Brinzolamide is a carbonic anhydrase inhibitor administered topically to the eye indicated for the treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. By lowering IOP, brinzolamide reduces the risk of nerve damage and visual field loss in patients with pathologic elevations of intraocular pressure. Brinzolamide reduces intraocular pressure to the same extent as dorzolamide, but ocular burning appears to be less with brinzolamide. Brinzolamide is a sulfonamide derivative and should not be administered to patients with sulfonamide hypersensitivity. The FDA approved brinzolamide in April 1998.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-Brinzolamide is for ophthalmic use only.
-Instruct patient on proper instillation of the ophthalmic suspension.
-Shake well prior to using.
-Wash hands before and after use.
-To avoid contamination, do not touch the tip of the dropper to the eye, fingertips, or other surfaces.
-If more than 1 ophthalmic drug is to be administered, the 2 drugs should be administered at least 10 minutes apart.
-Contact lenses should be removed prior to instilling the ophthalmic suspension; they can be reinserted after 15 minutes.
Carbonic anhydrase activity has been observed in the corneal endothelium, but the effect of long-term administration of brinzolamide has not been evaluated.
Oral carbonic anhydrase inhibitors are implicated in acid-base and electrolyte disturbances, however, none have been reported with the use of ophthalmic brinzolamide.
All carbonic anhydrase inhibitors can cause taste disturbances due to inhibition of carbonic anhydrase in the mouth. Dysgeusia (bitter, sour, or unusual taste) was reported in 5 to 10% of patients receiving brinzolamide. Blurred vision was reported in 5 to 10% of patients receiving brinzolamide. Other adverse reactions occurring in 1 to 5% of patients included blepharitis, dermatitis, foreign body sensation, headache, hyperemia, xerophthalmia, ocular discharge, ocular irritation, ocular keratitis, ocular pain, ocular pruritus, and rhinitis. The following adverse events were reported at an incidence less than 1%: conjunctivitis, diplopia, ocular fatigue, keratoconjunctivitis, keratopathy, lid margin crusting or sticky sensation, and lacrimation.
Brinzolamide is a sulfonamide. Although not reported with brinzolamide, administration of sulfonamides by any route can precipitate a possibly severe reaction in sulfonamide-sensitive patients. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides. These reactions have included agranulocytosis, aplastic anemia, fulminant hepatic necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and other blood dyscrasias.
Diarrhea, xerostomia, nausea and dyspepsia have been reported at an incidence of less than 1% with brinzolamide.
Alopecia and urticaria have been reported at an incidence of less than 1% with brinzolamide.
Pharyngitis and dyspnea have been reported at an incidence of less than 1% with brinzolamide.
Dizziness and hypertonia have been reported at an incidence of less than 1% with brinzolamide.
Hypersensitivity reactions, chest pain (unspecified), and kidney pain have been reported at an incidence of less than 1% with brinzolamide.
Brinzolamide is contraindicated in patients with hypersensitivity to any component of the product. Also, brinzolamide is a chemical sulfonamide possessing a structure and pharmacologic activity distinct from the bacteriostatic sulfonamides. Rarely, sulfonamides of any type can produce allergic reactions, some of which may be severe. Use brinzolamide with caution, if at all, in patients with a history of sulfonamide hypersensitivity. Brinzolamide is absorbed systemically and may cause the same types of adverse reactions that are attributable to sulfonamides. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides. Sensitization may recur when a sulfonamide is re-administered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, brinzolamide should be discontinued immediately.
Brinzolamide should be used cautiously in patients with renal impairment. Brinzolamide has not been studied in patients with severe renal disease (CrCl less than 30 mL/min) and is not recommended in such patients because brinzolamide and its metabolites are excreted predominantly by the kidney.
Brinzolamide has not been studied in patients with hepatic disease. Use brinzolamide with caution in these patients.
Brinzolamide has not been studied in patients with acute closed-angle glaucoma. Management of patients with acute closed-angle glaucoma requires therapeutic interventions in addition to ocular hypotensive agents.
There are no adequate and well-controlled studies evaluating the use of brinzolamide during human pregnancy. In animal embryo-fetal studies, decreased fetal body weight with reduced skeletal ossification were observed in the off-spring of rats administered oral brinzolamide doses of 18 mg/kg/day [375-times the recommended human ophthalmic dose (RHOD) based on mg/kg]. In rabbits, no treatment-related fetal effects were observed at doses up to 6 mg/kg/day (up to 125-times the RHOD). The no-observed-adverse-effect-level (NOAEL) for fetal toxicity in rats and rabbits was 6 mg/kg/day (125-times the RHOD). To minimize the amount of drug that reaches systemic circulation, apply pressure over the tear duct in the corner of the eye for 1 to 2 minutes after ophthalmic administration.
There are no data regarding the presence of brinzolamide in human milk, the effects on the breast-fed infant, or the effects on milk production. To minimize the amount of drug that reaches systemic circulation, apply pressure over the tear duct in the corner of the eye for 1 to 2 minutes after ophthalmic administration. It may be prudent to consider an alternative glaucoma therapy in a mother who is breast-feeding, such as dorzolamide and acetazolamide. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
The safety and effectiveness of brinzolamide in neonates, infants, and children have not been established.
Brinzolamide is formulated with the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Users of soft contact lenses should not administer brinzolamide while wearing the lenses. Contact lenses may be reinserted 15 minutes after instillation.
For the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma:
Ophthalmic dosage:
Adults: Instill 1 drop in the affected eye(s) 3 times daily. May be used concomitantly with other topical ophthalmic agents to lower intraocular pressure.
Maximum Dosage Limits:
-Adults
3 drops/day ophthalmic solution in each affected eye.
-Geriatric
3 drops/day ophthalmic solution in each affected eye.
-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
Use brinzolamide with caution in patients with hepatic disease; data are lacking.
Patients with Renal Impairment Dosing
CrCl less than 30 mL/min: Use is not recommended.
*non-FDA-approved indication
There are no drug interactions associated with Brinzolamide products.
Brinzolamide inhibits carbonic anhydrase II (CA-II). Following topical ocular administration, brinzolamide inhibits aqueous humor formation and reduces elevated intraocular pressure (IOP). Elevated IOP is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Carbonic anhydrase is an enzyme found in many tissues of the body, including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. Carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II, found primarily in red blood cells (RBCs), but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in IOP. Brinzolamide appears to have no clinically significant biochemical or hematologic effects when administered topically to the eye.
Brinzolamide is administered topically as an ophthalmic suspension. Approximately 60% of brinzolamide in plasma is protein bound. Brinzolamide is metabolized to N-desethyl brinzolamide which also binds to carbonic anhydrase and accumulates in erythrocytes. In the presence of brinzolamide, this metabolite mainly binds to CA-I. Plasma concentrations of both brinzolamide and the metabolite are low and generally below the level of assay detection (less than 10 ng/mL). Brinzolamide is eliminated primarily in the urine as unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N-desmethoxypropyl and O-desmethyl metabolites. N-Desethyl brinzolamide accumulated in erythrocytes to steady-state within 20 to 28 weeks reaching concentrations ranging from 6 to 30 micromol. Systemic CA-II was inhibited 70 to 75%, which is below the degree of inhibition expected to have a pharmacological effect on renal function or respiration in healthy subjects.
Affected cytochrome P450 isoenzymes: None
-Route-Specific Pharmacokinetics
Oral Route
An oral pharmacokinetic study was undertaken using doses that approximated the systemic exposure that would occur after ocular administration of brinzolamide at usual ocular doses because of the extensive distribution of brinzolamide to erythrocytes. Brinzolamide saturation of erythrocyte CA-II was achieved within 4 weeks (erythrocyte concentrations of approximately 20 micromol).
Other Route(s)
Ophthalmic Route
Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Brinzolamide distributes extensively into erythrocytes and exhibits a long half-life in whole blood (about 111 days) due to its affinity for carbonic anhydrase type II (CA-II).