Binzotim

• Primary Open-Angle Glaucoma (POAG): Reduction of elevated intraocular pressure (IOP) in patients who are insufficiently responsive to monotherapy.
• Ocular Hypertension (OHT): Lowering elevated IOP to reduce risk of optic nerve damage.
• Indicated as adjunctive therapy when monotherapy with either brinzolamide or timolol alone is inadequate.

• Adults and Elderly:
• Instill one drop in the affected eye(s) twice daily (approximately every 12 hours).
• Do not exceed the recommended dose.
• Shake well before use.
• Remove contact lenses before administration; wait 15 minutes before reinsertion.
• Pediatrics:
• Safety and efficacy not established in children under 18 years; use only if benefits outweigh risks.
• Renal Impairment:
• Use brinzolamide cautiously in patients with severe renal impairment (CrCl <30 mL/min) due to systemic accumulation risk.
• Hepatic Impairment:
• Use timolol cautiously in patients with hepatic impairment; dose adjustment may be necessary.
• Administration:
• Ophthalmic topical use only.

Brinzolamide is a carbonic anhydrase II inhibitor that reduces aqueous humor secretion by inhibiting bicarbonate ion formation in the ciliary body, lowering intraocular pressure. Timolol is a non-selective beta-adrenergic receptor blocker that decreases aqueous humor production by blocking beta-1 and beta-2 receptors in the ciliary epithelium. The combination exerts an additive effect in reducing elevated IOP by dual mechanisms — reducing fluid formation and increasing outflow — thus providing better pressure control than either agent alone.

• Absorption:
• Both drugs show minimal systemic absorption following topical ocular administration; however, brinzolamide binds extensively to erythrocytes and timolol is systemically absorbed with measurable plasma levels.
• Distribution:
• Brinzolamide binds intracellularly in erythrocytes; timolol distributes widely and crosses the blood-brain barrier.
• Metabolism:
• Brinzolamide undergoes limited hepatic metabolism; active metabolites exist but are minor.
• Timolol is extensively metabolized by hepatic CYP2D6 enzymes.
• Elimination:
• Brinzolamide is primarily excreted unchanged in urine; long half-life in erythrocytes (~111 days).
• Timolol is eliminated mostly by hepatic metabolism and renal excretion of metabolites; plasma half-life ~4-5 hours.
• Onset of Action:
• IOP reduction begins within 1 hour; maximal effect observed 2 to 6 hours after instillation.

• Pregnancy:
• Category C (FDA). Use only if potential benefits justify potential fetal risks.
• Timolol may cause fetal bradycardia or other beta-blocker associated effects.
• Brinzolamide’s carbonic anhydrase inhibition may affect fetal acid-base balance.
• Lactation:
• Both drugs are excreted in breast milk in unknown amounts.
• Caution advised; breastfeeding mothers should discuss risks with healthcare provider.

• Primary Class: Antiglaucoma agent
• Subclass: Combination of Carbonic Anhydrase Inhibitor (Brinzolamide) + Non-selective Beta Blocker (Timolol)

• Known hypersensitivity to brinzolamide, timolol, or any formulation components
• Bronchial asthma or severe chronic obstructive pulmonary disease (COPD)
• Sinus bradycardia, heart block greater than first degree, cardiogenic shock, overt cardiac failure
• Severe renal impairment (for brinzolamide component)
• Concurrent use of oral carbonic anhydrase inhibitors (due to additive effects)

• Respiratory Disease: Timolol may induce bronchospasm; avoid in asthma and COPD.
• Cardiac Conditions: Monitor heart rate and blood pressure; may cause bradycardia, hypotension.
• Renal Impairment: Brinzolamide should be avoided or used cautiously in severe renal impairment.
• Sulfonamide Sensitivity: Brinzolamide is a sulfonamide derivative; monitor for hypersensitivity.
• Ocular Reactions: May cause allergic conjunctivitis, dry eyes, or corneal edema.
• Systemic Absorption: May result in systemic beta-blocker effects such as fatigue or dizziness.
• Masking of Hypoglycemia: Beta blockers can mask hypoglycemia symptoms in diabetics.
• Contact Lens Use: Contains benzalkonium chloride which may discolor soft lenses; remove lenses prior to administration.

Common:

• Ocular irritation or discomfort
• Blurred vision
• Eye dryness
• Conjunctival hyperemia

Systemic:

• Fatigue
• Headache
• Dizziness

Less Common / Rare:

• Bradycardia
• Bronchospasm
• Allergic reactions (rash, eyelid edema)
• Taste perversion (dysgeusia)

• Other Beta Blockers: Additive effects, increased risk of bradycardia or hypotension.
• Oral Carbonic Anhydrase Inhibitors: Avoid concomitant use with brinzolamide due to risk of metabolic acidosis.
• Calcium Channel Blockers, Digoxin: Increased risk of cardiac conduction disturbances.
• Insulin or Oral Hypoglycemics: Beta blockers may mask hypoglycemia symptoms.
• CYP2D6 Inhibitors: May increase systemic timolol levels.
• Drug-Food: No significant food interaction; ophthalmic use limits systemic exposure.
• Alcohol: May potentiate hypotensive effects.

• Current glaucoma treatment guidelines recommend combination therapy such as brinzolamide + timolol for patients inadequately controlled on monotherapy.
• No recent major label changes or new safety warnings.
• Emphasis on careful monitoring of cardiac and respiratory status during treatment.

• Store at 15°C to 30°C (59°F to 86°F).
• Protect from excessive moisture and light.
• Do not freeze.
• Keep the bottle tightly closed.
• Shake well before use.
• Discard 4 weeks after opening.
• Keep out of reach of children.