Brinzolamide

Brinzolamide ophthalmic suspension is a carbonic anhydrase inhibitor indicated in the treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. Brinzolamide ophthalmic suspension is a carbonic anhydrase inhibitor indicated for in the treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma

The recommended dose is one drop of brinzolamide ophthalmic suspension in the affected eye(s) 3 times daily. Brinzolamide ophthalmic suspension may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 10 minutes apart. Instill one drop in the affected eye(s) 3 times daily If more than one topical ophthalmic drug is being used, the drugs should be administered at least 10 minutes apart

Sulfonamide hypersensitivity reactions Corneal edema may occur in patients with low endothelial cell counts

5.1Sulfonamide Hypersensitivity Reactions Brinzolamide

ophthalmic suspension is a sulfonamide and although administered topically, it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of brinzolamide ophthalmic suspension. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.

Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

5.2Corneal Endothelium Carbonic

anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Caution should be used when prescribing brinzolamide ophthalmic suspension to this group of patients.

5.3Severe Renal Impairment Brinzolamide

ophthalmic suspension has not been studied in patients with severe renal impairment [creatinine clearance (CrCl) less than 30 mL/min]. Because brinzolamide ophthalmic suspension and its metabolite are excreted predominantly by the kidney, brinzolamide ophthalmic suspension is not recommended in such patients.

5.4Acute Angle-Closure Glaucoma The

management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Brinzolamide ophthalmic suspension has not been studied in patients with acute angle-closure glaucoma.

5.5Risk of Contamination Avoid

allowing the tip of the dispensing container to contact the eye or surrounding structures or other surfaces, since the product can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from contaminated solutions.

5.6Contact Lens Wear The

preservative in brinzolamide ophthalmic suspension benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of brinzolamide ophthalmic suspension, but may be reinserted 15 minutes after instillation.

Brinzolamide ophthalmic suspension is contraindicated in patients who are hypersensitive to any component of this product. Hypersensitivity to any component of this product

8.1Pregnancy Risk Summary There

are no adequate and well-controlled studies in pregnant women to inform drug-associated risk. In reproductive toxicity studies, brinzolamide administered orally to rats induced fetal toxicity at 375-times the recommended human ophthalmic dose (RHOD) based on mg/kg. In rabbits, no fetal toxicity was observed following oral administration . The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4%, and of miscarriage is 15% to 20%, of clinically recognized pregnancies.

Data Animal Data Embryo-fetal studies were conducted in pregnant rats administered 0, 2, 6, or 18 mg/kg/day brinzolamide by oral gavage on gestation days 6 to 17, to target the period of organogenesis. Decreased fetal body weight with reduced skeletal ossification were observed at 18 mg/kg/day (375 times the RHOD based on mg/kg). The no-observed-adverse-effect-level (NOAEL) for fetal toxicity was 6 mg/kg/day (125 times the RHOD).

Decreased maternal weight gain was observed at 18 mg/kg/day. The NOAEL for maternal toxicity was 6 mg/kg/day (125 times the RHOD). Embryo-fetal studies were conducted in pregnant rabbits administered 0, 1, 3, or 6 mg/kg/day of brinzolamide by oral gavage on gestation days 6 to 18, to target the period of organogenesis.

No treatment-related fetal effects were observed at any dose. The NOAEL for fetal toxicity was 6 mg/kg/day (125 times the RHOD based on mg/kg). Maternal weight loss during pregnancy was observed at 3 mg/kg/day (63 times the RHOD) and above. The NOAEL for maternal toxicity was 1 mg/kg/day (21 times the RHOD).

A peri-/postnatal study was conducted in rats administered brinzolamide by oral gavage from gestation day 16 through lactation day 20. Decreased pup body weight was observed at 15 mg/kg/day (313 times the RHOD based on mg/kg). The NOAEL for developmental toxicity was 5 mg/kg/day (104 times the RHOD).

Following oral administration of 14 C-brinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.

Most common adverse reactions (incidence 5 to 10%) are blurred vision and bitter, sour, or unusual taste To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because

clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice. In clinical studies of brinzolamide ophthalmic suspension, the most frequently reported adverse reactions reported in 5% to 10% of patients were blurred vision and bitter, sour or unusual taste. Adverse reactions occurring in 1% to 5% of patients were blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus and rhinitis.

The following adverse reactions were reported at an incidence below 1%: allergic reactions, alopecia, chest pain, conjunctivitis, diarrhea, diplopia, dizziness, dry mouth, dyspnea, dyspepsia, eye fatigue, hypertonia, keratoconjunctivitis, keratopathy, kidney pain, lid margin crusting or sticky sensation, nausea, pharyngitis, tearing, and urticaria.