Бетак

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

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

Бетак Ophthalmic Solution has been shown to be effective in lowering intraocular pressure and is indicated in the treatment of ocular hypertension and chronic open-angle glaucoma. It may be used alone or in combination with other anti-glaucoma drugs.

In clinical studies Бетак Ophthalmic Solution (Бетак) was safely used to lower intraocular pressure in 47 patients with both glaucoma and reactive airway disease who were followed for a mean period of 15 months. However, caution should be used in treating patients with severe reactive airway disease or a history of asthma.

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 Бетак SUSPENSION 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 24 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.

After cap is removed, if tamper evident snap collar is loose, remove before using product.

Adults (including the elderly): recommended therapy is one drop of Бетак 0.5% Eye Drops to be instilled into the affected eye(s) twice a day.

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.

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.

Intraocular pressure should be reassessed approximately four weeks after starting treatment because response to Бетак 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 Бетак 0.5% Eye Drops in each affected eye twice daily. On the following day, discontinue the previous agent completely, and continue with Бетак 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 Бетак.

The recommended dose is one to two drops of Бетак Ophthalmic Solution (Бетак) in the affected eye(s) twice daily. In some patients, the intraocular pressure lowering responses to Бетак Ophthalmic Solution (Бетак) may require a few weeks to stabilize. As with any new medication, careful monitoring of patients is advised.

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

- 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.

Бетак 0.5% Eye Drops are contraindicated in patients with:

- Sinus bradycardia, sick sinus syndrome, sino-atrial block;

- Cardiogenic shock;

- Overt cardiac failure;

- Second or third degree AV block not controlled with pace-maker.;

- Hypersensitivity to the active substance (Бетак), to any of the excipients listed in section 6. or other beta-blocking agents.

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

Hypersensitivity to any component of this product. Бетак Ophthalmic Solution (Бетак) is contraindicated in patients with sinus bradycardia, greater than a first degree atrioventricular block, cardiogenic shock, or patients with overt cardiac failure.

For ocular use only.

General: Like other topically applied ophthalmic agents, betaxolol is absorbed systemically.

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 Бетак SUSPENSION 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 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 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 Бетак SUSPENSION 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 beta-adrenergic blocking agents is not recommended.

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: Betaxolol Eye Drops contain benzalkonium chloride which may cause irritation and is known to discolour soft contact lenses. Avoid contact with soft contact lenses. Patients must be instructed to remove contact lenses prior to application of Betaxolol Eye Drops and wait at least 15 minutes before reinsertion.

For ocular use only

General:

Like other topically applied ophthalmic drugs, Бетак is absorbed systemically. Due to beta-adrenergic component, Бетак, 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 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.

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. While Бетак has demonstrated a low potential for systemic effects, it should be used with caution in patients suspected of developing thyrotoxicosis.

Hyperthyroidism:

Beta-blockers may also mask the signs of hyperthyroidism.

Muscle weakness:

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

Corneal diseases:

In patients with angle-closure glaucoma, the immediate treatment objective is to re-open the angle by constriction of the pupil with a miotic agent, Бетак has no effect on the pupil, therefore, Бетак should be used with a miotic to reduce elevated intraocular pressure in angle-closure glaucoma.

Ophthalmic β-blockers may induce dryness of eyes. Patients with corneal diseases, Sicca Syndrome or similar tear film abnormalities should be treated with caution.

Other beta-blocking agents:

The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when Бетак 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 beta-adrenergic blocking agents is not recommended.

Anaphylactic reactions:

While taking beta-blockers, patients with 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:

β-blocking ophthalmological preparations may block systemic β-agonist effects e.g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving Бетак. 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:

This formulation of Бетак 0.5% Eye Drops contains benzalkonium chloride as a preservative which may be deposited in soft contact lenses. Hence, Бетак 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.

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.

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.

WARNINGS

Topically applied beta-adrenergic blocking agents may be absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported with topical application of beta-adrenergic blocking agents.

Бетак Ophthalmic Solution 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 heat block. Treatment with Бетак Ophthalmic Solution (Бетак) should be discontinued at the first signs of cardiac failure.

PRECAUTIONS

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.

Muscle Weakness. Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms (e.g., diplopia, ptosis, and generalized weakness).

Major Surgery. Consideration should be given to the gradual withdraw 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. Caution should be exercised in the treatment of glaucoma patients with excessive restriction of pulmonary function. There have been reports of asthmatic attacks and pulmonary distress during betaxolol treatment. Although rechallenges of some such 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.

Risk from Anaphylatic Reaction: While taking beta-blockers, patients with a history of atopy or a history of severe anaphylatic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Lifetime studies with betaxolol HCl 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 HCl was nonmutagenic.

Pregnancy: Pregnancy Category C. Reproduction, teratology, and peri- and postnatal 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, respectively. Betaxolol HCl 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. Бетак Ophthalmic Solution (Бетак) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: 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 Бетак Ophthalmic Solution (Бетак) is administered to nursing women.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Бетак 0.25% eye drops suspension 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 the patient must wait until the vision clears before driving or using machinery.

Бетак eye drops, solution 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 the vision clears before driving or using machinery.

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 beta-blockers.

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.

Description of selected adverse reactions

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

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.

Like other topically applied ophthalmic drugs, Бетак 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 beta-blockers.

Summary of the safety profile

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

The following undesirable effects have been observed and reported with the following frequencies: Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000) and very rare (<1/10000), not known (cannot be estimated from the available data).

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

Description of selected adverse reactions

Additional adverse reactions have been seen with ophthalmic beta-blockers and may potentially occur with Бетак eye drops solution:

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 Yellow card scheme at www.mhra.gov.uk/yellowcard.

The following adverse reactions have been reported in clinical trials with Бетак Ophthalmic Solution (Бетак).

Ocular: Discomfort of short duration was experienced by one in four patients, but none discontinued therapy; occasional tearing has been reported. Rare instances of decreased corneal sensitivity, erythema, itching sensation, corneal punctate staining, keratitis, anisocoria, edema, and photophobia have been reported.

Additional medical events reported with other formulations of betaxolol include blurred vision, foreign body sensation, dryness of the eyes, inflammation, discharge, ocular pain, decreased visual acuity, and crusty lashes.

Systemic: Systemic reactions following administration of Бетак Ophthalmic Solution 0.5% or Бетак Ophthalmic (Бетак) Suspension 0.25% have been rarely reported. These include:

Cardiovascular: Bradycardia, heart block and congestive failure.

Pulmonary: Pulmonary distress characterized by dyspnea, bronchospasm, thickened bronchial secretions, asthma and respiratory failure.

Central Nervous System: Insomnia, dizziness, vertigo, headaches, depression, lethargy, and increase in signs and symptoms of myasthenia gravis.

Other: Hives, toxic epidermal necrolysis, hair loss and glossitis.

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.

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

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

If overdose with Бетак eye drops occurs, treatment should be symptomatic and supportive.

A topical overdose of Бетак eye drops may be flushed from the eye(s) with warm tap water.

No information is available on overdosage of humans. 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 a systemically administered beta-1-adrenergic receptor blocker agent are bradycardia, hypotension and acute cardiac failure. A topical overdose of Бетак Ophthalmic Solution may be flushed from the eye(s) with warm tap water.

Pharmacotherapeutic 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. Бетак SUSPENSION provides IOP lowering activity equivalent to that demonstrated by Бетак 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.

Ophthalmologicals: Antiglaucoma Preparations & Miotics.

ATC Code: SO1E D02

Бетак is a cardioselective Beta₁ receptor blocker which, when applied topically to the eye, lowers intraocular pressure. It is thought to produce this effect by reducing the rate of production of aqueous humour.

Clinical Pharmacology

Several studies have indicated that Бетак 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 Бетак maintains or increases ocular blood flow/perfusion.

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 Бетак Suspension.

Бетак is highly lipophilic which results in good permeation of the cornea, allowing high intraocular levels of the drug. Бетак 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 Бетак is primarily by the renal rather than faecal route. The major metabolic pathways yield two carboxylic acid forms plus unchanged Бетак in the urine (approx. 16% of the administered dose).

Not Applicable.

Not known.

Shake before each use. Discard product 1 month after first opening.

No special instructions