4.1. Therapeutic indications

BETOPTIC SUSPENSION SINGLE DOSE lowers the intraocular pressure and is indicated in patients with chronic open-angle glaucoma and ocular hypertension.

4.2. Posology and method of administration

Adults (including Elderly)

The recommended dose is one drop in the affected eye(s) twice daily. In some patients, the intraocular pressure lowering responses to BETOPTIC SUSPENSION SINGLE DOSE may require a few weeks to stabilise. Careful monitoring of glaucoma patients is advised.

If the intraocular pressure of the patient is not adequately controlled on this regimen, concomitant therapy with pilocarpine and other miotics and/or adrenaline (epinephrine) and/or carbonic anhydrase inhibitors can be instituted.

Children

Safety and effectiveness in children have not been established.

The volume of each drop dispensed is 36 μl.

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.

4.3. Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in Section 6.

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

• Sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block not controlled with pace-maker. Overt cardiac failure, cardiogenic shock.

4.4. Special warnings and precautions for use

For ocular use only

General: Like other topically applied ophthalmic agents, betaxolol is absorbed systemically. Due to the 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 section 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. Treatment with BETOPTIC SUSPENSION SINGLE DOSE should be discontinued at the first signs of cardiac failure.

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.

Hyperthyroidism: Beta-adrenergic blocking agents may also mask the signs of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents, which might precipitate a thyroid storm.

Muscle weakness: Beta adrenergic blocking agents have been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g. diplopia, ptosis and generalised weakness).

Corneal diseases: In patients with angle-closure glaucoma, the immediate treatment objective is to reopen the angle by constriction of the pupil with a miotic agent. Betaxolol has little or no effect on the pupil. When BETOPTIC SUSPENSION SINGLE DOSE is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be used with a miotic and not alone.

Ophthalmic beta-blockers may induce dryness of eyes. Caution should be exercised in the use of beta-blocking agents in patients with corneal diseases, Sicca Syndrome or similar tear film abnormalities.

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 betaadrenergic blocking agents is not recommended (see section 4.5)

Anaphylactic reactions: While taking beta-blockers, patients with a 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: Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving betaxolol. 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.

Contact lenses: Contact lens wearers must remove their lenses prior to instillation of BETOPTIC SUSPENSION SINGLE DOSE and wait for 15 minutes after dosing before reinserting the contact lenses.

4.5. Interaction with other medicinal products and other forms of interaction

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, anti-arrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics and guanethidine. Close observation of the patient is recommended.

Betablockers can decrease the response to adrenaline used to treat anaphylactic reactions. Special caution should be exercised in patients with a history of atophy or anaphylaxis.

Betaxolol is an adrenergic blocking agent; therefore, caution should be exercised in patients using concomitant adrenergic psychotropic drugs.

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

If more than one topical medicinal product is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.

4.6. Fertility, pregnancy and lactation

Fertility

There are no data on the effects of Betaxolol Eye Drops on human fertility.

Pregnancy

Studies in animals with Betaxolol HCl was not shown to be teratogenic and there were no other adverse effects on reproduction at subtoxic dose levels (see section 5.3).

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 section 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 BETOPTIC SUSPENSION SINGLE DOSE is administered until delivery, the neonate should be carefully monitored during the first days of life.

Lactation

Beta-blockers are excreted in breast milk, having the potential to cause serious undesirable effects in the infant of the nursing mother. 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 betablockade in the infant. To reduce systemic absorption, see section 4.2.

4.7. Effects on ability to drive and use machines

Betoptic 0.25% eye drops suspension single dose has no or negligible influence on the ability to drive and use machines.

Temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs after instillation, the patient must wait until vision clears before driving or using machinery.

4.8. Undesirable effects

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 betablockers.

Summary of the safety profile

In clinical trials with Betaxolol eye drops the most common adverse reaction was ocular discomfort, occurring in 12.0% of patients.

The following adverse reactions have been reported during clinical trials or post marketing surveillance with Betaxolol eye drops and are classified according to the subsequent convention: 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) and frequency unknown/cannot be estimated from the available data.

Within each frequency-grouping, adverse reactions are presented in order of decreasing seriousness.

System Organ Classification

MedDRA Preferred Term (V 13.0)

Immune system disorders

Frequency unknown: hypersensitivity

Psychiatric disorders

Rare: anxiety, insomnia, depression

Nervous system disorders

Common: headache

Rare: syncope

Frequency unknown: dizziness

Eye disorders

Very common: ocular discomfort

Common: vision blurred, lacrimation increased

Uncommon: punctate keratitis, keratitis, conjunctivitis, blepharitis, visual impairment, photophobia, eye pain, dry eye, asthenopia, blepharospasm, eye pruritus, eye discharge, eyelid margin crusting, eye inflammation, eye irritation, conjunctival disorder, conjunctival oedema, ocular hyperaemia

Rare:

Cataract, decreased corneal sensitivity, erythema of eyelid

Cardiac disorders

Uncommon: bradycardia, tachycardia

Frequency unknown: arrhythmia

Vascular disorders

Rare: hypotension

Respiratory, thoracic and mediastinal disorders

Uncommon: asthma, dyspnoea, rhinitis

Rare: cough, rhinorrhoea

Gastrointestinal disorders

Uncommon: nausea

Rare: dysgeusia

Skin and subcutaneous tissue disorders

Rare: dermatitis, rash, alopecia

Reproductive system and breast disorders

Rare: libido decreased

General disorders and administration site conditions

Frequency unknown: asthenia

Description of selected adverse reactions:

Additional adverse reactions have been seen with ophthalmic beta-blockers and may potentially occur with BETOPTIC SUSPENSION SINGLE DOSE:

System Organ Classification

MedDRA preferred term (v 13.0)

Immune system disorders:

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

Metabolism and nutrition disorders

Frequency unknown: Hypoglycaemia.

Psychiatric disorders:

Frequency unknown: nightmares, memory loss, hallucinations, psychoses, confusion

Nervous system disorders:

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

Eye disorders:

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

Cardiac disorders:

Frequency unknown: Chest pain, palpitations, oedema, congestive heart failure, atrioventricular block, cardiac arrest, cardiac failure. A slowed AV-conduction or increase of an existing AVblock

Vascular disorders:

Frequency unknown: Raynaud's phenomenon, cold and cyanotic hands and feet, increase of an existing intermittent claudication.

Respiratory, thoracic, and mediastinal disorders:

Frequency unknown: Bronchospasm (predominantly in patients with pre-existing bronchospastic disease

Gastrointestinal disorders:

Frequency unknown: dyspepsia, diarrhoea, dry mouth, abdominal pain, vomiting

Skin and subcutaneous tissue disorders:

Frequency unknown: Psoriasiform rash or exacerbation of psoriasis

Musculoskeletal and connective tissue disorders:

Frequency unknown: Myalgia.

Reproductive system and breast disorders:

Frequency unknown: Sexual dysfunction, , impotence

General disorders and administration site conditions:

Frequency unknown: Fatigue.

An increase in Anti Nuclear Antibodies (ANA) has been seen; its clinical relevance is unclear.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard

4.9. Overdose

A topical overdose of BETOPTIC SUSPENSION SINGLE DOSE may be flushed from the eye(s) with warm tap water.

In case of accidental ingestion, symptoms of overdose from beta blockade may include bradycardia, hypotension, cardiac failure and bronchospasm.

If overdose with Betaxolol Eye Drops occurs, treatment should be symptomatic and supportive.