Source: FDA, National Drug Code (US) Revision Year: 2020
Bromfenac is a nonsteroidal anti-inflammatory drug (NSAID) that has anti-inflammatory activity. The mechanism of its action is thought to be due to its ability to block prostaglandin synthesis by inhibiting cyclooxygenase (COX) 1 and 2. Prostaglandins have been shown in many animal models to be mediators of certain kinds of intraocular inflammation. In studies performed in animal eyes, prostaglandins have been shown to produce disruption of the blood-aqueous humor barrier, vasodilation, increased vascular permeability, leukocytosis, and increased intraocular pressure.
The plasma concentration of bromfenac following ocular administration of PROLENSA (bromfenac ophthalmic solution) 0.07% in humans is unknown. Based on the maximum proposed dose of one drop to each eye (0.035 mg) and PK information from other routes of administration, the systemic concentration of bromfenac is estimated to be below the limit of quantification (50 ng/mL) at steady-state in humans.
Long-term carcinogenicity studies in rats and mice given oral doses of bromfenac up to 0.6 mg/kg/day (systemic exposure 30 times the systemic exposure predicted from the recommended human ophthalmic dose [RHOD] assuming the human systemic concentration is at the limit of quantification) and 5 mg/kg/day (340 times the predicted human systemic exposure), respectively, revealed no significant increases in tumor incidence.
Bromfenac did not show mutagenic potential in various mutagenicity studies, including the reverse mutation, chromosomal aberration, and micronucleus tests.
Bromfenac did not impair fertility when administered orally to male and female rats at doses up to 0.9 mg/kg/day and 0.3 mg/kg/day, respectively (systemic exposure 90 and 30 times the predicted human exposure, respectively).
Bromfenac 0.07% QD for the treatment of postoperative inflammation and reduction of ocular pain was evaluated in two multi-center, randomized, double-masked, parallel-group, and placebo (vehicle)-controlled studies. Patients undergoing cataract surgery self-administered bromfenac 0.07% or vehicle once daily, beginning 1 day prior to surgery, continuing on the morning of surgery and for 14 days after surgery. Complete clearance of ocular inflammation (0 cell and no flare) was assessed on Days 1, 3, 8, and 15 postsurgery using slit lamp biomicroscopy. The pain score was self-reported. The primary efficacy endpoint was the proportion of subjects who had complete clearance of ocular inflammation by Day 15. In the intent-to-treat analyses from both assessments, complete clearance at Day 8 and Day 15, bromfenac 0.07% was superior to vehicle as shown in the following table.
| Proportion of Subjects with Cleared Ocular Inflammation (0 cells and no flare) | ||||
|---|---|---|---|---|
| Study | Visit | Bromfenac 0.07% | Vehicle | Difference ()(Asymptotic 95 CI) |
| Study 1 | At Day 8 | 27/112 (24.1%) | 7/108 (6.5%) | 17.6 (8.4, 26.8) |
| At Day 15 | 51/112 (45.5%) | 14/108 (13.0%) | 32.5 (21.4, 43.8) | |
| Study 2 | At Day 8 | 33/110 (30.0%) | 14/110 (12.7%) | 17.3 (6.7, 27.9) |
| At Day 15 | 50/110 (45.5%) | 30/110 (27.3%) | 18.2 (5.7, 30.7) | |
| Proportion of Subjects Who Were Pain Free | ||||
| Study | Visit | Bromfenac 0.07% | Vehicle | Difference ()(Asymptotic 95 CI) |
| Study 1 | At Day 1 | 91/112 (81.3%) | 47/108 (43.5%) | 37.7 (25.9, 49.6) |
| Study 2 | At Day 1 | 84/110 (76.4%) | 61/110 (55.5%) | 20.9 (8.7, 33.1) |
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