Agobrim 0.15% Eye Drops

AGOBRIM 0.15% w/v EYE DROPS is indicated for the lowering of intraocular pressure in patients with open angle glaucoma or ocular hypertension.

The recommended dose is one drop of AGOBRIM 0.15% w/v EYE DROPS in the affected eye(s) twice daily, approximately 12 hours apart. AGOBRIM 0.15% w/v EYE DROPS ophthalmic solution may be used concomitantly with other topical ophthalmic medicinal products to lower intraocular pressure. If more than one topical ophthalmic product is being used, the product should be administered at least 5 minutes apart. Method of administration: Ocular use.

AGOBRIM 0.15% w/v EYE DROPS is contraindicated in patients who have exhibited hypersensitivity to brimonidine tartrate, benzalkonium chloride or to any of the excipients listed in section 6.1. AGOBRIM 0.15% w/v EYE DROPS is contraindicated in neonates and infants (under the age of 2 years).

Severe cardiovascular disease Although Brimonidine eye drops 0.15% w/v has minimal effects on the blood pressure of patients, caution should be exercised in treating patients with severe or unstable and uncontrolled cardiovascular disease.

Potentiation of vascular insufficiency AGOBRIM 0.15% w/v EYE DROPS may potentiate syndromes associated with vascular insufficiency. AGOBRIM 0.15% w/v EYE DROPS should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangitis obliterans. Patients using IOP-lowering medication should be routinely monitored for IOP (intraocular pressure).

Eye disorders If allergic reactions are observed, treatment with AGOBRIM 0.15% w/v EYE DROPS should be discontinued. Delayed ocular hypersensitivity reactions have been reported with brimonidine, as contained in AGOBRIM 0.15% w/v EYE DROPS, with some reported to be associated with an increase in (IOP) Intraocular pressure.

Contamination of AGOBRIM 0.15% w/v EYE DROPS after use There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products such as AGOBRIM 0.15% w/v EYE DROPS. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface (see u201cInformation for patientsu201d).

Special populations Paediatric use AGOBRIM 0.15% w/v EYE DROPS is contra-indicated in children under the age of 2 years (see u2018CONTRAINDICATIONSu2019). The safety and efficacy of brimonidine tartrate have not been studied in children below the age of 2 years. During post-marketing surveillance, apnoea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine either for congenital glaucoma or by accidental ingestion. Children 2 years of age and above, especially those weighing u2264 20 kg, should be treated with caution and closely monitored due to the high incidence and severity of somnolence. In a clinical study conducted in paediatric glaucoma patients (ages 2 to 7 years) the most commonly observed adverse reactions with brimonidine tartrate ophthalmic solution 0,2 % dosed three times daily were somnolence (50 - 83 % in patients ages 2 to 6 years) and decreased alertness. In paediatric patients 7 years of age (> 20 kg), somnolence appears to occur less frequently (25 %). Approximately 16 % of patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence.

Elderly use No overall differences in safety or efficacy have been observed between elderly and other adult patients.

Patients with hepatic and renal impairment AGOBRIM 0.15% w/v EYE DROPS has not been studied in patients with hepatic impairment. AGOBRIM 0.15% w/v EYE DROPS has not been studied in patients with renal impairment. The effect of dialysis on brimonidine pharmacokinetics in patients with renal failure is not known. Caution should be used in treating patients with hepatic and renal impairment.

Antihypertensives Because AGOBRIM 0.15% w/v EYE DROPS may reduce blood pressure, caution in using antihypertensives with AGOBRIM 0.15% w/v EYE DROPS is advised.

Digoxin Caution is advised when using AGOBRIM 0.15% w/v EYE DROPS with digoxin.

CNS depressants Although specific interaction studies have not been conducted with AGOBRIM 0.15% w/v EYE DROPS, the possibility of an additive or potentiating effect with CNS-depressants (alcohol, barbiturates, opiates, sedatives, or anaesthetics) should be considered. Alpha-agonists, as a class, may reduce pulse and blood pressure. Caution in using concomitant medicines such as beta-blockers (ophthalmic and systemic), anti-hypertensives and/or digoxin is advised.

Tricyclic antidepressants Tricyclic antidepressants have been reported to blunt the hypotensive effects of systemic clonidine. It is not known whether the concurrent use of these medicines with AGOBRIM 0.15% w/v EYE DROPS ophthalmic solution in humans can lead to resulting interference with the IOP lowering effect. Caution is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

Monoamine oxidase inhibitors Monoamine oxidase (MAO) inhibitors may interfere with the metabolism of AGOBRIM 0.15% w/v EYE DROPS and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amine. No data on the level of circulating catecholamines after Alphagan administration are available. Caution, however, is advised in patients taking medications which can affect the metabolism and uptake of circulating amines e.g. chlorpromazine, methylphenidate reserpine.

Pregnancy The safety of use during human pregnancy has not been established. AGOBRIM 0.15% w/v EYE DROPS should not be used during pregnancy.

Breastfeeding It is not known if brimonidine is excreted in human milk. Because of the potential for serious adverse reactions from AGOBRIM 0.15% w/v EYE DROPS in nursing infants AGOBRIM 0.15% w/v EYE DROPS should not be used by women nursing infants.

Fertility No data is available.

AGOBRIM 0.15% w/v EYE DROPS may cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential for a decrease in mental alertness. AGOBRIM 0.15% w/v EYE DROPS may also cause blurred vision or visual disturbance in some patients. The patient should wait until these symptoms have cleared before driving or using machinery.

The most reported ADRs are oral dryness, ocular hyperaemia, and burning/stinging. They are usually transient and not commonly of a severity requiring discontinuation of treatment. Adverse reactions reported are included in the table below.

a. Tabulated list of adverse reactions Skin and subcutaneous tissue disorders:

• Rash
• Face oedema
• Vasodilatation

Frequency not known

Immune system disorders:

• Allergic reactions

Frequent

Psychiatric disorders:

• Depression, insomnia
• Drowsiness

Frequent

Nervous system disorders:

• Headache
• Dizziness

Frequent

Taste perversion

Somnolence in adults and infants.

Syncope Less frequent

Eye disorders:

• Eyelid erythema
• Eyelid oedema
• Conjunctival hyperaemia
• Eye pruritus
• Allergic conjunctivitis
• Burning sensation
• Stinging
• Foreign body sensation
• Follicular conjunctivitis
• Photophobia
• Eye pain
• Eye dryness
• Conjunctival oedema
• Blepharitis
• Eye irritation
• Eye discharge
• Conjunctival haemorrhage
• Conjunctival folliculosis
• Conjunctivitis
• Epiphora
• Visual field defects
• Visual disturbances
• Worsened visual acuity
• Superficial punctate keratopathy
• Vitreous floaters

Blurred vision

Blepharoconjunctivitis

Cataract

Conjunctival blanching

Keratitis

Lid disorder

Tearing Frequent

Vitreous detachment

Vitreous disorder

Ocular allergic reaction

Corneal erosion.

Less frequent

Iritis

Miosis Frequency not known

Cardiac disorders:

• Palpitations

Less frequent

Bradycardia in adults. Neonates and infants, tachycardia.

Frequency not known

Vascular disorders:

• Hypertension
• Hypotension

Frequent

Respiratory, thoracic, and mediastinal disorders:

• Cough
• Dyspnoea

Frequent

Nasal dryness, Less frequent

Apnoea in neonates and infants.

Frequency not known

Infections and infestations:

• Sinusitis
• Flu syndrome
• Bronchitis
• Rhinitis
• Pharyngitis

Frequent

General disorders and administration site conditions:

• Asthenia
• Fatigue

Frequent

Hypothermia in infants Frequency not known

Musculoskeletal disorders:

• Hypotonia in infants

Frequency not known

Blood and lymphatic system disorders:

• Hypercholesterolaemia

Frequent

Gastrointestinal disorders:

• Dyspepsia
• Oral dryness
• Gastrointestinal disorder

Frequent

In cases where brimonidine has been used as part of the medical treatment of congenital glaucoma, symptoms of brimonidine overdose such as loss of consciousness, lethargy, somnolence, hypotension, hypotonia, bradycardia, hypothermia, cyanosis, pallor, respiratory depression and apnoea have been reported in neonates and infants receiving brimonidine.

Very limited information exists on accidental ingestion of brimonidine in adults and children; the only adverse reaction reported to date has been hypotension. Treatment, in the event of an oral overdose, includes supportive and symptomatic therapy. A patent airway should be maintained.