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Details

Stereochemistry ACHIRAL
Molecular Formula C15H14N2O2
Molecular Weight 254.2839
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NEPAFENAC

SMILES

NC(=O)CC1=C(N)C(=CC=C1)C(=O)C2=CC=CC=C2

InChI

InChIKey=QEFAQIPZVLVERP-UHFFFAOYSA-N
InChI=1S/C15H14N2O2/c16-13(18)9-11-7-4-8-12(14(11)17)15(19)10-5-2-1-3-6-10/h1-8H,9,17H2,(H2,16,18)

HIDE SMILES / InChI
Molecular Formula C15H14N2O2
Molecular Weight 254.2839
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://link.springer.com/article/10.1007/BF03299088 | http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=35377 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000MedR.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021862lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/10850857

Amfenac (AHR 5850) is a non-steroidal anti-inflammatory compound possessing antipyretic and analgesic properties. It is an inhibitor of cyclooxygenases. Amfenac sodium has been on the Japanese market since 1986 (as FENAZOX®, Meiji) in an oral dosage form (50 mg, four-times-daily) indicated for the treatment of pain and inflammation associated with rheumatoid and osteoarthritis and low back pain, as well as the treatment of pain and inflammation following surgery, injury or tooth extraction. Amfenac is an active moiety of nepafenac (amfenac amide), the prodrug has very weak cyclooxygenase inhibitory activity whereas amfenac exhibits more potent cyclooxygenase activity. Nepafenac at a concentration of 0.1% (NEVANAC) was approved for marketing in the US in 2005. Nepafenac is also approved for marketing in the European Union(EU) and Japan as well as over 60 other countries for the treatment of postoperative pain and inflammation associated with cataract surgery.

Originator

Approval Year

2005
131
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 64.3 µM [IC50]
Inhibitor
8297
 0.15 µM [IC50]
Inhibitor
8297
 0.25 µM [IC50]
Inhibitor
8297
 0.15 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8429
NEVANAC

Approved Use

NEVANAC ophthalmic suspension is a nonsteroidal, antiinflammatory prodrug indicated for the treatment of pain and inflammation associated with cataract surgery

Launch Date

2005
Primary
Approved
8429
FENAZOX

Approved Use

FENAZOX CAPSULES (Amfenac sodium hydrate) is usually used to relieve inflammation and pain in chronic rheumatoid arthritis, osteoarthritis, low back pain, shoulder periarthritis, cervico-omo-brachial syndrome, temporomandibular joint disease, post-operative state, post-traumatic state or post-odontectomy state.

Launch Date

1985
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
205.3 ng/mL
DRUG LABEL
https://iovs.arvojournals.org/article.aspx?articleid=2383342
1 drop single, ocular
dose: 1 drop
route of administration: Ocular
experiment type: SINGLE
co-administered:
NEPAFENAC aqueous humor
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.847 ng/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
1 drop 1 times / day steady-state, ocular
dose: 1 drop
route of administration: Ocular
experiment type: STEADY-STATE
co-administered:
NEPAFENAC unknown
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
331.1 ng × h/mL
DRUG LABEL
https://iovs.arvojournals.org/article.aspx?articleid=2383342
1 drop single, ocular
dose: 1 drop
route of administration: Ocular
experiment type: SINGLE
co-administered:
NEPAFENAC aqueous humor
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 drop 1 times / day multiple, topical
Recommended
Dose: 1 drop, 1 times / day
Route: topical
Route: multiple
Dose: 1 drop, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24345529
Page: p.209
unhealthy, 68.7+/- 9.08
n = 817
Health Status: unhealthy
Condition: Pain and inflammation associated with cataract surgery
Age Group: 68.7+/- 9.08
Sex: M+F
Population Size: 817
Sources:
https://pubmed.ncbi.nlm.nih.gov/24345529
Page: p.209
Disc. AE: Hypersensitivity...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity (0.12%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/24345529
Page: p.209
1 drop 1 times / day multiple, topical
Recommended
Dose: 1 drop, 1 times / day
Route: topical
Route: multiple
Dose: 1 drop, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain and inflammation associated with cataract surgery
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
Disc. AE: Bleeding, Healing delayed...
AEs leading to
discontinuation/dose reduction:
Bleeding
Healing delayed
Corneal disorder (NOS)
Keratitis
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
AEs

AEs

AESignificanceDosePopulation
Hypersensitivity 0.12%
Disc. AE
1 drop 1 times / day multiple, topical
Recommended
Dose: 1 drop, 1 times / day
Route: topical
Route: multiple
Dose: 1 drop, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/24345529
Page: p.209
unhealthy, 68.7+/- 9.08
n = 817
Health Status: unhealthy
Condition: Pain and inflammation associated with cataract surgery
Age Group: 68.7+/- 9.08
Sex: M+F
Population Size: 817
Sources:
https://pubmed.ncbi.nlm.nih.gov/24345529
Page: p.209
Bleeding Disc. AE
1 drop 1 times / day multiple, topical
Recommended
Dose: 1 drop, 1 times / day
Route: topical
Route: multiple
Dose: 1 drop, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain and inflammation associated with cataract surgery
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
Corneal disorder (NOS) Disc. AE
1 drop 1 times / day multiple, topical
Recommended
Dose: 1 drop, 1 times / day
Route: topical
Route: multiple
Dose: 1 drop, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain and inflammation associated with cataract surgery
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
Healing delayed Disc. AE
1 drop 1 times / day multiple, topical
Recommended
Dose: 1 drop, 1 times / day
Route: topical
Route: multiple
Dose: 1 drop, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain and inflammation associated with cataract surgery
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
Keratitis Disc. AE
1 drop 1 times / day multiple, topical
Recommended
Dose: 1 drop, 1 times / day
Route: topical
Route: multiple
Dose: 1 drop, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Pain and inflammation associated with cataract surgery
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf
Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP1A2
1524

CYP2C19
1478

CYP2E1
882

P-gp
1461
CYP
270

P-gp
1537

UGT enzymes
27
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1650
 inconclusive
P-gp
1650
 inconclusive
amfenac
4
CYP1A2
1692
 no
CYP1A2
1692
 no
amfenac
4
CYP2C19
1553
 no
CYP2C19
1553
 no
amfenac
4
CYP2C9
1819
 no
CYP2C9
1819
 no
amfenac
4
CYP2D6
1891
 no
CYP2D6
1891
 no
amfenac
4
CYP2E1
970
 no
CYP2E1
970
 no
amfenac
4
CYP3A4
1925
 no
CYP3A4
1925
 no
amfenac
4
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP
270
 inconclusive
amfenac
4
P-gp
1537
 inconclusive
P-gp
1537
 inconclusive
amfenac
4
UGT enzymes
27
 likely
UGT enzymes
27
 likely
amfenac
4
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:75922
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75922
ChemicalBook
CB01116872
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01116872
MolPort
MolPort-003-987-236
https://www.molport.com/shop/molecule-link/MolPort-003-987-236
Selleck Chemicals
Nepafenac
http://www.selleckchem.com/products/Nepafenac.html
ZINC
ZINC000005162311
http://zinc15.docking.org/substances/ZINC000005162311
eMolecules
10510502
https://www.emolecules.com/cgi-bin/more?vid=10510502
PubMed

PubMed

TitleDatePubMed
Antiinflammatory agents. 1. Synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid.
1979 Sep
Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. In vitro bioactivation and permeation of external ocular barriers.
2000 Aug
Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy.
2000 Aug
Topical nepafenac inhibits ocular neovascularization.
2003 Jan
Pharmacokinetics of topical ocular drug delivery: potential uses for the treatment of diseases of the posterior segment and beyond.
2003 Jun
Re: Prostaglandin E(2) inhibition and aqueous concentration of ketorolac 0.4% and nepafenac 0.1% in patients undergoing phacoemulsification.
2007 Dec
Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.
2007 Feb
Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation.
2007 Jul
Nepafenac-associated corneal melt.
2007 Nov
The effects of a cyclooxygenase-2 (COX-2) expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production.
2007 Nov 27
Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation.
2008 Apr
Re: Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac.
2008 Aug
Nepafenac dosing frequency for ocular pain and inflammation associated with cataract surgery.
2008 Dec
Topical nepafenac as an alternate treatment for cystoid macular edema in steroid responsive patients.
2008 Nov-Dec
Effect of nepafenac sodium 0.1% on delayed corneal epithelial healing and haze after photorefractive keratectomy: retrospective comparative study.
2008 Sep
Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma.
2009
Increased neuronal nitric oxide synthase activity in retinal neurons in early diabetic retinopathy.
2009 Nov 9
Vitreous nonsteroidal antiinflammatory drug concentrations and prostaglandin E2 levels in vitrectomy patients treated with ketorolac 0.4%, bromfenac 0.09%, and nepafenac 0.1%.
2009 Oct
Nepafenac-associated bilateral corneal melt after photorefractive keratectomy.
2009 Sep
Inflammatory mediators and angiogenic factors in choroidal neovascularization: pathogenetic interactions and therapeutic implications.
2010
The effects of nepafenac and amfenac on retinal angiogenesis.
2010 Feb 15
Topical nepafenac for treatment of exudative age-related macular degeneration.
2010 Mar
Randomized clinical trial of treatment for TMJ disc displacement.
2010 Nov
Nepafenac-assisted mydriasis in a rabbit model.
2010 Oct
Use of nepafenac (Nevanac) in combination with intravitreal anti-VEGF agents in the treatment of recalcitrant exudative macular degeneration requiring monthly injections.
2010 Oct 28
Nepafenac: an ophthalmic nonsteroidal antiinflammatory drug for pain after cataract surgery.
2013 Jun
Patents

Patents

20020035264
14
JP2007537168A
10
JP2010037262A
4
JP2010059058A
4

Sample Use Guides

In Vivo Use Guide
One drop of Nepafenac ophthalmic suspension, 0.3% should be applied to the affected eye one-time-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period. An additional drop should be administered 30 to 120 minutes prior to surgery.
Route of Administration: Topical
In Vitro Use Guide
Nepafenac exhibited only weak COX-1 inhibitory activity (IC50 = 64.3 uM). However, amfenac, an active metabolite of nepafenac, was a potent inhibitor of COX-1 (IC50 = 0.25 uM) and COX-2 activity (IC50 = 0.15 uM).
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:45:15 GMT 2023
Edited
by admin
on Fri Dec 15 15:45:15 GMT 2023
Record UNII
0J9L7J6V8C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NEPAFENAC
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
nepafenac [INN]
Common Name English
Nepafenac [WHO-DD]
Common Name English
NEPAFENAC [USAN]
Common Name English
NEPAFENAC [EMA EPAR]
Common Name English
2-(2-Amino-3-benzoylphenyl)acetamide
Systematic Name English
NEVANAC
Brand Name English
NEPAFENAC [MART.]
Common Name English
AL-6515
Code English
NEPAFENAC [ORANGE BOOK]
Common Name English
2-AMINO-3-BENZOYLBENZENEACETAMIDE
Systematic Name English
NEPAFENAC [USP-RS]
Common Name English
NEPAFENAC [MI]
Common Name English
NEPAFENAC [VANDF]
Common Name English
NEPAFENAC [JAN]
Common Name English
AHR-9434
Code English
Classification Tree Code System Code
NDF-RT N0000000160
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
NDF-RT N0000175721
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
NDF-RT N0000175722
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
NCI_THESAURUS C257
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
WHO-VATC QS01BC10
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
EMA ASSESSMENT REPORTS NEVANAC (AUTHORIZED: PAIN, POSTOPERATIVE)
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
WHO-ATC S01BC10
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
EMA ASSESSMENT REPORTS NEVANAC (AUTHORIZED: OPTHALMOLOGIC SURGICAL PROCEDURES)
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
Code System Code Type Description
MESH
C414203
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
PUBCHEM
151075
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
LACTMED
Nepafenac
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
CHEBI
75922
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
INN
7685
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
SMS_ID
100000085451
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
WIKIPEDIA
Nepafenac
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
DRUG BANK
DB06802
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
NCI_THESAURUS
C66228
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
RXCUI
298665
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY RxNorm
EPA CompTox
DTXSID0048638
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
RS_ITEM_NUM
1460317
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
EVMPD
SUB09197MIG
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
DAILYMED
0J9L7J6V8C
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
DRUG CENTRAL
1899
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
ChEMBL
CHEMBL1021
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
FDA UNII
0J9L7J6V8C
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
MERCK INDEX
m7823
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY Merck Index
IUPHAR
7564
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
CAS
78281-72-8
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
USAN
II-86
Created by admin on Fri Dec 15 15:45:15 GMT 2023 , Edited by admin on Fri Dec 15 15:45:15 GMT 2023
PRIMARY
Related Record Type Details
Structure of AMFENAC
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
Structure of AMFENAC
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC SINGLE DOSE

Tmax PHARMACOKINETIC SINGLE DOSE

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