Fixed Combination Glaucoma Treatment — Alpha-2 Agonist + Beta-blocker Pregnancy: Avoid — timolol crosses placenta (neonatal bradycardia); brimonidine may affect fetal CNS

Brimonidine / Timolol Fixed Combination

Brand names: Combigan

Adult dose

Dose: 1 drop twice daily

Route: Topical (ophthalmic)

Frequency: Twice daily (morning and evening)

Max: 1 drop twice daily

Contains brimonidine tartrate 0.2% + timolol maleate 0.5%. Fixed combination for patients requiring additional IOP reduction beyond monotherapy. Wait at least 5 minutes between different eye drops. Systemically, the brimonidine component can cause marked sedation and hypotension — particularly in children and elderly.

Paediatric dose

Route:

MHRA/CONTRAINDICATED in children under 2 years — brimonidine causes severe CNS depression, apnoea, bradycardia, and hypotension. Use with extreme caution and only under specialist supervision in children 2–12 years.

Dose adjustments

Renal

Use with caution — both components have some systemic absorption; timolol renally cleared

Hepatic

Use with caution — hepatic impairment affects brimonidine metabolism

Clinical pearls

MHRA warning — infants: brimonidine 0.2% has caused serious CNS depression including apnoea in infants — absolute contraindication under age 2; use with great caution in children under 12; carers must be vigilant for excess sedation and breathing changes
Brimonidine allergy: follicular conjunctivitis and contact dermatitis affecting eyelids develops in ~15–25% of patients with prolonged use — often misdiagnosed as worsening glaucoma or infection; treat by stopping brimonidine; allergy to one brimonidine product may not preclude use of lower-concentration formulation
MAO inhibitor absolute contraindication: brimonidine (alpha-2 agonist) + MAO inhibitor → severe hypertensive or hypotensive crisis depending on MAO subtype; screen all patients for MAO inhibitor use before prescribing
Nasolacrimal occlusion: reduces both brimonidine systemic absorption (sedation risk) and timolol absorption (cardiorespiratory risk) — particularly important in children, elderly, and patients with cardiac or respiratory comorbidity
Second-line to prostaglandin analogues: both Cosopt and Combigan are typically added as adjuncts when prostaglandin analogue monotherapy is insufficient — NICE NG81 recommends prostaglandin analogue first-line for most patients with POAG

Contraindications

Children under 2 years — ABSOLUTE contraindication (brimonidine CNS depression risk)
Asthma or COPD — timolol component
Bradycardia or heart block — timolol component
Concurrent MAO inhibitor therapy — brimonidine; severe hypotension
Concurrent tricyclic antidepressants — brimonidine interaction

Side effects

Ocular allergy — brimonidine causes follicular conjunctivitis and contact allergy in up to 25% with prolonged use; patients need to be aware of this late-onset allergy
Systemic CNS depression — drowsiness, fatigue (brimonidine — alpha-2 agonism in CNS)
Dry mouth and nose
Systemic beta-blocker effects — bronchospasm, bradycardia (timolol)
Conjunctival hyperaemia
Ocular stinging

Interactions

MAO inhibitors — severe hypertensive/hypotensive crisis with brimonidine; CONTRAINDICATED
Tricyclic antidepressants — reduce brimonidine's antihypertensive effect; interaction
Systemic beta-blockers — additive effect with timolol; risk of bradycardia/hypotension
CNS depressants — additive sedation with brimonidine component

Monitoring

IOP at 4–8 weeks
Pulse and blood pressure
Respiratory symptoms (bronchospasm — timolol)
Conjunctival examination for allergy (brimonidine — follicular reaction)
Sedation assessment — particularly in children and elderly

Reference: BNFc; BNF 90; NICE NG81 (Glaucoma); MHRA Brimonidine Paediatric Safety Warning; SPC Combigan. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways