Cozopt2%+0.5%

Cozopt is a fixed-dose topical ophthalmic combination approved for the following use:

Established/FDA-approved use

• Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blocker monotherapy and who, in the physician's judgment, require the additional IOP-lowering effect of a carbonic anhydrase inhibitor (i.e., patients who need combination therapy with both a topical beta-blocker and a topical carbonic anhydrase inhibitor).

Cozopt is not intended as first-line, single-agent therapy for patients who have not already been tried on other topical IOP-lowering agents; it is a combination product for patients already requiring multi-drug topical therapy.

Each mL of Dorzolamide + Timolol sterile ophthalmic solution contains Dorzolamide (as dorzolamide hydrochloride) 20 mg (2% w/v) and Timolol (as timolol maleate) 5 mg (0.5% w/v), along with benzalkonium chloride as preservative and other inactive ingredients.

Cozopt is a sterile, fixed-dose ophthalmic solution combining a carbonic anhydrase inhibitor (dorzolamide) with a non-selective beta-adrenergic blocking agent (timolol). It is used topically in the eye to reduce elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who require therapy with both drug classes. By combining two complementary mechanisms of aqueous humor suppression into a single drop, Cozopt simplifies dosing compared with using the two agents separately.

Cozopt belongs to the therapeutic class of fixed-dose anti-glaucoma / ocular hypotensive combinations, combining a topical carbonic anhydrase inhibitor with a non-selective beta-adrenergic blocking agent.

Dorzolamide + Timolol lowers intraocular pressure (IOP) through two complementary mechanisms that both reduce the rate of aqueous humor formation in the ciliary body, without a significant additive effect on outflow.

• Dorzolamide is a potent inhibitor of carbonic anhydrase II in the ciliary processes of the eye. By inhibiting this enzyme, it decreases bicarbonate ion formation and subsequently reduces sodium and fluid transport, thereby decreasing aqueous humor secretion and lowering IOP.
• Timolol is a non-selective beta-1/beta-2 adrenergic receptor blocking agent that reduces elevated as well as normal IOP, primarily by decreasing aqueous humor production, likely by blocking endogenous catecholamine (beta-adrenergic) stimulation of ciliary epithelium.

The onset of IOP-lowering effect with Dorzolamide + Timolol is seen within about an hour, with maximal effect typically achieved within 2 hours.

Cozopt is for topical ophthalmic use only (in the eye), not for injection or oral use.

• Wash hands before use.
• Tilt the head back, pull down the lower eyelid to form a small pocket, and instill one drop into the pocket without letting the dropper tip touch the eye or eyelid.
• Close the eye gently and apply pressure over the tear duct (nasolacrimal occlusion) for 1–2 minutes to reduce drainage into the nose and throat; this reduces systemic absorption and systemic side effects.
• If the patient wears contact lenses, they should be removed before instillation (due to the benzalkonium chloride preservative) and may be reinserted 15 minutes later.
• If a dose is missed, use it as soon as remembered unless it is almost time for the next dose; do not double the dose.

Cozopt has the following clinically significant interactions, mainly related to its timolol component:

• Oral beta-blockers: Concomitant use with oral beta-adrenergic blocking agents may produce additive effects on IOP and on systemic beta-blockade (e.g., additive bradycardia, hypotension); patients should be monitored closely.
• Oral carbonic anhydrase inhibitors: Concomitant use with oral carbonic anhydrase inhibitors along with Cozopt is not recommended due to the potential for additive systemic carbonic anhydrase inhibition and increased risk of adverse effects.
• Calcium channel blockers: Co-administration with oral or intravenous calcium channel blockers may result in additive effects on AV conduction and left ventricular function, potentially causing atrioventricular conduction disturbances, left ventricular failure, and hypotension.
• Catecholamine-depleting drugs (e.g., reserpine): May cause additive effects with timolol, resulting in hypotension and/or marked bradycardia.
• Digitalis glycosides: Both digitalis glycosides and timolol may have additive effects in prolonging atrioventricular conduction time.
• CYP2D6 inhibitors (e.g., quinidine): May increase systemic beta-blockade (e.g., decreased heart rate) due to reduced timolol metabolism.
• Epinephrine: Concomitant use has occasionally been associated with mydriasis (pupil dilation).

Adverse effects reported with Cozopt are mostly local/ocular; systemic effects can occur due to absorption of the timolol component.

Common

• Ocular burning and stinging on instillation
• Bitter taste in the mouth
• Superficial punctate keratitis
• Blurred vision
• Conjunctival hyperemia (eye redness)
• Ocular itching, tearing, or dryness

Less common/serious

• Corneal erosion or corneal edema
• Headache
• Iridocyclitis
• Systemic beta-blockade effects: bradycardia, hypotension, bronchospasm, fatigue, dizziness
• Rare hypersensitivity reactions including angioedema, urticaria, and, rarely, Stevens-Johnson syndrome (sulfonamide-related)

There are no adequate and well-controlled studies of Cozopt in pregnant women. Cozopt should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus, and only under direct medical supervision.

Cozopt should be used with caution in nursing mothers, as it is not known whether topical ophthalmic dorzolamide or timolol is excreted in human milk in clinically significant amounts; systemically administered beta-blockers do appear in breast milk. A physician should be consulted before use during breastfeeding, and the infant should be monitored for signs of beta-blockade if the mother uses this medicine.

The following precautions apply to Cozopt, largely reflecting the possibility of systemic absorption even with topical ocular use:

• Cardiac and respiratory disease: Although administered topically, timolol can be absorbed systemically and produce the same adverse cardiac and pulmonary reactions seen with systemic beta-blockers (see Contraindications for absolute restrictions); use with caution in patients with compensated cardiac failure, marked cardiac conduction abnormalities short of complete block, or a history of bronchospastic disease other than the contraindicated conditions.
• Diabetes mellitus: Use with caution in patients with diabetes, particularly those with labile glucose control, as beta-blockade may mask signs and symptoms of acute hypoglycemia (e.g., tachycardia).
• Thyroid disease: Beta-blockade may mask certain clinical signs of hyperthyroidism (e.g., tachycardia); abrupt withdrawal may precipitate thyroid storm in susceptible patients.
• Corneal endothelial disease: Dorzolamide should be used with caution in patients with low endothelial cell counts, as it may adversely affect the corneal endothelium and increase the risk of corneal edema.
• Sulfonamide hypersensitivity: Because dorzolamide is a sulfonamide, systemic side effects associated with oral carbonic anhydrase inhibitors (including serious sulfonamide reactions) may occur even with topical ophthalmic use.
• Anaphylactic reactions: Patients taking beta-blockers may have a blunted response to epinephrine used to treat anaphylaxis.
• Anesthesia: Beta-blockade may impair the ability of the heart to respond to beta-adrenergically mediated reflex stimuli during surgery; inform anesthesiologists that the patient is using Cozopt.
• Angle-closure glaucoma: Cozopt has not been specifically studied for this condition and should be used with additional appropriate therapy if used at all.
• Contact lenses: The product contains benzalkonium chloride, which may be absorbed by soft contact lenses; remove lenses before instillation and wait at least 15 minutes before reinserting.

No specific information on human overdosage with Cozopt ophthalmic solution is available. Accidental ingestion of the timolol component may produce symptoms of systemic beta-blockade such as bradycardia, hypotension, bronchospasm, and acute cardiac failure. Overdose of the dorzolamide component may theoretically produce electrolyte imbalance, development of an acidotic state, and possible central nervous system effects. If overdose or accidental ingestion is suspected, seek immediate medical attention or contact a poison control center; treatment should be symptomatic and supportive, guided by a physician, and should not rely on unsupervised home remedies.

Store at 2°C–25°C (36°F–77°F), away from light and moisture. Keep the bottle tightly closed and upright when not in use, and keep out of reach of children. Discard any unused solution 4 weeks after first opening the bottle.

Renal impairment: No formal dose adjustment has been established for topical Cozopt; because dorzolamide and its metabolite are eliminated primarily by the kidney, use with caution in patients with significant renal impairment.

Hepatic impairment: No specific dosage adjustment data are available; use with caution.

Elderly: No overall differences in safety or effectiveness have been observed between elderly and younger patients; standard adult dosing applies.

Pediatric patients: Safety and efficacy have not been established (see Pediatric Uses).

Cozopt is typically used long-term as chronic maintenance therapy for glaucoma or ocular hypertension, for as long as the treating ophthalmologist determines it is needed to control intraocular pressure. Intraocular pressure and ocular surface health should be monitored periodically during long-term use, and treatment should not be stopped abruptly without medical advice.

Carbonic anhydrase inhibitor (dorzolamide) combined with a non-selective beta-adrenergic blocking agent (timolol); anti-glaucoma / ocular hypotensive combination.

Dorzolamide + Timolol lowers intraocular pressure through two complementary, non-overlapping mechanisms that each reduce aqueous humor production: dorzolamide inhibits ciliary body carbonic anhydrase II, while timolol blocks beta-adrenergic stimulation of the ciliary epithelium. See Pharmacology for full mechanistic detail.

C

The safety and effectiveness of Cozopt in pediatric patients have not been established. Use in children should only be considered under direct specialist (pediatric ophthalmologist) supervision, with close monitoring for systemic beta-blockade effects, given children's greater relative systemic drug exposure from topical eye drops.