Mechanism of effect
Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid .
Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure (IOP).
Pharmacodynamic
Dorzolamide HCl Ophthalmic Solution contains Dorzolamide hydrochloride, an inhibitor of human carbonic anhydrase II. Following topical ocular administration, Dorzolamide HCl Ophthalmic Solution reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
Pharmacokinetics
When topically applied, Dorzolamide reaches the systemic circulation. Dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. Dorzolamide binds moderately to plasma proteins (approximately 33%).
Dosage
Usual Adult Dose for Intraocular Hypertension :
One drop in the affected eye(s) three times a day
Usual Adult Dose for Glaucoma (Open Angle) :
One drop in the affected eye(s) three times a day
Usual Pediatric Dose for Intraocular Hypertension :
Safety and effectiveness have been demonstrated in pediatric patients in a 3-month, multicenter, double-masked, active-treatment-controlled trial:
One drop in the affected eye(s) three times a day
Drug Interactions :
Salicylates (eg, aspirin) because the risk of their side effects may be increased by dorzolamide drops
Other carbonic anhydrase inhibitors (eg, acetazolamide, methazolamide) because the risk of their side effects may be increased by dorzolamide drops
Drug contraindications
excessive sensitivity to the drug or its componentAlerts
Dorzolamide HCl Ophthalmic Solution contains Dorzolamide, a sulfonamide; and although administered topically, it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of Dorzolamide HCl Ophthalmic Solution .
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products .
Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. There is an increased potential for developing corneal edema in patients with low endothelial cell counts.In clinical studies, local ocular adverse effects, primarily conjunctivitis and lid reactions, were reported with chronic administration of Dorzolamide HCl Ophthalmic Solution .
Many of these reactions had the clinical appearance and course of an allergic-type reaction that resolved upon discontinuation of drug therapy. The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents .
Points of recommendation
Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you :
• if you are pregnant, planning to become pregnant, or are breast-feeding
• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to any other sulfonamide (sulfa) medicine (eg, sulfamethoxazole)
• if you have kidney or liver problems
• if you have an eye injury or infection, or if you will be having eye surgery
Ask a Pharmacist