Brinzolamide

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
Brands: Azopt

Introduction

Carbonic anhydrase inhibitor;2 4 6 nonbacteriostatic sulfonamide derivative.1

Uses for Brinzolamide

Ocular Hypertension and Glaucoma

Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.1 3 4 5 6 8

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Efficacy comparable to that of dorzolamide in reducing IOP in patients with open-angle glaucoma or ocular hypertension;1 3 6 8 less effective than timolol.5

Safety and efficacy not established for the treatment of acute angle-closure glaucoma.1

Brinzolamide Dosage and Administration

Administration

For topical ophthalmic use only.1 Not for injection or oral use.1

Ophthalmic Administration

Apply topically to the affected eye(s) as an ophthalmic suspension.1

Shake suspension well prior to use.1

Avoid contamination of the suspension container.1

If more than one topical ophthalmic drug is used, administer the drugs at least 10 minutes apart.1

Dosage

Adults

Ocular Hypertension and Glaucoma
Ophthalmic

One drop of a 1% suspension in the affected eye(s) 3 times daily.1

Cautions for Brinzolamide

Contraindications

  • Known hypersensitivity to brinzolamide or any ingredient in the formulation.1

Warnings/Precautions

Sensitivity Reactions

Sulfonamide Sensitivity Reactions

Serious adverse events (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, other blood dyscrasias) associated with sulfonamide therapy possible.1

Usual precautions associated with systemic use of sulfonamides apply.1 Discontinue brinzolamide if serious reactions or signs or symptoms of hypersensitivity occur.1

General Precautions

Ocular Effects

Effect on corneal endothelium not fully evaluated.1

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats following oral administration; not known whether distributed into human milk following topical application to eye.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1 9

Geriatric Use

No overall differences in safety and efficacy relative to younger adults.1

Hepatic Impairment

Not studied in patients with hepatic impairment; use with caution.1

Renal Impairment

Not studied in patients with severe renal impairment (Clcr< 30 mL/minute).1 Not recommended in such patients, since brinzolamide and its metabolite are excreted mainly by the kidneys.1

Common Adverse Effects

Blurred vision, taste disturbances (bitter, sour, or unusual taste).1

Interactions for Brinzolamide

Specific Drugs

Drug

Interaction

Comments

Carbonic anhydrase inhibitors, oral

Additive systemic effects1

Concomitant use not recommended1

Ocular hypotensive agents

Additive IOP-lowering effects1

Used to therapeutic advantage1

Salicylates

Rare reports of toxicity associated with acid-base disturbances in patients receiving oral carbonic anhydrase inhibitors with high-dose salicylates1

Consider possibility of similar interaction with ophthalmic brinzolamide1

Brinzolamide Pharmacokinetics

Absorption

Bioavailability

Absorbed into systemic circulation following topical application to eye.1

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.1

Plasma Protein Binding

60%.1

Elimination

Metabolism

Not fully characterized.1

Elimination Route

Brinzolamide and N-desmethyl brinzolamide are eliminated in urine.1

Half-life

Brinzolamide: 111 days in whole blood.1

Stability

Storage

Ophthalmic

Suspension

4–30°C.1

Actions

  • Potent ocular hypotensive agent; can produce mean IOP reductions of about 16–19% in patients with elevated IOP.1 3 8

  • Highly specific inhibitor of CA-II, the main carbonic anhydrase isoenzyme involved in aqueous humor secretion.1 2 3 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.1 2

  • 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.1 5

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.1

  • Risk of temporary blurring of vision; use caution when driving or operating machinery.1

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the product.1

  • Importance of informing clinicians if an intercurrent ocular condition (e.g., trauma, infection) develops or ocular surgery is planned.1

  • Importance of administering different topical ophthalmic preparations at least 10 minutes apart.1

  • Importance of removing soft contact lenses prior to administering the drug and of delaying reinsertion of the lenses for at least 15 minutes after administration.1

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patient of other important precautionary information.1 (See Cautions.)

Preparations

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

Brinzolamide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Suspension

1%

Azopt (with benzalkonium chloride)

Alcon

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Azopt 1% Suspension (ALCON VISION): 10/$127.19 or 30/$357.19

Azopt 1% Suspension (ALCON VISION): 15/$172.99 or 45/$492.96

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Alcon. Azopt (brinzolamide) ophthalmic suspension 1% prescribing information. Fort Worth, TX; 2003 Dec.

2. DeSantis L. Preclinical overview of brinzolamide. Surv Ophthalmol. 2000; 44(Suppl 2):119-29.

3. Silver LH and the Brinzolamide Primary Therapy Study Group. Clinical efficacy and safety of brinzolamide (Azopt), a new topical carbonic anhydrase inhibitor for primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol. 1998; 126:400-8. [IDIS 414483] [PubMed 9744373]

4. Shin D and the Brinzolamide Adjunctive Therapy Study Group. Adjunctive therapy with brinzolamide 1% ophthalmic suspension (Azopt) in patients with open-angle glaucoma or ocular hypertension maintained on timolol therapy. Surv Ophthalmol. 2000; 44(Suppl 2):163-8.

5. March WF, Ochsner KI and the Brinzolamide Long-Term Therapy Study Group. The long-term safety and efficacy of brinzolamide 1.0% (Azopt) in patients with primary open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2000; 129:136-43. [IDIS 442914] [PubMed 10682964]

6. Anon. Brinzolamide-a new topical carbonic anhydrase inhibitor for glaucoma. Med Lett Drugs Ther. 1998; 40:95-6. [PubMed 9774966]

7. Ingram CJ, Brubaker RF. Effect of brinzolamide and dorzolamide on aqueous humor flow in human eyes. Am J Ophthalmol. 1999; 128:292-6. [IDIS 435005] [PubMed 10511022]

8. Sall K and the Brinzolamide Primary Therapy Study Group. The efficacy and safety of brinzolamide 1% ophthalmic suspension (Azopt) as a primary therapy in patients with open-angle glaucoma or ocular hypertension. Surv Ophthalmol. 2000; 44(Suppl 2):155-62.

9. Alcon, Fort Worth, TX: Personal communication.

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