Alcon Laboratories (U.K) Limited

Betoptic Suspension Single Dose 0.25% w/v, Eye Drops

Betaxolol (as hydrochloride) 0.25% w/v.

625 micrograms per single dose dispenser.

For excipients, see 6.1.

Eye drops, suspension

Sterile, preservative-free white to off-white suspension.

BETOPTIC SUSPENSION SINGLE DOSE eye drops contain a cardioselective beta-adrenergic receptor blocker which is indicated for the reduction of elevated intraocular pressure in patients with ocular hypertension and chronic open-angle glaucoma.

Shake well before each use.

Adults (including the elderly)

The usual dose is one drop twice daily. Standard ocular hypotensive agents may be used to supplement this treatment.

Children

Clinical studies to establish the safety and efficacy in children have not been performed up to now.

Hypersensitivity to any component of this medication or to beta-adrenoceptor blockers. BETOPTIC SUSPENSION SINGLE DOSE 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 SUSPENSION SINGLE DOSE 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 hypoglycaemia 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 hypoglycaemia.

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 medicated sympathetic reflex stimuli.

Pulmonary: Betaxolol is a cardioselective beta-blocker, and the ophthalmic suspension 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, generalised 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 SUSPENSION SINGLE DOSE 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 SUSPENSION SINGLE DOSE 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 SUSPENSION SINGLE DOSE 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 betaxolol used alone has little or no effect on pupil size, mydriasis resulting from concomitant epinephrine has been reported occasionally.

Although a drug interaction is unlikely because of the low systemic levels attained with ophthalmic doses of betaxolol, caution should be exercised in patients who are receiving verapamil concurrently.

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

Reproduction, teratology and peri- and postnatal studies have been conducted with orally administered betaxolol HC1 in rats and rabbits.

There was evidence of drug related postimplantation loss in rabbits and rats at dose levels above 12 mg/kg and 128 mg/kg, respectively. Betaxolol HC1 was not shown to be teratogenic, however, and there were no other adverse effects on reproduction at subtoxic dose levels. There are no adequate and well-controlled studies in pregnant women. Animal studies are insufficient with respect to effects on pregnancy. As the potential risk for humans is unknown, it is recommended to use BETOPTIC SUSPENSION SINGLE DOSE during pregnancy only if clearly necessary.

It is not known whether betaxolol HC1 is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BETOPTIC SUSPENSION SINGLE DOSE is administered to nursing women.

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

The following undesirable effects have been observed:

Psychiatric Disorders:

Rare (0.01%<0.1%): depression.

Nervous System Disorder:

Rare (>0.01%<0.1%): headache, insomnia.

Eye Disorders:

Common (1%<10%): ocular discomfort, eye irritation, ocular hyperaemia.

Uncommon (0.1%<1%): eye pruritus, abnormal sensation in eye, vision blurred, photophobia, lacrimation increased.

Rare (0.01%<0.1%): eye allergy, puncate keratitis, ptosis, madarosis, keratoconjunctivitis sicca.

Cardiac Disorders:

Rare (0.01%<0.1%): bradycardia.

Respiratory, Thoracic and Mediastinal Disorders:

Rare (0.01%<0.1%): dyspnoea, asthma.

Skin and Subcutaneous Tissue Disorders:

Rare (0.01%<0.1%): alopecia.

Musculoskeletal and Connective Tissue Disorders:

Rare (0.01%<0.1%): muscular weakness, myalgia.

Since topically applied beta-adrenergic blocking agents may be absorbed systemically, adverse reactions found with systemic administration of beta-1-adrenergic blocking agents may occur with topical administration (see 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's phenomenon, paraesthesia 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 hypoglycaemia. Beta-blocker use has also been reported to unmask or worsen symptoms associated with myasthenia gravis. An increase in Anti Nuclear Antibodies (ANA) has been seen; its clinical relevance is unclear.

No information is available on overdosage of humans after ocular application.

The oral LD50 of the drug ranged from 350-920 mg/kg in mice and 860-1050 mg/kg in rats. The symptoms which might be expected with an overdose of systemically administered beta-1-adrenergic receptor blocking agent are hypotension, bradycardia and acute cardiac failure.

No information is available on overdosage after ocular administration. A topical overdose of BETOPTIC SUSPENSION SINGLE DOSE may be flushed from the eye(s) with warm tap water.

Antiglaucoma Beta-Adrenergic Blocking Agent, ATC code: SO1 ED02.

Betaxolol, a cardioselective (beta-1-adrenergic) receptor blocking agent, does not have significant membrane-stabilising (local anaesthetic) activity and is devoid of intrinsic sympathomimetic action. Orally administered betaadrenergic 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 Effective Volume (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. BETOPTIC SUSPENSION SINGLE DOSE provides IOP lowering activity equivalent to that demonstrated by Betoptic Ophthalmic Solution 0.5%. Ophthalmic betaxolol has little or no effect on the constriction of the pupil and little 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 production as demonstrated by tonography and aqueous fluorophotometry.

The onset of action with betaxolol can generally be noted within 30 minutes and the maximal effect can usually be detected 2 hours after topical administration. A single dose provides a 12-hour reduction in intraocular pressure.

The polar nature of betaxolol can produce apparent ocular discomfort. In this formulation, betaxolol molecules are ionically bound to the amberlite resin. Upon instillation, the betaxolol molecules are displaced by ions in the tear film. This displacement process occurs over several minutes and enhances the ocular comfort observed for Betoptic Suspension.

Lifetime studies with betaxolol have been completed in mice at oral doses of 6, 20 or 60 mg/kg/day and in rats at 3, 12 or 48 mg/kg/day; betaxolol HCl demonstrated no carcinogenic effect. Higher dose levels were not tested.

In a variety of in vitro and in vivo bacterial and mammalian cell assays, betaxolol was non-mutagenic.

Amberlite (Poly (styrene-divinyl benzene) sulphonic acid)

Carbomer

Mannitol (E421)

Hydrochloric acid and/or sodium hydroxide

Purified water

Not applicable.

2 years.

Once open use immediately.

Discard any unused contents immediately after use.

Do not store above 25°C.

Do not freeze.

Store in the original package in order to protect from light.

Discard any unused contents immediately after use.

BETOPTIC SUSPENSION SINGLE DOSE is packaged in a plastic single dose dispenser containing 0.25 ml.

There are 50 single dose dispensers in a pack size.

The dispensers are in a strip of 5 enclosed in a foil overwrap.

No special requirements.

Alcon Laboratories (UK) Ltd

Pentagon Park

Boundary Way

Hemel Hempstead

Herts, HP2 7UD

United Kingdom

PA 290/61/3

Date of first authorisation: 13 July 1995

Date of last renewal: 13 July 2010

October 2011