INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo ALPHAGAN® Ophthalmic Solution
SCHEDULING STATUS:
Schedule 3

PROPRIETARY NAME
(and dosage form):

ALPHAGAN® Ophthalmic Solution

COMPOSITION
ALPHAGAN® Ophthalmic Solution contains: Brimonidine tartrate 2 mg/mL, equivalent to 1,32 mg/mL. brimonidine base
Preservative: Benzalkonium chloride 0,005% m/v

PHARMACOLOGICAL CLASSIFICATION
A. 15.4 Ophthalmic preparations. Other.

PHARMACOLOGICAL ACTION
ALPHAGAN® Ophthalmic Solution is a selective alpha-2-adrenergic agonist. Topical administration of brimonidine decreases intraocular pressure (IOP) in humans with minimal effect on cardio-vascular parameters. The selectivity accounts for the absence of mydriasis and vasoconstriction in microvessels associated with human retinal xenografts.
ALPHAGAN® Ophthalmic Solution has a rapid onset of action, with the peak ocular hypotensive effect occurring at two hours post-dosing. The duration of effect is 12 hours or greater.
Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action. ALPHAGAN® Ophthalmic Solution lowers IOP by reducing aqueous humour production and enhancing uveoscleral outflow.
After ocular administration of a 0,2% solution twice daily in humans for 10 days, plasma concentrations were low (mean Cmax - 0,06 ng/mL).Plasma concentrations peaked within 1 to 4 hours and declined with a systemic half-life of approximately 3 hours.
In humans, systemic metabolism of brimonidine is extensive, brimonidine does not accumulate. It is metabolised primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites. Approximately 87% of an orally - administered radioactive dose was eliminated within 120 hours, with 74% found in the urine.

INDICATIONS
ALPHAGAN® Ophthalmic Solution is indicated for lowering intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension, alone or in combination with other intraocular lowering medications.

CONTRA-INDICATIONS
ALPHAGAN® Ophthalmic Solution is contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication. It is also contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy
Paediatric use:
Safety and effectiveness in paediatric patients have not been established. Symptoms of bradycardia, hypotension, hypothermia, hypotonia and apnoea have been reported (rarely) in neonates receiving brimonidine.

WARNINGS
ALPHAGAN® Ophthalmic Solution contains benzalkonium chloride as a preservative. As the possibility of adverse effects on corneal permeability and the danger of disruption of the corneal epithelium with prolonged or repeated usage of benzalkonium chloride preserved ophthalmologic preparations cannot be excluded, regular ophthalmologic examination is required.
Caution should be exercised in the usage of benzalkonium chloride preserved topical medication over an extended period in patients with extensive ocular surface disease.

INTERACTIONS
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 alpha-adrenergic agonists orinterfere with their activity i.e. agonists or antagonists of the adrenergic receptor (e.g. isoprenaline, prazosin).
Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with ALPHAGAN® Ophthalmic Solution can lead to interference in the IOP lowering effect.

PREGNANCY AND LACTATION
There are no studies of ALPHAGAN® in pregnant women. ALPHAGAN® Ophthalmic Solution should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the foetus. It is not known whether ALPHAGAN® is excreted in human milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

DOSAGE AND DIRECTIONS FOR USE
The recommended dose is one drop of ALPHAGAN® Ophthalmic Solution in the affected eye(s) twice daily, approximately 12 hours apart. If more that one topical ophthalmic drug is to be used, the different drugs should be instilled 5-15 minutes apart.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects
For each indication the frequency of adverse reactions arising from clinical experience is given as follows: Very common (>1/10); Common (>1/100, <1/10); Uncommon (>1/1 000, <1/100); Rare (>1/10 000, <1/1 000); Very rare (<1/10 000).
The most commonly reported adverse events are oral dryness, ocular hyperaemia and burning/stinging, all occurring in 26 to 31% 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.
Eye disorders:
Very common: Ocular irritation including allergic reactions (hyperaemia, burning and stinging, pruritus, foreign body sensation, conjunctival follicles) and 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 visionand conjunctivitis.
Very rare: Iritis (anterior uveitis) and miosis.
Nervous system disorders:
Very common: Headache, fatigue/drowsiness
Common: Dizziness, asthenia
Uncommon: Depression
Very rare: Syncope, insomnia
Cardiac disorders:
Uncommon: Palpitations/arrythmias (including bradycardia and tachycardia)
Very rare: Hypertension, hypotension
Respiratory, thoracic and mediastinal disorders:
Common: Upper respiratory symptoms
Rare: Dyspnoea
Gastrointestinal disorders:
Common: Gastrointestinal symptoms
General disorders:
Very common: Oral dryness
Common: Abnormal taste
Uncommon: Systemic allergic reactions, nasal dryness
Special precautions
Although ALPHAGAN® Ophthalmic Solution had minimal effect on blood pressure and heart rate of patients in clinical studies, caution should be observed in treating patients with severe, uncontrolled cardiovascular disease.
ALPHAGAN® Ophthalmic Solution has not been studied in patients with hepatic or renal impairment; caution should be used in treating such patients.
ALPHAGAN® Ophthalmic Solution should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension or thromboangIitis obliterans.
Information for patients
The preservative in ALPHAGAN®, benzalkonium chloride, may be absorbed by soft contact lenses. Patients wearing soft contact lenses should be instructed to wait at least 15 minutes after using ALPHAGAN® Ophthalmic Solution to insert soft contact lenses.
As with other alpha-agonists, ALPHAGAN®can potentially cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities requiring mental alertness should be cautioned of the potential for a decrease in mental alertness.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
No information is available on overdosage in humans. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.

IDENTIFICATION
Clear, greenish-yellow solution.

PRESENTATION
ALPHAGANOphthalmic Solution is a sterile solution supplied in white opaque plastic dropper bottles with a cap, containing 5 mL solution.

STORAGE INSTRUCTIONS
Store below 25°C. To avoid contamination of the solution keep container tightly closed. Do not touch dropper tip to any surface. Discard contents 30 days after opening the bottle. Contents are sterile if seal is intact. KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
31/15.4/0377

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Allergan Pharmaceuticals (Pty) Ltd
Mount Royal Industrial Park
James Crescent
Halfway House
Johannesburg
South Africa

DATE OF PUBLICATION OF THIS PACKAGE INSERT
21 October 2005

New addition to this site: December 2006
Source: Hospital Pharmacy

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