Brinzolamide (Monograph)

Brand name: Azopt
Drug class: Carbonic Anhydrase Inhibitors
Chemical name: (R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide
Molecular formula: C₁₂H₂₁N₃O₅S₃
CAS number: 138890-62-7

Medically reviewed by Drugs.com on Dec 11, 2023. Written by ASHP.

Introduction

Carbonic anhydrase inhibitor; nonbacteriostatic sulfonamide derivative.

Uses for Brinzolamide

Ocular Hypertension and Glaucoma

Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.

Brinzolamide 1%: Efficacy when administered 3 times daily comparable to that of dorzolamide 2% administered 3 times daily in reducing IOP, but brinzolamide appeared to cause less ocular stinging and burning; reduction in IOP was approximately 4–5 mm Hg in clinical studies. When administered 2 or 3 times daily, less effective than timolol 0.5% administered twice daily.

Fixed-combination brinzolamide 1% and brimonidine tartrate 0.2%: IOP-lowering effect of the fixed combination administered 3 times daily was 1–3 mm Hg greater than that of either drug administered at the same dosage as monotherapy.

Safety and efficacy not established for the treatment of acute angle-closure glaucoma.

When selecting an initial ocular hypotensive agent, consider extent of the required IOP reduction, coexisting medical conditions, and drug characteristics (e.g., dosing frequency, adverse effects, cost). With single-agent regimens, the reduction in IOP is approximately 25–33% with topical prostaglandin analogs; 20–25% with topical β-adrenergic blocking agents, α-adrenergic agonists, or miotic (parasympathomimetic) agents; 20–30% with oral carbonic anhydrase inhibitors; 18% with topical rho kinase inhibitors; and 15–20% with topical carbonic anhydrase inhibitors.

A prostaglandin analog frequently is considered for initial therapy in the absence of other considerations (e.g., contraindications, cost considerations, intolerance, adverse effects, patient refusal) because of relatively greater activity, once-daily administration, and low frequency of systemic adverse effects; however, ocular adverse effects can occur.

Goal is to maintain an IOP at which visual field loss is unlikely to substantially reduce quality of life during the patient's lifetime.

Reduction of pretreatment IOP by ≥25% shown to slow progression of primary open-angle glaucoma. Set an initial target IOP (based on extent of optic nerve damage and/or visual field loss, baseline IOP at which damage occurred, rate of progression, life expectancy, and other considerations) and reduce IOP toward this goal. Adjust target IOP up or down as needed over course of disease.

Combination therapy with drugs from different therapeutic classes often required to control IOP.

Brinzolamide Dosage and Administration

Administration

Ophthalmic Administration

Apply topically to the affected eye(s) as an ophthalmic suspension containing brinzolamide alone or in fixed combination with brimonidine.

Shake suspension well prior to use.

Avoid contamination of the suspension container. (See Bacterial Keratitis under Cautions.)

Ophthalmic suspensions containing brinzolamide alone or in fixed combination with brimonidine contain benzalkonium chloride. Remove contact lenses before administering each dose; may reinsert lenses 15 minutes after the dose. (See Contact Lenses under Cautions.)

Administer other ophthalmic preparations at least 10 minutes apart from brinzolamide ophthalmic suspension and at least 5 minutes apart from brinzolamide and brimonidine ophthalmic suspension.

Dosage

Adults

Ocular Hypertension and Glaucoma

Ophthalmic

Brinzolamide 1% ophthalmic suspension: One drop in the affected eye(s) 3 times daily.

Brinzolamide 1% and brimonidine tartrate 0.2% ophthalmic suspension: One drop in the affected eye(s) 3 times daily.

If target IOP not achieved, may initiate additional or alternative ocular hypotensive agents. (See Ocular Hypertension and Glaucoma under Uses.) Because of potential for additive systemic effects, combined use with an oral carbonic anhydrase inhibitor not recommended.

Cautions for Brinzolamide

Contraindications

• Known hypersensitivity to brinzolamide or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Sulfonamide Sensitivity Reactions

Serious, sometimes fatal, adverse events (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias) associated with sulfonamide therapy are possible. Sensitization may recur when a sulfonamide is readministered, regardless of administration route.

Discontinue brinzolamide if serious reactions or signs or symptoms of hypersensitivity occur.

Use of Fixed Combinations

When used in fixed combination with brimonidine, consider the cautions, precautions, contraindications, and drug interactions associated with each drug in the fixed combination.

Corneal Endothelium

Carbonic anhydrase activity observed in the cytoplasm and around the plasma membranes of the corneal endothelium. Patients with low endothelial cell counts are at increased risk for development of corneal edema. Use with caution in such patients.

Angle-closure Glaucoma

Not studied in patients with acute angle-closure glaucoma, which requires therapeutic interventions in addition to ocular hypotensive agents.

Bacterial Keratitis

Bacterial keratitis reported with use of multiple-dose containers of topical ophthalmic preparations. Containers were inadvertently contaminated by patients, most of whom had concurrent corneal disease or disruption of the ocular epithelial surface.

Improper handling of ophthalmic preparations can result in contamination of the preparation by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic preparations. (See Advice to Patients.)

Contact Lenses

Ophthalmic suspensions containing brinzolamide alone or in fixed combination with brimonidine contain benzalkonium chloride, which may be absorbed by soft contact lenses. Remove contact lenses before administering each dose of these preparations; may reinsert lenses 15 minutes after the dose.

Specific Populations

Pregnancy

Category C.

Crossed placenta and was detected in fetal circulation and tissues in rats. No drug-related malformations or effects on organ or tissue development observed in rats, and reductions in fetal body weight were proportional to reductions in maternal weight gain. In rabbits, slight increase in fetal variations (e.g., accessory skull bones) observed.

No adequate and well-controlled studies in pregnant women. Use only if potential benefits justify possible risk to fetus.

Lactation

Distributed into milk in rats following oral administration; not known whether distributed into human milk following topical application to eye. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established.

A 3-month controlled clinical trial in 32 pediatric patients 4 weeks to 5 years of age failed to demonstrate IOP-lowering efficacy of twice-daily topical brinzolamide 1%; mean decrease in elevated IOP was 0–2 mm Hg. Increase in corneal diameter of 1 mm was observed in 5 patients.

Geriatric Use

No overall differences in safety and efficacy relative to younger adults.

Renal Impairment

Not studied in patients with severe renal impairment (Cl_cr< 30 mL/minute). Not recommended in such patients, since brinzolamide and its metabolite are excreted mainly by the kidneys.

Common Adverse Effects

Blurred vision, taste disturbances (bitter, sour, or unusual taste).

Drug Interactions

Specific Drugs

Brinzolamide Pharmacokinetics

Absorption

Bioavailability

Absorbed into systemic circulation following topical application to eye. However, plasma concentrations of parent drug and N-desethyl metabolite generally are below quantitation limits of assay.

Distribution

Extent

Brinzolamide accumulates in erythrocytes due to carbonic anhydrase-II (CA-II) binding; N-desmethyl metabolite accumulates in erythrocytes due to CA-I binding.

Plasma Protein Binding

60%.

Elimination

Metabolism

Not fully characterized.

Elimination Route

Eliminated mainly in urine as unchanged drug; N-desethylbrinzolamide also recovered in urine along with lower concentrations of N-desmethoxypropyl and O-desmethyl metabolites.

Half-life

Brinzolamide: 111 days in whole blood.

Stability

Storage

Ophthalmic

Suspension

Brinzolamide: 4–30°C.

Brinzolamide and brimonidine: 2–25°C.

Actions

• Can produce mean IOP reductions of about 16–19% in patients with elevated IOP.

• Highly specific inhibitor of CA-II, the main carbonic anhydrase isoenzyme involved in aqueous humor secretion. Inhibition of carbonic anhydrase in the ciliary process of the eye decreases the rate of aqueous humor secretion and IOP by slowing bicarbonate formation and reducing sodium and fluid transport.

• Accumulates in erythrocytes as a result of CA-II binding; however, sufficient CA-II activity remains so that adverse effects resulting from systemic carbonic anhydrase inhibition are not observed.

Advice to Patients

• Risk of adverse effects, including sensitivity reactions; discontinue therapy and consult clinician if serious or unusual ocular or systemic reactions or signs of sensitivity occur.

• Risk of temporary blurring of vision; use caution when driving or operating machinery.

• Importance of learning and adhering to proper administration techniques to avoid contamination of the suspension with common bacteria that can cause ocular infections (e.g., bacterial keratitis). Instruct patients that the tip of the dispensing container should not touch the eye, surrounding structures, or any other surface. Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic preparations. Importance of always replacing the container cap immediately after use and of not using suspensions that are cloudy or discolored or are past the labeled expiration date.

• Advise patients to immediately contact their clinician for advice regarding continued use of the current multidose container if they experience an intercurrent ocular condition (e.g., trauma, infection) or require ocular surgery.

• Importance of shaking the ophthalmic suspension well prior to each use.

• Importance of administering other ophthalmic preparations at least 10 minutes apart from brinzolamide ophthalmic suspension and at least 5 minutes apart from brinzolamide and brimonidine ophthalmic suspension.

• Importance of removing contact lenses prior to administering a dose of brinzolamide ophthalmic suspension or brinzolamide and brimonidine ophthalmic suspension and of delaying reinsertion of the lenses for at least 15 minutes after the dose, since benzalkonium chloride in the preparation may be absorbed by soft contact lenses.

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patient of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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