Drugs List

Therapeutic Indications

Uses

Elevated IOP in ocular hypertension when beta blocker alone insufficient
Elevated IOP in open-angle glaucoma when beta blocker alone is insufficient

Contraindications

Children under 2 years
Asthma
Breastfeeding
Cardiogenic shock
History of asthma
Non-paced second degree atrioventricular block
Non-paced third degree atrioventricular block
Severe chronic obstructive pulmonary disease
Sinoatrial exit block
Sinus bradycardia
Uncontrolled cardiac failure

Precautions and Warnings

Atopy
Children aged 2 to 18 years
History of allergies including anaphylaxis
Soft contact lenses
Cardiac failure
Cardiovascular disorder
Corneal disorder
Depression
Diabetes mellitus
First degree atrioventricular block
Hepatic impairment
History of obstructive pulmonary disease
Hyperthyroidism
Hypotension
Ischaemic heart disease
Metabolic acidosis
Myasthenia gravis
Pregnancy
Prinzmetal's angina
Raynaud's syndrome
Renal impairment
Severe peripheral circulatory disorder
Spontaneous hypoglycaemia
Uncontrolled phaeochromocytoma

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Anaesthetist should be made aware patient is taking this medication
Control cardiac failure before starting treatment
May mask symptoms of hyperthyroidism
May unmask the symptoms of myasthenia gravis
Advise patient blurred vision may affect ability to drive/operate machinery
Contains benzalkonium chloride. Not to be used with soft contact lenses
In combined therapy, administer eye products at least five minutes apart
To reduce systemic absorption compress lacrimal sac during administration
Monitor patient with history of severe cardiac disease for signs of failure
Monitor pulse rates in patients with potential for cardiac failure
Beta blockers may reduce the response to adrenaline in anaphylaxis
Contains phosphate: Risk of calcification in existing notable cornea damage
Systemic absorption & adverse effects of systemic beta blockers may occur
Do not withdraw this drug suddenly
Withdraw drug gradually, especially in patients with cardiac ischaemia
Discontinue if allergic reaction occurs
Advise patient to avoid touching the eye/other surfaces with container tip
If soft contact lenses worn,insert them 15 minutes after using eye drops

Pregnancy and Lactation

Pregnancy

Use timolol with brimonidine tartate eye drops with caution during pregnancy.

The manufacturer does not recommend the use of timolol with brimonidine tartate during pregnancy unless the benefits of maternal therapy outweigh the potential risks to the fetus.

Timolol
Risks are concerned with a reduction in placental weight and intrauterine growth restriction. If timolol eye drops are used during pregnancy, it is advisable to consider lacrimal sac compression and removal of any excess on the skin with a tissue. Animal studies in mice, rats and rabbits found no evidence of teratogenicity at doses up to 40 times the maximum daily dose. However, fetotoxicity was observed in rabbits at this dose.

Newborns exposed to timolol in the uterus should be closely monitored for bradycardia during the first few days after birth (Briggs, 2015).

Brimonidine tartate
At the time of writing, there is limited published information regarding the use of brimonidine tartate during pregnancy. Animal studies have shown reproductive toxicity at high maternotoxic doses but the risk to humans is unknown.

Lactation

Timolol with brimonidine eye drops are contraindicated during breastfeeding.

Use of timolol with brimonidine eye drops when breastfeeding is contraindicated by the manufacturer.

Timolol
Timolol is excreted into breast milk. In one case report, a woman with elevated intraocular pressure applied ophthalmic 0.5% timolol drops to one eye twice daily, resulting in excretion of the drug in her breast milk. Most authorities consider that the levels seen were below the daily dose that would be below that expected to produce cardiac effects in the infant (Briggs, 2015).

Brimonidine tartrate
It is unknown if brimonidine tartate is excreted into breast milk but it has been shown to be excreted into the milk of lactating rats. There is concern of possible CNS depression, apnea, lethargy and bradycardia in infants exposed to brimonidine and hence its use is not recommended during breastfeeding.

Side Effects

Abdominal pain
Allergic conjunctivitis
Allergic contact dermatitis
Allergic reaction
Alopecia
Angioedema
Arrhythmias
Asthenia
Asthenopia
Blepharitis
Blurred vision
Bradycardia
Bronchospasm
Burning and stinging of the eyes
Cardiac arrest
Cardiac failure
Cerebral ischaemia
Cerebrovascular accident
Chest pain
Choroidal detachment (following filtration surgery)
Cold extremities
Congestive cardiac failure
Conjunctival blanching
Conjunctival follicles
Conjunctival hyperaemia
Conjunctival oedema
Conjunctivitis
Corneal disorders
Corneal erosion
Corneal oedema
Cough
Decreased corneal sensitivity
Depression
Diarrhoea
Diplopia
Dizziness
Dry eyes
Dry mouth
Dyspepsia
Dyspnoea
Epiphora
Erythema
Exacerbation of myasthenia gravis
Exacerbation of psoriasis
Eye irritation
Eye pain
Eyelid erythema
Eyelid oedema
Eyelid pain
Eyelid pruritus
Facial oedema
Fatigue
Gastro-intestinal symptoms
Headache
Heart block
Hypertension
Hypoglycaemia
Hypotension
Insomnia
Iridocyclitis
Iritis
Keratitis
Memory loss
Miosis
Myalgia
Nasal dryness
Nausea
Nightmares
Ocular discharge
Ocular pruritus
Oedema
Palpitations
Papillary hypertrophy
Paraesthesia
Photophobia
Pruritus
Psoriasiform rash
Ptosis
Rash
Raynaud's phenomenon
Reduced libido
Respiratory failure
Rhinitis
Sensation of foreign body in eye
Sexual dysfunction
Somnolence
Superficial punctate keratitis
Syncope
Tachycardia
Taste disturbances
Upper respiratory symptoms
Urticaria
Vasodilation
Visual disturbances
Vitreous detachment
Vitreous disorder
Vomiting

Presentation

Eye drop solution containing:

Timolol 5mg (as timolol maleate 6.8mg)/ml
Brimonidine tartrate 2mg (equivalent to brimonidine 1.3mg)/ml

Drugs List

Therapeutic Indications

Uses

Elevated IOP in ocular hypertension when beta blocker alone insufficient
Elevated IOP in open-angle glaucoma when beta blocker alone is insufficient

Dosage

Adults

Contraindications

Children under 2 years
Asthma
Breastfeeding
Cardiogenic shock
History of asthma
Non-paced second degree atrioventricular block
Non-paced third degree atrioventricular block
Severe chronic obstructive pulmonary disease
Sinoatrial exit block
Sinus bradycardia
Uncontrolled cardiac failure

Precautions and Warnings

Atopy
Children aged 2 to 18 years
History of allergies including anaphylaxis
Soft contact lenses
Cardiac failure
Cardiovascular disorder
Corneal disorder
Depression
Diabetes mellitus
First degree atrioventricular block
Hepatic impairment
History of obstructive pulmonary disease
Hyperthyroidism
Hypotension
Ischaemic heart disease
Metabolic acidosis
Myasthenia gravis
Pregnancy
Prinzmetal's angina
Raynaud's syndrome
Renal impairment
Severe peripheral circulatory disorder
Spontaneous hypoglycaemia
Uncontrolled phaeochromocytoma

Advise diabetic patients that hypoglycaemic symptoms may be reduced/altered
Anaesthetist should be made aware patient is taking this medication
Control cardiac failure before starting treatment
May mask symptoms of hyperthyroidism
May unmask the symptoms of myasthenia gravis
Advise patient blurred vision may affect ability to drive/operate machinery
Contains benzalkonium chloride. Not to be used with soft contact lenses
In combined therapy, administer eye products at least five minutes apart
To reduce systemic absorption compress lacrimal sac during administration
Monitor patient with history of severe cardiac disease for signs of failure
Monitor pulse rates in patients with potential for cardiac failure
Beta blockers may reduce the response to adrenaline in anaphylaxis
Contains phosphate: Risk of calcification in existing notable cornea damage
Systemic absorption & adverse effects of systemic beta blockers may occur
Do not withdraw this drug suddenly
Withdraw drug gradually, especially in patients with cardiac ischaemia
Discontinue if allergic reaction occurs
Advise patient to avoid touching the eye/other surfaces with container tip
If soft contact lenses worn,insert them 15 minutes after using eye drops

Pregnancy and Lactation

Pregnancy

Use timolol with brimonidine tartate eye drops with caution during pregnancy.

The manufacturer does not recommend the use of timolol with brimonidine tartate during pregnancy unless the benefits of maternal therapy outweigh the potential risks to the fetus.

Timolol
Risks are concerned with a reduction in placental weight and intrauterine growth restriction. If timolol eye drops are used during pregnancy, it is advisable to consider lacrimal sac compression and removal of any excess on the skin with a tissue. Animal studies in mice, rats and rabbits found no evidence of teratogenicity at doses up to 40 times the maximum daily dose. However, fetotoxicity was observed in rabbits at this dose.

Newborns exposed to timolol in the uterus should be closely monitored for bradycardia during the first few days after birth (Briggs, 2015).

Brimonidine tartate
At the time of writing, there is limited published information regarding the use of brimonidine tartate during pregnancy. Animal studies have shown reproductive toxicity at high maternotoxic doses but the risk to humans is unknown.

Lactation

Timolol with brimonidine eye drops are contraindicated during breastfeeding.

Use of timolol with brimonidine eye drops when breastfeeding is contraindicated by the manufacturer.

Timolol
Timolol is excreted into breast milk. In one case report, a woman with elevated intraocular pressure applied ophthalmic 0.5% timolol drops to one eye twice daily, resulting in excretion of the drug in her breast milk. Most authorities consider that the levels seen were below the daily dose that would be below that expected to produce cardiac effects in the infant (Briggs, 2015).

Brimonidine tartrate
It is unknown if brimonidine tartate is excreted into breast milk but it has been shown to be excreted into the milk of lactating rats. There is concern of possible CNS depression, apnea, lethargy and bradycardia in infants exposed to brimonidine and hence its use is not recommended during breastfeeding.

Side Effects

Abdominal pain
Allergic conjunctivitis
Allergic contact dermatitis
Allergic reaction
Alopecia
Angioedema
Arrhythmias
Asthenia
Asthenopia
Blepharitis
Blurred vision
Bradycardia
Bronchospasm
Burning and stinging of the eyes
Cardiac arrest
Cardiac failure
Cerebral ischaemia
Cerebrovascular accident
Chest pain
Choroidal detachment (following filtration surgery)
Cold extremities
Congestive cardiac failure
Conjunctival blanching
Conjunctival follicles
Conjunctival hyperaemia
Conjunctival oedema
Conjunctivitis
Corneal disorders
Corneal erosion
Corneal oedema
Cough
Decreased corneal sensitivity
Depression
Diarrhoea
Diplopia
Dizziness
Dry eyes
Dry mouth
Dyspepsia
Dyspnoea
Epiphora
Erythema
Exacerbation of myasthenia gravis
Exacerbation of psoriasis
Eye irritation
Eye pain
Eyelid erythema
Eyelid oedema
Eyelid pain
Eyelid pruritus
Facial oedema
Fatigue
Gastro-intestinal symptoms
Headache
Heart block
Hypertension
Hypoglycaemia
Hypotension
Insomnia
Iridocyclitis
Iritis
Keratitis
Memory loss
Miosis
Myalgia
Nasal dryness
Nausea
Nightmares
Ocular discharge
Ocular pruritus
Oedema
Palpitations
Papillary hypertrophy
Paraesthesia
Photophobia
Pruritus
Psoriasiform rash
Ptosis
Rash
Raynaud's phenomenon
Reduced libido
Respiratory failure
Rhinitis
Sensation of foreign body in eye
Sexual dysfunction
Somnolence
Superficial punctate keratitis
Syncope
Tachycardia
Taste disturbances
Upper respiratory symptoms
Urticaria
Vasodilation
Visual disturbances
Vitreous detachment
Vitreous disorder
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: August 2021

Reference Sources

Summary of Product Characteristics: Combigan. Allergan Ltd. Revised November 2020.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Timolol, Last revised: 19 October 2020
Last accessed: 06 August 2021

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Brimonidine, Last revised: 19 July 2021
Last accessed: 06 August 2021