a2 -agonists (alpha-agonists).

Brimonidine tartrate

One ml solution contains 2.0 mg brimonidine tartrate, equivalent to 1.3 mg of brimonidine. Excipient(s): Contains benzalkonium chloride 0.05 mg/ml.

Eye drops, solution. Clear, greenish-yellow to light greenish-yellow solution.

Reduction of elevated intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension. As monotherapy in patients in whom topical beta-blocker therapy is contraindicated. As adjunctive therapy to other intraocular pressure lowering medications when the target IOP is not achieved with a single agent

Recommended dosage in adults (including the elderly)

The recommended dose is one drop of Alphagan in the affected eye(s) twice daily, approximately 12 hours apart. No dosage adjustment is required for the use in elderly patients.

As with any eye drops, to reduce possible systemic absorption, it is recommended that the lachrymal sac be compressed at the medial canthus (punctal occlusion) for one minute. This should be performed immediately following the instillation of each drop.

If more than one topical ophthalmic drug is to be used, the different drugs should be instilled 5-15 minutes apart.

Use in renal and hepatic impairment

Alphagan has not been studied in patients with hepatic or renal impairment.

Use in paediatric subjects

No clinical studies have been performed in adolescents (12 to 17 years).

Alphagan is not recommended for use in children below 12 years and is contraindicated in neonates and infants (less than 2 years of age). It is known that severe adverse reactions can occur in neonates. The safety and efficacy of Alphagan have not been established in children.

Not recommended.

− Hypersensitivity to the active substance or to any of the excipients.

− Neonates and infants.

− Patients receiving monoamine oxidase (MAO) inhibitor therapy and patients on antidepressants which affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin).

Children of 2 years of age and above, especially those in the 2-7 age range and/or weighing < 20 Kg, should be treated with caution and closely monitored due to the high incidence of somnolence.

Caution should be exercised in treating patients with severe or unstable and uncontrolled cardiovascular disease.

Some (12.7%)patients in clinical trials experienced an ocular allergic type reaction with Alphagan. If allergic reactions are observed, treatment with Alphagan should be discontinued.

Alphagan should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangiitis obliterans.

Alphagan has not been studied in patients with hepatic or renal impairment; caution should be used in treating such patients.

The preservative in Alphagan, benzalkonium chloride, may cause eye irritation. Avoid contact with soft contact lenses. Remove contact lenses prior to application and wait at least 15 minutes before reinsertion. Known to discolour soft contact lenses.

Although specific drug interactions studies have not been conducted with Alphagan, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anaesthetics) should be considered.

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.

After the application of Alphagan, clinically insignificant decreases in blood pressure were noted in some patients. Caution is advised when using drugs such as antihypertensives and/or cardiac glycosides concomitantly with Alphagan.

Caution is advised when initiating (or changing the dose of) a concomitant systemic agent (irrespective of pharmaceutical form) which may interact with α-adrenergic agonists or interfere with their activity i.e. agonists or antagonists of the adrenergic receptor e.g. (isoprenaline, prazosin).

The most commonly reported ADRs are oral dryness, ocular hyperaemia and burning/stinging, all occurring in 22 to 25% of patients. They are usually transient and not commonly of a severity requiring discontinuation of treatment.

Symptoms of ocular allergic reactions occurred in 12.7% of subjects (causing withdrawal in 11.5% of subjects) in clinical trials with the onset between 3 and 9 months in the majority of patients.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The following terminologies have been used in order to classify the occurrence of undesirable effects: Very Common (1/10); Common (1/100 to <1/10); Uncommon (1/1,000 to <1/100); Rare (1/10,000 to <1/1,000); Very rare (<1/10,000), not known (cannot be estimated from the available data).

Cardiac disorders

Uncommon: palpitations/arrhythmias (including bradycardia and tachycardia)

Nervous system disorders

Very common: headache, drowsiness

Common: dizziness, abnormal taste

Very rare: syncope

Eye disorders

Very common:

− ocular irritation including allergic reactions (hyperaemia, burning and stinging, pruritus, foreign body sensation, conjunctival follicles)

− blurred vision

Common:

− local irritation (eyelid hyperaemia and oedema, blepharitis, conjunctival oedema and discharge, ocular pain and tearing)

− photophobia

− corneal erosion and staining

− ocular dryness

− conjunctival blanching

− abnormal vision

− conjunctivitis

Very rare:

− iritis (anterior uveitis)

− miosis

Respiratory, thoracic and mediastinal disorders

Common: upper respiratory symptoms

Uncommon: nasal dryness

Rare: dyspnoea

Gastrointestinal disorders

Very common: oral dryness

Common: gastrointestinal symptoms

Vascular disorders

Very rare: hypertension, hypotension

General disorders and administration site conditions

Very common: fatigue

Common: asthenia

Immune system disorders

Uncommon: systemic allergic reactions

Psychiatric disorders

Uncommon: depression

Very rare: insomnia

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, hypotension, hypotonia, bradycardia, hypothermia, cyanosis and apnoea have been reported in neonates and infants receiving brimonidine.

In a 3-month, phase 3 study in children aged 2-7 years with glaucoma, inadequately controlled by beta-blockers, a high prevalence of somnolence (55%) was reported with Alphagan as adjunctive treatment. In 8% of children, this was severe and led to discontinuation of treatment in 13%. The incidence of somnolence decreased with increasing age, being least in the 7-year-old age group (25%), but was more affected by weight, occurring more frequently in those children weighing 20 kg (63%) compared to those weighing >20 kg (25%).

Allergan

(POM)

29 June 2009