSULFONYL)PHENYL)-3-PHENYL-2(5H)-FURANONE
Common Name English
ROFECOXIB [HSDB]
Common Name English
Classification Tree Code System Code
WHO-VATC QM01AH02
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
NCI_THESAURUS C80509
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
CFR 21 CFR 216.24
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
FDA ORPHAN DRUG 181703
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
LIVERTOX NBK548628
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
WHO-ATC M01AH02
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
FDA ORPHAN DRUG 601917
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
Code System Code Type Description
DRUG BANK
DB00533
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
EVMPD
SUB04261MIG
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
NCI_THESAURUS
C1832
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
NSC
720256
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
EPA CompTox
DTXSID2023567
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
IUPHAR
2893
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
CHEBI
8887
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
WIKIPEDIA
ROFECOXIB
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
USAN
JJ-32
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
MERCK INDEX
m9647
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY Merck Index
SMS_ID
100000091590
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
FDA UNII
0QTW8Z7MCR
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
PUBCHEM
5090
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
CAS
162011-90-7
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
ChEMBL
CHEMBL122
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
HSDB
7262
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
DRUG CENTRAL
2397
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
INN
7768
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
NSC
758705
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
MESH
C116926
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY
RXCUI
232158
Created by admin on Wed Apr 02 07:55:36 GMT 2025 , Edited by admin on Wed Apr 02 07:55:36 GMT 2025
PRIMARY RxNorm
Related Record Type Details
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
IC50
METABOLIC ENZYME -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC