Bromfenac

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Bromfenac
Bromfenac.svg
Systematic (IUPAC) name
2-[2-amino-3-(4-bromobenzoyl)phenyl]acetic acid
Clinical data
Trade names Bromday, Prolensa
AHFS/Drugs.com monograph
MedlinePlus a611018
Pregnancy cat.
  • C
Legal status
Routes Oral (discontinued)
ophthalmic
Identifiers
CAS number 91714-94-2 YesY
ATC code S01BC11
PubChem CID 60726
DrugBank DB00963
ChemSpider 54730 YesY
UNII 864P0921DW YesY
KEGG D07541 YesY
ChEBI CHEBI:240107 YesY
ChEMBL CHEMBL1077 YesY
Chemical data
Formula C15H12BrNO3 
Mol. mass 334.16g/mol
 YesY (what is this?)  (verify)

Bromfenac is a non-steroidal anti-inflammatory drug (NSAID) marketed in the US as an ophthalmic solution (current 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. 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 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. 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. 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 It was brought to market in July, 1997, and was withdrawn June 22, 1998 following numerous reports of hepatotoxicity in patients who had taken the medication for longer than the recommended 10-day period. The dose was one 25 mg capsule every 6 to 8 hours, or two capsules if taken with a high-fat meal, up to a maximum of 150 mg per day.

Clinical use[edit]

The FDA approval for Bromday is for use one day before and two weeks following cataract surgery for the treatment of ocular inflammation and pain.

Pharmacology and clinical studies[edit]

The high degree of penetration and potency of bromfenac 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. 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 bromfenac 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 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 three drops of bromfenac (pre-op day, day of surgery, post-op day 1), 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 bromfenac, only 2.9% of bromfenac 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.

Bromfenac is the first of a new generation of post-operative medications with once daily dosing.

Chemistry[edit]

Bromfenac can be synthesized by the route outlined below.[1]

Bromfenac synth.png

References[edit]

  1. ^ 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[edit]