Betaxolol 0.5% Eye Drops

For excipients see 6.1

Eye drops, solution

Reduction of elevated intraocular pressure in conditions such as ocular hypertension and chronic open-angle glaucoma.

Adults: recommended therapy is one drop of Betaxolol 0.5% Eye Drops in the affected eye(s) twice a day.

Elderly: Dosage need not be modified for the elderly as there has been wide experience with the use of Betaxolol 0.5% Eye Drops in elderly patients.

Children: No clinical studies have been performed to establish safety and efficacy in children. Therefore, this product is currently not recommended for use in children.

When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity.

Intraocular pressure should be reassessed approximately four weeks after starting treatment because response to Betaxolol 0.5% Eye Drops may take a few weeks to stabilise.

If necessary, concomitant treatment with miotics, adrenaline and/or carbonic anhydrase inhibitors can be instituted. In order to prevent the active substance(s) from being washed out when additional ophthalmic medication is used, an interval of at least 10 minutes between each application is recommended. The use of two topical beta-adrenergic agents is not recommended.

Transfer from a single antiglaucoma agent: Continue the agent and add one drop of Betaxolol 0.5% Eye Drops in each affected eye twice daily. On the following day, discontinue the previous agent completely, and continue with Betaxolol 0.5% Eye Drops.

When several antiglaucoma agents are being used, the patient should be assessed on an individual basis. Adjustment should involve one agent at a time at intervals of not less than one week.

Patients should be instructed to remove soft contact lenses before using betaxolol.

Betaxolol 0.5% Eye Drops are contraindicated in patients with:

- Sinus bradycardia, sick sinus syndrome sino-atrial block;

- Cardiogenic shock;

- Overt cardiac failure;

- Second or third degree AV block not controlled with pace-maker.;

- Hypersensitivity to the active substance (betaxolol), to any of the excipients. or other beta-blocking agents.

- Reactive airway disease including severe bronchial asthma or a history of severe bronchial asthma, severe chronic obstructive pulmonary disease.

Like other topically applied ophthalmic drugs, betaxolol is absorbed systemically. Due to beta-adrenergic component, betaxolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. To reduce the systemic absorption, see 4.2.

Cardiac disorders:

In patients with cardiovascular diseases (e.g. coronary heart disease, Prinzmetal's angina and cardiac failure) and hypotension therapy with beta-blockers should be critically assessed and the therapy with other active substances should be considered. Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and of adverse reactions.

Due to its negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block.

Vascular disorders

Patients with severe peripheral circulatory disturbance/disorders (i.e. severe forms of Raynaud's disease or Raynaud's syndrome) should be treated with caution.

Respiratory disorders:

Respiratory reactions, including death due to bronchospasm in patients with asthma have been reported following administration of some ophthalmic beta-blockers.

Patients with mild/moderate bronchial asthma, a history of mild/moderate bronchial asthma or, mild/moderate chronic obstructive pulmonary disease (COPD) should be treated with caution.

Hypoglycaemia/diabetes

Beta-blockers should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia.

Beta-blockers may also mask the signs of hyperthyroidism.

Corneal diseases

Ophthalmic β-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.

Other beta-blocking agents

The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when betaxolol is given to the patients already receiving a systemic beta-blocking agent. The response of these patients should be closely observed. The use of two topical beta-adrenergic blocking agents is not recommended (see section 4.5).

Anaphylactic reactions

While taking beta-blockers, patients with history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge with such allergens and unresponsive to the usual dose of adrenaline used to treat anaphylactic reactions.

Choroidal detachment

Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.

Surgical anaesthesia

β-blocking ophthalmological preparations may block systemic β-agonist effects e.g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving betaxolol.

This formulation of Betaxolol 0.5% Eye Drops contains benzalkonium chloride as a preservative which may be deposited in soft contact lenses. Hence, Betaxolol 0.5% Eye Drops should not be used while wearing these lenses. The lenses should be removed before instillation of the drops and not reinserted earlier than 15 minutes after use.

When Betaxolol 0.5% Eye Drops is used to reduce intraocular pressure in angle-closure glaucoma, it should be used with a miotic and not alone.

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures.

Patients should also be instructed that ocular solutions, if handled improperly can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

Patients should also be advised that if they develop any intercurrent ocular condition (e.g. trauma, ocular surgery or infection), they should immediately seek their physician's advice concerning the continued use of present multi-dose container.

There have been reports of bacterial keratitis associated with the use of topical ophthalmic products.

No specific drug interaction studies have been performed with betaxolol.

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral calcium channel blockers, beta-adrenergic blocking agents, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, guanethidine.

Mydriasis resulting from concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine) has been reported occasionally.

Clonidine: increased risk of "rebound hypertension" on discontinuation of clonidine.

Anaesthetic drugs: increased risk of myocardial depression and hypotension due to blockage of cardiac response to reflex sympathetic stimuli.

Cimetidine, hydralazine, phenothiazines and alcohol: may increase plasma level of betaxolol

Pregnancy

There are no adequate data for the use of betaxolol in pregnant women. Betaxolol should not be used during pregnancy unless clearly necessary.

To reduce the systemic absorption, see 4.2.

Epidemiological studies have not revealed malformative effects but show a risk for intra uterine growth retardation when beta-blockers are administered by the oral route. In addition, signs and symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If Betaxolol Eye Drops is administered until delivery, the neonate should be carefully monitored during the first days of life.

Lactation

Beta-blockers are excreted in breast milk. However, at therapeutic doses of betaxolol in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant. To reduce the systemic absorption, see 4.2.

There are currently no data available on the effects of Betaxolol 0.5% Eye Drops. on the ability to drive or use machinery. It has to be taken into account that dizziness, fatigue, transient ocular irritation, blurred vision and lacrimation may occur occasionally.

Like other topically applied ophthalmic drugs, betaxolol is absorbed into the systemic circulation. This may cause similar undesirable effects as seen with systemic beta-blocking agents. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. Listed adverse reactions include reactions seen within the class of ophthalmic beta-blockers.

The following undesirable effects have been observed and reported with the following frequencies: Very common (1/10); common (1/100 to <1/10); uncommon (1/1000, <1/100), rare (1/10000, <1/1000) and very rare (<1/10000), not known (cannot be estimated from the available data).

Immune system disorders:

Rare: Systemic allergic reactions including angioedema, urticaria, localized and generalized rash, pruritus, anaphylactic reaction.

Metabolism and nutrition disorders:

Rare: Hypoglycaemia, masking of the symptoms of thyrotoxicosis.

Psychiatric disorders:

Rare: Insomnia, sleep disorders, depression, hallucinations, psychoses, confusion, nightmares

Frequency unknown: memory loss.

Nervous system disorders:

Rare: dizziness, paraesthesia, headache.

Frequency unknown: Syncope, cerebrovascular accident, cerebral ischemia, increases in signs and symptoms of myasthenia gravis.

Eye disorders:

Common: discomfort

Uncommon: tearing on instillation of the drops

Rare: Signs and symptoms of ocular irritation (e.g. burning, stinging, itching, tearing, redness), pain, corneal punctuate staining, decreased corneal sensitivity, dry eyes, blepharitis, keratitis, blurred vision, aniscoria, photophobia and blepharoconjunctivitis.

Frequency unknown: choroidal detachment following filtration surgery (see 4.4 Special warnings and special precautions for use), corneal erosion, ptosis, diplopia.

Cardiac disorders:

Rare: Bradycardia, atrioventricular block, cardiac failure.

Frequency unknown: congestive heart failure, chest pain, palpitations, oedema, arrhythmia and cardiac arrest

Vascular disorders:

Rare: Hypotension, Raynaud's phenomenon, cold hands and feet, exacerbation of intermittent claudication.

Respiratory, thoracic, and mediastinal disorders:

Rare: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease), dyspnoea, asthma.

Frequency unknown: cough.

Gastrointestinal disorders:

Rare: nausea, vomiting, diarrhoea.

Frequency unknown: Dysgeusia, dyspepsia, dry mouth, abdominal pain.

Skin and subcutaneous tissue disorders:

Rare: Alopecia, skin rash.

Frequency unknown: psoriasiform rash or exacerbation of psoriasis

Musculoskeletal and connective tissue disorders:

Frequency unknown: Myalgia.

Reproductive system and breast disorders:

Rare: Sexual dysfunction

Frequency unknown: decreased libido.

General disorders and administration site conditions:

Rare: fatigue

Frequency unknown: Asthenia,

Investigations:

Rare: increase in anti-nuclear antibodies (ANA). Clinical relevance unclear.

No specific data are available.

Overdosage is unlikely to occur as one 5ml bottle of Betaxolol 0.5% Eye Drops contains only 25 mgs of Betaxolol hydrochloride. However, in the rare event that overdosage occurs the most common signs and symptoms to be expected following overdosage with a beta-adrenergic receptor blocking agent are symptomatic bradycardia, hypotension, bronchospasm, and acute cardiac failure. If overdosage occurs, the following measures should be considered:

1 Gastric lavage, if ingested.

2 Symptomatic bradycardia: Atropine sulphate, 0.25 to 2mg intravenously, should be used to induce vagal blockade. If bradycardia persists, intravenous isoprenaline hydrochloride should be administered cautiously. In refractory cases, the use of a cardiac pacemaker may be considered.

3 Hypotension: A sympathomimetic pressor agent such as dopamine, dobutamine or noradrenaline should be used. In refractory cases, the use of glucagon has been reported to be useful.

4 Bronchopasm: Isoprenaline hydrochloride should be used. Additional therapy with aminophylline may be considered.

5 Acute cardiac failure: conventional therapy with digitalis, diuretics and oxygen should be instituted immediately. In refractory cases, the use of intravenous aminophylline is suggested. This may be followed, if necessary, by glucagon which has been reported to be useful.

6 Heart block (second or third degree): Isoprenaline hydrochloride or a pacemaker should be used.

Betaxolol is a cardio-selective (β-1-adrenergic) beta blocker, which does not possess significant intrinsic sympathomimetic or local anaesthetic (membrane-stabilising) activity.

When applied topically in the eye, it reduces both elevated and normal intraocular pressure by inhibiting the production of aqueous humour. Unlike miotics, Betaxolol reduces intraocular pressure with little or no effect on pupil size or accommodation.

Controlled clinical studies have shown that ophthalmic betaxolol has minimal effect on pulmonary and cardiovascular parameters. It has been used succesfully in patients who have undergone laser trabeculoplasty and in aphakic patients.

Given topically, 0.5% betaxolol solution results in plasma levels of approximately 0.5 ng/ml. Clinical doses of oral betaxolol result in plasma levels of 10-40 ng/ml, with a half-life of 12 hours. Betaxolol, administered systemically, appears to be metabolised to inactive compounds.

Pre-clinical safety data does not add anything of further significance to the prescriber.

Benzalkonium chloride

Disodium edetate

Sodium chloride

Water for injection

Benzalkonium chloride may be deposited in soft contact lenses. These lenses should therefore be removed before instillation of the eye drops and not reinserted earlier than 15 minutes after use.

Do not store above 30°C

To avoid contamination do not touch dropper tip to any surface

The container is a 5ml bottle of low density polyethylene (LDPE) with a polystyrene spiked cap closure which contains Betaxolol 0.5% Eye Drops solution.

No special instructions

FDC International Ltd

Unit 6 Fulcrum 1

Solent Way

Whiteley

Fareham

Hants

PO15 7FE

United Kingdom

PL 15872/0007

29 July 2005

5 January 2012