Bromfenac

Bromfenac
Clinical data
Trade names Bromday, Prolensa (US), Yellox (EU)
AHFS/Drugs.com Monograph
MedlinePlus a611018
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		 Oral (discontinued),
    ophthalmic
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Protein binding 99.8%
    Metabolism CYP2C9
    Metabolites Lactam, others
    Elimination half-life 1.4 hours in aqueous humour
    Excretion 82% urine, 13% faeces
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    Chemical and physical data
    Formula C15H12BrNO3
    Molar mass 334.16 g/mol
    3D model (JSmol)
    Melting point 284 to 286 °C (543 to 547 °F) (bromfenac sodium·1.5H2O)
      (verify)

    Bromfenac is a nonsteroidal anti-inflammatory drug (NSAID)[1] marketed in the US as an ophthalmic solution (current 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 Europe, the trade name is Yellox. Bromfenac is indicated for the treatment of ocular inflammation and pain after cataract surgery.[3]

    Medical use

    The FDA and European approvals for bromfenac are for use one day before and two weeks following cataract surgery for the treatment of ocular inflammation and pain.[2][3] The drug has been shown to reduce macular edema and thickness of the retina (an indicator for inflammation) and improve visual acuity after surgery.[4]

    Contraindications

    Bromfenac is contraindicated for people with adverse reactions to NSAIDs, such as asthma or rashes.[3][5]

    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.[3][5]

    Interactions

    No systematic interaction studies have been performed. There are no known cases of interactions with antibiotic eye drops.[3][5] 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.[5]

    Pharmacokinetics

    Bromfenac lactam, the main metabolite in urine

    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.[3][5]

    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.[3][5]

    The high degree of penetration and potency of bromfenac can be attributed to the halogenation of the molecule: by adding a bromine the NSAID becomes highly lipophilic which allows for rapid, sustained drug levels in the ocular tissues.

    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: 120638-55-3 ), which is soluble in water, methanol and aqueous bases, insoluble in chloroform and aqueous acids, and melts at 284 to 286 °C (543 to 547 °F) under decomposition.[6]

    History

    For ophthalmic use, bromfenac has been prescribed more than 20,000,000 times across the world.[5] As an eye drop, it has been available since 2000, starting in Japan where it was sold as Bronuck.[7] It was first FDA approved for use in the United States in 2005, and it was marketed as Xibrom, twice-daily.[8] In October 2010 Bromday received FDA approval as a new, once-daily formulation. More recently, in 2013, Prolensa has also been approved by the FDA.[8] Bromfenac eye drops have been marketed in Europe since 2011[5] and are available on worldwide markets with agreements from Bausch & Lomb,[5] 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 in patients who had taken the medication for longer than the recommended 10-day period.[9][10]

    References

    1. ↑ Rovere, Giuseppe; Nadal-Nicolás, Francisco M.; Sobrado-Calvo, Paloma; García-Bernal, David; Villegas-Pérez, Maria Paz; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta (2016-11-01). "Topical Treatment With Bromfenac Reduces Retinal Gliosis and Inflammation After Optic Nerve Crush". Investigative Ophthalmology & Visual Science. 57 (14): 6098–6106. doi:10.1167/iovs.16-20425. ISSN 1552-5783. PMID 27832276.
    2. 1 2 Drugs.com: Monograph for bromfenac sodium.
    3. 1 2 3 4 5 6 7 Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
    4. ↑ Sheppard, J. D. (2016). "Topical bromfenac for prevention and treatment of cystoid macular edema following cataract surgery: a review". Clinical ophthalmology (Auckland, N.Z.). 10: 2099–2111. doi:10.2147/OPTH.S86971. PMC 5087782. PMID 27822006.
    5. 1 2 3 4 5 6 7 8 9 "Yellox Summary of Product Characteristics" (PDF). European Medicines Agency. 11 January 2016.
    6. ↑ Dinnendahl, V; Fricke, U, eds. (2012). Arzneistoff-Profile (in German). 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
    7. ↑ "Ethical Products for Medical Professionals". Senju Pharmaceutical. Retrieved 11 December 2016.
    8. 1 2 FDA Professional Drug Information for Xibrom.
    9. ↑ Hunter, Ellen B.; Johnston, Philip E.; Tanner, Gordon; Pinson, C. Wright; Awad, Joseph A. (1999). "Bromfenac(Duract)-associated hepatic failure requiring liver transplantation". The American Journal of Gastroenterology. 94 (8): 2299. doi:10.1111/j.1572-0241.1999.01321.x. PMID 10445569.
    10. ↑ "Duract (bromfenac) Information". FDA. Retrieved 11 December 2016.
    This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.