BROMFENAC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H12BrNO3
Molecular Weight	334.165
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C(CC(O)=O)C=CC=C1C(=O)C2=CC=C(Br)C=C2

InChI

InChIKey=ZBPLOVFIXSTCRZ-UHFFFAOYSA-N

InChI=1S/C15H12BrNO3/c16-11-6-4-9(5-7-11)15(20)12-3-1-2-10(14(12)17)8-13(18)19/h1-7H,8,17H2,(H,18,19)

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203168s000lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/pro/bromfenac-ophthlamic-solution.html | http://www.rxlist.com/xibrom-drug.htm

Bromfenac is a topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use. It is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery. The mechanism of its action is thought to be due to its ability to block prostaglandin synthesis by inhibiting cyclooxygenase 1 and 2. The most commonly reported adverse reactions in 3 to 8% of patients were anterior chamber inflammation, foreign body sensation, eye pain, photophobia and vision blurred.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24796327	Inhibitor 8297		5.56 nM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24796327	Inhibitor 8297		7.45 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Ocular pain 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203168s000lbl.pdf	Primary		Approved 8429	PROLENSA Approved Use Bromfenac Ophthalmic Solution, 0.09% is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery. Bromfenac Ophthalmic Solution is a nonsteroidal anti-inflammatory drug (NSAID) indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract extraction (1). Launch Date 2013
Postoperative inflammation 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203168s000lbl.pdf	Primary		Approved 8429	PROLENSA Approved Use Bromfenac ophthalmic solution (0.07%) is indicated for the treatment of postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery. Launch Date 2013

C_max

Value	Dose	Co-administered	Analyte	Population
58.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19049295	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		BROMFENAC aqueous humor	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
313.8 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19049295	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		BROMFENAC aqueous humor	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19049295	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		BROMFENAC aqueous humor	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.2% OTHER GOV https://www.ema.europa.eu/en/documents/assessment-report/yellox-epar-public-assessment-report_en.pdf	unknown, unknown		BROMFENAC plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.09 % 2 times / day steady, ophthalmic Recommended Dose: 0.09 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.09 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17720085	unhealthy, 20 years n = 1 Health Status: unhealthy Age Group: 20 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/17720085	Disc. AE: Corneal melt... AEs leading to discontinuation/dose reduction: Corneal melt (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/17720085
200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	unhealthy, 23.7 years n = 21 Health Status: unhealthy Age Group: 23.7 years Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	Other AEs: Headache, Nausea... Other AEs: Headache (1 patient) Nausea (1 patient) Dizziness (2 patients) Drowsiness (1 patient) Vomiting (1 patient) Hypotension (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/
25 mg 4 times / day steady, oral Recommended Dose: 25 mg, 4 times / day Route: oral Route: steady Dose: 25 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10492497	unhealthy, 60 years n = 1 Health Status: unhealthy Age Group: 60 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/10492497	Disc. AE: Hepatitis fulminant... AEs leading to discontinuation/dose reduction: Hepatitis fulminant (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/10492497
0.1 % single, ophthalmic Highest studied dose Dose: 0.1 % Route: ophthalmic Route: single Dose: 0.1 % Sources: https://pubmed.ncbi.nlm.nih.gov/19049295	unhealthy, 72.2 years (range: 24–95 years) n = 54 Health Status: unhealthy Condition: cataract Age Group: 72.2 years (range: 24–95 years) Sex: M+F Population Size: 54 Sources: https://pubmed.ncbi.nlm.nih.gov/19049295	Sources: https://pubmed.ncbi.nlm.nih.gov/19049295

AEs

AE	Significance	Dose	Population
Corneal melt	1 patient Disc. AE	0.09 % 2 times / day steady, ophthalmic Recommended Dose: 0.09 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.09 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17720085	unhealthy, 20 years n = 1 Health Status: unhealthy Age Group: 20 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/17720085
Drowsiness	1 patient	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	unhealthy, 23.7 years n = 21 Health Status: unhealthy Age Group: 23.7 years Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/
Headache	1 patient	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	unhealthy, 23.7 years n = 21 Health Status: unhealthy Age Group: 23.7 years Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/
Hypotension	1 patient	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	unhealthy, 23.7 years n = 21 Health Status: unhealthy Age Group: 23.7 years Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/
Nausea	1 patient	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	unhealthy, 23.7 years n = 21 Health Status: unhealthy Age Group: 23.7 years Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/
Vomiting	1 patient	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	unhealthy, 23.7 years n = 21 Health Status: unhealthy Age Group: 23.7 years Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/
Dizziness	2 patients	200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/	unhealthy, 23.7 years n = 21 Health Status: unhealthy Age Group: 23.7 years Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/9690243/
Hepatitis fulminant	grade 5, 1 patient Disc. AE	25 mg 4 times / day steady, oral Recommended Dose: 25 mg, 4 times / day Route: oral Route: steady Dose: 25 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10492497	unhealthy, 60 years n = 1 Health Status: unhealthy Age Group: 60 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/10492497

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-071612	http://www.3bsc.com/index/pro_info.php?id=112687
AA Blocks	AA01EAYD	https://www.aablocks.com/goods/Goods/detail?id=AA01EAYD
AEchem Scientific Corp., USA	AE1-002733	http://www.aechemsc.com/info_products/AE1-002733.php
AHH Chemical co.,ltd	MT-02309	http://www.ahhchemical.com/product/MT-02309.html
AHH Chemical co.,ltd	MT-48752	http://www.ahhchemical.com/product/MT-48752.html
AK Scientific, Inc. (AKSCI)	2285AH	http://www.aksci.com/item_detail.php?cat=2285AH
Aaron Chemicals	AR01EBQ5	http://www.aaronchem.com/91714-93-1
AbMole Bioscience	M2471	http://www.abmole.com/products/bromfenac-sodium.html
Acadechem	ACDS-067861	http://www.acadechemical.com/product/142560
Acorn PharmaTech	ACN-046782	http://www.acornpharmatech.com/
Adooq BioScience	A13244	https://www.adooq.com/bromfenac-sodium.html
Alfa Chemistry	AP91714931	https://reagents.alfa-chemistry.com/product/bromfenac-sodium-cas-91714-93-1-18539.html
Alfa Chemistry	91714-93-1	https://www.alfa-chemistry.com/bromfenac-sodium-cas-91714-93-1-item-109704.htm
Alfa Chemistry	ACM91714931	https://www.alfa-chemistry.com/bromfenac-sodium-cas-91714-93-1-item-109704.htm
Ambeed	A142956	https://www.ambeed.com/products/91714-93-1.html
Angel Pharmatech	AG308412	http://www.angelpharmatech.com/91714-93-1.html
ApexBio Technology	B1684	http://www.apexbt.com/bromfenac-sodium.html
Ark Pharm	AK601232	http://www.arkpharminc.com/products/91714-93-1.html
Aurora Fine Chemicals LLC	A17.911.578	http://online.aurorafinechemicals.com/info?ID=A17.911.578
AvaChem Scientific	2601	http://www.avachem.com/productSearch.asp?2601
BLD Pharm	BD69762	http://www.bldpharm.com/products/91714-93-1.html
BOC Sciences	91714-93-1	https://www.bocsci.com/bromfenac-sodium-cas-91714-93-1-item-100549.html
BioChemPartner	BCP05811	http://www.biochempartner.com/91714-93-1-BCP05811
BioCrick	BCC4641	http://www.biocrick.com/Bromfenac-Sodium-BCC4641.html
BioSynth	J-004372	https://www.biosynth.com/en/products/all-products/products/J-004372.html
BioSynth	Q-200752	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-200752.html
Boerchem	BC238440	http://www.boerchem.com/?product_38608.html
Boroncore	BC005156	http://www.boroncore.com/91714-93-1.html
CSNpharm	CSN18760	https://www.csnpharm.com/products/bromfenac-sodium.html
ChemMol	30107437	http://www.chemmol.com/chemmol/30107437.html
ChemMol	30113928	http://www.chemmol.com/chemmol/30113928.html
ChemMol	44005322	http://www.chemmol.com/chemmol/44005322.html
ChemShuttle	159933	http://www.chemshuttle.com/catalogsearch/result/?q=120638-55-3&cat=
Chemspace	CSSB00016998065	https://chem-space.com/CSSB00016998065
Clearsynth	CS-O-06165	https://www.clearsynth.com/en/CSO06165.html
Finetech	FT-0660252	http://www.finetechnology-ind.com/prod/detail/pub/120638-55-3.html
Finetech	FT-0602701	http://www.finetechnology-ind.com/prod/detail/pub/91714-93-1.html
Glentham Life Sciences	GL4176	http://www.glentham.com/products/product/GL4176/
Hairui	HR118924	http://www.hairuichem.com/en/product/120638-55-3.html
MolPort	MolPort-005-938-273	https://www.molport.com/shop/molecule-link/MolPort-005-938-273
Molcore	MC511369	https://www.molcore.com/product/120638-55-3
Molcore	MC579839	https://www.molcore.com/product/91714-93-1
MuseChem	A000173	https://www.musechem.com/product/A000173.html
MuseChem	I005027	https://www.musechem.com/product/I005027.html
Selleck Chemicals	S4248	http://www.selleckchem.com/products/bromfenac-sodium.html
Sigma-Aldrich	SML0289_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/sml0289?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S052204	http://www.sinfoobiotech.com/product/1055602
Synblock Inc	SB17363	http://www.synblock.com/product/91714-93-1.html
Synchem UG and Co KG	70546	http://www.synchem.de/chemical_Bromfenac%20Sodium.html
Yuhao Chemical	LX2757	http://www.chemyuhao.com/91714-93-1.html
abcr GmbH	AB479725	http://www.abcr.de/shop/en/AB479725
eNovation Chemicals	D572919	https://www.enovationchem.com/ProductDetails.asp?ProductID=D572919
eNovation Chemicals	D634813	https://www.enovationchem.com/ProductDetails.asp?ProductID=D634813
eNovation Chemicals	D673682	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673682
eNovation Chemicals	D767265	https://www.enovationchem.com/ProductDetails.asp?ProductID=D767265

PubMed

Title	Date	PubMed
Bromfenac (Duract)-associated hepatic failure requiring liver transplantation.	1999 Aug	10445569
Acute liver failure.	2001 May	17031171
Effects of nonsteroidal anti-inflammatory drugs on experimental allergic conjunctivitis in Guinea pigs.	2003 Dec	14733714
Drug-induced hepatotoxicity.	2003 Jul 31	12890847
Gateways to clinical trials.	2003 Jun	12851663
Effects of topical corticosteroids and nonsteroidal anti-inflammatory drugs on prostaglandin e2-induced aqueous flare elevation in pigmented rabbits.	2003 Nov-Dec	14688425
Drug-induced liver injury.	2004 Mar 1	14986274
Analgesics for acute pain: Meeting the United States Food and Drug Administration's requirements for proof of efficacy.	2004 May-Jun	15100587
New drugs and dosage forms.	2005 May 1	15892212
Ximelagatran: direct thrombin inhibitor.	2006	17319469
How can 'Hy's law' help the clinician?	2006 Apr	16552792
Hy's law: predicting serious hepatotoxicity.	2006 Apr	16552790
A systematic review of NSAIDs withdrawn from the market due to hepatotoxicity: lessons learned from the bromfenac experience.	2006 Apr	16456879
Hepatic disorders in patients treated with COX-2 selective inhibitors or nonselective NSAIDs: a case/noncase analysis of spontaneous reports.	2006 Aug	16982289
Three cases of corneal melting after instillation of a new nonsteroidal anti-inflammatory drug.	2006 Dec	17172918
Misuse and abuse of topically applied nonsteroidal anti-inflammatory drugs.	2006 Dec	17172917
Global experience with Xibrom (bromfenac ophthalmic solution) 0.09%: the first twice-daily ophthalmic nonsteroidal anti-inflammatory drug.	2006 Fall	17060789
Ocular permeation and inhibition of retinal inflammation: an examination of data and expert opinion on the clinical utility of nepafenac.	2006 Feb	16466612
Three cases of corneal melting after instillation of a new nonsteroidal anti-inflammatory drug.	2006 Feb	16371788
Comparison of cyclooxygenase inhibitory activity and ocular anti-inflammatory effects of ketorolac tromethamine and bromfenac sodium.	2006 Jun	16846546
Effects of an opioid (oxycodone/paracetamol) and an NSAID (bromfenac) on driving ability, memory functioning, psychomotor performance, pupil size, and mood.	2006 Jun	16772806
Topical bromfenac sodium for long-term management of vernal keratoconjunctivitis.	2007	17440276
Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.	2007 Feb	17341147
Effect of ophthalmic solution components on acrylic intraocular lenses.	2007 Jan	17189806
Corneal melting and perforation in Stevens Johnson syndrome following topical bromfenac use.	2007 Sep	17720085
In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac.	2007 Sep	17720067
24-hour evaluation of the ocular distribution of (14)C-labeled bromfenac following topical instillation into the eyes of New Zealand White rabbits.	2008 Aug	18665811
Re: Pharmacokinetics and pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac.	2008 Aug	18655957
Ocular pharmacokinetics of a single dose of bromfenac sodium ophthalmic solution 0.1% in human aqueous humor.	2008 Dec	19049295
Topical ocular delivery of NSAIDs.	2008 Jun	18437583
Comparison of ketorolac 0.4% and bromfenac 0.09% at trough dosing: aqueous drug absorption and prostaglandin E2 levels.	2008 Sep	18721711
Management of ocular inflammation and pain following cataract surgery: focus on bromfenac ophthalmic solution.	2009	19668566
Evaluation of the potential for drug-induced liver injury based on in vitro covalent binding to human liver proteins.	2009 Dec	19720731
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.	2009 Dec 2	19956587
Topical bromfenac 0.09% vs. ketorolac 0.4% for the control of pain, photophobia, and discomfort following PRK.	2009 Feb	19241773
Cyclooxygenase (COX)-inhibiting drug reduces HSV-1 reactivation in the mouse eye model.	2009 Mar	19274523
Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery.	2009 May	19183412
Retrospective review of the efficacy of topical bromfenac (0.09%) as an adjunctive therapy for patients with neovascular age-related macular degeneration.	2009 Nov-Dec	19898185
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	19934822
Ophthalmic utility of topical bromfenac, a twice-daily nonsteroidal anti-inflammatory agent.	2009 Oct	19735215
Differential effects of non-steroidal anti-inflammatory drugs on mitochondrial dysfunction during oxidative stress.	2009 Oct 1	19810214
Efficacy of ophthalmic nonsteroidal antiinflammatory drugs in suppressing anterior capsule contraction and secondary posterior capsule opacification.	2009 Sep	19683162
Efficacy of bromfenac sodium ophthalmic solution in preventing cystoid macular oedema after cataract surgery in patients with diabetes.	2010 Dec	19725815
Ocular pharmacokinetics of 0.45% ketorolac tromethamine.	2010 Dec 1	21179226
Chem2Bio2RDF: a semantic framework for linking and data mining chemogenomic and systems chemical biology data.	2010 May 17	20478034
Cytotoxicity of topical medications used for infection and inflammation control after cataract surgery in cultured corneal endothelial cells.	2010 Sep	20938094
Difluprednate ophthalmic emulsion 0.05% (Durezol) administered two times daily for managing ocular inflammation and pain following cataract surgery.	2010 Sep 7	20856594
In vitro approach to assess the potential for risk of idiosyncratic adverse reactions caused by candidate drugs.	2012 Aug 20	22646477
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014 Jan	24085192
Multiparametric assay using HepaRG cells for predicting drug-induced liver injury.	2015 Jul 2	25934330

Patents

Sample Use Guides

In Vivo Use Guide

Instill one drop into the affected eye once daily beginning 1 day prior to surgery, continued on the day of surgery, and through the first 14 days postsurgery.

Route of Administration: Topical

In Vitro Use Guide

ARPE-19 cells treated with 4X and 2X clinical doses of bromfenac ophthalmic solution (BOS) showed mean CV of 16.95±3.04% (p<0.001), and 28.45±2.33% (p0.05). The ΔΨM was decreased and the caspase 3 /7 activity increased in ARPE-19 cells treated with all BOS concentrations when compared to untreated ARPE 19 controls (15.15±1.05). The ΔΨM of ARPE-19 cells were 2.74±0.36 (p<0.001), 2.35±0.33 (p<0.001), 2.63±0.20 (p<0.001), 5.30±0.18 (p<0.001) and 5.22±0.15 (p<0.001) for 4X, 2X, X, X/2 and X/4 concentrations respectively. The ROS activity was significantly increased for all BOS concentrations when compared to untreated control. Caspase 3/7 activity was significantly increased for all BOS concentrations.

Name

Type

Language

BROMFENAC

Official Name

English

bromfenac [INN]

Common Name

English

Bromfenac [WHO-DD]

Common Name

English

BROMFENAC [VANDF]

Common Name

English

BROMFENAC [MI]

Common Name

English

ISV-303

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C257