Zolopt BR

Approved Indications:

• Reduction of Elevated Intraocular Pressure (IOP) in patients with:
• Primary Open-Angle Glaucoma (POAG)
• Ocular Hypertension (OHT)
• Indicated when monotherapy with a topical beta-blocker or prostaglandin analogue is insufficient or inappropriate.

Clinically Accepted Off-Label Uses:

• Adjunctive treatment in pseudoexfoliation glaucoma
• Secondary glaucoma types where combination therapy is justified (under specialist guidance)

Adults (Including Elderly):

• Recommended dose: One drop in the affected eye(s) twice daily (every 12 hours)
• Shake well before use.
• Contact lenses should be removed prior to administration and reinserted after 15 minutes.

Pediatric Use:

• Not recommended for children under 2 years of age due to brimonidine-related CNS depression.
• Use in children 2–17 years only if clearly indicated and under strict medical supervision.

Renal Impairment:

• Use with caution; systemic absorption of brinzolamide may lead to accumulation in moderate-to-severe renal impairment (CrCl <30 mL/min).

Hepatic Impairment:

• No formal studies; caution is advised due to potential systemic effects.

Administration Route: Topical (ophthalmic)

Brinzolamide is a carbonic anhydrase II inhibitor that reduces intraocular pressure by decreasing aqueous humor production through inhibition of bicarbonate ion formation in the ciliary processes. Brimonidine tartrate is an α2-adrenergic receptor agonist that lowers intraocular pressure by dual mechanisms: reducing aqueous humor production and enhancing uveoscleral outflow. The combination provides additive IOP-lowering effects, beneficial in patients inadequately controlled on monotherapy.

• Absorption: Systemic absorption is minimal when administered topically, though detectable levels of both drugs are found in plasma.
• Distribution: Brinzolamide binds extensively to erythrocyte carbonic anhydrase; brimonidine crosses the blood-brain barrier.
• Metabolism:
• Brinzolamide: hepatic metabolism; metabolites not well characterized.
• Brimonidine: extensively metabolized in the liver.
• Elimination:
• Brinzolamide: excreted mainly via urine as unchanged drug and metabolites.
• Brimonidine: excreted through urine (~74%).
• Half-life:
• Brinzolamide: long intracellular half-life (~111 days in erythrocytes)
• Brimonidine: ~2 hours (systemic)

• Pregnancy: Not assigned (FDA). Use only if potential benefit justifies potential fetal risk.
• Brinzolamide: Risk of fetal harm based on class effects of carbonic anhydrase inhibitors.
• Brimonidine: Animal studies show potential fetal harm; avoid in pregnancy unless absolutely necessary.
• Lactation:
• Unknown whether brinzolamide or brimonidine is excreted in human milk.
• Due to potential for serious adverse effects in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug.

• Primary Class: Antiglaucoma Agents
• Subclass: Combination of Carbonic Anhydrase Inhibitor + Alpha-2 Adrenergic Receptor Agonist

• Hypersensitivity to brinzolamide, brimonidine, or any formulation components
• Neonates and infants under 2 years of age
• Concomitant use with monoamine oxidase inhibitors (MAOIs)
• Severe renal impairment (CrCl <30 mL/min)

• CNS Depression: Brimonidine may cause CNS effects (lethargy, somnolence) especially in children.
• Allergic Reactions: May cause allergic conjunctivitis, allergic blepharitis, and allergic dermatitis.
• Sulfonamide Reactions: Brinzolamide is a sulfonamide; may cause systemic effects including hypersensitivity.
• Renal/Hepatic Impairment: Caution is advised; systemic exposure may be increased.
• Dry Eye & Ocular Irritation: Patients with preexisting ocular surface disease should be monitored.
• Delayed Hypersensitivity: Discontinue at first signs of rash or systemic allergic reaction.

Common:

• Ocular:
• Blurred vision
• Eye irritation
• Dry eyes
• Conjunctival hyperemia
• Systemic:
• Drowsiness
• Fatigue
• Headache

Less Common:

• Dysgeusia (altered taste)
• Eye pain or discomfort
• Foreign body sensation

Serious (Rare):

• Hypersensitivity reactions (rash, angioedema)
• Bradycardia, hypotension
• Severe CNS depression (especially in children)

• CNS depressants: Increased risk of sedation with alcohol, barbiturates, opioids.
• MAOIs: Contraindicated due to risk of severe hypotension.
• Antihypertensives & Cardiac Glycosides: Additive hypotensive or bradycardic effects.
• Carbonic anhydrase inhibitors (oral or topical): Potential for additive systemic effects (e.g., metabolic acidosis).
• CYP450 Interactions: Brimonidine is metabolized via liver enzymes; strong inhibitors or inducers may affect efficacy or toxicity.

• EMA & FDA: No major label changes in the past 12 months.
• Guidelines: Preferred combination therapy in patients uncontrolled with monotherapy per recent AAO Preferred Practice Patterns (American Academy of Ophthalmology).
• Brimonidine remains contraindicated in infants due to severe CNS side effects—highlighted in safety communications.

• Store at: 15°C to 30°C
• Protect from: Light and excessive moisture
• Do not freeze.
• Handling: Shake well before each use.
• Once opened, discard after 28 days.
• Keep out of reach of children.