Xibrom (Bromfenac Sodium Ophthalmic) - Description and Clinical Pharmacology

Sterile

DESCRIPTION

XIBROM (bromfenac ophthalmic solution) 0.09% is a sterile, topical, nonsteroidal anti-inflammatory drug (NSAID) for ophthalmic use. Each mL of Xibrom contains 1.035 mg bromfenac sodium equivalent to 0.9 mg bromfenac free acid. Bromfenac sodium is designated chemically as sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate, with an empirical formula of C₁₅H₁₁BrNNaO₃ • 1½H₂O. The structural formula of bromfenac sodium is:

Bromfenac sodium is a yellow to orange crystalline powder. The molecular weight of bromfenac sodium is 383.17. XIBROM ophthalmic solution is supplied as a sterile aqueous 0.09% solution, with a pH of 8.3. The osmolality of XIBROM ophthalmic solution is approximately 300 mOsmol/kg. Each mL of XIBROM ophthalmic solution contains: Active: bromfenac sodium hydrate 0.1035%. Inactives: benzalkonium chloride (0.05 mg/mL), boric acid, disodium edetate (0.2 mg/mL), polysorbate 80 (1.5 mg/mL), povidone (20 mg/mL), sodium borate, sodium sulfite anhydrous (2 mg/mL), sodium hydroxide to adjust the pH, and water for injection, USP.

CLINICAL PHARMACOLOGY

Mechanism of Action:

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 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.

Pharmacokinetics:

The plasma concentration of bromfenac following ocular administration of 0.09% XIBROM (bromfenac ophthalmic solution) in humans is unknown. Based on the maximum proposed dose of one drop to each eye (0.09mg) 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.

Clinical Trials:

Clinical efficacy was evaluated in two randomized, double-masked, placebo-controlled U.S. trials in which subjects with a summed ocular inflammation score ≥3 after cataract surgery were assigned to XIBROM or placebo in a 2:1 ratio following surgery. One drop of XIBROM or vehicle was self-instilled in the study eye twice a day for 14 days, beginning the day after surgery. The primary endpoint was reduction of ocular inflammation (to trace inflammation or clearing) assessed 14 days post-surgery using a slit lamp binocular microscope. In the intent-to-treat analyses of both studies, a significant effect of XIBROM on ocular inflammation after cataract surgery was demonstrated (62-66% vs. 40-48%).