AMFENAC SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H12NO3.Na.H2O
Molecular Weight	295.2657
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.[Na+].NC1=C(C=CC=C1CC([O-])=O)C(=O)C2=CC=CC=C2

InChI

InChIKey=QZNJPJDUBTYMRS-UHFFFAOYSA-M

InChI=1S/C15H13NO3.Na.H2O/c16-14-11(9-13(17)18)7-4-8-12(14)15(19)10-5-2-1-3-6-10;;/h1-8H,9,16H2,(H,17,18);;1H2/q;+1;/p-1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB06802https://www.ncbi.nlm.nih.gov/pubmed/871089
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

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D05143	Inhibitor 8297	64.3 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D05143	Inhibitor 8297	0.15 µM [IC50]
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10850857	Inhibitor 8297	0.25 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10850857	Inhibitor 8297	0.15 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cataract 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021862s008lbl.pdf	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 1.12432316E12
Pain 614 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=35377	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 5.04835211E11

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

AE	Significance	Dose	Population
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

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 CYP2E1 882 P-gp 1461	CYP 270 P-gp 1537 UGT enzymes 27

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive	amfenac 4
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4

Drug as victim

Target	Modality	Activity	Metabolite
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive	amfenac 4
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive	amfenac 4
UGT enzymes 27	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	likely
UGT enzymes 27	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	likely	amfenac 4

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac.	2003 Oct	14635785
Comparison of the analgesic efficacy and safety of nepafenac ophthalmic suspension compared with diclofenac ophthalmic solution for ocular pain and photophobia after excimer laser surgery: a phase II, randomized, double-masked trial.	2006 Apr	16750464
Nepafenac: a unique nonsteroidal prodrug.	2006 Fall	17060788
The effect of a selective cyclooxygenase-2 (COX-2) inhibitor on the proliferation rate of retinoblastoma cell lines.	2006 May	16123787
Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.	2007 Feb	17341147
Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology.	2007 Feb	17259381
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	17592313
Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK).	2007 Nov-Dec	18165210
Case of corneal melting associated with the use of topical nepafenac.	2007 Sep	17721306
The use of a cyclooxygenase-2 inhibitor (Nepafenac) in an ocular and metastatic animal model of uveal melanoma.	2007 Sep	17434930
Nepafenac dosing frequency for ocular pain and inflammation associated with cataract surgery.	2008 Dec	19040348
Corneal melting after use of nepafenac in a patient with chronic cystoid macular edema after cataract surgery.	2008 Mar	18327052
Ketorolac versus nepafenac in cataract surgery.	2008 Mar	18299048
Amfenac increases the radiosensitivity of uveal melanoma cell lines.	2008 May	18049486
Topical nepafenac as an alternate treatment for cystoid macular edema in steroid responsive patients.	2008 Nov-Dec	18664937
Etiology and treatment of the inflammatory causes of cystoid macular edema.	2009	22096351
Intracameral dexamethasone reduces inflammation on the first postoperative day after cataract surgery in eyes with and without glaucoma.	2009	19668589
Inhibition of surgically induced miosis and prevention of postoperative macular edema with nepafenac.	2009	19668569
Management of ocular inflammation and pain following cataract surgery: focus on bromfenac ophthalmic solution.	2009	19668566
Gateways to clinical trials.	2009 Apr	19536362
Increased neuronal nitric oxide synthase activity in retinal neurons in early diabetic retinopathy.	2009 Nov 9	19936028
Differential effects of non-steroidal anti-inflammatory drugs on mitochondrial dysfunction during oxidative stress.	2009 Oct 1	19810214
Nepafenac-associated bilateral corneal melt after photorefractive keratectomy.	2009 Sep	19654513
Inflammatory mediators and angiogenic factors in choroidal neovascularization: pathogenetic interactions and therapeutic implications.	2010	20871825
Diabetic cataract-pathogenesis, epidemiology and treatment.	2010	20634936
Comparison of three strains of diabetic rats with respect to the rate at which retinopathy and tactile allodynia develop.	2010 Aug 15	20806092
Ocular pharmacokinetics of 0.45% ketorolac tromethamine.	2010 Dec 1	21179226
Impact of nepafenac 0.1% on macular thickness and postoperative visual acuity after cataract surgery in patients at low risk for cystoid macular oedema.	2010 Jan	19229275
Topical nepafenac for treatment of exudative age-related macular degeneration.	2010 Mar	19364332
Nepafenac-assisted mydriasis in a rabbit model.	2010 Oct	20674259

Patents

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).

Name

Type

Language

AMFENAC SODIUM

Official Name

English

AMFENAC SODIUM [USAN]

Common Name

English

AHR-5850D

Code

English

FENAZOX

Brand Name

English

AMFENAC SODIUM SALT MONOHYDRATE

Common Name

English

AMFENAC SODIUM SALT MONOHYDRATE [MI]

Common Name

English

AMFENAC SODIUM HYDRATE [JAN]

Common Name

English

Sodium (2-amino-3-benzoylphenyl)acetate monohydrate

Systematic Name

English

AMFENAC SODIUM [MART.]

Common Name

English

BENZENEACETIC ACID, 2-AMINO-3-BENZOYL-, SODIUM SALT, MONOHYDRATE

Common Name

English

AMFENAC SODIUM HYDRATE

Common Name

English

SODIUM AMFENAC

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257