Bimator0.03%+0.5%

Bimator is a fixed-dose combination ophthalmic solution (bimatoprost, a prostaglandin analog, plus timolol, a non-selective beta-blocker) indicated for the following:

Established/FDA-approved use

• Reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who require additional IOP lowering and are insufficiently responsive to a topical beta-blocker or another single IOP-lowering agent used alone.

Place in therapy

Bimator is intended for patients who need more IOP reduction than a single agent (either bimatoprost alone or timolol alone) provides; it is not typically used as first-line monotherapy when a single agent would be adequate, since combination therapy carries a broader side-effect profile from both components.

Each mL of the ophthalmic solution contains Bimatoprost 0.3 mg (0.03%) and Timolol (as timolol maleate) equivalent to 5 mg (0.5%) of timolol base, formulated as a sterile, preserved, isotonic eye drop solution, as commonly marketed for Bimatoprost + Timolol.

Bimator is a fixed-dose combination topical ophthalmic solution combining two IOP-lowering medicines with complementary mechanisms: bimatoprost, a synthetic prostamide analog that increases aqueous humor outflow, and timolol maleate, a non-selective beta-adrenergic blocker that reduces aqueous humor production. Combining the two agents in a single drop allows a greater reduction in intraocular pressure than either component alone, while reducing the number of daily drops a patient must instill compared with using both medicines separately.

Bimator belongs to the ophthalmic anti-glaucoma combination class, combining a prostaglandin analog (prostamide) with a non-selective beta-adrenergic blocking agent.

Mechanism of Action

Bimatoprost + Timolol lowers intraocular pressure through two complementary mechanisms. The bimatoprost component is believed to lower IOP mainly by increasing aqueous humor outflow through both the trabecular meshwork and the uveoscleral (uveal) outflow pathway. The timolol component reduces IOP primarily by decreasing the production (secretion) of aqueous humor by the ciliary epithelium, with little or no effect on pupil size or accommodation. The combined effect produces greater IOP reduction than either mechanism alone.

Pharmacokinetics

Nasolacrimal occlusion or gentle eyelid closure for about 2 minutes after instilling Bimatoprost + Timolol reduces systemic absorption of the timolol component and lowers the risk of systemic side effects.

For topical ophthalmic (eye drop) use only. Not for injection or oral use. See Dosage and Administration for full instillation technique for Bimator.

Clinically Significant Interactions

• Oral beta-blockers or other systemic beta-adrenergic blocking agents: Possible additive effects on intraocular pressure and/or known systemic effects of beta-blockade (e.g., additive bradycardia, hypotension) when combined with the timolol component of Bimator; use with caution and appropriate monitoring.
• Oral calcium channel blockers: Concomitant use with the timolol component may increase the risk of atrioventricular conduction disturbances, left ventricular failure, and hypotension.
• Catecholamine-depleting drugs (e.g., reserpine): Additive effect with the timolol component may produce hypotension and/or marked bradycardia (vertigo, syncope, or postural hypotension).
• Digoxin: The timolol component may have an additive effect in prolonging atrioventricular conduction time; monitor heart rate.
• Other topical or systemic IOP-lowering agents (e.g., other prostaglandin analogs, alpha-agonists, carbonic anhydrase inhibitors): Additive IOP-lowering effect is possible but has not been shown to be consistently beneficial; concomitant use of two prostaglandin analogs is generally not recommended.
• Insulin or oral hypoglycemic agents: The timolol component may mask signs and symptoms of hypoglycemia (e.g., tachycardia); use with caution in diabetic patients.
• CYP2D6 inhibitors (e.g., quinidine): May increase systemic exposure to the timolol component, increasing the likelihood of systemic beta-blockade.

Common Side Effects

• Conjunctival hyperemia (eye redness) - the most commonly reported effect
• Growth of eyelashes (increased length, thickness, number, and pigmentation)
• Eye pruritus (itching)
• Ocular irritation, burning, or stinging on instillation
• Dry eye
• Increased iris pigmentation (see Precautions and Warnings)
• Headache

Less Common but Notable

• Periorbital and eyelid skin pigmentation changes (darkening)
• Blurred vision, tearing, or photophobia
• Systemic effects from the timolol component (uncommon with topical use but possible): bradycardia, hypotension, fatigue, bronchospasm/dyspnea in susceptible patients
• Superficial punctate keratitis

Pregnancy: There are no adequate and well-controlled studies of Bimator in pregnant women. Animal studies with bimatoprost and with timolol have shown some evidence of fetal risk at systemic exposures substantially higher than those produced by topical ophthalmic use. Bimator should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and only under the direct supervision of a physician.

Lactation: It is not known whether bimatoprost is excreted in human breast milk, but timolol has been detected in human breast milk after systemic administration. Because of the potential for serious adverse effects, including systemic beta-blockade, in a nursing infant, a decision should be made whether to discontinue breastfeeding or discontinue Bimator, taking into account the importance of the medicine to the mother, and only in consultation with a physician.

General Precautions

• Pigmentation changes: Bimator can gradually change eye color by increasing the amount of brown pigment in the iris; this change may be permanent and may continue after treatment is stopped. Eyelash and periorbital skin pigmentation changes are usually reversible on discontinuation. Patients should be informed of the possibility of permanent iris color change before starting treatment, particularly in patients with mixed-color irides.
• Eyelash changes: Gradual increase in eyelash length, thickness, number, and pigmentation may occur; generally reversible on discontinuation.
• Systemic beta-blocker effects: Although Bimator is applied topically, sufficient systemic absorption of the timolol component can occur to produce effects seen with systemic beta-blockers, including bradycardia, hypotension, bronchospasm, worsening of heart failure, and masking of the signs of hypoglycemia in diabetic patients or of hyperthyroidism. Nasolacrimal occlusion or eyelid closure after instillation reduces systemic absorption and should be encouraged.
• Intraocular inflammation/macular edema: Prostaglandin analogs, including the bimatoprost component, have been associated with macular edema, including cystoid macular edema; use with caution in aphakic patients, pseudophakic patients with a torn posterior lens capsule, or patients with known risk factors for macular edema.
• Bacterial keratitis: Multiple-dose containers of topical ophthalmic products have been associated with bacterial keratitis from inadvertent contamination; patients should be instructed on proper handling and to avoid allowing the dropper tip to touch the eye or surrounding structures.
• Anaphylactic reactions while on beta-blockers: Patients on beta-blockers who experience anaphylactic or anaphylactoid reactions may be more difficult to treat with usual doses of epinephrine.
• Contact lenses: Should be removed prior to instillation and may be reinserted after the labeled interval, since the preservative may be absorbed by soft contact lenses.
• Do not exceed recommended dosing frequency: Using Bimator more often than once daily may decrease the IOP-lowering effect.

Topical ophthalmic overdosage of Bimator is unlikely to cause acute toxicity, but accidental ingestion of the solution could produce systemic effects of beta-blockade from the timolol component, such as bradycardia, hypotension, bronchospasm, and cardiac failure, along with possible symptoms related to bimatoprost. If overdose or accidental ingestion is suspected, seek immediate medical attention or contact emergency services/a poison control center right away. Do not attempt to manage a suspected overdose of Bimator at home; treatment in a medical facility is supportive, based on presenting symptoms.

Prior to opening, store in a refrigerator (2°C-8°C). After the bottle is first opened, it may be stored at room temperature (below 25°C) for up to 4 weeks; discard any remaining solution after this period. Protect from light and moisture, and keep out of reach of children. Always check the specific product label, as storage instructions can vary by manufacturer/brand.

Pediatric Use

Safety and efficacy of Bimator have not been established in pediatric patients; it is not recommended for use in this population.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger adult patients using Bimator.

Renal Impairment

Bimator has not been specifically studied in patients with renal impairment; use with appropriate caution regarding systemic beta-blocker effects.

Hepatic Impairment

Bimator has not been specifically studied in patients with hepatic impairment; use with appropriate caution.

Bimator is generally used long-term for chronic control of intraocular pressure in open-angle glaucoma or ocular hypertension. Duration of treatment should be determined by an ophthalmologist based on regular monitoring of intraocular pressure, optic nerve status, and visual fields; it is not intended for short-term or as-needed use, and treatment should not be stopped or altered without medical advice.

Ophthalmic anti-glaucoma combination: Prostaglandin analog (prostamide) + Non-selective beta-adrenergic blocking agent.

Bimatoprost + Timolol lowers intraocular pressure via two complementary actions: the bimatoprost component increases aqueous humor outflow through the trabecular meshwork and uveoscleral pathways, while the timolol component decreases aqueous humor production by the ciliary body; together these actions produce a greater reduction in intraocular pressure than either agent used alone.

Category C

Safety and efficacy of Bimator have not been established in pediatric patients, and it is not recommended for use in children. As with other topical beta-blocker-containing ophthalmic products, caution regarding systemic beta-blockade would be warranted if used off-label in a pediatric patient under specialist supervision, since children may be more susceptible to systemic absorption effects.