Instructions for use Betoftan eye drops suspension 2.5 mg/ml bottle 5 ml
Composition
active ingredient: 1 ml of drops contains betaxolol hydrochloride (calculated on 100% dry matter) 2.8 mg, which is equivalent to 2.5 mg of betaxolol;
excipients: sodium polystyrene sulfonate, carbomer (974P), N-lauroyl sarcosine, boric acid, mannitol (E421), disodium edetate, benzalkonium chloride, sodium hydroxide solution and/or diluted hydrochloric acid, water for injections.
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 the development of glaucomatous scotoma. The higher the level of intraocular pressure, the greater the likelihood of damage to the optic nerve and loss of visual field. After instillation into the eye, betaxolol is able to reduce both elevated and normal intraocular pressure, regardless of whether it is accompanied by glaucoma; 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.
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 calcium channel blocking ability 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 with timolol, a non-selective beta-blocker. In addition, no negative effects on the blood supply to the optic nerve were 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 ratios. 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.
Clinical trial results indicate that the betaxolol suspension was much better tolerated than the solution.
The polar nature of betaxolol may cause discomfort in the eyes. In Betoftan®, betaxolol molecules are ionically bound to amberlite resin. After instillation, 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 Betoftan®.
Preclinical safety data
Lifespan studies with betaxolol administered orally at doses of 6, 20 or 60 mg/kg/day in mice and 3, 12 or 48 mg/kg/day in rats 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, with low first-pass losses and a relatively long elimination half-life of approximately 16-22 hours. Betaxolol is excreted mainly by the kidneys, to a lesser extent in the feces. The main metabolites are 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.
Clinical characteristics.
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 have been conducted on the interaction of betaxolol 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.
The incidence of adverse reactions with topical ocular administration is lower than with systemic administration. For reduced systemic absorption, see section 4.2.
Corneal diseases
Topical ocular administration of beta-blockers 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. 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").
To reduce intraocular pressure in patients with angle-closure glaucoma, Betoftan® should only be used in combination with miotics.
Choroidal detachment
Choroidal detachment has been reported with the use of aqueous suppressant therapy (e.g., timolol, acetazolamide) following filtration procedures.
Surgical anesthesia
Beta-blocking anesthetic drugs may block the effects of systemic beta-agonists, such as adrenaline. If the patient is taking betaxolol, the anesthesiologist should be informed.
Performing nasolacrimal occlusion or keeping the eyelids closed for 2 minutes can reduce systemic absorption of the drug. This may reduce systemic effects and increase local effects of the drug.
General
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.
In patients with cardiovascular diseases (e.g. coronary heart disease, Prinzmetal's angina and heart failure) and arterial hypotension, the need for beta-blocker therapy should be critically assessed and the use of other active substances should be considered. Patients with cardiovascular diseases should be monitored. Due to the adverse effect 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 of bronchospasm, have been reported in patients with asthma after the use of some β-blockers. This drug should be prescribed with caution to patients with mild/moderate asthma, including a history of it, or mild/moderate chronic obstructive pulmonary disease (COPD).
Hypoglycemia/diabetes
Beta-blockers should be used with caution in patients prone to spontaneous hypoglycemia and in patients with labile diabetes, as beta-blockers may mask the 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 stronger reaction when the drug is re-administered with the same allergens, and may also not respond to the usual doses of adrenaline used to treat anaphylactic reactions.
Contact lenses
Betoftan® contains benzalkonium chloride, which may cause eye irritation and discolour soft contact lenses. Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses before using Betoftan® 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 the drug on human reproductive function.
Pregnancy
There are no adequate data from the use of betaxolol in pregnant women. Regarding reduced systemic absorption, see section "Method of administration and dosage".
Epidemiological studies have not shown any adverse effects on foetal development, but there is a risk of intrauterine growth retardation with oral beta-blockers. In addition, symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in neonates treated with beta-blockers before delivery.
Betaxolol should not be used during pregnancy unless clearly necessary. However, if Betaxolol is used before delivery, the newborn should be closely monitored in the first few days after birth.
Breastfeeding period
Beta-blockers are excreted in human milk, which may cause serious adverse effects in a breastfed 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 breast milk in quantities that would cause clinical symptoms of beta-blockade in the newborn. For reduced systemic absorption, see section 4.2.
Ability to influence reaction speed when driving vehicles or other mechanisms
Betoftan® 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.
Use in adults, including the elderly
The recommended dose is 1 drop of Betoftan® instilled into the conjunctival sac of the affected eye(s) twice daily. Some patients may require several weeks of Betoftan® to stabilize the hypotensive effect. Close monitoring of glaucoma patients 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 and 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.
The efficacy and safety of Betoftan® eye drops in patients under 18 years of age have not been established.
Use in liver and kidney dysfunction
Betoftan® has not been studied in this category of patients.
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 Betoftan® eye drops in patients under 18 years of age have not been established.
Overdose
In case of accidental ingestion of the drug, symptoms of overdose may include bradycardia, hypotension, heart failure, and bronchospasm.
In case of overdose with Betoftan®, treatment should be symptomatic and supportive.
Adverse reactions
Cardiac: bradycardia, tachycardia, arrhythmia.
Vascular disorders: arterial hypotension.
From the nervous system: headache, syncope, dysgeusia, dizziness.
On the part of the organs of vision: discomfort in the eye, blurred vision, increased tearing, sensation of a foreign body in the eyes, punctate keratitis, keratitis, conjunctivitis, blepharitis, decreased visual acuity, visual impairment, photophobia, eye pain, dry eyes, asthenopia, blepharospasm, unusual sensation in the eye, itching of the eyes, discharge from the eyes, formation of scales on the edges of the eyelids, eye inflammation, eye irritation, conjunctival disorders, conjunctival edema, ocular hyperemia, cataract, ophthalmological disorders, eyelid erythema.
Respiratory, thoracic and mediastinal disorders: asthma, dyspnea, respiratory disorders, cough, rhinorrhea, rhinitis.
Gastrointestinal: nausea, dysgeusia.
Skin and subcutaneous tissue disorders: dermatitis, rash, alopecia.
General disorders: asthenia.
On the part of the immune system: hypersensitivity.
Mental: anxiety, decreased libido, insomnia, depression.
As with other topical ophthalmic medicinal products, betaxolol is absorbed into the systemic circulation. This may cause the same 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 have been observed within the class of ophthalmic beta-blockers.
Additional adverse reactions that have been observed with the use of ophthalmic beta-blockers and may occur with the use of Betoftan® eye drops:
Immune system disorders: systemic allergic reactions including angioedema, urticaria, localized and generalized rashes, pruritus, anaphylactic reaction, toxic epidermal necrolysis.
Metabolism and nutrient absorption disorders: hypoglycemia.
On the part of the psyche: depression, nightmares, memory loss, hallucinations, psychosis, confusion.
From the nervous system: syncope, cerebral circulation disorders, cerebral ischemia, increased symptoms of myasthenia gravis, paresthesia.
Ophthalmological disorders:
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.
Cardiac: chest pain, palpitations, edema, congestive heart failure, atrioventricular block, cardiac arrest, heart failure.
Vascular: 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: psoriatic rash or exacerbation of psoriasis.
Musculoskeletal and connective tissue disorders: myalgia.
Reproductive system and breast disorders: 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.
The shelf life after opening the bottle is 28 days.
Do not use the drug after the expiration date indicated on the package.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
5 ml in bottle No. 1 in a cardboard pack.
Vacation category
According to the recipe.
Producer
PJSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Frunze St., 74.
