Brinzolamide is a carbonic anhydrase inhibitor. It is administered topically to the eye 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. Final FDA approval for brinzolamide (Azopt) was granted in April 1998.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Brinzolamide is administered topically to the eye. Shake well prior to using.
-If more than one ophthalmic drug is to be administered, the two drugs should be administered at least 10 minutes apart. Contact lenses should be removed prior to instilling brinzolamide; 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 5-10% of patients receiving brinzolamide. Blurred vision was reported in 5-10% of patients receiving brinzolamide. Other adverse reactions occurring in 1-5% 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 < 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 < 1% with brinzolamide.
Alopecia and urticaria have been reported at an incidence < 1% with brinzolamide.
Pharyngitis and dyspnea have been reported at an incidence < 1% with brinzolamide.
Dizziness and hypertonia have been reported at an incidence < 1% with brinzolamide.
Hypersensitivity reactions, chest pain (unspecified), and kidney pain have been reported at an incidence < 1% with brinzolamide.
No overall differences in efficacy or safety of brinzolamide have been observed between elderly and younger adult patients.
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.
Brinzolamide should be used cautiously in patients with renal impairment. Brinzolamide has not been studied in patients with severe renal disease (CrCl < 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.
Brinzolamide is classified in FDA pregnancy category C. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, brinzolamide should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.
According to the manufacturer, a decision should be made whether to discontinue nursing or to discontinue brinzolamide. It is not known whether this drug is excreted in human milk. It may be prudent to consider an alternative glaucoma therapy in a woman who is breast-feeding, such as dorzolamide and acetazolamide (see individual monographs). 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 ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The safety and effectiveness of brinzolamide in 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:
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:
3 drops/day ophthalmic solution in each affected eye.
3 drops/day ophthalmic solution in each affected eye.
Safety and efficacy have not been established.
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 < 30 mL/min: Use is not recommended.
There are no drug interactions associated with Brinzolamide products.
Brinzolamide inhibits carbonic anhydrase II (CA-II). Carbonic anhydrase catalyzes the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. Many body tissues contain carbonic anhydrase; CA-II is the isozyme that plays a key role in controlling aqueous humor production and pressure in the eye. Carbonic anhydrase II is found in the ciliary body of the eye and works by decreasing bicarbonate ion concentrations in ocular fluid. This results in decreased aqueous humor secretion and subsequently a reduction in intraocular pressure (IOP). Carbonic anhydrase II is also present in red blood cells and other cells that secrete hydrogen or hydrogen compounds. 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.
Following 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). 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 (< 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.
Because of the extensive distribution of brinzolamide to erythrocytes, 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. Brinzolamide saturation of erythrocyte CA-II was achieved within 4 weeks (erythrocyte concentrations of approximately 20 micromol). N-Desethyl brinzolamide accumulated in erythrocytes to steady-state within 20-28 weeks reaching concentrations ranging from 6-30 micromol. Systemic CA-II was inhibited 70-75%; this level of inhibition is below the level necessary to exert a pharmacological effect on either renal function or respiration in healthy subjects (product literature).
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).
Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. 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).