Betoptic Suspension Single Dose

1. Name Of The Medicinal Product

BETOPTIC SUSPENSION SINGLE DOSE 0.25% w/v, Eye Drops

2. Qualitative And Quantitative Composition

Betaxolol 0.25% w/v (as hydrochloride)

For excipients, see 6.1.

3. Pharmaceutical Form

Eye Drop Suspension

BETOPTIC SUSPENSION SINGLE DOSE is a sterile, preservative-free suspension for topical ocular administration which has been developed for patients with hypersensitivity to preservatives.

4. Clinical Particulars

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 36μl.

4.3 Contraindications

Hypersensitivity to any component of this medication. BETOPTIC SUSPENSION SINGLE DOSE is contraindicated in patients with sinus bradycardia, second or third degree heart block, cardiogenic shock, or a history of overt cardiac failure.

4.4 Special Warnings And Precautions For Use

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

Respiratory. Although cardioselective beta-blockers have less effect on lung function than non-selective beta-blockers, caution should be exercised in the treatment of glaucoma patients with obstructive airway disease. There have been reports of asthmatic attacks and pulmonary distress during Betoptic treatment in such patients. In individual cases, the risk to benefit ratio for each patient should be considered. An increase in airway resistance can be relieved by inhaled beta2-mimetics.

In controlled clinical studies, ophthalmic betaxolol has shown little effect on respiratory and cardiovascular function.

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.

There have been reports of dry eyes associated with the topical ocular use of beta-blocking agents. Caution should be exercised in the use of beta-blocking agents in patients with Sicca Syndrome or similar tear film abnormalities.

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

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.

Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or bradycardia.

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

4.6 Pregnancy And Lactation

Reproduction studies have been conducted with orally administered betaxolol HCl 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 (1500 and 16,000 times the maximum recommended human ocular dose), respectively. Betaxolol HCl was not shown to be teratogenic, however, and there were no other adverse effects on reproduction at subtoxic dose levels. However, there are no adequate and well controlled studies in pregnant women. Betoptic Suspension Single Dose should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.

It is not known whether betaxolol HCl is excreted in human milk. Caution should be exercised when BETOPTIC SUSPENSION SINGLE DOSE is administered to nursing women.

4.7 Effects On Ability To Drive And Use Machines

The ability to drive and use machines is unlikely to be affected, other than any problems associated with transient blurred vision following the use of BETOPTIC SUSPENSION SINGLE DOSE.

4.8 Undesirable Effects

Ocular Effects

Common: discomfort (stinging and burning)

Uncommon: tearing

Rare: blurred vision, corneal disease, such as corneal punctate staining, superficial punctuate keratitis, decreased corneal sensitivity, allergic reactions, dry eye, foreign body sensation, erythema, itching and photophobia.

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

Systemic Effects:

Nervous:

Rare: insomnia, depression

Body as a Whole:

Rare: headache

Cardiovascular:

Rare: bradycardia

Respiratory:

Rare: dyspnoea, asthma

Skin and Appendages:

Rare: alopecia

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). These may include bradycardia, a slowed AV-conduction or increase of an existing AV-block, hypotension, heart failure, cold and cyanotic extremities, Raynaud 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 hypoglycemia. An increase in Anti Nuclear Antibodies (ANA) has been seen; its clinical relevance is unclear.

4.9 Overdose

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 beta1- 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.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Therapeutic Group: Ophthalmologicals – Antiglaucoma Preparations & Miotics.

ATC Code: S01E D02

Betaxolol, a cardioselective (beta1-adrenergic) receptor blocking agent, does not have significant membrane-stabilising (local anaesthetic) activity and is devoid of intrinsic sympathomimetic action. Orally administered beta-adrenergic blocking agents may 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 FEV1, Forced Vital Capacity (FVC), FEV1/FVC and no evidence of cardiovascular beta-adrenergicblockade 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. It is thought to produce this effect by reducing the rate of production of aqueous humour as demonstrated by tonography and aqueous fluorophotometry. 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 respiratory and cardiovascular function.

Several studies have indicated that Betaxolol may have a beneficial effect on visual function for up to 48 months in patients with chronic open angle glaucoma and up to 60 months in patients with ocular hypertension. Moreover there is evidence that betaxolol maintains or increases ocular blood flow/perfusion.

5.2 Pharmacokinetic Properties

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 approximately 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 (approximately 16% of the administered dose).

The onset of action of 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 SINGLE DOSE.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Amberlite poly (styrene-divinyl benzene) sulphonic acid

Carbomer

Mannitol

Hydrochloric acid and/or Sodium Hydroxide

Purified Water

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

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

6.6 Special Precautions For Disposal And Other Handling

Shake before each use.

BETOPTIC SUSPENSION SINGLE DOSE is preservative-free, therefore do not reuse.

Discard single dose dispenser after use.

7. Marketing Authorisation Holder

Alcon Laboratories (UK) Ltd,

Pentagon Park,

Boundary Way,

Hemel Hempstead,

Herts., HP2 7UD.

8. Marketing Authorisation Number(S)

PL 0649/0124

9. Date Of First Authorisation/Renewal Of The Authorisation

9 December 1998

10. Date Of Revision Of The Text

September 2003