Combigan®

GoodRx

Brimonidine 0.2% / Timolol 0.5% · ophthalmic solution

Antiglaucoma

Approved uses

Elevated IOP in glaucoma or ocular hypertension needing adjunctive or replacement therapy

1 drop in the affected eye(s) BID, approximately 12 hours apart

IOP falls 4.4 to 7.6 mmHg, more than timolol at every timepoint but not brimonidine at 5 PM.

Switch from concomitant brimonidine plus timolol

1 drop BID approximately 12 hours apart, replacing timolol 0.5% BID plus brimonidine 0.2% TID

Contraindications

Bronchial asthma or a history of bronchial asthma.
Severe chronic obstructive pulmonary disease.
Sinus bradycardia.
Second or third degree atrioventricular block.
Overt cardiac failure.
Cardiogenic shock.
Neonates and infants younger than 2 years old.
Hypersensitivity to any component.

Available Forms

0.2%/0.5% solution, 5 mL in 10 mL bottle, 10 mL in 10 mL bottle, 15 mL in 15 mL bottle

Mechanism of Action

Fixed combination of brimonidine, a relatively selective alpha-2 adrenergic agonist with a dual mechanism of reduced aqueous production and increased uveoscleral outflow, and timolol, a nonselective beta-1 and beta-2 adrenergic receptor inhibitor without intrinsic sympathomimetic or membrane-stabilizing activity. Both components lower elevated IOP, with peak ocular hypotensive effect at about 2 hours for brimonidine and 1 to 2 hours for timolol.

Warnings & Precautions

Severe respiratory or cardiac reactions: The timolol component is absorbed systemically; death from bronchospasm in patients with asthma and, rarely, death associated with cardiac failure have been reported with ophthalmic timolol, which may also impair compensatory tachycardia and increase risk of hypotension.
Cardiac failure: Beta-blockade may precipitate more severe failure where sympathetic support of the circulation is needed, and continued myocardial depression can lead to failure in patients with no prior history; discontinue at the first sign or symptom.
Obstructive pulmonary disease: Patients with mild or moderate COPD or nonasthmatic bronchospastic disease should in general not receive a beta-blocker; bronchial asthma, a history of asthma, and severe COPD are outright contraindications.
Vascular insufficiency: Caution in depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, or thromboangiitis obliterans.
Increased allergen reactivity: Patients with atopy or prior severe anaphylaxis may be more reactive on repeat challenge and unresponsive to usual epinephrine doses.
Muscle weakness: Beta-blockade may potentiate myasthenic symptoms including diplopia, ptosis, and generalized weakness, and timolol has rarely increased weakness in myasthenia gravis.
Masked hypoglycemia: Beta-blockade may mask the signs and symptoms of acute hypoglycemia; caution in labile diabetes and in patients on insulin or oral hypoglycemics.
Masked thyrotoxicosis: Beta-blockade may mask tachycardia; abrupt withdrawal may precipitate thyroid storm.
Ocular hypersensitivity: Reported with brimonidine 0.2% solutions, in some cases accompanied by an increase in IOP.
Pediatric somnolence: In the supporting pediatric study of brimonidine 0.2% TID added to a beta-blocker, somnolence occurred in 50% to 83% of children aged 2 to 6 and about 25% at age 7 and older, with roughly 16% discontinuing for it.
Surgical reflex impairment: Beta-blockade blunts the reflex cardiac response to anesthesia; protracted severe hypotension and difficulty restarting the heartbeat have been reported.
Additive systemic beta-blockade: Oral or IV beta-blockers, calcium antagonists, digitalis, catecholamine-depleting drugs such as reserpine, and CYP2D6 inhibitors such as quinidine and SSRIs can compound bradycardia, AV conduction delay, and hypotension.
CNS depressants: Additive or potentiating sedation with alcohol, barbiturates, opiates, sedatives, or anesthetics.
MAO inhibitors: May interfere with brimonidine metabolism and increase systemic hypotension; on this label a caution, not a contraindication.
Bacterial keratitis: Reported with contaminated multidose containers, in most cases in eyes with concurrent corneal disease or epithelial disruption.
Soft contact lenses: Benzalkonium chloride may be absorbed by soft lenses; remove before instillation and reinsert after 15 minutes.

Common Side Effects

Ocular: Allergic conjunctivitis, conjunctival folliculosis, conjunctival hyperemia, eye pruritus, ocular burning, and stinging in approximately 5% to 15%; blepharitis, corneal erosion, epiphora, eye discharge, dryness, irritation, pain, eyelid edema, eyelid erythema, eyelid pruritus, foreign body sensation, superficial punctate keratitis, and visual disturbance in 1% to 5%.
Systemic: Asthenia, depression, headache, hypertension, oral dryness, and somnolence in 1% to 5%.
Postmarketing: Bradycardia, tachycardia, syncope, hypersensitivity, iritis, keratoconjunctivitis sicca, miosis, nausea, and eyelid erythema extending to the cheek or forehead; frequency not estimable.
Infant exposure: Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence reported in infants receiving brimonidine.
Timolol component: Cystoid macular edema, choroidal detachment after filtration surgery, decreased corneal sensitivity, pseudopemphigoid, ptosis, refractive changes, cardiac arrest, heart block, and bronchospasm predominantly in pre-existing bronchospastic disease.

Pregnancy & Lactation

Pregnancy: No adequate and well-controlled studies in pregnant women, and postmarketing and published data are insufficient to establish a drug-associated risk. Oral brimonidine during organogenesis produced no adverse developmental effects at 580 times (rats) and 37 times (rabbits) the recommended human ophthalmic dose, and oral timolol showed no fetal malformations up to 4,200 times.

Lactation: Not recommended during lactation because of the potential for CNS depression and apnea in the breastfed infant. Timolol is detected in human milk; brimonidine excretion in human milk is unknown but occurs in rat milk.

Pediatric Use

Contraindicated under 2 years; safety and effectiveness established from age 2 and older.