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 on Jul 2, 2018

Introduction

Carbonic anhydrase inhibitor;^{1 2 3 4 5 6 7 8 9 10} nonbacteriostatic sulfonamide derivative.^{1 2 3 4 5 6 7 8 9}

Uses for Dorzolamide Hydrochloride

Ocular Hypertension and Glaucoma

Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.^{1 2 3 4 5 6 7 8 9 10}

Fixed-combination preparation containing dorzolamide and timolol (Cosopt) used topically to reduce 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.³² Fixed-combination preparation associated with slightly smaller decrease in IOP than combination therapy with dorzolamide (administered 3 times daily) and timolol (administered twice daily).³²

A first-line “add-on” agent when more than one drug is needed.⁵ Add-on therapy with dorzolamide to existing timolol therapy is as effective and better tolerated than add-on therapy with pilocarpine.¹⁴

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

Inhibition of Perioperative IOP Increases

Used prophylactically before neodymium yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy†.²⁵

Administration of 1 drop (20 µL) of dorzolamide 2% 1 hour prior to capsulotomy is more effective in preventing postoperative increases in IOP than placebo and as effective as oral acetazolamide 125 mg administered 1 hour prior to the procedure.²⁵

Dorzolamide Hydrochloride Dosage and Administration

Administration

Ophthalmic Administration

Apply topically to the affected eye(s) as an ophthalmic solution.^{1 2 3 4 5 6 7 8 9 10 13 14 15}

Avoid contamination of the solution container.¹

Remove soft contact lenses prior to administration of each dose (since benzalkonium chloride preservative may be absorbed by the lenses); may reinsert lenses 15 minutes after administration.^{1 32}

If more than one topical ophthalmic drug is used, administer the drugs at least 10 minutes apart.^{1 32}

Dosage

Available as dorzolamide hydrochloride; dosage expressed in terms of dorzolamide.^{1 32}

Adults

Ocular Hypertension and Glaucoma

Ophthalmic

Dorzolamide 2% solution: 1 drop in the affected eye(s) 3 times daily.^{1 2 5 6 7 9 10}

Fixed-combination with timolol: 1 drop in the affected eye(s) twice daily.³²

Cautions for Dorzolamide Hydrochloride

Contraindications

• Known hypersensitivity to dorzolamide or any ingredient in the formulations (e.g., benzalkonium chloride).^{1 32}

• Fixed-combination preparation with timolol also contraindicated in patients with bronchial asthma or a history of bronchial asthma and in patients with severe chronic obstructive pulmonary disease, sinus bradycardia, atrioventricular block greater than first degree, overt cardiac failure, or cardiogenic shock.³²

Warnings/Precautions

Warnings

Timolol Component

When using fixed-combination preparation containing timolol maleate, consider the warnings, cautions, precautions, and contraindications associated with timolol.³²

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 32}

Usual precautions associated with systemic use of sulfonamides apply.^{1 32} Discontinue dorzolamide if serious reactions or signs or symptoms of hypersensitivity occur.^{1 32}

Major Toxicities

Ocular Effects

Conjunctivitis or lid reactions reported with long-term therapy;^{1 32} may resolve upon discontinuance of therapy.^{1 32} If these reactions occur, discontinue therapy and evaluate patient before restarting dorzolamide (since a more serious allergic-type reaction may occur).^{1 29 32}

Choroidal detachment reported with administration of aqueous suppressant therapy (e.g., dorzolamide, timolol) following filtration procedures.^{1 32 a}

Specific Populations

Pregnancy

Category C.^{1 32}

Lactation

Not known whether distributed into human milk following topical application to eye.^{1 32} Discontinue nursing or the drug.^{1 32}

Pediatric Use

Safety and efficacy not established.^{1 9}

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults,^{1 30 32 33} but increased sensitivity cannot be ruled out.^{30 33}

Hepatic Impairment

Not studied in patients with hepatic impairment; use with caution.^{1 32}

Renal Impairment

Not studied in patients with severe renal impairment (Cl_cr<30 mL/minute).^{1 32} Not recommended in such patients, since dorzolamide and its metabolite are excreted mainly by the kidneys.¹

Common Adverse Effects

Ocular burning or stinging, taste disturbances (bitter, sour, or unusual taste), superficial punctate keratitis, conjunctival hyperemia, blurred vision, ocular itching.^{1 32}

Interactions for Dorzolamide Hydrochloride

When using fixed-combination preparation containing timolol maleate, consider the drug interactions associated with timolol.³²

Dorzolamide is metabolized by CYP isoenzymes.^{1 9 10}

Specific Drugs

Dorzolamide Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Peak concentrations in cornea, iris/ciliary body, and aqueous humor achieved within 1–2 hours following ocular instillation in rabbits.^{9 10}

Some systemic absorption may occur; low potential for causing systemic effects.^{1 3 6 9 10 21}

Onset

Reduction in IOP generally peaks within 2–3 hours after topical administration.^{4 6 8 10}

Duration

Reduction in IOP persists for 8 hours or longer.^{4 6 8 10}

Distribution

Extent

Distributed into cornea, aqueous humor, iris/ciliary body, and retina following ocular instillation in rabbits.^{9 10}

Approximately 19% bound to ocular pigment (isolated from bovine iris/ciliary body).⁹

Systemically absorbed dorzolamide is preferentially distributed into erythrocytes.^{1 3 9 10 20}

Not known whether dorzolamide crosses the placenta or is distributed into human milk.¹

Plasma Protein Binding

Approximately 33%.^{1 10 32}

Elimination

Metabolism

Metabolized in liver by cytochrome P-450 isoenzymes to N-desethyldorzolamide (active).^{1 9 10}

Elimination Route

Excreted in urine, principally (about 80%) as unchanged drug.^{1 10 20}

Half-life

Nonlinear elimination from erythrocytes.^{1 32} Initial elimination half-life is rapid; terminal elimination half-life is 120 days.^{1 3 10}

Stability

Storage

Ophthalmic

Solution

Dorzolamide 2% solution: 15–30°C.¹ Protect from light.¹

Fixed-combination preparation: 15–25°C.³² Protect from light.³²

Actions

• Potent ocular hypotensive agent;^{1 2 3 4 5 6 7 8 9 10} can produce mean IOP reductions of about 17–23% in patients with elevated IOP.^{1 4 5 7}

• Highly specific inhibitor of CA-II, the main carbonic anhydrase isoenzyme involved in aqueous humor secretion.^{1 3 4 9 10 15}

  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 9 10 18}

• Tolerance does not occur; reduction in mean IOP maintained over at least 12 months after initial stabilization.^{7 30}

• 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.^{1 9 21}

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.^{1 32}

• 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).^{1 32} Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic solutions.^{1 8}

• Importance of informing clinicians if an intercurrent ocular condition (e.g., trauma, infection) develops or ocular surgery is planned.^{1 32}

• Importance of administering different topical ophthalmic preparations at least 10 minutes apart.^{1 32}

• 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 32}

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 32}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 32}

• Importance of informing patient of other important precautionary information.^{1 32} (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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