- Bromfenac
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Bromfenac 
Systematic (IUPAC) name 2-[2-amino-3-(4-bromobenzoyl)phenyl]acetic acid Clinical data AHFS/Drugs.com monograph MedlinePlus a611018 Pregnancy cat. C Legal status ℞-only (US) Routes Oral (discontinued)
ophthalmicIdentifiers CAS number 91714-94-2 
ATC code S01BC11 PubChem CID 60726 DrugBank DB00963 ChemSpider 54730 UNII 864P0921DW KEGG D07541 ChEBI CHEBI:240107 ChEMBL CHEMBL1077 Chemical data Formula C15H12BrNO3 Mol. mass 334.16g/mol SMILES eMolecules & PubChem - 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)
Key:ZBPLOVFIXSTCRZ-UHFFFAOYSA-N
(what is this?) (verify)Bromfenac is a non-steroidal anti-inflammatory drug (NSAID) marketed in the US as an ophthalmic solution (current brand name Bromday, prior formulation brand name Xibrom, which has since been discontinued.) by ISTA Pharmaceuticals for short-term, local use. Bromday is the once-daily formulation of Bromfenac, while Xibrom, which has since been discontinued, was the twice-daily formulation. Bromfenac is indicated for the treatment of ocular inflammation and pain after cataract surgery, though it may be prescribed in an off-label manner by the physician.
For ophthalmic use, Bromfenac has been prescibed more than 20,000,000 times across the world. As an eye drop, it has been availalbe 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. October 2010 was the FDA approval of the new once-daily formulation of Bromfenac called Bromday. The Bromfenac molecule will be marketed in Europe and other 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 It was brought to market in July, 1997, and was withdrawn June 22, 1998 following numerous reports of liver failure in patients who had taken the medication for longer than the recommended 10-day period. The dose was one 25mg capsule every 6 to 8 hours, or two capsules if taken with a high-fat meal, up to a maximum of 150mg per day.
Contents
Clinical use
The FDA approval for Bromday, which is the only currently available formulation of Bromfenac available in the USA, is for use one day before and two weeks following cataract surgery for the treatment of ocular inflammation and pain.
Pharmacology and clinical studies
The high degree of penetration and potency of Bromday can be attributed to the halogenation of the molecule: by adding a bromine moiety the NSAID becomes highly lipophilic which allows for rapid, sustained drug levels in the ocular tissues.
The Bromfenac Comparative trial was done to determine the optimal concentration for a once daily formulation. Interestingly, the standard 0.09% concentration performed as well as a double strength 0.18% concentration indicating that the COX enzyme receptors were already saturated and blocked by the bromfenac molecule.
In the Bromday FDA Pivotal Trial patients were evaluated with two end-points: a primary efficacy endpoint of the summed ocular inflammation score (SOIS) at post-operative day 15 and a secondary efficacy endpoint of patients reporting a pain score of “none” on post-operative day 1. Note that both arms of this study, the Bromday arm and the placebo arm, were not given any sort of corticosteroid to control inflammation. All anti-inflammatory activity for these post-op cataract patients was from the Bromday NSAID alone.
For post-operative inflammation at day 15, the patients receiving Bromday had an SOIS level of just 1.1 compared to 2.8 for the patients in the placebo arm. This was statistically significant with a superb P value of <0.0001 for day 3, day 8, day 15, and day 22. When patients were asked about their pain level the day after surgery, after having received a total of just three drops of Bromday (pre-op day, day of surgery, post-op day 1), an amazing 94.8% of patients reported “none”, compared to 70.5% for placebo.
Patients who had lack of efficacy were allowed to exit the trial as a safety and comfort measure. For patients receiving Bromday, only 2.9% of Bromday patients elected to do so. This is more than 10 times better than the placebo group where nearly 33% of patients discontinued their participation in the study. These results show that Bromday given just once per day, as a sole anti-inflammatory agent was clinically effective at reducing post-operative inflammation and pain.
Bromday is the first of a new generation of post-operative medications with convenient once daily dosing. More importantly, Bromday brings the same high level of penetration and potency seen previously in Xibrom with half the dosing, half the medication load, and half the level of BAK (benzalkonium chloride) preservative.
Chemistry
Bromfenac can be synthesized by the route outlined below.[1]
References
- ^ Walsh, David A.; Moran, H. Wayne; Shamblee, Dwight A.; Uwaydah, Ibrahim M.; Welstead, William J.; Sancilio, Lawrence F.; Dannenburg, Warren N. (1984). "Antiinflammatory agents. 3. Synthesis and pharmacological evaluation of 2-amino-3-benzoylphenylacetic acid and analogs". Journal of Medicinal Chemistry 27 (11): 1379–88. doi:10.1021/jm00377a001. PMID 6436487.
External links
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