Usage
Brimonidine + Timolol is prescribed for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers.
Pharmacological Classification: Ophthalmic glaucoma agents – combination of an alpha-2 adrenergic agonist (brimonidine) and a non-selective beta-adrenergic blocker (timolol).
Mechanism of Action: Brimonidine reduces aqueous humor production and increases uveoscleral outflow. Timolol decreases aqueous humor production. The combined effect results in a greater reduction of IOP than either agent alone.
Alternate Names
Brimonidine tartrate/timolol maleate ophthalmic solution
Brand Names: Combigan, APO-Brimonidine-Timop, JAMP-Brimonidine-Timolol, and various generics.
How It Works
Pharmacodynamics: Brimonidine acts as an alpha-2 adrenergic agonist, stimulating alpha-2 receptors in the ciliary body, decreasing aqueous humor production, and increasing uveoscleral outflow. Timolol is a non-selective beta-blocker, reducing aqueous humor production by inhibiting beta-adrenergic receptors in the ciliary body. The combined effect leads to a significant reduction in IOP.
Pharmacokinetics:
- Absorption: Both brimonidine and timolol are absorbed systemically following topical ocular administration, though systemic exposure is low.
- Metabolism: Brimonidine is primarily metabolized in the liver. Timolol is partially metabolized in the liver.
- Elimination: Brimonidine is primarily excreted in the urine. Timolol is excreted primarily unchanged in the urine.
Mode of Action:
- Brimonidine: Binds to alpha-2 adrenergic receptors in the ciliary body, inhibiting adenylate cyclase activity and reducing aqueous humor production. Also increases uveoscleral outflow.
- Timolol: Blocks beta-1 and beta-2 adrenergic receptors in the ciliary body, decreasing aqueous humor production.
Elimination pathways: Primarily renal excretion for both drugs, with some hepatic metabolism.
Dosage
Standard Dosage
Adults: One drop in the affected eye(s) twice daily, approximately 12 hours apart.
Children: Not recommended for children under 2 years of age. Safety and efficacy in children 2-17 years have not been established. Use only if potential benefit outweighs the risk.
Special Cases:
- Elderly Patients: No dosage adjustment is generally necessary. Monitor for potential systemic effects of beta-blockade.
- Patients with Renal Impairment: Use with caution. Timolol has been associated with pronounced hypotension in patients with severe renal impairment on dialysis.
- Patients with Hepatic Dysfunction: Use with caution.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes (may mask hypoglycemia), cardiovascular disease (monitor for bradycardia, hypotension, and worsening heart failure), reactive airway disease, and myasthenia gravis.
Clinical Use Cases
Brimonidine + Timolol is not typically used in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indication is chronic glaucoma and ocular hypertension management.
Dosage Adjustments
Dosage adjustments may be needed for patients with renal or hepatic impairment, cardiovascular disease, or respiratory disease. Close monitoring is recommended.
Side Effects
Common Side Effects
Ocular: Burning or stinging, foreign body sensation, ocular hyperemia, pruritus, blurred vision, dry eye, tearing, eyelid erythema or edema.
Systemic: Headache, dry mouth, drowsiness, fatigue, allergic reactions (rare).
Rare but Serious Side Effects
Ocular: Iritis, uveitis, corneal erosion.
Systemic: Bradycardia, hypotension, syncope, heart failure exacerbation, bronchospasm, depression.
Long-Term Effects
Long-term use may result in dry eye or worsening of pre-existing cardiovascular or respiratory conditions.
Adverse Drug Reactions (ADR)
Severe allergic reactions, significant bradycardia or hypotension, bronchospasm.
Contraindications
- Hypersensitivity to brimonidine, timolol, or any component of the formulation.
- Reactive airway disease including asthma or severe COPD.
- Sinus bradycardia, second- or third-degree atrioventricular block, overt cardiac failure, or cardiogenic shock.
- Patients receiving monoamine oxidase (MAO) inhibitor therapy.
- Neonates and infants (under 2 years of age).
Drug Interactions
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Australia); Not Assigned (US FDA). Not recommended during pregnancy unless clearly necessary. Potential for fetal harm.
- Breastfeeding: Not recommended. Timolol is excreted in breast milk. Potential for neonatal side effects.
Drug Profile Summary
- Mechanism of Action: Decreases aqueous humor production and increases uveoscleral outflow (brimonidine); Decreases aqueous humor production (timolol).
- Side Effects: Ocular irritation, dry mouth, drowsiness, bradycardia, hypotension.
- Contraindications: Asthma/COPD, severe heart conditions, MAO inhibitor use, infants.
- Drug Interactions: Beta-blockers, calcium channel blockers, CNS depressants, TCAs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: One drop twice daily.
- Monitoring Parameters: IOP, heart rate, blood pressure.
Popular Combinations
Not applicable. Brimonidine + Timolol is itself a fixed-dose combination.
Precautions
- General Precautions: Monitor for ocular and systemic side effects. Assess cardiovascular and respiratory status before initiating therapy.
- Specific Populations: Use with caution in pregnant/breastfeeding women, children, elderly patients, and those with diabetes, cardiovascular disease, or respiratory disease.
- Lifestyle Considerations: Alcohol may potentiate hypotensive effects. May cause drowsiness and blurred vision; caution with driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Brimonidine + Timolol?
A: One drop in the affected eye(s) twice daily, approximately 12 hours apart.
Q2: Can Brimonidine + Timolol be used in children?
A: Not recommended for children under 2. Use with caution in children over 2 only if potential benefit outweighs risk.
Q3: What are the common side effects?
A: Ocular burning/stinging, blurred vision, dry eye, headache, dry mouth, drowsiness.
Q4: What are the serious side effects?
A: Bradycardia, hypotension, heart failure exacerbation, bronchospasm.
Q5: Can pregnant or breastfeeding women use this medication?
A: Not recommended unless the benefit outweighs the risk. Consult a physician.
Q6: What are the contraindications for Brimonidine + Timolol?
A: Asthma/COPD, certain heart conditions, MAOI use, infants under 2.
Q7: Does this medication interact with other drugs?
A: Yes. It can interact with beta-blockers, calcium channel blockers, CNS depressants, and certain antidepressants.
Q8: Should I avoid any activities while taking this medication?
A: Use caution when driving or operating machinery, as it may cause blurred vision and drowsiness.
Q9: What should I do if I miss a dose?
A: Instill the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and return to your regular dosing schedule. Do not instill two drops at once.
Q10: How should I store this medication?
A: Store at room temperature and protect from light. Discard the bottle four weeks after opening.
