Instructions for use Betoptic S eye drops 0.25% dropper bottle, drop-tainer 5 ml
Composition
active ingredient: betaxolol hydrochloride;
1 ml of suspension contains 2.8 mg of betaxolol hydrochloride, which is equivalent to 2.5 mg of betaxolol;
excipients: mannitol (E 421), polystyrenesulfonic acid, carbomer 974P, disodium edetate, benzalkonium chloride, N-lauroylsarcosine, boric acid, sodium hydroxide and/or concentrated hydrochloric acid (for pH adjustment), purified water.
Dosage form
Eye drops.
Main physicochemical properties: white to almost white suspension.
Pharmacotherapeutic group
Drugs used in ophthalmology. Antiglaucoma drugs and miotics. Beta-adrenergic blockers. ATX code S01E D02.
Pharmacological properties
Pharmacodynamics.
Betaxolol is a cardioselective beta-1-adrenergic receptor blocker that does not have significant membrane-stabilizing (local anesthetic) and pronounced sympathomimetic effects.
Increased intraocular pressure is a major risk factor for glaucomatous scotoma. The higher the intraocular pressure, the greater the likelihood of optic nerve damage and visual field loss. After instillation into the eye, betaxolol is able to reduce both elevated and normal intraocular pressure, regardless of whether it is accompanied by glaucoma or not; the mechanism of its hypotensive action is associated with a decrease in the production of intraocular fluid, as shown by tonography and fluorophotometry. Betaxolol begins to act after 30 minutes, and the maximum effect is usually achieved 2 hours after topical application. A single dose provides a reduction in intraocular pressure for 12 hours.
BETOPTIC® S in the form of a suspension (betaxolol 0.25%) provides a reduction in intraocular pressure equivalent to that demonstrated by BETOPTIC® S in the form of a solution (betaxolol 0.5%).
The vasorelaxant effect of betaxolol on peripheral vessels has been demonstrated in an in vivo study in dogs. The vasorelaxant effect of betaxolol and its ability to block calcium channels have also been demonstrated in several in vivo studies using ocular and non-ocular vascular models in rats, guinea pigs, rabbits, dogs, pigs and cows. The neuroprotective effect of betaxolol has been demonstrated in both in vivo and in vitro experiments on rabbit retina, rat cortical cultures and chick retinal cultures.
Data from controlled clinical trials in patients with chronic open-angle glaucoma and ocular hypertension indicate that treatment with betaxolol provides a more prolonged positive effect on the visual field than that obtained with timolol, a non-selective beta-blocker. Furthermore, no negative effect on the blood supply to the optic nerve was observed with betaxolol. Betaxolol maintains or improves ocular blood flow/perfusion.
When applied topically in the form of eye drops, betaxolol has little or no effect on mydriasis and has minimal effects on pulmonary and cardiovascular function. Ophthalmic betaxolol had no significant effect on pulmonary function as measured by forced expiratory volume in one second, maximum vital capacity, and their ratio. No evidence of cardiovascular beta-adrenergic blockade was observed during the study.
When administered orally, beta-adrenergic blockers reduce cardiac output in healthy volunteers and in patients with heart disease. In patients with severe myocardial dysfunction, beta-adrenergic receptor antagonists may inhibit the sympathetic stimulatory effect necessary to maintain adequate cardiac function.
The results of clinical studies indicate that BETOPTIC® S suspension was much better tolerated than BETOPTIC® S solution.
The polar nature of betaxolol may cause discomfort in the eyes. In BETOPTIC® S, the betaxolol molecules are ionically bound to amberlite resin. After instillation, the betaxolol molecules are transported by sodium ions into the tear film. This transport process occurs within a few minutes and enhances the ophthalmic comfort of BETOPTIC® S.
Preclinical safety data
Lifespan studies with betaxolol administered orally at doses of 6, 20 or 60 mg/kg/day in mice and in rats at doses of 3 or 12 or 48 mg/kg/day demonstrated no carcinogenic effect.
During various experiments on bacterial and mammalian cells both in vitro and in vivo, no mutagenic effect of betaxolol was observed.
Studies of the effects of betaxolol on reproductive function, as well as teratology, perinatal and postnatal studies conducted in rats and rabbits with oral administration of betaxolol hydrochloride, showed evidence of an association of post-implantation loss in rats and rabbits with the use of the drug at a dose exceeding 12 mg/kg and 128 mg/kg, respectively.
Betaxolol hydrochloride did not show any teratogenic effects, nor was any other negative effect on reproductive function observed at subtoxic doses.
Betaxolol is highly lipophilic, resulting in a high degree of corneal penetration and high drug concentrations in ocular tissues. The plasma levels of betaxolol after topical administration are low. In clinical pharmacokinetic studies, plasma concentrations were below the limit of quantification of 2 ng/ml. Betaxolol is well absorbed orally, has low first-pass losses, and has a relatively long elimination half-life of approximately 16–22 hours. Betaxolol is excreted primarily by the kidneys, to a lesser extent in the feces. The main metabolites are the two carboxylic acid forms and unchanged betaxolol, which are excreted in the urine (approximately 16% of the administered dose).
Betaxolol begins to act, as a rule, after 30 minutes, and the maximum effect is usually achieved 2 hours after topical application. A single dose provides a reduction in intraocular pressure for 12 hours.
Indication
To reduce intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension (both monotherapy and in combination with other drugs).
Contraindication
Hypersensitivity to the active substance or to any of the components of the drug.
Sinus bradycardia, sick sinus syndrome, sinoatrial node dysfunction, second or third degree atrioventricular block not controlled by a pacemaker. Severe heart failure or cardiogenic shock.
Reactive airway disease, including severe bronchial asthma or a history of severe bronchial asthma, severe chronic obstructive pulmonary disease.
Interaction with other medicinal products and other types of interactions
No specific studies of betaxolol have been conducted regarding its interactions with other drugs.
There is a possibility of additive effects leading to hypotension and/or marked bradycardia when ophthalmic solutions containing beta-blockers are used concomitantly with oral calcium channel blockers, beta-adrenergic blocking agents, antiarrhythmic agents (including amiodarone) or digitalis glycosides, parasympathomimetics, guanethidine.
Beta-blockers may reduce sensitivity to adrenaline, which is used to treat anaphylactic reactions. They should be prescribed with caution in patients with atopy or a history of anaphylaxis.
Mydriasis has been reported rarely with concomitant use of ophthalmic beta-blockers and adrenaline (epinephrine).
If several topical eye medications are used at the same time, wait at least 5 minutes between applications. Eye ointments should be applied last.
Since betaxolol is an adrenoceptor blocker, it should be prescribed with caution to patients who are concurrently taking adrenergic psychotropic drugs due to the risk of enhancing their effects.
Application features
For ophthalmic use only.
After the first opening of the bottle, the protective ring intended to control the first opening should be removed.
The incidence of adverse reactions with topical ocular administration is lower than with systemic administration. For information on reducing systemic absorption, see section 4.2.
Corneal diseases
Topical administration of beta-blockers to the eye may cause dry eyes. Beta-blockers should be used with caution in patients with corneal diseases.
Other beta-blockers
When betaxolol is used in patients already receiving a systemic beta-blocker, the effect on intraocular pressure may be increased, or the effects of systemic beta-blockade are known. When beta-blockers are used in this category of patients, the reaction should be carefully monitored. It is not recommended to use two topical beta-adrenergic agents simultaneously (see section "Interaction with other medicinal products and other types of interactions").
When using BETOPTIC® S eye drops to reduce intraocular pressure in patients with angle-closure glaucoma, it should only be used in combination with miotics.
Choroidal detachment
Choroidal detachment has been reported following filtration surgery with the use of drugs that suppress tear production (e.g., timolol, acetazolamide).
Surgical anesthesia
Beta-blocking anesthetic drugs may block the action of systemic beta-agonists, such as adrenaline. If the patient is taking betaxolol, the anesthesiologist should be informed.
Nasolacrimal occlusion or keeping the eyelids closed for 2 minutes may reduce systemic absorption of the drug. This may reduce systemic effects and increase local effects of the drug.
Like other topical ophthalmic drugs, betaxolol is absorbed systemically. Due to the presence of a beta-adrenergic component, the same cardiovascular, respiratory and other adverse reactions as those seen with systemic beta-adrenergic receptor blockers may occur with betaxolol.
Cardiac disorders
In patients with cardiovascular disease (e.g. coronary heart disease, Prinzmetal's angina and heart failure) and hypotension, the need for beta-blocker therapy should be critically assessed and alternative therapy should be considered. Patients with cardiovascular disease should be monitored for signs of deterioration and adverse reactions. Due to the adverse effects of beta-blockers on conduction time, they should only be prescribed with caution in patients with first-degree heart block.
Vascular disorders
Caution should be exercised in treating patients with severe peripheral circulatory disorders (i.e. severe Raynaud's disease or Raynaud's syndrome).
Respiratory tract disorders
Respiratory reactions, including fatal cases due to bronchospasm, have been reported in patients with asthma after the use of some beta-blockers. This drug should be prescribed with caution to patients with mild/moderate asthma and a history of mild/moderate asthma or mild/moderate chronic obstructive pulmonary disease (COPD).
Hypoglycemia/diabetes
Beta-blockers should be used with caution in patients prone to spontaneous hypoglycemia or in patients with labile diabetes, since beta-blockers may mask the signs and symptoms of acute hypoglycemia.
Hyperthyroidism
Beta-blockers can also mask the signs of hyperthyroidism.
Muscle weakness
Beta-blockers may increase muscle weakness associated with certain symptoms of myasthenia gravis (e.g., diplopia, ptosis, and general weakness).
Anaphylactic reactions
When using beta-blockers, patients with a history of atopy or severe anaphylactic reactions to various allergens in history may have a higher reactivity when the drug is re-challenged with the same allergens, and may also not respond to the usual doses of adrenaline used to treat anaphylactic reactions.
Contact lenses
BETOPTIC® S contains benzalkonium chloride, which may cause eye irritation and is known to discolour soft contact lenses. Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses before using BETOPTIC® S eye drops and to wait 15 minutes before reinserting contact lenses.
Use during pregnancy or breastfeeding
Reproductive function
There are no data on the effect of this medicinal product on human reproductive function.
Pregnancy
There are no adequate data from the use of betaxolol in pregnant women. For information on reduced systemic absorption, see section "Method of administration and dosage".
Epidemiological studies have not shown any adverse effects on fetal development, but there is a risk of intrauterine growth retardation with oral beta-blockers. In addition, signs and symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in neonates exposed to beta-blockers before delivery.
Betaxolol should not be used during pregnancy unless clearly necessary. However, if BETOPTIC® S is used before delivery, the newborn should be closely monitored in the first days after birth.
Breastfeeding period
Beta-blockers are excreted in human milk, which may cause serious adverse effects in the breast-fed infant. However, when therapeutic doses of betaxolol are used in the form of eye drops, it is unlikely that amounts of the drug will enter the breast milk in quantities that would cause clinical symptoms of beta-blockade in the newborn. For information on reducing systemic absorption, see section 4.2.
Ability to influence reaction speed when driving vehicles or other mechanisms
BETOPTIC® S has no or negligible influence on the ability to drive or use machines. Temporary blurred vision or other visual disturbances may adversely affect the ability to drive or use machines. If blurred vision occurs during instillation, the patient should wait until the vision clears before driving or using machines.
Method of administration and doses
For ophthalmic use.
Dosage
The recommended dose is 1 drop of BETOPTIC® S in the conjunctival sac of the affected eye(s) twice daily. In some patients, several weeks of BETOPTIC® S may be required to stabilize the hypotensive effect. Close monitoring of patients with glaucoma is recommended.
If the patient's intraocular pressure is not adequately controlled with the recommended doses, concomitant therapy with other antiglaucoma drugs may be used.
After instillation, tight eyelid closure or nasolacrimal occlusion is recommended. This reduces systemic absorption of drugs administered into the eye, which reduces the likelihood of systemic side effects.
In case of concomitant therapy with other topical ophthalmic drugs, an interval of 10-15 minutes should be observed between their use.
Use in children and adolescents
The efficacy and safety of BETOPTIC® S eye drops in patients under 18 years of age have not been established.
Use in liver and kidney dysfunction
BETOPTIC® S has not been studied in this patient population.
Method of application
Before using the drug, the bottle should be shaken well.
To prevent contamination of the dropper tip and suspension, care must be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip.
Children.
The efficacy and safety of BETOPTIC® S eye drops in patients under 18 years of age have not been established.
Overdose
In case of accidental ingestion, symptoms of beta-blocker overdose may include bradycardia, hypotension, heart failure, and bronchospasm.
In case of overdose with BETOPTIC® S, treatment should be symptomatic and supportive.
Side effects
Safety data summary
The most common side effect observed during clinical trials of BETOPTIC® S was ocular discomfort, which occurred in 12% of patients.
The following adverse reactions have been observed during clinical trials with the drug and are classified as follows: 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), rare (< 1/10,000). Within each group, adverse reactions are presented in order of decreasing seriousness.
| Organ system | Adverse reactions according to the MedDRA classification (version 13.0) |
| Cardiological disorders | Uncommon: bradycardia, tachycardia |
| From the nervous system | Common: headache Isolated: syncope |
| Ophthalmological disorders | Very common: feeling of discomfort in the eye Common: blurred vision, increased tearing, foreign body sensation in the eyes Uncommon: punctate keratitis, keratitis, conjunctivitis, blepharitis, visual acuity reduced, visual disturbance, photophobia, eye pain, dry eye, asthenopia, blepharospasm, abnormal sensation in eyes, eye itching, eye discharge, eyelid margin scaling, eye inflammation, eye irritation, conjunctival disorder, conjunctival oedema, ocular hyperaemia Uncommon: cataract, ophthalmological disorders |
| Respiratory, thoracic and mediastinal disorders | Uncommon: asthma, dyspnoea, respiratory disorders, rhinitis Uncommon: cough, rhinorrhea |
| Gastrointestinal tract | Uncommon: nausea Uncommon: dysgeusia |
| Skin and subcutaneous tissue disorders | Uncommon: dermatitis, rash |
| From the vascular side | Uncommon: hypotension |
| Mental disorders | Single: restlessness |
| Reproductive function and mammary glands | Uncommon: decreased libido |
The following adverse reactions have been identified from post-marketing experience. The frequency of their occurrence cannot be estimated from the available data.
| Organ system | Adverse reactions according to the MedDRA classification (version 13.0) |
| On the part of the immune system | increased sensitivity |
| Mental disorders | insomnia, depression |
| From the nervous system | dizziness |
| Ophthalmological disorders | eyelid erythema |
| Cardiological disorders | arrhythmia |
| Skin and subcutaneous tissue disorders | alopecia |
| General disorders and administration site conditions | asthenia |
Description of the listed adverse reactions
As with other topical ophthalmic medicinal products, betaxolol is absorbed into the systemic circulation. This may lead to similar undesirable effects as with systemic beta-blockers. The incidence of systemic adverse reactions with topical ocular administration is lower than with systemic administration. The adverse reactions listed include those observed within the class of ophthalmic beta-blockers.
Immune system disorders: systemic allergic reactions including angioedema, urticaria, localized and generalized rashes, pruritus, anaphylactic reaction, toxic epidermal necrolysis.
Metabolism and absorption of nutrients: hypoglycemia.
Mental disorders: depression, nightmares, memory loss, hallucinations, psychosis, confusion.
Nervous system: syncope, cerebrovascular accident, cerebral ischemia, increased signs and symptoms of myasthenia gravis, paresthesia.
Ophthalmological disorders: signs and symptoms of eye irritation (e.g. burning, stinging, itching, tearing, redness), blepharitis, choroidal detachment after filtration surgery (see section "Special instructions"), decreased corneal sensitivity, corneal erosion, ptosis, diplopia.
Cardiological disorders: chest pain, palpitations, edema, congestive heart failure, atrioventricular block, cardiac arrest, heart failure.
From the vascular system: arterial hypotension, Raynaud's phenomenon, cold extremities, increased intermittent claudication.
Respiratory, thoracic and mediastinal disorders: bronchospasm (predominantly in patients with pre-existing bronchospastic disease).
Gastrointestinal: dyspepsia, diarrhea, abdominal pain, vomiting, dry mouth, glossitis.
Skin and subcutaneous tissue disorders: psoriasis-like rashes or exacerbation of psoriasis.
Musculoskeletal and connective tissue disorders: myalgia.
From the reproductive system and mammary glands: sexual dysfunction, impotence.
General disorders and administration site conditions: asthenia/fatigue.
Additionally, increased levels of antinuclear antibodies were found; clinical relevance has not been established.
Expiration date
2 years.
Shelf life after first opening the bottle is 4 weeks.
Storage conditions
Keep the bottle in the cardboard box. Store at a temperature of 8–30 °C. Keep out of the reach of children. Keep the bottle tightly closed.
Packaging
5 ml in a dropper bottle; 1 bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
Alcon Couvreur/Alcon Couvreur.
Location of the manufacturer and address of its place of business.
Rijksweg 14, Puurs-Sint-Amands, 2870, Belgium.
