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Dorzolamide

Class: Carbonic Anhydrase Inhibitors
ATC Class: S01EC03
Chemical Name: (4S,6S)-4-(Ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide monohydrochloride
Molecular Formula: C10H16N2O4S3•HCl
CAS Number: 130693-82-2
Brands: Trusopt

Medically reviewed by Drugs.com on Dec 21, 2020. Written by ASHP.

Introduction

Carbonic anhydrase inhibitor; nonbacteriostatic sulfonamide derivative.

Uses for Dorzolamide

Ocular Hypertension and Glaucoma

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

Fixed-combination dorzolamide and timolol: Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension who have not responded adequately (i.e., failed to achieve target IOP as determined after multiple measurements over time) to a topical β-adrenergic blocking agent.

Efficacy of dorzolamide 2% administered 3 times daily comparable to that of betaxolol 0.5% administered twice daily in reducing elevated IOP but less than that of timolol 0.5% administered twice daily. Dorzolamide reduced IOP by approximately 3–5 mm Hg in clinical studies.

Fixed-combination dorzolamide 2% and timolol 0.5%: When administered twice daily, IOP-lowering effect was 1–3 mm Hg greater than that of dorzolamide 2% administered 3 times daily or timolol 0.5% administered twice daily and approximately 1 mm Hg less than that achieved with concurrent use of dorzolamide 2% administered 3 times daily and timolol 0.5% administered twice daily.

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.

Dorzolamide Dosage and Administration

Administration

Ophthalmic Administration

Apply topically to the affected eye(s) as an ophthalmic solution containing dorzolamide alone or in fixed combination with timolol.

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

Dorzolamide ophthalmic solution and some formulations of dorzolamide and timolol ophthalmic solution contain benzalkonium chloride. Remove contact lenses before administering each dose of these preparations; may reinsert lenses 15 minutes after the dose. (See Contact Lenses under Cautions.)

Administer preservative-free dorzolamide and timolol ophthalmic solution topically to one or both eyes immediately after opening the container, then immediately discard any solution remaining in the opened single-use container.

If more than one topical ophthalmic preparation is used, administer the preparations at least 5 minutes apart.

Dosage

Available as dorzolamide hydrochloride; dosage expressed in terms of dorzolamide.

Pediatric Patients

Ocular Hypertension and Glaucoma
Ophthalmic

Dorzolamide 2% ophthalmic solution in pediatric patients: 1 drop in the affected eye(s) 3 times daily.

Dorzolamide 2% and timolol 0.5% ophthalmic solution in pediatric patients ≥2 years of age: 1 drop in the affected eye(s) twice daily.

Adults

Ocular Hypertension and Glaucoma
Ophthalmic

Dorzolamide 2% ophthalmic solution: 1 drop in the affected eye(s) 3 times daily.

Dorzolamide 2% and timolol 0.5% ophthalmic solution: 1 drop in the affected eye(s) twice 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.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations; use with caution.

Renal Impairment

Not recommended in patients with severe renal impairment (Clcr<30 mL/minute). (See Renal Impairment under Cautions.)

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Dorzolamide

Contraindications

  • Known hypersensitivity to dorzolamide or any ingredient in the formulation (e.g., benzalkonium chloride).

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 dorzolamide if serious reactions or signs or symptoms of hypersensitivity occur.

Use of Fixed Combinations

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

Bacterial Keratitis

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

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

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

Management of acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents.

Contact Lenses

Dorzolamide ophthalmic solution and some formulations of dorzolamide and timolol ophthalmic solution 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. Use only if potential benefits justify possible risks to the fetus.

Lactation

Not known whether distributed into human milk following topical application to eye. Discontinue nursing or the drug.

Pediatric Use

Dorzolamide ophthalmic solution: Safety and efficacy in pediatric patients established in a 3-month, double-blind, controlled trial.

Dorzolamide and timolol ophthalmic solution: Safety and efficacy of the drugs (administered individually) established in pediatric patients ≥2 years of age; use of these drugs in this age group supported by evidence from adequate and well-controlled studies in children and adults. Safety and efficacy not established in pediatric patients <2 years of age.

Geriatric Use

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

Hepatic Impairment

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

Renal Impairment

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

Common Adverse Effects

Ocular burning, stinging, or discomfort; taste disturbances (bitter, sour, or unusual taste); superficial punctate keratitis; conjunctival hyperemia; blurred vision; ocular pruritus.

Interactions for Dorzolamide

Metabolized by CYP isoenzymes.

Specific Drugs

Drug

Interaction

Comments

Carbonic anhydrase inhibitors, oral

Possible additive systemic effects

Concomitant use not recommended

Salicylates

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

Consider possibility of similar interaction with ophthalmic dorzolamide

Dorzolamide Pharmacokinetics

Absorption

Bioavailability

Peak concentrations in cornea, iris/ciliary body, and aqueous humor achieved within 1–2 hours following ocular instillation in rabbits.

Some systemic absorption may occur; low potential for causing systemic effects.

Onset

Reduction in IOP generally peaks within 2–3 hours after topical administration.

Duration

Reduction in IOP persists for 8 hours or longer.

Distribution

Extent

Distributed into cornea, aqueous humor, iris/ciliary body, and retina following ocular instillation in rabbits.

Approximately 19% bound to ocular pigment (isolated from bovine iris/ciliary body).

Systemically absorbed dorzolamide is preferentially distributed into erythrocytes.

Not known whether dorzolamide crosses the placenta or is distributed into human milk.

Plasma Protein Binding

Approximately 33%.

Elimination

Metabolism

Metabolized in liver by CYP isoenzymes to N-desethyldorzolamide (active).

Elimination Route

Excreted in urine, principally (about 80%) as unchanged drug.

Half-life

Nonlinear elimination from erythrocytes. Initial elimination half-life is rapid; terminal elimination half-life is 120 days.

Stability

Storage

Ophthalmic

Solution

Dorzolamide solution: 15–30°C. Protect from light.

Preserved dorzolamide and timolol solution: 20–25°C. Protect from light.

Preservative-free dorzolamide and timolol solution: 20–25°C in the original foil pouch for protection from light; discard any unused containers 15 days after first opening the pouch. Do not freeze.

Actions

  • Ocular hypotensive agent; can produce mean IOP reductions of about 17–23% 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.

  • Tolerance does not occur; reduction in mean IOP maintained over at least 12 months after initial stabilization.

  • Accumulates in erythrocytes after long-term topical administration 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 (e.g., conjunctivitis, lid reactions) or signs of sensitivity occur.

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the solution 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 solutions. Instruct patients receiving preservative-free formulations to administer the solution immediately after opening the single-use container and then immediately discard any remaining solution.

  • Advise patients to immediately contact their clinician for advice regarding continued use if they experience an intercurrent ocular condition (e.g., trauma, infection) or ocular reaction (particularly conjunctivitis and lid reactions) or require ocular surgery.

  • If using more than one topical ophthalmic preparation, importance of administering the preparations at least 5 minutes apart.

  • Importance of removing contact lenses prior to administering a dose of dorzolamide ophthalmic suspension or preserved dorzolamide and timolol 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.

  • 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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Dorzolamide Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

2% (of dorzolamide)*

Dorzolamide Hydrochloride Ophthalmic Solution

Trusopt

Merck

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Dorzolamide Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

2% (of dorzolamide) with Timolol Maleate 0.5% (of timolol)*

Cosopt

Akorn

Cosopt PF

Akorn

Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution

Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution Preservative Free

AHFS DI Essentials™. © Copyright 2022, Selected Revisions December 21, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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