Alcon Laboratories (U.K) Limited

Betoptic 0.5% w/v Eye Drops, Solution

Betaxolol 0.5% w/v (as hydrochloride)

Excipients: Benzalkonium Chloride 0.01%w/v

For full list of excipients, see section 6.1.

Eye drops, solution

A clear, colourless to pale yellow sterile, eye drops solution.

Betoptic is indicated for the reduction of elevated intraocular pressure in patients with ocular hypertension and chronic open angle glaucoma.

Adults (including the elderly)

The usual dose is one drop to be instilled into the affected eye(s) twice daily.

Children

Betoptic is not recommended for use in children.

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

Betoptic is contraindicated in patients with sinus bradycardia, greater than a first degree atrioventricular block, cardiogenic shock or patients with uncontrolled congestive cardiac failure.

Topically applied beta-blockers can be systemically resorbed. Consequently, the same undesirable effects can appear as with systemically administered beta-blockers.

Following measures are, after application of the eye drops useful to reduce systemic resorption:

• Keep the eyelid closed for 2 minutes.

• Close the lacrimal duct with the finger for 2 minutes.

Ophthalmic betaxolol has been shown to have a minor effect on heart rate and blood pressure in clinical studies. Caution should be used in treating patients with a history of cardiac failure or heart block. Treatment with Betoptic should be discontinued at the first signs of cardiac failure.

Diabetes Mellitus

Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia.

Thyrotoxicosis

Beta-adrenergic blocking agents may mask certain clinical signs (e.g., tachycardia) 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.

Major Surgery

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

Pulmonary

Betaxolol is a cardioselective beta-blocker, and the ophthalmic administration has produced only minimal effects in patients with obstructive airways disease. However, wheezing, bronchospasm and dyspnoea have occurred in some patients. Although rechallenges of some patients with ophthalmic betaxolol has not adversely affected pulmonary function test results, the possibility of adverse pulmonary effects in patients sensitive to beta-blockers cannot be ruled out. Caution should be exercised in the treatment of patients with excessive restriction of pulmonary function.

The risk of inducing bronchospasm must be appreciated in patients with symptomatic or poorly controlled asthma or obstructive airway diseases. Appropriate precautions, including consideration of alternative glaucoma therapies, should be taken.

Myasthenia

Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g. diplopia, ptosis, generalized weakness). Beta-adrenergic blockade has been reported to unmask or worsen symptoms associated with myasthenia gravis.

Ocular

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 is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be used with a miotic and not alone.

Limited clinical experience suggests that the product is suitable for use in aphakic patients.

Betoptic should not be applied while wearing contact lenses; lenses should not be inserted for 15 minutes after instillation of product.

Each interaction that is associated with systemically administered beta blockers can, in principle, appear with the use of beta blocker eye drops.

Patients who are receiving a beta-adrenergic blocking agent orally and Betoptic should be observed for potential additive effect either on the intraocular pressure or on the known systemic effects of beta blockade. Orally administered beta-adrenergic blocking agents reduce cardiac output in healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor antagonists may inhibit the sympathetic stimulatory effect necessary to maintain adequate cardiac function.

Because of possible additive effects, and especially the production of hypotension and/or bradycardia, close observation of the patient is recommended when a beta blocker is administered with other products with similar cardiovascular effects or catecholamine-depleting drugs such as reserpine.

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

Although Betoptic used alone has little or no effect on pupil size, mydriasis resulting from concomitant therapy with Betoptic and adrenaline has been reported occasionally.

If supplementary eye preparations are to be used, the patient should wait 15 minutes between the two applications.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Postimplantation loss, but no teratogenicity, was seen in animals administered betaxolol at doses greatly in excess of those occurring with Betoptic Eye Drops (see Section 5.3). As the potential risk for humans is unknown, it is recommended to use Betoptic during pregnancy only if clearly necessary.

Lactation

It is not known whether Betaxolol HCl is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Betoptic is administered to nursing women.

The instillation of Betoptic may temporarily impair vision. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machinery.

The most frequently occurring undesirable effects are eye discomfort, irritation and hyperaemia following instillation.

Systemic reactions following topical administration of betaxolol have been rarely reported.

The following undesirable effects have been observed:

Psychiatric disorders

Rare (>1/1 0,000 to 1/1000): Depression

Nervous System Disorders

Rare (>1/10,000 to 1/1000): Headache, insomnia

Eye disorders

Common (>1/100 to 1/10): Ocular discomfort, eye irritation, ocular hyperaemia

Uncommon (>1/1000 to 1/100): Eye pruritus, abnormal sensation in eye, vision blurred, photophobia, lacrimation increased

Rare (>1/10,000 to 1/1000): Eye allergy, punctuate keratitis, ptosis, madarosis, keratoconjunctivitis sicca.

Cardiac disorders

Rare (>1/10000 to 1/1000): Bradycardia

Respiratory, thoraric and mediastinal disorders

Rare (>1/10,000 to 1 /1000): Dyspnoea, asthma

Skin and Subcutaneous Tissue disorders

Rare (>1/10,000 to 1/1000): Alopecia

MusculosketaI and connective tissue disorders

Rare (>1/10 ,000 to 1/1000): Muscular weakness, myalgia

Since topically applied beta-adrenergic blocking agents may be absorbed systemically, adverse reactions found with systemic administration of beta,-adrenergic blocking agents may occur with topical administration (see section 4.4 Special Warnings).

These may include bradycardia, a slowed AV-conduction or increase of an existing AV-block, hypotension, heart failure, cold and cyanotic extremities, Raynaud phenomenon, parasthesia of the extremities, increase of an existing intermittent claudication, fatigue, headaches, impaired vision, hallucinations, psychoses, confusion, impotence, dizziness, sleep disturbances, depression, nightmares, gastro-intestinal problems, nausea, vomiting, diarrhoea, bronchospasm in patients with bronchial asthma or a history of asthmatic complaints, disorder of the skin, especially rash, and dry eyes. Beta blockers may mask the symptoms of thyrotoxicosis or hypoglycemia. An increase in Anti Nuclear Antibodies (ANA) has been seen; its clinical relevance is unclear.

A topical overdose of Betoptic may be flushed from the eye(s) with lukewarm tap water.

Treatment of a suspected overdose or accidental ingestion is symptomatic and supportive.

Ophthalmologicals: Antiglaucoma Preparation & Miotics

ATC Code: S01E D02

Betaxolol, a cardioselective (beta-1-adrenergic) receptor blocking -agent, does not have significant membrane-stabilizing (local anesthetic) and is devoid of intrinsic sympathomimetic action. Orally administered beta-adrenergic blocking agents reduce cardiac output in healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor antagonists may inhibit the sympathetic stimulatory effect necessary to maintain adequate cardiac function.

Betaxolol has no significant effect on pulmonary function as measured by Forced Expiratory Volume in one second (FEV₁,), Forced Vital capacity (FVC), FEV₁ / FVC and no evidence of cardiovascular beta-adrenergic-blockade during exercise was observed.

When instilled in the eye, Betaxolol has the action of reducing elevated as well as normal intraocular pressure (IOP), whether or not accompanied by glaucoma. Ophthalmic Betaxolol has little or no effect on the constriction of the pupil and minimal effect on pulmonary and cardiovascular parameters.

Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss Betaxolol has the action of reducing elevated as well as normal intraocular pressure, and the mechanism of ocular hypotensive action appears to be a reduction of aqueous humour production as demonstrated by tonography and aqueous fluorophotometry.

Following topical administration, Betaxolol is absorbed systemically. Plasma concentrations of approximately 0.2 ng/ml were detected following administration of Betoptic S Suspension. (Hollo et al, IOVS, vol 47, no 1, pp235-240, 2006).

Betaxolol is highly lipophilic which results in good permeation of the cornea, allowing high intraocular levels of the drug. Betaxolol is characterised by its good oral absorption, low first pass loss and a relatively long half-life of approx 16-22 hours. The elimination of betaxolol is primarily by the renal rather than faecal route. The major metabolic pathways yield two carboxylic acid forms plus unchanged betaxolol in the urine (approx. 16% of the administered dose).

Reproduction, teratology and peri-and postnatal studies conducted with orally administered betaxolol HCl in rats and rabbits showed evidence of drug-related post-implantation loss in rabbits and rats at dose levels above 12 mg/kg and 128 mg/kg, respectively. Betaxolol HCI was not shown to be teratogenic, however, there were no other adverse effects on reproduction at subtoxic dose levels.

No other preclinical findings were seen that are of relevance to the prescriber.

Disodium edetate

Sodium chloride,

Benzalkonium chloride,

Sodium hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

Purified water

Not applicable.

3 years unopened.

After opening, 4 weeks.

Do not store above 25°C. Store in original package.

Discard remaining contents 4 weeks after first opening.

LDPE bottles with natural LDPE plug Drop-Tainer® and blue polystyrene or polypropylene cap containing 5ml or 10ml of solution.

Not all pack sizes may be marketed.

No special instructions.

Alcon Laboratories (UK) Ltd.,

Pentagon Park,

Boundary Way,

Hemel Hmpstead,

Hertfordshire, HP2 7UD,

United Kingdom

PA 290/61/1

Date of first authorisation: 27^th August 1986

Date of the last renewal: 27^th August 2006

October 2007