PARECOXIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H18N2O4S
Molecular Weight	370.422
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC(=O)NS(=O)(=O)C1=CC=C(C=C1)C2=C(C)ON=C2C3=CC=CC=C3

InChI

InChIKey=TZRHLKRLEZJVIJ-UHFFFAOYSA-N

InChI=1S/C19H18N2O4S/c1-3-17(22)21-26(23,24)16-11-9-14(10-12-16)18-13(2)25-20-19(18)15-7-5-4-6-8-15/h4-12H,3H2,1-2H3,(H,21,22)

HIDE SMILES / InChI

Molecular Formula	C19H18N2O4S
Molecular Weight	370.422
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB08439 | http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090B1_28_CC-FDA-Tab-Q.htmhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf | http://www.rotlaw.com/legal-library/bextra-valdecoxib/
Curator's Comment: Description was created based on several sources, including https://www.medicines.org.uk/emc/medicine/8771

Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib was manufactured and marketed under the brand name Bextra. Bextra was indicated for relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis. For the treatment of primary dysmenorrhea. But in 2005 FDA requested that Pfizer withdraw Bextra from the American market, because the Agency had concluded that the overall risk versus benefit profile of Bextra was unfavorable. That conclusion was based on the potential increased risk for serious cardiovascular (CV) adverse events, an increased risk of serious skin reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme) compared to other NSAIDs, and the fact that Bextra had not been shown to offer any unique advantages over the other available NSAIDs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15494548	Inhibitor 8297		0.005 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090B1_28_CC-FDA-Tab-Q.htm \| https://www.medicines.org.uk/emc/PIL.14519.latest.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/25135338	Inhibitor 8297		5.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pain, postoperative 9 Sources: https://www.medicines.org.uk/emc/PIL.14519.latest.pdf	Palliative	Approved 8429	Dynastat Approved Use Dynastat is used for the short-term treatment of pain in adults after an operation. Launch Date 2002
Osteoarthritis 157 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf	Palliative	Withdrawn	BEXTRA Approved Use BEXTRA Tablets are indicated: For relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis. For the treatment of primary dysmenorrhea. Launch Date 2001
Rheumatoid arthritis 316 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf	Palliative	Withdrawn	BEXTRA Approved Use BEXTRA Tablets are indicated: For relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis. For the treatment of primary dysmenorrhea. Launch Date 2001
Primary dysmenorrhea 16 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf	Primary	Withdrawn	BEXTRA Approved Use BEXTRA Tablets are indicated: For relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis. For the treatment of primary dysmenorrhea. Launch Date 2001

C_max

Value	Dose	Analyte	Population
161.1 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341se8-003_bextra_lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
12 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
14 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
16 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
26 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
24 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg 2 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
26 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1385 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16599270/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.8 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg 2 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2 ng/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1479 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341se8-003_bextra_lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
167 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
175 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
198 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
332 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
341 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg 2 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
371 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
9062 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16599270/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	VALDECOXIB serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
15 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
18 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
31 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	5 mg 2 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
33 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	10 mg 2 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
36 ng × h/mL OTHER GOV https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf	20 mg 2 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	1-HYDROXYVALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.11 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341se8-003_bextra_lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16599270/	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:		VALDECOXIB serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341se8-003_bextra_lbl.pdf	10 mg 1 times / day steady-state, oral dose: 10 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		VALDECOXIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P2.pdf Page: p.28	unhealthy, 18-92 n = 420 Health Status: unhealthy Condition: Rheumatoid arthritis Age Group: 18-92 Sex: M+F Population Size: 420 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P2.pdf Page: p.28	Other AEs: Gastrointestinal ulcer haemorrhage... Other AEs: Gastrointestinal ulcer haemorrhage (significant, 0.48%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P2.pdf Page: p.28
40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17133774 Page: p.462	unhealthy, 32.3 ±10.9 n = 101 Health Status: unhealthy Condition: Acute ankle sprain Age Group: 32.3 ±10.9 Sex: M+F Population Size: 101 Sources: https://pubmed.ncbi.nlm.nih.gov/17133774 Page: p.462	Disc. AE: Allergic rash, Dizziness... Other AEs: Dyspepsia, Gastritis... AEs leading to discontinuation/dose reduction: Allergic rash (grade 2, 1%) Dizziness (grade 2, 1%) Other AEs: Dyspepsia (2%) Gastritis (5.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/17133774 Page: p.462
40 mg 2 times / day multiple, oral Highest studied dose Dose: 40 mg, 2 times / day Route: oral Route: multiple Dose: 40 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.71	unhealthy n = 430 Health Status: unhealthy Condition: Rheumatoid arthritis Sex: M+F Population Size: 430 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.71	Disc. AE: Hypertension, Peripheral edema... AEs leading to discontinuation/dose reduction: Hypertension (1.7%) Peripheral edema (1.7%) Abdominal pain (2.7%) Duodenal ulcer (0.2%) Dyspepsia (2.2%) Gastric ulcer (1.5%) Nausea (0.5%) Vomiting (0.2%) Rash (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.71
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://ec.europa.eu/health/documents/community-register/2005/200501269150/anx_9150_en.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Osteoarthritis \| Adult rheumatoid arthritis Sources: https://ec.europa.eu/health/documents/community-register/2005/200501269150/anx_9150_en.pdf Page: p.3	Disc. AE: Gastrointestinal perforation, Gastrointestinal ulcer... Other AEs: Exfoliative dermatitis... AEs leading to discontinuation/dose reduction: Gastrointestinal perforation (grade 3-5) Gastrointestinal ulcer (grade 3-5) Gastrointestinal bleeding (grade 3-5) Other AEs: Exfoliative dermatitis Sources: https://ec.europa.eu/health/documents/community-register/2005/200501269150/anx_9150_en.pdf Page: p.3
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Osteoarthritis \| Adult rheumatoid arthritis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.1	Disc. AE: Toxic epidermal necrolysis, Stevens-Johnson syndrome... AEs leading to discontinuation/dose reduction: Toxic epidermal necrolysis (grade 3-5) Stevens-Johnson syndrome (grade 3-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.1
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.1, 9	unhealthy Health Status: unhealthy Condition: Osteoarthritis \| Adult rheumatoid arthritis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.1, 9	Other AEs: Erythema multiforme... Other AEs: Erythema multiforme (grade 3-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.1, 9
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.9	unhealthy Health Status: unhealthy Condition: Osteoarthritis \| Adult rheumatoid arthritis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.9	Other AEs: Anaphylactic reaction, Angioedema... Other AEs: Anaphylactic reaction Angioedema Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21341lbl.pdf Page: p.9
20 mg 1 times / day multiple, oral (max) Recommended Dose: 20 mg, 1 times / day Route: oral Route: multiple Dose: 20 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.70	unhealthy n = 1114 Health Status: unhealthy Condition: Rheumatoid arthritis Sex: M+F Population Size: 1114 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.70	Disc. AE: Peripheral edema, Halitosis... AEs leading to discontinuation/dose reduction: Peripheral edema (2.2%) Halitosis (0.3%) Abdominal pain (5.5%) Dyspepsia (6.2%) Gastroenteritis (1.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.70
40 mg 1 times / day multiple, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: multiple Dose: 40 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.69	unhealthy n = 430 Health Status: unhealthy Condition: Arthritis Sex: M+F Population Size: 430 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.69	Disc. AE: Abdominal pain, Diarrhea... AEs leading to discontinuation/dose reduction: Abdominal pain (1.6%) Diarrhea (0.7%) Dyspepsia (1.4%) Nausea (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_medr_P3.pdf Page: p.69

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 1478 CYP1A2 1524 CYP2E1 882 OAT1 599 OAT3 642	CYP2C19 991 CYP1A2 1054 UGT 192

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	no
OAT1 603	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/dmpk/advpub/0/advpub_DMPK-10-RG-048/_pdf/-char/ja#page=11 Page: 11.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	yes
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	yes	SC-66905 3
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	yes
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	yes	SC-66905 3
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	yes	SC-66905 3
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=21 Page: 21.0	yes	SC-66905 3
OAT3 644	inhibitor 3277 Sources: https://www.jstage.jst.go.jp/article/dmpk/advpub/0/advpub_DMPK-10-RG-048/_pdf/-char/ja#page=11 Page: 11.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=12 Page: 12.0	major
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=12 Page: 12.0	major		yes (co-administration study) Comment: co-administration with ketoconazole or Fluconazole increase VALDECOXIB AUC and Cmax Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=12 Page: 12.0
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=12 Page: 12.0	minor
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=12 Page: 12.0	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=12 Page: 12.0	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=13 Page: 13.0	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-341_Bextra_biopharmr_P1.pdf#page=36 Page: 36.0	yes	SC-66905 3

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63634	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63634
ChemicalBook	CB4754453	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4754453
MolPort	MolPort-000-883-874	https://www.molport.com/shop/molecule-link/MolPort-000-883-874
Selleck Chemicals	valdecoxib	http://www.selleckchem.com/products/valdecoxib.html
ZINC	ZINC000000006694	http://zinc15.docking.org/substances/ZINC000000006694
eMolecules	877479	https://www.emolecules.com/cgi-bin/more?vid=877479

PubMed

Title	Date	PubMed
Parecoxib (parecoxib sodium).	2001	11465874
Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral cyclooxygenase-2-specific inhibitor, compared with ketorolac, naproxen, and placebo.	2001 Sep	11589257
Efficacy and safety of intravenous parecoxib sodium in relieving acute postoperative pain following gynecologic laparotomy surgery.	2002 Aug	12151917
Upper GI mucosal effects of parecoxib sodium in healthy elderly subjects.	2002 Jan	11808971
Intravenous parecoxib sodium foracute pain after orthopedic knee surgery.	2002 Jun	12083587
[Control of postoperative pain. First COX-2 inhibitor for injection].	2002 Jun 27	12154482
The influence of parecoxib, a parenteral cyclooxygenase-2 specific inhibitor, on the pharmacokinetics and clinical effects of midazolam.	2002 Sep	12198057
Parecoxib sodium, a parenteral cyclooxygenase 2 selective inhibitor, improves morphine analgesia and is opioid-sparing following total hip arthroplasty.	2003 Apr	12657858
Valdecoxib-induced toxic epidermal necrolysis in a patient allergic to sulfa drugs.	2003 Apr	12680487
Pharmacokinetics and metabolism of a COX-2 inhibitor, valdecoxib, in mice.	2003 Apr	12642477
The role of cyclooxygenase selective inhibitors in the gastrointestinal tract.	2003 Dec	14602052
[Development of opioid tolerance -- molecular mechanisms and clinical consequences].	2003 Jan	12522725
A comparison of the upper gastrointestinal mucosal effects of valdecoxib, naproxen and placebo in healthy elderly subjects.	2003 Jul 1	12848634
Gateways to clinical trials.	2003 Jun	12851663
Clinical pharmacology of selective COX-2 inhibitors.	2003 May-Aug	14552704
Effects of rofecoxib, celecoxib, and parecoxib on anti-IgE-induced histamine release from human skin mast cells and basophils.	2003 Oct	14510734
Expression of cyclooxygenase isozymes during morphogenesis and cycling of pelage hair follicles in mouse skin: precocious onset of the first catagen phase and alopecia upon cyclooxygenase-2 overexpression.	2003 Oct	14632179
Valdecoxib is as effective as diclofenac in the management of rheumatoid arthritis with a lower incidence of gastroduodenal ulcers: results of a 26-week trial.	2003 Oct	12810937
[Pain therapy in rheumatism. After 65 years of age coxibs are the best choice].	2003 Oct 16	14655447
Single doses of parecoxib sodium intravenously are as effective as ketorolac in reducing pain after oral surgery.	2003 Sep	12966478
Selective cyclo-oxygenase-2 inhibition with parecoxib acutely impairs endothelium-dependent vasodilatation in patients with essential hypertension.	2003 Sep	12923398
Development and validation of an automated SPE-LC-MS/MS assay for valdecoxib and its hydroxylated metabolite in human plasma.	2003 Sep 15	12946532
Effect of selective inhibition of cyclooxygenase-2 on lipopolysaccharide-induced hyperalgesia.	2004	15035779
[Pharmacology and classification of cyclooxygenase inhibitors].	2004 Apr	15366670
Parecoxib sodium demonstrates gastrointestinal safety comparable to placebo in healthy subjects.	2004 Aug	15232360
Differential effects of selective COX-2 inhibitors on cell cycle regulation and proliferation of glioblastoma cell lines.	2004 Jan	14726653
The analgesic effects that underlie patient satisfaction with treatment.	2004 Jul	15275801
Parecoxib: new preparation. A NSAID for postoperative pain: no proven advantage.	2004 Jun	15233140
Gateways to clinical trials.	2004 Mar	15071612
Differential inhibition of fracture healing by non-selective and cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs.	2004 May	15099653
Parecoxib for parenteral analgesia in postsurgical patients.	2004 May	15039473
Valdecoxib versus rofecoxib in acute postsurgical pain: results of a randomized controlled trial.	2004 May	15120774
Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic.	2004 May	15117884
Analgesic efficacy of preoperative parecoxib sodium in an orthopedic pain model.	2004 May-Jun	15153593
The analgesic efficacy of intramuscular parecoxib sodium in postoperative dental pain.	2004 Nov	15622663
A clinical trial demonstrates the analgesic activity of intravenous parecoxib sodium compared with ketorolac or morphine after gynecologic surgery with laparotomy.	2004 Oct	15507939
Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects.	2004 Oct	15352969
Parecoxib impairs early tendon repair but improves later remodeling.	2004 Oct-Nov	15494342
[Use of low molecular weight heparin (Clexane) together with selective COX-2 inhibitor (Dynastat--once or twice per day)].	2005	16313051
Cardiovascular and gastrointestinal effects of COX-2 inhibitors and NSAIDs: achieving a balance.	2005	16168077
Update on cyclooxygenase inhibitors: has a third COX isoform entered the fray?	2005 Aug	16083531
COX-2 inhibition prevents downregulation of key renal water and sodium transport proteins in response to bilateral ureteral obstruction.	2005 Aug	15840770
Severe bronchospasm after parenteral parecoxib: cyclooxygenase-2 inhibitors: not the answer yet.	2005 Feb	15681964
Prostaglandin-mediated control of rat brain kynurenic acid synthesis--opposite actions by COX-1 and COX-2 isoforms.	2005 Jul	15517427
COX-2 inhibitors--a lesson in unexpected problems.	2005 Mar 17	15713947
COX-2 inhibitors--lessons in drug safety.	2005 Mar 17	15713946
A randomized, double-blind comparison between parecoxib sodium and propacetamol for parenteral postoperative analgesia after inguinal hernia repair in adult patients.	2005 May	15845675
Constitutive cyclo-oxygenase-2 does not contribute to the development of human visceral pain hypersensitivity.	2006 Aug	16122956
Single dose parecoxib significantly improves ventilatory function in early extubation coronary artery bypass surgery: a prospective randomized double blind placebo controlled trial.	2006 Feb	16361300
Combination therapy using the cyclooxygenase-2 inhibitor Parecoxib and radioimmunotherapy in nude mice with small peritoneal metastases of colonic origin.	2006 Jan	15868166

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is 40 mg administered intravenously (IV) or intramuscularly (IM), followed every 6 to 12 hours by 20 mg or 40 mg as required, not to exceed 80 mg/day.

Route of Administration: Parenteral

In Vitro Use Guide

100 uM parecoxib inhibited rat osteoclast differentiation by 94%

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:37:26 GMT 2023` Edited by `admin` on `Fri Dec 15 16:37:26 GMT 2023`
Record UNII	9TUW81Y3CE
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PARECOXIB

Official Name

English

PROPANAMIDE, N-((4-(5-METHYL-3-PHENYL-4-ISOXAZOLYL)PHENYL)SULFONYL)-

Systematic Name

English

SC-69124

Code

English

Parecoxib [WHO-DD]

Common Name

English

N-((P-(5-METHYL-3-PHENYL-4-ISOXAZOLYL)PHENYL)SULFONYL)PROPIONAMIDE

Common Name

English

PARECOXIB [USAN]

Common Name

English

parecoxib [INN]

Common Name

English

PARECOXIB [EMA EPAR]

Common Name

English

RAYZON

Brand Name

English

PARECOXIB [MI]

Common Name

English

XAPIT

Brand Name

English

Classification Tree Code System Code

WHO-ATC

M01AH04