Dorzolamide + Timolol

• Primary open-angle glaucoma: To reduce elevated intraocular pressure (IOP).
• Ocular hypertension: Treatment to lower elevated IOP to prevent optic nerve damage.
• Other types of glaucoma where reduction of IOP is desired and monotherapy is insufficient or not tolerated.
• Off-label: May be used in secondary glaucoma types when appropriate.

Route: Ophthalmic solution (eye drops).

Adults:

• Instill one drop of the fixed combination in the affected eye(s) twice daily (approximately every 12 hours).
• Maximum recommended dose: two drops in each eye daily.
• If other topical ophthalmic drugs are used, administer at least 10 minutes apart.

Pediatrics:

• Safety and efficacy not established; use only if clearly indicated and supervised.

Elderly:

• No specific dose adjustment; monitor for systemic beta-blocker effects.

Renal/Hepatic Impairment:

• Use with caution; systemic absorption possible, especially in impaired patients.

Administration Notes:

• Remove contact lenses prior to instillation; wait 15 minutes before reinserting.
• Avoid contamination of the dropper tip.
• Shake gently before use.

Dorzolamide is a topical carbonic anhydrase inhibitor that decreases aqueous humor production by inhibiting the enzyme carbonic anhydrase II in the ciliary processes of the eye. This reduces intraocular fluid formation and lowers intraocular pressure. Timolol is a non-selective beta-adrenergic receptor blocker that reduces aqueous humor production by blocking beta receptors in the ciliary epithelium. The combination results in additive lowering of IOP through dual mechanisms without significant effect on aqueous outflow.

• Absorption: Both drugs have minimal systemic absorption after topical ocular administration.
• Distribution: Timolol distributes systemically after ocular absorption with plasma half-life of about 4–5 hours; dorzolamide accumulates in erythrocytes.
• Metabolism: Timolol metabolized primarily by hepatic CYP2D6; dorzolamide not extensively metabolized.
• Elimination: Timolol eliminated renally; dorzolamide excreted unchanged mainly via kidneys.
• Onset: IOP lowering effect seen within 1 hour; peak effect in 2–4 hours.
• Duration: Effect lasts approximately 12 hours, suitable for twice-daily dosing.

• Pregnancy: FDA Category C
• Animal studies show adverse fetal effects at high doses; insufficient human data.
• Use only if potential benefits outweigh risks.
• Lactation:
• Timolol is excreted in breast milk; potential beta-blocker effects in infants.
• Dorzolamide data limited.
• Caution advised; consider risks vs benefits.

• Primary class: Ophthalmic antiglaucoma agent
• Subclass: Combination of carbonic anhydrase inhibitor and non-selective beta-blocker

• Known hypersensitivity to dorzolamide, timolol, sulfonamides, or any formulation components.
• Bronchial asthma or severe chronic obstructive pulmonary disease (COPD).
• Sinus bradycardia, second- or third-degree atrioventricular block, overt cardiac failure, or cardiogenic shock.
• History of severe allergic reactions to sulfonamides (for dorzolamide).

• Use with caution in patients with respiratory disease (e.g., asthma, COPD).
• May mask signs of hypoglycemia in diabetics.
• Caution in patients with cardiac conditions (e.g., heart block, bradycardia).
• May cause local ocular irritation; discontinue if severe.
• Rare risk of systemic beta-blockade effects (bradycardia, hypotension).
• Monitor intraocular pressure regularly.
• Avoid abrupt withdrawal in patients with cardiovascular disease.
• Use cautiously in renal impairment (due to dorzolamide).

Common:

• Ocular burning or stinging
• Blurred vision
• Eye discomfort or dryness
• Conjunctivitis
• Tearing

Less Common:

• Taste perversion (bitter/metallic taste)
• Headache
• Dizziness
• Fatigue

Rare / Serious:

• Bronchospasm or respiratory distress
• Bradycardia, heart block
• Hypotension
• Allergic reactions including rash, urticaria
• Stevens-Johnson syndrome (very rare)

• Other beta-blockers: additive systemic beta-blockade effects.
• Calcium channel blockers and antiarrhythmics: increased risk of bradycardia or heart block.
• Oral carbonic anhydrase inhibitors: increased risk of metabolic acidosis.
• CYP2D6 inhibitors (e.g., quinidine) may increase systemic timolol levels.
• Drugs that cause bronchospasm may exacerbate respiratory effects.

• Guidelines recommend fixed combinations like dorzolamide-timolol for patients inadequately controlled on monotherapy.
• Emphasis on patient adherence benefits with fixed-dose combinations.
• Recent safety data continue to highlight caution in patients with respiratory or cardiac comorbidities.
• No major changes in approved indications; monitoring advised for systemic beta-blocker effects.

• Store at 15°C to 25°C (59°F to 77°F).
• Protect from freezing and excessive heat.
• Keep bottle tightly closed when not in use.
• Discard open bottles after 4 weeks to prevent contamination.
• Avoid direct sunlight exposure.