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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. Last updated on Dec 21, 2020.

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

Ocular Hypertension and Glaucoma

Dorzolamide: Reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension.1 2 3 4 5 6 7 8 9 10

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.32

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.5 7 9 10 Dorzolamide reduced IOP by approximately 3–5 mm Hg in clinical studies.1

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.32

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).130 132 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.130 131

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.130 131 132 134

Goal is to maintain an IOP at which visual field loss is unlikely to substantially reduce quality of life during the patient's lifetime.130 132

Reduction of pretreatment IOP by ≥25% shown to slow progression of primary open-angle glaucoma.130 131 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.130 131 132 Adjust target IOP up or down as needed over course of disease.130 131 132

Combination therapy with drugs from different therapeutic classes often required to control IOP.131 133

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.1 2 3 4 5 6 7 8 9 10 13 14 15 32

Avoid contamination of the solution container.1 (See Bacterial Keratitis under Cautions.)

Dorzolamide ophthalmic solution and some formulations of dorzolamide and timolol ophthalmic solution contain benzalkonium chloride.1 32 Remove contact lenses before administering each dose of these preparations; may reinsert lenses 15 minutes after the dose.1 32 (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.34

If more than one topical ophthalmic preparation is used, administer the preparations at least 5 minutes apart.1 32

Dosage

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

Pediatric Patients

Ocular Hypertension and Glaucoma
Ophthalmic

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

Dorzolamide 2% and timolol 0.5% ophthalmic solution in pediatric patients ≥2 years of age: 1 drop in the affected eye(s) twice daily.32

Adults

Ocular Hypertension and Glaucoma
Ophthalmic

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

Dorzolamide 2% and timolol 0.5% ophthalmic solution: 1 drop in the affected eye(s) twice daily.32

If target IOP not achieved, may initiate additional or alternative ocular hypotensive agents.130 131 133 (See Ocular Hypertension and Glaucoma under Uses.) Because of potential for additive systemic effects, combined use with an oral carbonic anhydrase inhibitor not recommended.1

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations; use with caution.1

Renal Impairment

Not recommended in patients with severe renal impairment (Clcr<30 mL/minute).1 (See Renal Impairment under Cautions.)

Geriatric Patients

Manufacturer makes no specific dosage recommendations.1

Cautions for Dorzolamide

Contraindications

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

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.1 32 Sensitization may recur when a sulfonamide is readministered, regardless of administration route.1

Discontinue dorzolamide if serious reactions or signs or symptoms of hypersensitivity occur.1 32

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.32

Bacterial Keratitis

Bacterial keratitis reported with use of multiple-dose containers of topical ophthalmic solutions.1 Containers were inadvertently contaminated by patients, most of whom had concurrent corneal disease or disruption of the ocular epithelial surface.1

Improper handling of ophthalmic solutions can result in contamination of the solution by common bacteria known to cause ocular infections.1 Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic solutions.1 (See Advice to Patients.)

Corneal Endothelium

Carbonic anhydrase activity observed in the cytoplasm and around the plasma membranes of the corneal endothelium.1 Patients with low endothelial cell counts are at increased risk for development of corneal edema.1 Use with caution in such patients.1

Angle-closure Glaucoma

Management of acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents.1

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.1 32 Remove contact lenses before administering each dose of these preparations; may reinsert lenses 15 minutes after the dose.1 32

Specific Populations

Pregnancy

Category C.1 32 Use only if potential benefits justify possible risks to the fetus.1

Lactation

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

Pediatric Use

Dorzolamide ophthalmic solution: Safety and efficacy in pediatric patients established in a 3-month, double-blind, controlled trial.1

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.32 Safety and efficacy not established in pediatric patients <2 years of age.32

Geriatric Use

No overall differences in safety and efficacy relative to younger adults.1 30 32 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 (Clcr<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, stinging, or discomfort; taste disturbances (bitter, sour, or unusual taste); superficial punctate keratitis; conjunctival hyperemia; blurred vision; ocular pruritus.1 32

Interactions for Dorzolamide

Metabolized by CYP isoenzymes.1 9 10

Specific Drugs

Drug

Interaction

Comments

Carbonic anhydrase inhibitors, oral

Possible additive systemic effects1 32

Concomitant use not recommended1

Salicylates

Rare reports of toxicity associated with acid-base and electrolyte disturbances in patients receiving oral carbonic anhydrase inhibitors with high-dose salicylates1 32

Consider possibility of similar interaction with ophthalmic dorzolamide1 32

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

Preserved dorzolamide and timolol solution: 20–25°C.32 Protect from light.32

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.34 Do not freeze.34

Actions

  • 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 Instruct patients that the tip of the dispensing container should not touch the eye, surrounding structures, or any other surface.1 Serious damage to the eye and subsequent loss of vision may result from using contaminated ophthalmic solutions.1 8 Instruct patients receiving preservative-free formulations to administer the solution immediately after opening the single-use container and then immediately discard any remaining solution.34

  • 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.1 32 34

  • If using more than one topical ophthalmic preparation, importance of administering the preparations at least 5 minutes apart.1 32

  • 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.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.

* 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 2021, Selected Revisions December 21, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Merck & Company. Trusopt (dorzolamide hydrochloride 2%) ophthalmic solution prescribing information. Whitehouse Station; NJ; 2014 Feb.

2. Serle JB. Pharmacological advances in the treatment of glaucoma. Drugs Aging. 1994; 5:156-70. http://www.ncbi.nlm.nih.gov/pubmed/7803944?dopt=AbstractPlus

3. Biollaz J, Munafo A, Buclin T et al. Whole-blood pharmacokinetics and metabolic effects of the topical carbonic anhydrase inhibitor dorzolamide. Eur J Clin Pharmacol. 1995; 47:453-60.

4. Lippa EA, Carlson LE, Ehinger B et al. Dose response and duration of action of dorzolamide, a topical carbonic anhydrase inhibitor. Arch Ophthalmol. 1992; 110:495-99. http://www.ncbi.nlm.nih.gov/pubmed/1562255?dopt=AbstractPlus

5. Anon. A topical carbonic anhydrase inhibitor for glaucoma. Med Lett Drug Ther. 1995; 37:76-7.

6. Wilkerson M, Cyrlin M, Lippa EA et al. Four-week safety and efficacy study of dorzolamide, a novel, active topical carbonic anhydrase inhibitor. Arch Ophthalmol. 1993; 111:1343-50. http://www.ncbi.nlm.nih.gov/pubmed/8216014?dopt=AbstractPlus

7. Strahlman E, Tipping R, Vogel R and the International Dorzolamide Study Group. A double-masked, randomized 1-year study comparing dorzolamide (Trusopt), timolol, and betaxolol. Arch Ophthalmol. 1995; 113:1009-16. http://www.ncbi.nlm.nih.gov/pubmed/7639651?dopt=AbstractPlus

8. Yamazaki Y, Miyamoto S, Sawa M. Effect of MK-507 on aqueous humor dynamics in normal human eyes. Jpn J Ophthalmol. 1994; 38:92-6. http://www.ncbi.nlm.nih.gov/pubmed/7933704?dopt=AbstractPlus

9. Sugrue MF, Harris A, Adamsons I. Dorzolamide hydrochloride a topically active, carbonic anhydrase inhibitor for the treatment of glaucoma. Drugs Today. 1997; 33:283-98.

10. Balfour JA, Wilde MI. Dorzolamide: a review of its pharmacology and therapeutic potential in the management of glaucoma and ocular hypertension. Drugs Aging. 1997; 10:384-403. http://www.ncbi.nlm.nih.gov/pubmed/9143858?dopt=AbstractPlus

11. Heijl A, Strahlman E, Sverrisson T et al. A comparison of dorzolamide and timolol in patients with pseudoexfoliation and glaucoma or ocular hypertension. Ophthalmology. 1997; 104:137-42. http://www.ncbi.nlm.nih.gov/pubmed/9022118?dopt=AbstractPlus

12. Wang RF, Serle JB, Podos SM et al. MK-507 (L-671,152), a topically active carbonic anhydrase inhibitor, reduces aqueous humor production in monkeys. Arch Ophthalmol. 1991; 109:1297-99. http://www.ncbi.nlm.nih.gov/pubmed/1929960?dopt=AbstractPlus

13. Strahlman ER, Vogel R, Tipping R et al et al. The use of dorzolamide and pilocarpine as adjunctive therapy to timolol in patients with elevated intraocular pressure. Ophthalmology. 1996; 103:1283-93. http://www.ncbi.nlm.nih.gov/pubmed/8764800?dopt=AbstractPlus

14. Laibovitz R, Boyle J, Snyder E et al. Dorzoloamide versus pilocarpine as adjunctive therapies to timolol: a comparison of patient preference and impact on daily life. Clin Ther. 1996; 18:821-32. http://www.ncbi.nlm.nih.gov/pubmed/8930426?dopt=AbstractPlus

15. Hartenbaum D. The efficacy of dorzolamide, a topical carbonic anhydrase inhibitor, in combination with timolol in the treatment of patients with open-angle glaucoma and ocular hypertension. Clin Ther. 1996; 18:460-5. http://www.ncbi.nlm.nih.gov/pubmed/8829021?dopt=AbstractPlus

16. Maus TL, Larsson LI, McLaren JW et al. Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow in humans. Arch Ophthalmol. 1997; 115:45-9. http://www.ncbi.nlm.nih.gov/pubmed/9006424?dopt=AbstractPlus

17. Podos SM, Serle JB. Topically active carbonic anhydrase inhibitors for glaucoma. Arch Ophthalmol. 1991; 109:38-40. http://www.ncbi.nlm.nih.gov/pubmed/1987945?dopt=AbstractPlus

18. Derick RJ. Glaucoma therapy: carbonic anhydrase inhibitors. In: Havener WH. Havener’s ocular pharmacology. 6th ed. St. Louis: The CV Mosby Company; 1983:172-80.

19. Harris A, Arend O, Arend S et al. Effects of topical dorzolamide on retinal and retrobulbar hemodynamics. Acta Ophthalmol Scand. 1996; 74:569-72. http://www.ncbi.nlm.nih.gov/pubmed/9017044?dopt=AbstractPlus

20. Maren TH, Conroy CW, Wynns GC et al. Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor. J Ocular Pharmacol Ther. 1997; 13:23-30.

21. Strahlman E, Tipping R, Vogel R et al. A six-week dose-response study of the ocular hypotensive effect of dorzolamide with a one-year extension. Am J Ophthalmol. 1996; 122:183-94. http://www.ncbi.nlm.nih.gov/pubmed/8694086?dopt=AbstractPlus

22. Hasegawa T, Hara K, Hata S. Binding of dorzolamide and its metabolite, n-deethylated dorzolamide, to human erythrocytes in vitro. Drug Metabol Dispos. 1994; 22:377-82.

23. Matuszewski BK, Constanzer ML, Woolf EJ et al. Determination of MK-507, a novel topically effective carbonic anhydrase inhibitor, and its de-ethylated metabolite in human whole blood, plasma, and urine by high-performance liquid chromatography. J Chromatogr. 1994; 653:77-85.

24. Kohlhaas M, Mammen A, Richard G. Change in corneal sensitivity after topical dorzolamide administration: a comparative study. Ophthalmologe. 1997; 94:424-7. http://www.ncbi.nlm.nih.gov/pubmed/9312318?dopt=AbstractPlus

25. Ladas ID, Baltatzis S, Panagiotidis D et al. Topical 2.0% dorzolamide vs oral acetazolamide for prevention of intraocular pressure rise after neodymium: YAG laser posterior capsulotomy. Arch Ophthalmol. 1997; 115:1241-4. http://www.ncbi.nlm.nih.gov/pubmed/9338667?dopt=AbstractPlus

26. Fineman MS, Katz LJ, Wilson RP. Topical dorzolamide-induced hypotony and ciliochoroidal detachment in patients with previous filtration surgery. Arch Ophthalmol. 1996; 114:1031-2. http://www.ncbi.nlm.nih.gov/pubmed/8694722?dopt=AbstractPlus

27. Konowal A, Epstein RJ, Dennis RF et al. Irreversible corneal decompensation in patients treated with topical dorzolamide. Invest Ophthalmol Vis Sci. 1996; 37:S79.

28. Sugrue MF, Mallorga P, Schwam H et al. Preclinical studies on L-671,152, a topically effective ocular hypotensive carbonic anhydrase inhibitor. Br J Pharmacol. 1989; 98(Suppl):820P. http://www.ncbi.nlm.nih.gov/pubmed/2611526?dopt=AbstractPlus

29. Reviewers’ comments (personal observations).

30. Merck, West Point, PA; Personal communication.

31. Kohlhaas H, Mammen A, Richard G. Change in corneal sensitivity after topical dorzolamide administration: a comparative study. Ophthalmology. 1997; 94:424-7.

32. Akorn. Cosopt (dorzolamide hydrochloride 2% and timolol maleate 0.5%) ophthalmic solution prescribing information. Lake Forest, IL; 2018 Jan.

33. Diamond JP. Systemic adverse effects of topical ophthalmic agents: implications for older patients. Drugs Aging. 1997; 11:352-60. http://www.ncbi.nlm.nih.gov/pubmed/9359022?dopt=AbstractPlus

34. Akorn. Cosopt PF (dorzolamide hydrochloride 2% and timolol maleate 0.5%) ophthalmic solution prescribing information. Lake Forest, IL; 2017 Jun.

130. Prum BE Jr, Rosenberg LF, Gedde SJ et al. Primary open-angle glaucoma preferred practice pattern guideline [published corrigendum appears in Ophthalmology. 2018; 125: 949]. San Francisco, CA: American Academy of Ophthalmology; 2015. From the American Academy of Ophthalmology website. https://www.aao.org/preferred-practice-pattern/primary-open-angle-glaucoma-ppp-2015

131. Liebmann JM, Lee JK. Current therapeutic options and treatments in development for the management of primary open-angle glaucoma. Am J Manag Care. 2017; 23(15 Suppl):S279-S292. http://www.ncbi.nlm.nih.gov/pubmed/29164845?dopt=AbstractPlus

132. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014; 311:1901-11. http://www.ncbi.nlm.nih.gov/pubmed/24825645?dopt=AbstractPlus

133. Gupta D, Chen PP. Glaucoma. Am Fam Physician. 2016; 93:668-74. http://www.ncbi.nlm.nih.gov/pubmed/27175839?dopt=AbstractPlus

134. Inoue K. Managing adverse effects of glaucoma medications. Clin Ophthalmol. 2014; 8:903-13. http://www.ncbi.nlm.nih.gov/pubmed/24872675?dopt=AbstractPlus