Dorzolamide

Pharmacologic Category

Carbonic Anhydrase Inhibitor (Ophthalmic); Ophthalmic Agent, Antiglaucoma

Dosing: Adult

Ocular hypertension/glaucoma (open-angle): Ophthalmic: Instill 1 drop in the affected eye(s) 3 times daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.

CrCl <30 mL/minute: Use is not recommended (has not been studied).

Dorzolamide and its metabolite (N-desethyl: less potent than parent) are excreted renally. Patients with renal impairment, particularly neonates and geriatric patients, should be monitored carefully for untoward effects due to reduced dorzolamide elimination.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (have not been studied); use with caution.

Dosing: Pediatric

Reduction of intraocular pressure:

Monotherapy: Infants, Children, and Adolescents: Ophthalmic: Instill 1 drop to affected eye(s) 3 times daily (Ott 2005; Quaranta 2018).

Combination therapy (with latanoprost): Limited data available: Infants, Children, and Adolescents: Ophthalmic: Instill 1 drop to affected eye(s) 2 times daily (Quaranta 2018).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Renal Impairment: Pediatric

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.

CrCl <30 mL/minute: All patients: Use is not recommended (has not been studied).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Use: Labeled Indications

Ocular hypertension/glaucoma (open-angle): Treatment of elevated intraocular pressure.

* See Uses in AHFS Essentials for additional information.

Class and Related Monographs

Ophthalmic Carbonic Anhydrase Inhibitors

Administration: Ophthalmic

If more than one topical ophthalmic drug is being used, administer the drugs at least 5 minutes apart. Remove contact lens prior to administration and wait 15 minutes before reinserting. Avoid allowing the tip of the dispensing container to contact the eye or surrounding structures. Use eyelid closure or nasolacrimal occlusion when applying topical medications to reduce systemic absorption.

Administration: Pediatric

Ophthalmic: Wash hands before use. Unscrew the cap by turning in the direction of the arrows on top of the cap. Pull lower eyelid down slightly to form a pocket for the eye drop and tilt head back; administer 1 drop. Apply gentle pressure to lacrimal sac immediately following instillation (1 minute) or instruct patient to gently close eyelid after administration to decrease systemic absorption of ophthalmic drops (Urtti 1993; Zimmerman 1984). Avoid contact of bottle tip with skin or eye; ocular solutions can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may occur from using contaminated solutions. Some solutions contain benzalkonium chloride; remove contact lenses prior to administration and wait at least 15 minutes after instillation before reinserting soft contact lenses. If more than one topical ophthalmic drug is being used, separate administration by at least 5 minutes.

Storage/Stability

Store at 15°C to 30°C (59°F to 86°F). Protect from light.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat glaucoma.

• It is used to lower high eye pressure.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Blurred vision

• Burning

• Stinging

• Bad taste

• Dry eyes

• Watery eyes

• Sensitivity to lights

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Vision changes

• Eye pain

• Severe eye irritation

• Swelling of eye or eyelid

• Severe sulfonamide reaction like rash; red, swollen, blistered, or peeling skin; red or irritated eyes; mouth, throat, nose, or eye sores; fever, chills, or sore throat

• Cough that is new or worse

• Loss of strength and energy

• Any bruising or bleeding

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Contraindications

Hypersensitivity to dorzolamide or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Bacterial keratitis: Inadvertent contamination of multiple-dose ophthalmic solutions has caused bacterial keratitis.

• Ocular effects: Local ocular adverse effects (primarily conjunctivitis and lid reactions) were reported with chronic administration; many resolved upon discontinuation of drug therapy. Choroidal detachment has been reported after filtration procedures.

• Sulfonamide (“sulfa”) allergy: Dorzolamide is a sulfonamide; although administered ocularly, systemic absorption may occur and could result in hypersensitivity. Discontinue use if signs of hypersensitivity or a serious reaction occur.

• Systemic effects: Systemic absorption and adverse effects (similar to sulfonamides) including, blood dyscrasias, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias may occur with ophthalmic use.

Disease-related concerns:

• Corneal endothelium: Use with caution in patients with low endothelial cell counts; may be at increased risk of corneal edema.

• Hepatic impairment: Use with caution in patients with hepatic impairment (has not been studied).

• Renal impairment: Use is not recommended in patients with severe renal impairment (CrCl <30 mL/minute) (has not been studied).

Special populations:

• Contact lens wearers: Some products contain benzalkonium chloride which may be absorbed by soft contact lenses; remove lens prior to administration and wait 15 minutes before reinserting.

Other warnings/precautions:

• Appropriate use: Should be used in combination with therapeutic interventions for the treatment of acute angle-closure glaucoma.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Evaluate the patient's or caregiver's ability to safely administer the correct dose of ophthalmic medication.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies following systemic administration. IOP is usually lower during pregnancy. If topical medications for the treatment of glaucoma in pregnant women cannot be discontinued because small increases in IOP cannot be tolerated, the minimum effective dose should be used in combination with punctal occlusion to decrease exposure to the fetus (Johnson, 2001).

Breast-Feeding Considerations

It is not known if dorzolamide is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Briggs' Drugs in Pregnancy & Lactation

• Dorzolamide Ophthalmic

Adverse Reactions

Frequency not always defined.

Dermatologic: Skin rash

Gastrointestinal: Bitter taste (~25% following administration), fatigue, headache, nausea

Genitourinary: Urolithiasis

Hypersensitivity: Local ocular hypersensitivity reaction (~10%)

Neuromuscular & skeletal: Weakness

Ocular: Burning sensation of eyes (~33%), eye discomfort (~33%), stinging of eyes (~33%), superficial punctate keratitis (10% to 15%), blurred vision (1% to 5%), conjunctivitis (1% to 5%), eyelid irritation (1% to 5%), eye redness (1% to 5%), lacrimation (1% to 5%), photophobia (1% to 5%), xerophthalmia (1% to 5%), iridocyclitis

<1%, postmarketing and/or case reports: Angioedema, bronchospasm, choriodal detachment (following filtration procedures), contact dermatitis, crusting of eyelid, dizziness, dyspnea, epistaxis, myopia (transient), ocular pain, paresthesia, pruritus, Stevens-Johnson syndrome, throat irritation, toxic epidermal necrolysis, urticaria, xerostomia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Carbonic Anhydrase Inhibitor Allergy

Metabolism/Transport Effects

Substrate of CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: Monitor therapy

Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Risk X: Avoid combination

Monitoring Parameters

Ophthalmic exams (optic nerve and visual field assessment), serial measurement of intraocular pressure (IOP). Frequency of follow up based upon whether target IOP achieved, if there is any progression of damage, and how long disease has been controlled (AAO 2019).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Ophthalmic:

Trusopt: 2% (10 mL)

Generic: 2% (10 mL)

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Ophthalmic:

Trusopt: 2% (5 mL) [contains benzalkonium chloride]

Trusopt (Preservative Free): 2% (0.2 mL, 5 mL)

Generic: 2% (5 mL, 10 mL)

Anatomic Therapeutic Chemical (ATC) Classification

• S01EC03

Generic Available (US)

Yes

Pricing: US

Solution (Dorzolamide HCl Ophthalmic)

2% (per mL): $4.08 - $6.68

Solution (Trusopt Ophthalmic)

2% (per mL): $9.10

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Reversible inhibition of the enzyme carbonic anhydrase II and IV in the ciliary epithelium resulting in reduction of hydrogen ion secretion at renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water to decrease production of aqueous humor to reduce intraocular pressure.

Pharmacodynamics/Kinetics

Duration of action: 8 to 12 hours

Absorption: Topical: Reaches systemic circulation where it accumulates in RBCs during chronic dosing as a result of binding to CA-II

Distribution: In RBCs during chronic administration

Protein binding: ~33%

Metabolism: To N-desethyl metabolite (less potent than parent drug)

Half-life elimination: Terminal RBC half-life: 147 days; washes out of RBCs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about 4 months

Excretion: Urine (as unchanged drug and metabolite, N-desethyl)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Dorzolamide HCl; Dorzolamide Hydrochloride

FDA Approval Date

December 09, 1994

References

American Academy of Ophthalmology (AAO) PPP Glaucoma Panel, Hoskins Center for Quality Eye Care. Glaucoma summary benchmarks - 2019. https://www.aao.org/summary-benchmark-detail/glaucoma-summary-benchmarks-2019#PrimaryOpen-AngleGlaucoma(InitialEvaluation). Updated October 2019. Accessed December 23, 2019.

Biollaz J, Munafo A, Buclin T, et al, “Whole Blood Pharmacokinetics and Metabolic Affects of the Topical Carbonic Anhydrase Inhibitor Dorzolamide,” Eur J Clin Pharmacol, 1995, 47(5):455-60.[PubMed 7720769]

Carlsen J, Durcan J, Zabriskie N, Swartz M, Crandall A. Nephrolithiasis with dorzolamide. Arch Ophthalmol. 1999;117(8):1087-1088. doi:10.1001/archopht.117.8.1087.[PubMed 10448757]

Douglass R, Heckman G. Drug-related taste disturbance: a contributing factor in geriatric syndromes. Can Fam Physician. 2010;56(11):1142-1147.[PubMed 21075995]

Dorzolamide [prescribing information]. Bridgewater, NJ: Bausch & Lomb, Inc; July 2016

Hoffmanová I, Sánchez D. Metabolic acidosis and anaemia associated with dorzolamide in a patient with impaired renal function. Br J Clin Pharmacol. 2018;84(4):796-799. doi:10.1111/bcp.13499.[PubMed 29333622]

Johnson SM, Martinez M, and Freedman S, "Management of Glaucoma in Pregnancy and Lactation," Surv Ophthalmol, 2001, 45(5):449-54.[PubMed 11274697]

Lee SJ, Kim M. Allergic contact dermatitis caused by dorzolamide eyedrops. Clin Ophthalmol. 2015;9:575-577. doi:10.2147/OPTH.S74555.[PubMed 25897195]

Maren TH, Conroy CW, Wynns GC, Levy NS. Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor. J Ocul Pharmacol Ther. 1997;13(1):23-30. doi:10.1089/jop.1997.13.23.[PubMed 9029437]

Morris S, Geh V, Nischal KK, Sahi S, Ahmed MA. Topical dorzolamide and metabolic acidosis in a neonate. Br J Ophthalmol. 2003;87(8):1052-1053. doi:10.1136/bjo.87.8.1052.[PubMed 12881361]

Ott EZ, Mills MD, Arango S, Getson AJ, Assaid CA, Adamsons IA. A randomized trial assessing dorzolamide in patients with glaucoma who are younger than 6 years. Arch Ophthalmol. 2005;123(9):1177-1186.[PubMed 16157797 ]

Quaranta L, Biagioli E, Riva I, et al. The Glaucoma Italian Pediatric Study (GIPSy): 3-year results. J Glaucoma. 2018;27(10):856-863.[PubMed 30095601]

Trusopt (dorzolamide) [prescribing information]. Whitehouse Station, NJ: Merck and Co, Inc; 2014.

Turgut B, Türkçüoğlu P, Güler M, Akyol N, Celiker U, Demir T. Anosmia as an adverse effect of dorzolamid. Acta Ophthalmol Scand. 2007;85(2):228-229. doi:10.1111/j.1600-0420.2006.00857.x.[PubMed 17305746]

Urtti A, Salminen L. Minimizing systemic absorption of topically administered ophthalmic drugs. Surv Ophthalmol. 1993;37(6):435-456.[PubMed 8100087 ]

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(10):1343-50.[PubMed 8216014]

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Brand Names: International

Apisopt (JO); Biodrop (AR); Bolano (TW); Ciplamide (EG); Citol Dorzo (PY); Dorsamed (UA); Dorsopt (EG); Dorzolam (CO); Dorzox (IN); Drendor-TEC (CR, DO, GT, HN, NI, PA, SV); Lamisopt (SG); Nodom (LV); Oftidor (LV); Piobaj (CR, DO, GT, HN, NI, PA, SV); Sefson (PE); Strigdar (EG); Trusamide (AU); Trusopt (AE, AR, AT, AU, BB, BE, BG, BH, BM, BO, BR, BS, BZ, CH, CL, CO, CR, CY, CZ, DE, DK, DO, EC, EE, EG, FI, FR, GB, GR, GT, GY, HK, HN, HR, HU, IE, IL, IS, IT, JM, JO, KR, KW, LB, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, PL, PR, PT, QA, RO, RU, SA, SE, SG, SI, SK, SR, SV, TH, TR, TT, TW, UY, VE, VN); Xola (AE, KW, QA, SA); Zolichek (SG)

Last Updated 10/9/20