Drugs List

Administration

For ocular administration.

Shake the bottle.

Contraindications

Children under 18 years

Pregnancy (see Pregnancy )

Renal impairment - creatinine clearance below 30ml/min

Bronchial asthma
History of bronchial asthma
Severe chronic obstructive pulmonary disease

Sinus bradycardia
Sick sinus syndrome
Sino-atrial block
Second or third degree atrioventricular block not controlled with a pace-maker
Uncontrolled cardiac failure
Cardiogenic shock

Severe allergic rhinitis

Hyperchloraemic acidosis

The carbonic anhydrase inhibitor, brinzolamide, is a sulfonamide substance and should not be used in patients with sulfonamide sensitivity.

Precautions and Warnings

Breastfeeding (see Lactation )

Due to the beta-adrenergic effects of timolol, use with caution in patients with a history of severe cardiac disease, and monitor for signs of cardiac failure, pulse rate changes, worsening of Prinzmetal's angina, severe peripheral and central circulatory disorders and hypotension. Cardiac failure should be controlled before treatment initiation. As with any beta-blocking agent, pulmonary adverse effects including death due to bronchospasm may occur.

Use with caution in patients with first degree block due to negative effects on conduction time.

Use with caution in myasthenia gravis.

May mask signs and symptoms of acute hypoglycaemia - use with caution in patients subject to spontaneous hypoglycaemia or with labile insulin-dependent diabetes.

May mask signs of hyperthyroidism.

Use with caution in patients with mild/moderate chronic obstructive pulmonary disease.

Discontinue if serious acid-base disturbances or hypersensitivity reactions occur.

Patients with a history of atopy or severe anaphylactic reactions may be unresponsive to the usual doses of adrenaline whilst taking this product.

Use with caution and monitor intraocular pressure in patients with pseudoexfoliative glaucoma or pigmentary glaucoma.

Use with caution in elderly patients as their ability to perform tasks requiring mental alertness and/or physical coordination may be impaired.

Monitor patients with diabetes mellitus, corneal dystrophies or other possibilities for compromised corneas, as corneal hydration may be affected. The wearing of contact lenses may increase the risk for the cornea. Choroidal detachment has been reported following therapy.

Before surgery the anaesthesiologist should be informed that the patient is receiving timolol, which may block systemic beta-agonist effects.

Contains benzalkonium chloride. Soft contact lenses should be removed before instillation of the eye drops and may be reinserted after 15 minutes.

Benzalkonium chloride has also been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy - monitor closely with frequent or prolonged use.

Application may cause transient blurring of vision; patients should avoid driving or operating machinery until vision is clear.

Brinzolamide and timolol suspension eye drops are indicated in open-angle glaucoma or ocular hypertension. They have not been studied in narrow angle glaucoma and are not recommended for this condition.

CSM Warnings

Pregnancy and Lactation

Pregnancy

Brinzolamide and timolol eye drop suspension should only be used in pregnancy if cleary essential.

There are no adequate data from the use of brinzolamide in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.

Well-controlled epidemiological studies with systemic use of beta-blockers did not indicate malformative effects, but some pharmacological effects such as bradycardia have been observed in foetuses or neonates. When systemic beta-blockers are used in pregnancy, potential effects such as decreased heart rate, hypoglycaemia and respiratory problems in the newborn are to be considered. concerns about Intra-uterine growth restriction have also been raised. Data on a limited number of exposed pregnancies indicate no adverse effects of timolol in eye drops on pregnancy or on the health of the foetus/newborn child but bradycardia and arrhythmia have been reported in one case in the foetus of a woman treated with timolol eye drops.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

It is not known whether brinzolamide is excreted in human breast milk. Animal studies have shown excretion of brinzolamide in breast milk. Timolol does appear in human breast milk. The manufacturer considers that, at therapeutic doses of brinzolamide and timolol, no effects on the breastfed newborns/infants are anticipated.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Blurred vision
Insomnia
Depression
Dysgeusia
Eye pain
Eye irritation
Sensation of foreign body in eye
Corneal erosion
Superficial punctate keratitis
Dry eyes
Ocular discharge
Eye pruritus
Ocular hyperaemia
Blepharitis
Allergic conjunctivitis
Corneal disorders
Anterior chamber inflammation
Conjunctival hyperaemia
Lid margin crusting
Asthenopia
Abnormal sensation in eye
Eyelid pruritus
Eyelid erythema
Decrease in blood pressure
Chronic obstructive pulmonary disease
Pharyngolaryngeal pain
Rhinorrhoea
Cough
Hair disorder
Lichen planus
Nasopharyngitis
Pharyngitis
Sinusitis
Rhinitis
Decreased erythrocyte count
Increased blood chloride
Angioedema
Urticaria
Rash
Pruritus
Anaphylaxis
Hypersensitivity reactions
Hypoglycaemia
Apathy
Reduced libido
Nightmares
Nervousness
Impaired memory
Somnolence
Motor disturbances
Amnesia
Paraesthesia
Tremor
Hypoaesthesia
Ageusia
Cerebral ischaemia
Cerebrovascular accident
Syncope
Myasthenia gravis
Headache
Dizziness
Keratitis
Keratopathy
Optic disc oedema
Increased intra-ocular pressure
Corneal deposits
Corneal staining
Corneal oedema
Conjunctivitis
Diplopia
Photophobia
Photopsia
Ocular discomfort
Keratoconjunctivitis
Scleral disorders
Subconjunctival cyst
Increased lacrimation
Visual disturbances
Eye swelling
Madarosis
Eyelid oedema
Ptosis
Tinnitus
Vertigo
Cardio-respiratory depression
Angina pectoris
Bradycardia
Variation in heart rate
Arrhythmias
Palpitations
Tachycardia
Increased heart rate
Cardiac arrest
Cardiac failure
Atrioventricular block
Increased blood pressure
Hypertension
Hypotension
Raynaud's phenomenon
Dyspnoea
Asthma
Epistaxis
Throat irritation
Nasal congestion
Upper respiratory tract congestion
Dry mouth
Oesophagitis
Vomiting
Diarrhoea
Nausea
Dyspepsia
Upper abdominal pain
Abdominal discomfort
Stomach pain
Increased bowel action
Gastrointestinal disorder
Oral paraesthesia and hypoaesthesia
Flatulence
Abnormal liver function tests
Maculopapular rash
Alopecia
Skin tightness
Dermatitis
Erythema
Back pain
Muscle spasm
Myalgia
Arthralgia
Painful extremities
Renal pain
Polakiuria
Erectile dysfunction
Pain
Asthenia
Chest discomfort
Fatigue
Feeling abnormal
Irritability
Chest pain
Peripheral oedema
Malaise
Hyperchloraemia
Lacrimal gland disorders
Pterygium
Respiratory disorders

Drugs List

Dosage

Wash hands prior to use.

Shake well before use.

Avoid contact of the container with the eye or other surfaces as contamination leading to ophthalmic infection may occur.

To reduce systemic absorption compress the lacrimal sac during administration and for one minute afterwards.

Leave an interval of at least 5 minutes before instilling another ophthalmic medication.

Soft contact lenses should be removed before instillation of the eye drops and may be reinserted after 15 minutes.

Discard 4 weeks after first opening.

If a dose is missed, treatment should be continued with the next dose as planned. The dose should not exceed one drop in the affected eye(s) twice daily.

When substituting another ophthalmic antiglaucoma agent with brinzolamide and timolol, the other other agent should be discontinued and brinzolamide and timolol started the following day.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For ocular administration.

Shake the bottle.

Contraindications

Children under 18 years

Pregnancy (see Pregnancy )

Renal impairment - creatinine clearance below 30ml/min

Bronchial asthma
History of bronchial asthma
Severe chronic obstructive pulmonary disease

Sinus bradycardia
Sick sinus syndrome
Sino-atrial block
Second or third degree atrioventricular block not controlled with a pace-maker
Uncontrolled cardiac failure
Cardiogenic shock

Severe allergic rhinitis

Hyperchloraemic acidosis

The carbonic anhydrase inhibitor, brinzolamide, is a sulfonamide substance and should not be used in patients with sulfonamide sensitivity.

Precautions and Warnings

Breastfeeding (see Lactation )

Due to the beta-adrenergic effects of timolol, use with caution in patients with a history of severe cardiac disease, and monitor for signs of cardiac failure, pulse rate changes, worsening of Prinzmetal's angina, severe peripheral and central circulatory disorders and hypotension. Cardiac failure should be controlled before treatment initiation. As with any beta-blocking agent, pulmonary adverse effects including death due to bronchospasm may occur.

Use with caution in patients with first degree block due to negative effects on conduction time.

Use with caution in myasthenia gravis.

May mask signs and symptoms of acute hypoglycaemia - use with caution in patients subject to spontaneous hypoglycaemia or with labile insulin-dependent diabetes.

May mask signs of hyperthyroidism.

Use with caution in patients with mild/moderate chronic obstructive pulmonary disease.

Discontinue if serious acid-base disturbances or hypersensitivity reactions occur.

Patients with a history of atopy or severe anaphylactic reactions may be unresponsive to the usual doses of adrenaline whilst taking this product.

Use with caution and monitor intraocular pressure in patients with pseudoexfoliative glaucoma or pigmentary glaucoma.

Use with caution in elderly patients as their ability to perform tasks requiring mental alertness and/or physical coordination may be impaired.

Monitor patients with diabetes mellitus, corneal dystrophies or other possibilities for compromised corneas, as corneal hydration may be affected. The wearing of contact lenses may increase the risk for the cornea. Choroidal detachment has been reported following therapy.

Before surgery the anaesthesiologist should be informed that the patient is receiving timolol, which may block systemic beta-agonist effects.

Contains benzalkonium chloride. Soft contact lenses should be removed before instillation of the eye drops and may be reinserted after 15 minutes.

Benzalkonium chloride has also been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy - monitor closely with frequent or prolonged use.

Application may cause transient blurring of vision; patients should avoid driving or operating machinery until vision is clear.

Brinzolamide and timolol suspension eye drops are indicated in open-angle glaucoma or ocular hypertension. They have not been studied in narrow angle glaucoma and are not recommended for this condition.

CSM Warnings

Pregnancy and Lactation

Pregnancy

Brinzolamide and timolol eye drop suspension should only be used in pregnancy if cleary essential.

There are no adequate data from the use of brinzolamide in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.

Well-controlled epidemiological studies with systemic use of beta-blockers did not indicate malformative effects, but some pharmacological effects such as bradycardia have been observed in foetuses or neonates. When systemic beta-blockers are used in pregnancy, potential effects such as decreased heart rate, hypoglycaemia and respiratory problems in the newborn are to be considered. concerns about Intra-uterine growth restriction have also been raised. Data on a limited number of exposed pregnancies indicate no adverse effects of timolol in eye drops on pregnancy or on the health of the foetus/newborn child but bradycardia and arrhythmia have been reported in one case in the foetus of a woman treated with timolol eye drops.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

It is not known whether brinzolamide is excreted in human breast milk. Animal studies have shown excretion of brinzolamide in breast milk. Timolol does appear in human breast milk. The manufacturer considers that, at therapeutic doses of brinzolamide and timolol, no effects on the breastfed newborns/infants are anticipated.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

Instillation of eye drops may cause transient blurring of vision. Avoid driving or operating machinery until vision is clear.

Ability to perform tasks requiring mental alertness and/or physical coordination may be impaired in elderly patients.

Counselling

Advise patient to wash their hands prior to use.

Shake the bottle.

Advise patient to avoid contact of the container with the eye or other surfaces as contamination leading to ophthalmic infection may occur.

Advise patients to leave an interval of at least 5 minutes before instilling another ophthalmic medication.

Advise patient to compress the lacrimal sac during administration and for one minute afterwards, to reduce systemic absorption.

Advise patients that instillation of eye drops may cause transient blurring of vision and to avoid driving or operating machinery until vision is clear.

Advise patient to remove soft contact lenses before instillation of the eye drops and re-insert them after 15 minutes.

Advise patient to discard eye drops 4 weeks after first opening.

Side Effects

Blurred vision
Insomnia
Depression
Dysgeusia
Eye pain
Eye irritation
Sensation of foreign body in eye
Corneal erosion
Superficial punctate keratitis
Dry eyes
Ocular discharge
Eye pruritus
Ocular hyperaemia
Blepharitis
Allergic conjunctivitis
Corneal disorders
Anterior chamber inflammation
Conjunctival hyperaemia
Lid margin crusting
Asthenopia
Abnormal sensation in eye
Eyelid pruritus
Eyelid erythema
Decrease in blood pressure
Chronic obstructive pulmonary disease
Pharyngolaryngeal pain
Rhinorrhoea
Cough
Hair disorder
Lichen planus
Nasopharyngitis
Pharyngitis
Sinusitis
Rhinitis
Decreased erythrocyte count
Increased blood chloride
Angioedema
Urticaria
Rash
Pruritus
Anaphylaxis
Hypersensitivity reactions
Hypoglycaemia
Apathy
Reduced libido
Nightmares
Nervousness
Impaired memory
Somnolence
Motor disturbances
Amnesia
Paraesthesia
Tremor
Hypoaesthesia
Ageusia
Cerebral ischaemia
Cerebrovascular accident
Syncope
Myasthenia gravis
Headache
Dizziness
Keratitis
Keratopathy
Optic disc oedema
Increased intra-ocular pressure
Corneal deposits
Corneal staining
Corneal oedema
Conjunctivitis
Diplopia
Photophobia
Photopsia
Ocular discomfort
Keratoconjunctivitis
Scleral disorders
Subconjunctival cyst
Increased lacrimation
Visual disturbances
Eye swelling
Madarosis
Eyelid oedema
Ptosis
Tinnitus
Vertigo
Cardio-respiratory depression
Angina pectoris
Bradycardia
Variation in heart rate
Arrhythmias
Palpitations
Tachycardia
Increased heart rate
Cardiac arrest
Cardiac failure
Atrioventricular block
Increased blood pressure
Hypertension
Hypotension
Raynaud's phenomenon
Dyspnoea
Asthma
Epistaxis
Throat irritation
Nasal congestion
Upper respiratory tract congestion
Dry mouth
Oesophagitis
Vomiting
Diarrhoea
Nausea
Dyspepsia
Upper abdominal pain
Abdominal discomfort
Stomach pain
Increased bowel action
Gastrointestinal disorder
Oral paraesthesia and hypoaesthesia
Flatulence
Abnormal liver function tests
Maculopapular rash
Alopecia
Skin tightness
Dermatitis
Erythema
Back pain
Muscle spasm
Myalgia
Arthralgia
Painful extremities
Renal pain
Polakiuria
Erectile dysfunction
Pain
Asthenia
Chest discomfort
Fatigue
Feeling abnormal
Irritability
Chest pain
Peripheral oedema
Malaise
Hyperchloraemia
Lacrimal gland disorders
Pterygium
Respiratory disorders

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 ).

Reference Sources

British National Formulary, 63rd Edition (2012) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Summary of Product Characteristics: Azarga. Alcon Laboratories (UK) Ltd. Revised February 2012.