Zolopt

Approved Indications:

• Primary Open-Angle Glaucoma (POAG): Used as monotherapy or adjunctive therapy to lower intraocular pressure (IOP) in adults with open-angle glaucoma.
• Ocular Hypertension: Indicated for the reduction of elevated IOP in patients with ocular hypertension.

Off-Label / Clinically Accepted Uses:

• Pseudoexfoliative Glaucoma: Sometimes used as adjunct therapy in patients unresponsive to or intolerant of beta-blockers or prostaglandin analogs.
• Angle-closure Glaucoma (Post-laser): Used in some settings to control IOP spikes following laser peripheral iridotomy.

Adults:

• Monotherapy: 1 drop of 1% brinzolamide ophthalmic suspension in the affected eye(s) 2 times daily.
• Adjunctive Therapy: May be administered 3 times daily if used with other IOP-lowering medications (e.g., beta-blockers).

Pediatric Use:

• Safety and efficacy have not been established in children under 18 years; not routinely recommended.

Elderly:

• No dosage adjustment required; monitor intraocular pressure regularly.

Renal Impairment:

• Contraindicated in severe renal impairment (CrCl <30 mL/min); brinzolamide is primarily renally excreted.

Hepatic Impairment:

• Use with caution in hepatic dysfunction; no formal dose adjustment established.

Administration:

• For topical ophthalmic use only.
• Shake well before use.
• Avoid contact of the dropper tip with the eye or any surface.
• If using multiple eye drops, separate by at least 10 minutes.

Brinzolamide is a carbonic anhydrase inhibitor (CAI). It specifically inhibits carbonic anhydrase II found in the ciliary processes of the eye. Inhibition of this enzyme reduces the production of bicarbonate ions, thereby decreasing sodium and fluid transport. This results in reduced aqueous humor secretion and subsequently lowering of intraocular pressure (IOP), which is crucial in preventing optic nerve damage in glaucoma patients.

• Absorption: Following topical ocular administration, brinzolamide is absorbed systemically and accumulates in red blood cells due to high affinity for carbonic anhydrase II.
• Distribution: Widely distributed in erythrocytes; low plasma concentration due to intracellular accumulation.
• Metabolism: Primarily metabolized in the liver to N-desethylbrinzolamide (active) and other less active metabolites.
• Elimination: Excreted mainly unchanged in the urine; half-life ranges from 111 to 115 days in erythrocytes.
• Bioavailability: Systemic absorption occurs but is minimal at therapeutic ocular doses.
• Onset of Action: Reduction in IOP occurs within 1 to 2 hours, with peak effect around 2 to 4 hours post-administration.

• Pregnancy: Brinzolamide is classified as Pregnancy Category C. Animal studies have shown adverse fetal effects at high systemic exposures, but there are no adequate human studies. Use only if the potential benefit justifies the potential risk.
• Lactation: It is unknown whether brinzolamide is excreted in human breast milk. However, due to potential systemic absorption and possible effects on the nursing infant, caution is advised. Consider discontinuing breastfeeding or the drug, based on clinical judgment.

• Primary Class: Carbonic Anhydrase Inhibitor (Topical)
• Subclass: Ophthalmic Antiglaucoma Agent – Non-beta blocker

• Hypersensitivity to brinzolamide or any component of the formulation.
• Severe renal impairment (CrCl <30 mL/min).
• History of sulfonamide hypersensitivity (due to structural similarity).

• Sulfonamide Reaction: Though administered topically, brinzolamide is a sulfonamide derivative; systemic reactions including Stevens-Johnson syndrome may occur rarely.
• Hepatic Impairment: Use with caution due to limited clinical data.
• Corneal Edema: Caution in patients with compromised corneal endothelium (e.g., Fuchs dystrophy).
• Acid-Base Imbalance: Systemic absorption may lead to metabolic acidosis, particularly in patients with renal dysfunction.
• Blurred Vision: May cause transient blurring; advise caution when driving or operating machinery.
• Contact Lens Use: Contains benzalkonium chloride, which may be absorbed by soft contact lenses. Remove lenses prior to instillation and reinsert after 15 minutes.

Common:

• Ocular:
• Blurred vision
• Ocular discomfort
• Foreign body sensation
• Eye pain or burning
• Conjunctival hyperemia
• Systemic:
• Dysgeusia (bitter taste)
• Headache

Less Common/Rare:

• Dry eyes
• Keratitis
• Allergic conjunctivitis
• Fatigue
• Nausea
• Skin rash

Serious (Rare):

• Stevens-Johnson syndrome (very rare, sulfonamide-related)
• Metabolic acidosis in patients with renal impairment

• Oral Carbonic Anhydrase Inhibitors (e.g., acetazolamide): Additive systemic effects, including metabolic acidosis—avoid combination.
• High-dose Salicylates: Risk of salicylate toxicity if systemic absorption of brinzolamide occurs.
• CYP450 Interactions: Brinzolamide is not significantly metabolized via CYP enzymes; minimal involvement in hepatic drug-drug interactions.

• No major changes to approved indications or dosing in recent FDA, EMA, or NICE updates.
• Ongoing pharmacovigilance monitors rare adverse events, especially sulfonamide-type hypersensitivity reactions.
• NICE guidelines continue to list brinzolamide as a second-line or adjunctive therapy for ocular hypertension and glaucoma when first-line agents are insufficient.

• Temperature: Store at 15°C to 30°C (59°F to 86°F).
• Humidity: Protect from moisture.
• Light Protection: Store in original container; protect from light.
• Handling: Shake well before use.
• Do Not Freeze.
• After opening, use within 4 weeks; discard unused solution after this period.