Betaxolol 0.5% Eye Drops

1. Name Of The Medicinal Product

Betaxolol 0.5% Eye Drops

2. Qualitative And Quantitative Composition

Active Ingredient

Betaxolol 5.0 mg/ml (as Betaxolol hydrochloride 5.6 mg/ml)

For excipients see 6.1

3. Pharmaceutical Form

Eye drops, solution

4. Clinical Particulars

4.1 Therapeutic Indications

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

4.2 Posology And Method Of Administration

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.

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.

4.3 Contraindications

Betaxolol 0.5% Eye Drops are contraindicated in patients with:

• Bradycardia

• Cardiogenic shock;

• Overt cardiac failure;

• Second and third degree AV block;

• Hypersensitivity to any component of this product or other beta-blocking

agents.

4.4 Special Warnings And Precautions For Use

Like other topically applied ophthalmic drugs, Betaxolol 0.5% Eye Drops may be absorbed systemically and adverse reactions seen with oral beta-blockers may occur.

Patients who are receiving a beta-adrenergic blocking agent orally and Betaxolol 0.5% Eye Drops should be observed for a potential additive effect either on the intraocular pressure or on the known systemic effects of beta blockage.

Patients should not receive two topical ophthalmic beta-adrenergic blocking agents concurrently.

Use with caution in patients with diabetes (especially labile diabetes) or in patients suspected of developing thyrotoxicosis.

Consideration should be given to the gradual withdrawal of beta-adrenergic blocking agents prior to general anaesthesia because of the reduced ability of the heart to respond to beta-adrenergically mediated sympathetic reflex stimuli.

Although cardioselective beta-blockers has less effect on lung function than other beta-blockers, they should be used with caution in the treatment of glaucoma patients with obstructive pulmonary disease. There have been reports of asthmatic attacks and pulmonary distress during betaxolol treatment in such patients. An increase in airways resistance may be relieved by inhaled beta2 agonists.

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.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Although Betaxolol 0.5% Eye Drops alone has little or no effect on pupil size, mydriasis has occasionally been reported when Betaxolol is given with adrenaline.

The effect on intraocular pressure or the known effects of systemic beta-blockade such as hypotension or bradycardia may be exaggerated when Betaxolol 0.5% Eye Drops is given to patients already receiving an oral beta-blocking agent. The response of these patients should be closely monitored.

As Betaxolol 0.5% Eye Drops may be absorbed systemically, the following interactions seen with oral beta-blockers may occur:

Calcium channel blockers (verapamil and diltiazem): negative effect on contractility and atrio-ventricular conduction can lead to cardiac failure and hypotension.

Digitalis glycosides: in association with calcium channel blockers may increase atrio-ventricular conduction time.

Catecholamine-depleting drugs (rauwolfia alkolids, reserpine etc): potentiation of hypotension and/or marked bradycardia.

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

Class I anti-arrhythmic drugs (eg disopyramide, quinidine) and amiodarone:

potentiation of bradycardia, sinus arrest and AV block.

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

4.6 Pregnancy And Lactation

There are no adequeate and well-controlled studies of betaxolol eye drops in pregnant women. Therefore, use during pregnancy is not recommended unless the benefit outweighs the potential risk.

It is not known whether betaxolol is excreted in human milk. Therefore caution should be exercised when the eye drops are administered to nursing mothers.

4.7 Effects On Ability To Drive And Use Machines

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.

4.8 Undesirable Effects

Eye Disorders:

Common: Discomfort

Uncommon: Tearing on instillation of the drops.

Rare: Decreased corneal sensitivity, erythema, itching, stinging, burning, pain, corneal punctate staining, dry eyes, impaired vision, keratitis, aniscoria, photophobia and allergic reactions including anaphylaxis and blepharoconjunctivitis.

Since topically applied beta-adrenergic blocking agents may be absorbed systemically, adverse reactions found with systemic administration of beta₁- adrenergic blocking agents may occur with topical administration (see 4.4 Special Warnings). Systemic reactions following topical adminstration of betaxolol have only rarely been reported.

Cardiovascular Disorders:

Rare: bradycardia; slowed AV-conduction; exacerbation of AV-block; heart failure

Gastrointestinal Disorders:

Rare: nausea; vomiting; diarrhoea,

Investigations:

Rare: increase in Anti Nuclear Antibodies (ANA) - clinical relevance

unclear

Metabolic Disorders:

Rare: masking of the symptoms of thyrotoxicosis or hypoglycemia.

Nervous System Disorders:

Rare: headache; fatigue; dizziness; paraesthesia

Psychiatric Disorders:

Rare: insomnia; sleep disorders; depression; hallucinations; psychoses;

confusion; nightmares

Reproductive System Disorders:

Rare: impotence

Respiratory Disorders:

Rare: dyspnoea; asthma; bronchospasm

Skin and Subcutaneous Tissue Disorders:

Rare: alopecia; rash

Vascular Disorders:

Rare: hypotension; cold or cyanotic extremities; Raynaud's phenomenon; exacerbation of intermittent claudication

4.9 Overdose

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.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

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.

5.2 Pharmacokinetic Properties

Given topically, 0.5% betaxolol solution results in plasma levels of approximately 0.5ng/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.

5.3 Preclinical Safety Data

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzalkonium chloride

Diosodium edetate

Sodium chloride

Water for injection

6.2 Incompatibilities

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.

6.3 Shelf Life

Unopened: 24 months

Opened: 28 days

6.4 Special Precautions For Storage

Do not store above 30^oC

To avoid contamination do not touch dropper tip to any surface

6.5 Nature And Contents Of Container

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.

6.6 Special Precautions For Disposal And Other Handling

No special instructions

7. Marketing Authorisation Holder

FDC International Ltd

Unit 6 Fulcrum 1

Solent Way

Whiteley

Fareham

Hants

PO15 7FE

United Kingdom

8. Marketing Authorisation Number(S)

PL 15872/0007

9. Date Of First Authorisation/Renewal Of The Authorisation

29 July 2005

10. Date Of Revision Of The Text

17 June 2009