Bromfenac is a benzene acetic acid nonsteroidal anti-inflammatory drug (NSAID) indicated for the treatment of postoperative inflammation and the prevention of ocular pain in patients undergoing cataract surgery. It is available for ophthalmic administration. The use of ophthalmic NSAIDs may result in keratitis; use for more than 24 hours before surgery or beyond 14 days after surgery may increase the risk for and the severity of adverse corneal events. Monitor patients closely for corneal health.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-Apply topically to the eye.
-Remove contact lenses before instillation of solution; lenses may be reinserted 10 minutes after administration.
-Instruct patient on proper instillation of eye solution.
-Do not touch the tip of the dropper to the eye, fingertips, or other surface.
-If more than one ophthalmic medication is being used, separate administration by at least 5 minutes.
-Do not share bottle with other patients.
Most adverse effects from ophthalmic bromfenac are related to the eye, but systemic adverse reactions can occur. Of patients that received bromfenac ophthalmic solution, 2% to 7% had abnormal sensation in eye, conjunctival hyperemia, ocular irritation (e.g., burning/stinging), ocular pruritus, and eye redness. Ocular pain has been reported in 3% to 8% of patients. Headache, iritis, ocular hypertension, and vitreous floaters occurred in 1% to 8% of patients. Anterior chamber inflammation, foreign body sensation, photophobia, and blurred vision occurred in 3% to 8% of patients. Delayed ocular wound healing may occur. Use of topical NSAIDs may result in keratitis. Continued use of ophthalmic NSAID solutions may result in epithelial breakdown, corneal thinning, and corneal erosion that can lead to ulceration or perforation. Patients with evidence of corneal breakdown should immediately discontinue use and be closely monitored, as these events may be sight threatening. Dosing recommendation adherence may reduce the risk of serious adverse events.
There have been reports that ocularly administered NSAIDs may cause increased bleeding in ocular tissues (including hyphema) in conjunction with ocular surgery. Bromfenac may increase the bleeding time due to platelet aggregation inhibition.
Topical bromfenac is associated with impaired wound healing. All topical NSIADS may slow or delay healing. Concomitant use of topical NSAIDs and topical steroids may increase the potential for healing problems.
Bromfenac should be used with caution in patients who are receiving other medications that may prolong bleeding time (e.g., anticoagulant therapy), and in patients with known bleeding tendencies, preexisting coagulopathy, or hemophilia due to the drugs effect on platelet function and vascular response to bleeding. Like other NSAIDs, bromfenac can prolong bleeding time. There have been reports that ocularly applied NSAIDs may cause increased bleeding of ocular tissues (including hyphemas) in conjunction with ocular procedures. Postmarketing experience with ophthalmic NSAIDs suggests that patients with complicated ocular surgery, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular disease affecting the ocular surface (e.g., xerophthalmia, dry eye syndrome), rheumatoid arthritis, or repeat ocular surgeries within a short period of time may be at increased risk for corneal adverse events that may become sight-threatening. Ocular NSAIDs should be used with caution in these patients. Post-marketing experience also suggests that use more than 24 hours prior to ocular surgery or use beyond 14 days post-surgery may increase patient risk for the occurrence and severity of corneal adverse events.
Some ophthalmic formulations of bromfenac contain sodium sulfite and should therefore not be used in patients with a known sulfite hypersensitivity. Also, bromfenac is not recommended in patients who have experienced a severe salicylate hypersensitivity or NSAID hypersensitivity reaction with symptoms such as angioedema, bronchospasm, or shock because of the cross-sensitivity that may occur between aspirin and NSAIDs. Patients with aspirin-induced nasal polyps, asthma, urticaria and allergic reactions are at the highest risk of developing bronchoconstriction or anaphylaxis and may not be good candidates for bromfenac receipt. Also, sulfite sensitivity is seen more frequently in patients with asthma as compared with patients without asthma.
The safety and efficacy of bromfenac ophthalmic solution has not been established for neonates, infants, children and adolescents.
There are no adequate and well-controlled studies of bromfenac ophthalmic solution in pregnant women. Only very small amounts, if any, are systemically absorbed, suggesting an unlikely risk of clinically significant exposure to the embryo or fetus. Treatment of rats with oral doses up to 0.9 mg/kg/day (systemic exposure 90 times the systemic exposure predicted from the recommended human ophthalmic dose assuming the human systemic concentration is detectable) and rabbits at oral doses up to 7.5 mg/kg/day (150 times predicted human systemic exposure) revealed no evidence of teratogenicity; however, embryo-fetal lethality and maternal toxicity were produced in rats and rabbits given 0.9 mg/kg/day and 7.5 mg/kg/day, respectively. Premature closure of the fetal ductus arteriosus has occurred with third trimester use of oral and injectable NSAIDs. Prostaglandin synthetase inhibitors also have the potential to prolong pregnancy and inhibit labor if taken during the third trimester.
There are no data on the presence of ophthalmic bromfenac in human milk, the effects of the drug on the breast-fed infant, or the effects of the drug on milk production. Caution should be exercised if bromfenac ophthalmic solution is given to a woman who is breast-feeding. Because only very small amounts are present in systemic circulation after ophthalmic administration, the amount of drug excreted into human milk is not expected to be clinically significant. Other orally administered NSAIDs (e.g., ibuprofen) are considered compatible with breast-feeding; therefore, it is likely that ophthalmically administered bromfenac would also be compatible. However, due to the lack of well-controlled studies specific to the use of bromfenac in lactating women, its use should be approached with caution. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for bromfenac and any potential adverse effects on the breast-fed infant from bromfenac or the underlying maternal condition.
Patients need to remove contact lenses before administering bromfenac ophthalmic solution. Bromfenac ophthalmic solution contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Also, contact lens removal is needed for drug penetration into the eye. Contact lenses may be reinserted 10 minutes after administration of bromfenac ophthalmic solution.
For the treatment of postoperative ocular inflammation and ocular pain following cataract surgery:
Ophthalmic dosage (Bromday 0.09% solution or Prolensa 0.07% solution):
Adults: One drop (0.07 mg or 0.09 mg) instilled into affected eye(s) once daily beginning 24 hours prior to cataract surgery, continued on the day of surgery, and through the first 14 days of the postoperative period.
Ophthalmic dosage (Xibrom 0.09% solution):
Adults: One drop (0.09 mg) instilled into affected eye(s) twice daily beginning 24 hours after cataract surgery, continued through the first 14 days of the postoperative period.
Ophthalmic dosage (BromSite 0.075% solution):
Adults: One drop (0.075 mg) instilled into affected eye(s) twice daily beginning 1 day prior to surgery, continued on the day of surgery, and through the first 14 days of the postoperative period.
Maximum Dosage Limits:
-Adults
1 drop/day per affected eye for Bromday or Prolensa solutions; 2 drops/day per affected eye for Bromsite or Xibrom solutions.
-Geriatric
1 drop/day per affected eye for Bromday or Prolensa solutions; 2 drops/day per affected eye for Bromsite or Xibrom solutions.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments of the ophthalmic solution in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments of the ophthalmic solution in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Bromfenac products.
The analgesic effects of bromfenac are due to the inhibition of the enzyme cyclooxygenase (COX). The enzymes COX-1 and COX-2 catalyze the conversion of arachidonic acid to prostaglandin G2 (PGG2), which is the first step in the synthesis of prostaglandins and thromboxanes that are involved in rapid physiological responses. COX isoenzymes are also responsible for a peroxidase reaction, which is not affected by NSAIDs. In addition, NSAIDs do not suppress leukotriene synthesis by lipoxygenase pathways. Because prostaglandins sensitize pain receptors, inhibition of prostaglandin synthesis (via cyclooxygenase inhibition) is believed to be responsible for the analgesic effects of bromfenac. Most NSAIDs do not alter the pain threshold or affect existing prostaglandins, so the analgesic action is most likely peripheral. The anti-inflammatory effects of bromfenac may also result from inhibition of prostaglandin synthesis as well as inhibition of leukocyte migration. Antipyresis can occur due to peripheral dilation caused by a central action on the hypothalamus. This results in an increased cutaneous blood flow and subsequent heat loss. COX-1 is constitutively expressed in almost all tissues, while COX-2 appears to only be constitutively expressed in the brain, kidney, bones, reproductive organs, and some neoplasms (e.g., colon and prostate cancers). COX-1 is responsible for prostaglandin synthesis in response to stimulation by circulating hormones, as well as maintenance of normal renal function, gastric mucosal integrity, and hemostasis. However, COX-2 is inducible in many cells in response to certain mediators of inflammation (e.g., interleukin-1, tumor necrosis factor, lipopolysaccharide, mitogens, and reactive oxygen intermediates).
-Ophthalmic Activity: Following topical application to the eye, bromfenac inhibits miosis by inhibiting the biosynthesis of ocular prostaglandins. Prostaglandins play a role in the miotic response produced during ocular surgery by constricting the iris sphincter independently of cholinergic mechanisms. In the eye, prostaglandins also have been shown to disrupt the blood-aqueous humor barrier, cause vasodilation, increase vascular permeability, promote leukocytosis, and increase intraocular pressure (IOP). The degree of ocular inflammatory response is correlated with prostaglandin-induced increases in ciliary epithelium permeability. When applied topically to the eye, NSAIDs inhibit the synthesis of prostaglandins in the iris, ciliary body, and conjunctiva. Thus, NSAIDs may prevent many of the manifestations of ocular inflammation. Bromfenac does not affect intraocular pressure or tonographic aqueous outflow resistance and does not interfere with the action of acetylcholine administered during ocular surgery. Bromfenac also does not prevent increases in intraocular pressure or decreases in aqueous outflow induced by topical corticosteroids.
Bromfenac is administered topically as an ophthalmic solution. Systemic exposure following ophthalmic administration is low. The metabolism and elimination of ophthalmically-administered bromfenac have not been characterized.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
Bromfenac serum concentrations are expected to be below the quantification limit (50 ng/mL) after ophthalmic administration of 0.09 mg to each eye twice daily. Following administration of twice daily bromfenac 0.075% solution, bromfenac plasma concentrations ranged from below the limit of quantification (0.2 ng/mL) to 2.42 ng/mL at 30 to 60 minutes post-dose.