brimonidine tartrate + timolol maleate: clinical use

Prescribing considerations

• Confirm that topical beta-blocker monotherapy has provided insufficient pressure control.
• Assess cardiovascular and respiratory history because ophthalmic timolol is systemically absorbed.
• Use caution in hepatic or renal impairment because the combination has not been studied in these groups.
• Review diabetes, spontaneous hypoglycaemia, hyperthyroidism, peripheral vascular disease, corneal disease and dry-eye risk.
• It has not been studied in closed-angle glaucoma.

Contraindications and cautions

• Hypersensitivity to either active substance, beta blockers or an excipient.
• Current or previous bronchial asthma, reactive airway disease or severe chronic obstructive pulmonary disease.
• Sinus bradycardia, sick-sinus syndrome, sinoatrial block, uncontrolled second- or third-degree atrioventricular block, overt cardiac failure or cardiogenic shock.
• Neonates and infants younger than two years.
• Concurrent monoamine oxidase inhibitor treatment.
• Antidepressants affecting noradrenergic transmission, including tricyclic antidepressants and mianserin.

Monitoring

• Intraocular-pressure response and disease progression.
• Pulse, blood pressure and symptoms of cardiac or respiratory deterioration in susceptible patients.
• Ocular allergy, which can have delayed onset and may be associated with raised intraocular pressure.
• Corneal surface and dry-eye symptoms during prolonged exposure to benzalkonium chloride.
• Drowsiness and systemic toxicity if exceptionally used in an older child; routine paediatric use is not recommended.

Clinical pharmacology

Brimonidine is a selective alpha-2 adrenoceptor agonist that reduces aqueous-humour formation and enhances uveoscleral outflow. Timolol is a non-selective beta-1 and beta-2 antagonist that reduces aqueous-humour formation. Both can enter the systemic circulation after ocular administration.

Formulation and product differences

• Both selected products are clear, greenish-yellow, multidose eye-drop solutions containing benzalkonium chloride and phosphate buffer.
• The selected generic is described as particle-free and is supplied as a single-bottle pack; Combigan may be supplied in one- or three-bottle packs, although not every pack size is marketed.
• Both should be discarded 28 days after opening. Unopened shelf life and stated storage wording differ, so check the individual pack and leaflet.

Eye drops

Route: Ophthalmic

Strengths: 2 mg/mL + 5 mg/mL