Bromfenac is a

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a Indication (medicine), therapeutic drug class which Analgesic, reduces pain, Anti-inflammatory, decreases inflammation, Antipyretic, decreases fever, and Antithrombotic, prevents bl ...

(NSAID) marketed in the US as an ophthalmic solution (brand names Prolensa and Bromday, prior formulation brand name Xibrom, which has since been discontinued) by ISTA Pharmaceuticals for short-term, local use. Prolensa and Bromday are the once-daily formulation of bromfenac, while Xibrom was approved for twice-daily administration. In the European Union, the brand name is Yellox. Bromfenac is indicated for the treatment of ocular inflammation and pain after

cataract surgery Cataract surgery, also called lens replacement surgery, is the removal of the natural lens (anatomy), lens of the human eye, eye that has developed a cataract, an opaque or cloudy area. The eye's natural lens is usually replaced with an artific ...

Medical uses

Bromfenac is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of postoperative ocular inflammation following cataract extraction. The drug has been shown to reduce macular edema and thickness of the

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

(an indicator for inflammation) and improve visual acuity after surgery.

Contraindications

Bromfenac is contraindicated for people with adverse reactions to NSAIDs, such as asthma or rashes.

Side effects

Bromfenac eye drops are generally well tolerated. Comparatively common side effects in clinical studies included abnormal sensations in eye (0.5% of people treated with bromfenac), mild to moderate erosion of the

cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...

(0.4%), eye

pruritus An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

(0.4%), eye pain (0.3%) and redness (0.3%). Serious side effects such as corneal perforation were not reported in studies but only during post-marketing in less than one patient in 1000.

Interactions

No systematic interaction studies have been performed. There are no known cases of interactions with antibiotic eye drops.

Blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

levels remain very low during bromfenac therapy, so interactions with drugs taken by mouth are unlikely.

Pharmacology

Mechanism of action

As an NSAID, bromfenac works by inhibiting

prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...

synthesis by blocking the

cyclooxygenase Cyclooxygenase (COX), officially known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme (specifically, a family of isozymes, ) that is responsible for biosynthesis of prostanoids, including thromboxane and prostaglandins such a ...

(COX) enzymes. It preferably acts on COX-2 and only has a low affinity for COX-1.

Pharmacokinetics

Bromfenac is well absorbed through the cornea and reaches highest concentrations in the

aqueous humour The aqueous humour is a transparent water-like fluid similar to blood plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the po ...

after 150 to 180 minutes, with a

biological half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...

of 1.4 hours and high drug levels being maintained for at least 12 hours. It is mainly concentrated in the aqueous humour and

conjunctiva In the anatomy of the eye, the conjunctiva (: conjunctivae) is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with gobl ...

, and much less in the

lens A lens is a transmissive optical device that focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements'') ...

and

vitreous body The vitreous body (''vitreous'' meaning "glass-like"; , ) is the clear gel that fills the space between the Lens (vision), lens and the retina of the eye, eyeball (the vitreous chamber) in humans and other vertebrates. It is often referred to as ...

. Concentrations in the blood plasma are too low to be measured quantitatively. 99.8% of the substance are bound to plasma proteins. The enzyme mainly responsible for metabolization of bromfenac is

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

, and metabolites include the

lactam A lactam is a Cyclic compound, cyclic amide, formally derived from an amino alkanoic acid through cyclization reactions. The term is a portmanteau of the words ''lactone'' + ''amide''. Nomenclature Greek_alphabet#Letters, Greek prefixes in alpha ...

and several conjugated compounds. 82% are excreted via the urine, and 13% via the

faeces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

. Compared to amfenac, the halogenation of bromfenac's chemical structure (the

bromine Bromine is a chemical element; it has chemical symbol, symbol Br and atomic number 35. It is a volatile red-brown liquid at room temperature that evaporates readily to form a similarly coloured vapour. Its properties are intermediate between th ...

atom at C4) increases its penetration into ocular tissues, and increases its potency for COX enzyme inhibition. Brom vs Amf

Chemistry

Along with

indomethacin Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation. It works by inhibiting the production of pr ...

diclofenac Diclofenac, sold under the brand name Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It can be taken orally (swallowed by mouth), inserted rectally as a ...

and others, bromfenac belongs to the acetic acid group of NSAIDs. It is used in form of bromfenac sodium · 1.5 H₂O ( CAS number: ), which is soluble in water,

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

and aqueous bases, insoluble in

chloroform Chloroform, or trichloromethane (often abbreviated as TCM), is an organochloride with the formula and a common solvent. It is a volatile, colorless, sweet-smelling, dense liquid produced on a large scale as a precursor to refrigerants and po ...

and aqueous acids, and melts at under decomposition.

History

For ophthalmic use, bromfenac has been prescribed more than 20,000,000 times across the world. As an eye drop, it has been available since 2000, starting in Japan where it was sold as ''Bronuck''. It was first FDA approved for use in the United States in 2005, and it was marketed as ''Xibrom'', twice-daily. for Xibrom. In October 2010 ''Bromday'' received US FDA approval as a new, once-daily formulation. In 2013, ''Prolensa'' has also been approved by the FDA. Bromfenac eye drops have been marketed in the European Union since 2011, and are available on worldwide markets with agreements from Bausch & Lomb, Croma-Pharma, and other companies. Bromfenac was formerly marketed in the United States by Wyeth-Ayerst in an oral formulation called ''Duract'' for short-term relief of pain (less than 10 days at a time). It was brought to market in July 1997, and was withdrawn 22 June 1998, following numerous reports of

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdr ...

in patients who had taken the medication for longer than the recommended 10-day period.

References

{{Portal bar , Medicine Nonsteroidal anti-inflammatory drugs 2-Aminobenzophenones 4-Bromophenyl compounds Hepatotoxins Acetic acids Ophthalmology drugs