Binzotim1%+0.5%

Binzotim ophthalmic suspension is a fixed-dose combination indicated for the following:

Established/FDA-approved use

• Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to monotherapy with a topical beta-blocker or a topical carbonic anhydrase inhibitor (i.e., used when a single-agent eye drop does not lower eye pressure enough).

Guideline-supported / adjunct use

• As an adjunctive or replacement therapy in patients already being treated with the individual components (brinzolamide and timolol) given separately, to simplify the dosing regimen (combination therapy).

Binzotim is not intended as first-line, single-agent therapy; it is used specifically as combination treatment when IOP control with one class of agent alone is inadequate.

Each mL of Brinzolamide + Timolol ophthalmic suspension contains:

• Brinzolamide 10 mg (1% w/v) — a carbonic anhydrase inhibitor
• Timolol 5 mg (0.5% w/v, as timolol maleate) — a non-selective beta-adrenergic blocking agent

Also contains benzalkonium chloride as a preservative and other inactive ingredients (e.g., carbomer, mannitol, tyloxapol, edetate disodium, sodium chloride, purified water) to form a sterile ophthalmic suspension.

Binzotim is a sterile, fixed-dose combination ophthalmic suspension that combines two agents which lower intraocular pressure through complementary mechanisms.

Brinzolamide is a carbonic anhydrase inhibitor that decreases aqueous humor secretion by the ciliary body, while timolol is a non-selective beta-adrenergic blocking agent that also reduces aqueous humor production. Combining the two provides additive IOP-lowering effect compared with either agent used alone.

Binzotim is supplied as a white to off-white suspension for topical application to the eye and must be shaken well before each use.

Binzotim belongs to the therapeutic class of anti-glaucoma agents, specifically a fixed-dose combination of a carbonic anhydrase inhibitor (CAI) and a non-selective beta-adrenergic blocker, both formulated for topical ophthalmic use.

Brinzolamide + Timolol lowers intraocular pressure (IOP) through two complementary, additive mechanisms that both act to reduce aqueous humor production (rather than increasing its outflow):

Onset of IOP-lowering effect is seen within hours of dosing, with the additive effect of the two components generally producing a greater reduction in IOP than either agent alone.

Binzotim is for topical ophthalmic use only. Wash hands before use, shake the bottle well, tilt the head back, pull down the lower eyelid to form a pocket, and instill one drop without letting the dropper tip touch the eye or any surface (to avoid contamination). Close the eye gently for 1–2 minutes and apply nasolacrimal occlusion. Wait at least 5 minutes before instilling any other eye medication.

Clinically significant interactions with Binzotim relate mainly to its timolol (beta-blocker) component, since some systemic absorption occurs even with topical ophthalmic use:

• Oral calcium channel blockers, beta-blockers, antiarrhythmics (e.g., verapamil, diltiazem, amiodarone), or digoxin: concurrent use with Binzotim may result in additive effects, causing hypotension, bradycardia, AV conduction disturbances, or cardiac failure.
• Other oral or topical beta-adrenergic blocking agents: concomitant use with Binzotim may cause additive effects on IOP or on systemic beta-blockade; combined use is generally not recommended.
• Oral carbonic anhydrase inhibitors (e.g., acetazolamide): concurrent use with Binzotim is not recommended due to potential for additive systemic carbonic anhydrase inhibitor effects.
• CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine): may increase systemic beta-blockade (e.g., bradycardia) when used with Binzotim.
• Epinephrine (adrenaline) and other sympathomimetics: beta-blockade from Binzotim may blunt tachycardia produced by epinephrine, and patients on Binzotim who experience anaphylaxis may be resistant to usual doses of epinephrine used to treat the reaction.
• Insulin or oral hypoglycemic agents: beta-blockade from Binzotim may mask signs and symptoms of hypoglycemia (e.g., tachycardia); use with caution in diabetics.
• Clonidine: beta-blockers may exaggerate rebound hypertension that can follow abrupt clonidine withdrawal.

The most commonly reported side effects of Binzotim include:

• Blurred vision
• Eye irritation, redness, or discomfort
• Dysgeusia (unusual/bitter taste in the mouth after eye drop instillation)
• Dry eye
• Eye pain or a foreign-body sensation
• Punctate keratitis (superficial corneal inflammation)
• Ocular allergic reactions

Less common but clinically important effects (related mainly to systemic absorption of the timolol component) include bradycardia, hypotension, fatigue, headache, and (rarely) bronchospasm in susceptible individuals. Seek medical advice if any side effect is severe or persistent.

Pregnancy: There are no adequate and well-controlled studies of Binzotim in pregnant women. Binzotim should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus. A physician should be consulted before use in pregnancy.

Lactation: Timolol has been detected in human breast milk after ophthalmic administration, and it is not known whether brinzolamide is excreted in breast milk. Because of the potential for serious adverse effects (including beta-blockade) in breastfed infants, a decision should be made whether to discontinue breastfeeding or discontinue Binzotim, taking into account the importance of treatment to the mother; consult a physician before use while breastfeeding.

Binzotim should be used with caution and under medical supervision in the following situations:

• Sulfonamide hypersensitivity: brinzolamide is a sulfonamide derivative; systemic sulfonamide-type reactions (rare but potentially serious, including Stevens-Johnson syndrome) are possible even with topical ocular use.
• Cardiac disease: patients with compensated cardiac failure, bradyarrhythmias, or a history of heart disease should be monitored, as the timolol component can slow heart rate and reduce cardiac contractility even when applied topically to the eye.
• Diabetes mellitus: timolol may mask the signs and symptoms (e.g., tachycardia) of acute hypoglycemia; use with caution in patients on insulin or oral hypoglycemics.
• Thyrotoxicosis: beta-blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism; abrupt withdrawal may precipitate thyroid storm.
• Myasthenia gravis and other conditions with muscle weakness: timolol's beta-blocking effect may potentiate muscle weakness symptoms such as diplopia, ptosis, and generalized weakness.
• Severe renal impairment: brinzolamide is primarily eliminated by the kidney; use with caution and monitor as recommended by the physician.
• Corneal endothelial compromise: caution is advised in patients with low endothelial cell counts, as carbonic anhydrase inhibitors can affect corneal fluid balance.
• Anaphylactic reactions: patients on beta-blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylaxis.
• Choroidal detachment: has been reported with aqueous-suppressant therapy after glaucoma filtration procedures.
• Do not touch the dropper tip to the eye or any surface, to avoid contamination of the suspension.
• Remove soft contact lenses before instilling Binzotim; they may be reinserted 15 minutes after dosing.

Ocular overdose of Binzotim is unlikely to occur with normal use, but accidental ingestion or excessive ocular application may cause systemic effects related to the timolol component, such as bradycardia, hypotension, bronchospasm, heart block, acute cardiac failure, or (rarely) systemic effects from brinzolamide such as electrolyte imbalance, drowsiness, or headache.

If overdose or accidental ingestion is suspected, seek immediate medical attention or contact a poison control center/emergency services right away. Do not attempt home treatment. Bring the medicine container/bottle when seeking care so the treating physician can identify the exact product.

Store upright at 2°C to 25°C (36°F to 77°F), away from light and moisture. Discard any unused portion 4 weeks after first opening the bottle. Keep out of reach of children.

Pediatric patients: Safety and effectiveness of Binzotim in pediatric patients (below 18 years of age) have not been established; use in children is generally not recommended unless specifically directed by a pediatric ophthalmologist.

Elderly (geriatric) patients: No overall differences in safety or effectiveness have been observed between elderly and younger adult patients; no dose adjustment is required based on age alone.

Hepatic impairment: No specific dose adjustment has been established; use with routine caution.

Renal impairment: Use with caution in patients with severe renal impairment (see Precautions and Warnings), as brinzolamide is primarily renally eliminated.

Binzotim is generally 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. Regular follow-up visits, including IOP measurement and monitoring for corneal and cardiovascular effects, are recommended. Do not stop Binzotim abruptly without consulting your physician, as intraocular pressure may rise again.

Carbonic anhydrase inhibitor + non-selective beta-adrenergic blocker (fixed-dose anti-glaucoma combination)

Brinzolamide + Timolol reduces intraocular pressure by decreasing the production (formation) of aqueous humor through two complementary pathways: brinzolamide inhibits carbonic anhydrase II in the ciliary body epithelium (reducing bicarbonate ion and fluid formation), while timolol blocks beta-adrenergic receptors in the same tissue, also reducing aqueous humor secretion. Because both components act on aqueous production (rather than outflow), their combined effect on lowering IOP is additive.

Category C

Safety and efficacy of Binzotim in pediatric patients have not been established. There is limited clinical experience with this fixed-dose combination in children, and it is not routinely recommended for pediatric glaucoma unless specifically prescribed by a pediatric ophthalmologist who has weighed the potential risks (including systemic beta-blocker effects, to which infants and young children may be more sensitive) against the benefits.