Adult: Available preparation:
Brimonidine 2 mg and timolol 5 mg per mL of eye drop solution
For the reduction of elevated IOP in patients who are inadequately responsive to topical β-blockers: Instil 1 drop into the affected eye(s) bid, approx 12 hours apart.
Contraindications
Reactive airway disease including bronchial asthma or history of bronchial asthma, severe COPD; sick sinus syndrome, sinus bradycardia, sinoatrial block, 2nd- or 3rd-degree AV block not controlled with a pacemaker, overt cardiac failure, cardiogenic shock. Children <2 years. Concomitant use with antidepressants which affect noradrenergic transmission (e.g. TCAs, mianserin); concomitant use with or within 14 days of discontinuing MAOI therapy.
Special Precautions
Patient with CV disease (e.g. CHD, Prinzmetal's angina, compensated cardiac failure, 1st-degree heart block), severe peripheral circulatory disorder (e.g. severe forms of Raynaud's syndrome); mild or moderate COPD, history of bronchospastic disease (other than bronchial asthma); spontaneous hypoglycaemia, diabetes mellitus (particularly labile diabetes), metabolic acidosis, untreated phaeochromocytoma; myasthenia gravis, corneal disease, history of atopy or severe anaphylactic reaction to variety of allergens; dry eye, depression, cerebrovascular insufficiency, orthostatic hypotension, thromboangiitis obliterans. Patients undergoing surgery. Avoid abrupt withdrawal (particularly in patients with suspected thyrotoxicosis). Timolol may mask the signs and symptoms of hypoglycaemia and hyperthyroidism (particularly tachycardia). Renal and hepatic impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Allergic conjunctivitis, allergic blepharitis, delayed ocular hypersensitivity reactions, dry eye; choroidal detachment (post-filtration procedures); may precipitate or potentiate symptoms of vascular insufficiency, may aggravate symptoms of myasthenia gravis. Cardiac disorders: Palpitations, bradycardia, tachycardia, arrhythmia. Eye disorders: Conjunctival hyperaemia, burning or stinging sensation in the eye, corneal erosion, superficial punctate keratitis, conjunctival folliculosis, visual disturbance, epiphora, foreign body sensation, eye discharge, pain, pruritus, or irritation; eyelid oedema, pruritus, or erythema; blurred vision. Gastrointestinal disorders: Oral dryness. General disorders and administration site conditions: Asthenia. Nervous system disorders: Headache, somnolence. Psychiatric disorders: Depression. Vascular disorders: Hypertension, hypotension. Potentially Fatal: Severe respiratory reactions including bronchospasm in patients with asthma. Rarely, cardiac failure.
Remove contact lenses before administration and reinsert them after at least 15 minutes. This drug may cause transient blurring of vision, visual disturbance, fatigue, and/or drowsiness, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor IOP and blood pressure. Assess for signs of systemic effects of β-blockade.
Drug Interactions
Brimonidine: May diminish therapeutic effect with mianserin and TCAs. MAOIs may interfere with the metabolism of brimonidine, which may result in increased systemic side effects (e.g. hypotension). Concomitant use with CNS depressants (e.g. barbiturates, sedatives, opiates, anaesthetics) may produce additive or potentiated CNS depressant effects.
Timolol: Effect on IOP or the known effects of systemic β-blockade may be potentiated when given with systemic (e.g. oral or IV) β-adrenergic blockers. Potential additive effects leading to hypotension and/or marked bradycardia with oral or IV Ca channel blockers, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, reserpine, or guanethidine. May block the systemic β-agonist effect of epinephrine; concomitant use of ophthalmic timolol and epinephrine may result in mydriasis. May enhance the hypertensive reaction to the sudden withdrawal of clonidine. Enhanced systemic β-blockade (e.g. decreased heart rate) with CYP2D6 inhibitors (e.g. fluoxetine, paroxetine, quinidine). May attenuate compensatory tachycardia and may increase the risk of hypotension with anaesthetics. May enhance the hypoglycaemic effects of antidiabetic agents.
Food Interaction
Brimonidine: May have additive or potentiated CNS depressant effect with alcohol.
Action
Description: Mechanism of Action: Brimonidine is a selective α2-adrenergic agonist. It is suspected to reduce IOP by decreasing aqueous humour production and enhancing uveoscleral outflow.
Timolol is a non-selective β-adrenergic receptor blocker and has no significant intrinsic sympathomimetic, direct myocardial depressant, or membrane-stabilising activity. It reduces IOP by decreasing aqueous humour production or by possibly increasing the outflow of aqueous humour. Onset: Timolol: IOP reduction: 30 minutes. Duration: Timolol: 24 hours. Pharmacokinetics: Absorption: Brimonidine: Time to peak plasma concentration: 1-4 hours.
Timolol: Time to peak plasma concentration: 1-3 hours. Distribution: Brimonidine: Plasma protein binding: Approx 29%.
Timolol: Enters breast milk. Plasma protein binding: Approx 60%. Metabolism: Brimonidine: Extensively metabolised in the liver.
Timolol: Partially metabolised in the liver. Excretion: Brimonidine: Via urine. Elimination half-life: Approx 3 hours.
Timolol: Elimination half-life: 4 hours.
Chemical Structure
Brimonidine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2435, Brimonidine. https://pubchem.ncbi.nlm.nih.gov/compound/Brimonidine. Accessed Nov. 28, 2022.
Timolol Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 33624, Timolol. https://pubchem.ncbi.nlm.nih.gov/compound/Timolol. Accessed Feb. 23, 2023.
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