Dorzolamide

Dorzolamide is an antihypertensive agent belonging to Carbonic Anhydrase Inhibitor.

Dorzolamide is a carbonic anhydrase inhibitor used to treat high intraocular pressure in ocular hypertension and open-angle glaucoma.

When topically applied, dorzolamide reaches the systemic circulation where it accumulates in RBCs during chronic dosing as a result of binding to CA-II. The time to peak plasma concentration and Duration of Action of Dorzolamide was found to be approximately 2 hours. and 8-12 hours respectively. It is distributed in RBCs during chronic administration and approximately 33% bound to plasma proteins. In the Liver, Dorzolamide is slowly metabolized to N-desethyldorzolamide, which has a less potent pharmacological activity on CA-II and some inhibitory effect on CA-I. 80% unchanged drug and metabolite, N-desethyl is excreted in the urine.

Dorzolamide shows common side effects like burning or stinging sensation in the eye, mild eye discomfort, bitterness in the mouth, etc.

Dorzolamide is available in the form of an Ophthalmic solution.

Dorzolamide is available in India, the US, the UK, Canada, Europe, China, Italy, the Philippines, Japan, and Australia.

Dorzolamide belonging to the Carbonic Anhydrase Inhibitor acts as an antihypertensive agent.

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. Dorzolamide Reversible inhibits the enzyme carbonic anhydrase II and IV in the ciliary epithelium resulting in the reduction of hydrogen ion secretion at the renal tubule and increased renal excretion of sodium, potassium, bicarbonate, and water to reduce the production of aqueous humor to reduce intraocular pressure.

The onset of action of Dorzolamide occurs within 1-2 hours.

The Duration of Action for Dorzolamide in the body is approximately 8-12 hours.

The Tmax was found within 2 hours following the administration of Dorzolamide.

Dorzolamide is available in the form of an Ophthalmic solution.

Ophthalmic dorzolamide comes as a solution (liquid) to instill in the eye. Dorzolamide eye drops are usually instilled in one drop three times a day.

Dorzolamide is a carbonic anhydrase inhibitor used to treat high intraocular pressure in ocular hypertension and open-angle glaucoma. It works by reducing the pressure in the eye.

Dorzolamide is an antihypertensive agent belonging to Carbonic Anhydrase Inhibitor.

Dorzolamide decreases the secretion of hydrogen ions at the renal tubule and increases the excretion of bicarbonate, potassium, sodium, and water, which in turn reduces aqueous humor secretion.

Dorzolamide is approved for use in the following clinical indications

• Intraocular Hypertension

Dorzolamide is indicated for the management of elevated intraocular pressure in patients with ocular hypertension.

• Intraocular Hypertension or open-angle glaucoma

Dorzolamide is used for the management of open-angle glaucoma.

• Intraocular hypertension

Adult

Ophthalmic: Instill one drop in the affected eye(s) 3 times daily.

Pediatric

Ophthalmic: Instill 1 drop to the affected eye(s) 3 times daily

• Glaucoma (open-angle)

Adult

Ophthalmic: Instill 1 drop in the affected eye 3 times daily.

Pediatric

Ophthalmic: Instill 1 drop to the affected eye(s) 3 times daily

No information is available.

Dorzolamide is contraindicated in patients with

• Hypersensitivity to any component of the product; contains benzalkonium chloride as a preservative.
• Severe renal impairment (CrCl<30 mL/min)

• 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) include, blood dyscrasias, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias may occur with ophthalmic use.

• 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).

• Contact lens wearers

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

No information is available.

There are no adequate studies on women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant the use of the drug in pregnant women despite potential risks. This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.

No information is available.

Common Adverse effects

• Ocular burning, stinging, discomfort
• Bitter taste
• Superficial punctate keratitis
• Ocular allergic reactions

Rare Adverse effects

• Blurred vision
• Ocular dryness
• Photophobia
• Ocular redness
• Tearing
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Angioedema
• Bronchospasm
• Dyspnea
• Epistaxis

• Oral Carbonic Anhydrase Inhibitors

There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and Dorzolamide. The concomitant administration of Dorzolamide and oral carbonic anhydrase inhibitors is not recommended.

• High-Dose Salicylate Therapy

Although acid-base and electrolyte disturbances were not reported in the clinical trials with dorzolamide hydrochloride ophthalmic solution, these disturbances have been reported with oral carbonic anhydrase inhibitors and have, in some instances, resulted in drug interactions (e.g., toxicity associated with high-dose salicylate therapy). Therefore, the potential for such drug interactions should be considered in patients receiving Dorzolamide.

• Alpha-/Beta-Agonists (Indirect-Acting)

Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting).

• Amantadine

Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine.

The common side effects of Dorzolamide includes the following

Common

• Burning, stinging, or discomfort when the medicine is applied
• itching, redness, swelling, or other sign of eye or eyelid irritation

Less common

• Burning, dry, or itching eyes
• discharge from the eye
• excessive tearing
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

Rare

• Blood in the urine
• Blurred vision
• Nausea or vomiting
• Pain in the side, back, or abdomen
• Skin rash
• Tearing

• Pregnancy

Pregnancy Teratogenic Effects. Pregnancy Category C.

Developmental toxicity studies with dorzolamide hydrochloride in rabbits at oral doses of ≥ 2.5 mg/kg/day (31 times the recommended human ophthalmic dose) revealed malformations of the vertebral bodies. These malformations occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased fetal weights. No treatment-related malformations were seen at 1.0 mg/kg/day (13 times the recommended human ophthalmic dose). There are no adequate and well-controlled studies on pregnant women. Dorzolamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Dorzolamide a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• Pediatric Use

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of dorzolamide eye drops in children.

• Geriatric Use

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of dorzolamide eye drops in the elderly.

Electrolyte imbalance, development of an acidotic state, and possible central nervous system effects may occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.

Pharmacodynamic

Dorzolamide is a carbonic anhydrase inhibitor that reduces elevated intraocular pressure in open-angle glaucoma or ocular hypertension. When used in combination with topical beta-adrenergic antagonists, dorzolamide has an additive effect of lowering intraocular pressure. The peak ocular hypotensive effect of dorzolamide is observed at about 2 hours following ophthalmic administration.

Pharmacokinetics

• Absorption

When topically applied, dorzolamide reaches the systemic circulation where it accumulates in RBCs during chronic dosing as a result of binding to CA-II. The time to peak plasma concentration of Dorzolamide was found to be approximately 2 hours. The Duration of Action for Dorzolamide in the body is approximately 8-12 hours.

• Distribution

It is distributed in RBCs during chronic administration. Dorzolamide is approximately 33% bound to plasma proteins.

• Metabolism and Excretion

In the Liver, Dorzolamide is slowly metabolized to N-desethyldorzolamide, which has a less potent pharmacological activity on CA-II and some inhibitory effect on CA-I. Like the parent drug, N-desethyldorzolamide is also stored in RBCs, where it binds to CA-I. 80% unchanged drug and metabolite, N-desethyl is excreted in the urine.

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• https://reference.medscape.com/drug/trusopt-dorzolamide343604#:~:text=USES: Dorzolamide is used to,of fluid within the eye.

• https://www.uptodate.com/contents/dorzolamide-drug-information?search=dorzolamide&source=panel_search_result&selectedTitle=1~8&usage_type=panel&kp_tab=drug_general&display_rank=1#F162720