Bromfenac Explained

Bromfenac is a nonsteroidal anti-inflammatory drug (NSAID)[1] marketed in the US as an ophthalmic solution (brand names Prolensa and Bromday,[2] 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.[3]

Medical uses

Bromfenac is indicated for the treatment of postoperative ocular inflammation following cataract extraction.[4] [5]

The drug has been shown to reduce macular edema and thickness of the retina (an indicator for inflammation) and improve visual acuity after surgery.[6]

Contraindications

Bromfenac is contraindicated for people with adverse reactions to NSAIDs, such as asthma or rashes.[7]

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 (0.4%), eye pruritus (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 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 synthesis by blocking the cyclooxygenase (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 after 150 to 180 minutes, with a biological half-life 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, and much less in the lens and vitreous body.

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, and metabolites include the lactam and several conjugated compounds. 82% are excreted via the urine, and 13% via the faeces.

Compared to amfenac, the halogenation of bromfenac's chemical structure (the bromine atom at C4) increases its penetration into ocular tissues, and increases its potency for COX enzyme inhibition.[8]

Chemistry

Along with indomethacin, diclofenac 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 and aqueous bases, insoluble in chloroform and aqueous acids, and melts at NaNC under decomposition.[9]

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.[10] It was first FDA approved for use in the United States in 2005, and it was marketed as Xibrom, twice-daily.[11] In October 2010 Bromday received US FDA approval as a new, once-daily formulation.[12] 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.[13]

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 in patients who had taken the medication for longer than the recommended 10-day period.[14] [15]

Notes and References

  1. Rovere G, Nadal-Nicolás FM, Sobrado-Calvo P, García-Bernal D, Villegas-Pérez MP, Vidal-Sanz M, Agudo-Barriuso M . Topical Treatment With Bromfenac Reduces Retinal Gliosis and Inflammation After Optic Nerve Crush . Investigative Ophthalmology & Visual Science . 57 . 14 . 6098–6106 . November 2016 . 27832276 . 10.1167/iovs.16-20425 . free .
  2. Web site: Bromfenac Sodium Monograph for Professionals . Drugs.com . 21 April 2020 . 23 November 2020.
  3. Book: Austria-Codex. Haberfeld H . Österreichischer Apothekerverlag. Vienna. 2015. German.
  4. Web site: Yellox EPAR . European Medicines Agency (EMA) . 17 September 2018 . 23 November 2020.
  5. Web site: Prolensa- bromfenac sodium solution/ drops . DailyMed . 1 March 2020 . 23 November 2020.
  6. Sheppard JD . Topical bromfenac for prevention and treatment of cystoid macular edema following cataract surgery: a review . Clinical Ophthalmology . 10 . 2099–2111 . 2016 . 27822006 . 5087782 . 10.2147/OPTH.S86971 . free .
  7. Web site: Yellox Summary of Product Characteristics. European Medicines Agency. 11 January 2016. 11 December 2016. 20 December 2016. https://web.archive.org/web/20161220121602/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001198/WC500107575.pdf. dead.
  8. Schechter BA . Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies . Clinical Ophthalmology . 13 . 1439–1460 . 2019 . 31534309 . 6682171 . 10.2147/OPTH.S208700 . free .
  9. Book: Arzneistoff-Profile. Dinnendahl V, Fricke U . Govi Pharmazeutischer Verlag. Eschborn, Germany. 2012. 26. 2. 978-3-7741-9846-3. German.
  10. Web site: Ethical Products for Medical Professionals. Senju Pharmaceutical. 11 December 2016. 20 December 2016. https://web.archive.org/web/20161220095025/http://www.senju.co.jp/english/products/mp.html. dead.
  11. for Xibrom.
  12. Silverstein SM, Jackson MA, Goldberg DF, Muñoz M . The efficacy of bromfenac ophthalmic solution 0.07% dosed once daily in achieving zero-to-trace anterior chamber cell severity following cataract surgery . Clinical Ophthalmology . 8 . 965–972 . 2014-05-16 . 24876763 . 4037304 . 10.2147/OPTH.S60292 . free .
  13. Web site: 2009-10-02 . Bausch & Lomb subsidiaries, CROMA to co-promote bromfenac in Europe . 2024-06-03 . Ophthalmology Times . en.
  14. Hunter EB, Johnston PE, Tanner G, Pinson CW, Awad JA . Bromfenac (Duract)-associated hepatic failure requiring liver transplantation . The American Journal of Gastroenterology . 94 . 8 . 2299–301 . August 1999 . 10.1111/j.1572-0241.1999.01321.x . 10445569 . 33021811 .
  15. Web site: Duract (bromfenac) Information. FDA. 11 December 2016.