Instructions for use Alfa-Brion eye drops solution 2 mg/ml bottle 5 ml
Composition
active ingredient: brimonidine tartrate;
1 ml of solution contains brimonidine tartrate 2.0 mg, equivalent to brimonidine 1.3 mg;
Excipients: benzalkonium chloride; polyvinyl alcohol; sodium chloride; sodium citrate; citric acid, monohydrate; sodium hydroxide; diluted hydrochloric acid; water for injections.
Dosage form
Eye drops, solution.
Main physicochemical properties: clear liquid of greenish-yellow color.
Pharmacotherapeutic group
Sympathomimetics for the treatment of glaucoma. ATX code S01E A05.
Pharmacological properties.
Pharmacological properties
Pharmacodynamics
Brimonidine is an alpha-2-adrenergic receptor agonist that is 1000-fold more selective for alpha-2-adrenergic receptors than alpha-1-adrenergic receptors. This selectivity is responsible for the absence of mydriasis and microvascular vasoconstriction associated with human retinal xenografts.
Topical application of brimonidine tartrate reduces intraocular pressure (IOP) in humans with minimal effects on cardiovascular and pulmonary parameters. There are limited data on the use of brimonidine in patients with bronchial asthma, in which no adverse effects were observed.
Brimonidine has a rapid onset of action with peak ocular hypotensive effect occurring 2 hours after application. In two one-year studies, brimonidine reduced IOP by approximately 4–6 mmHg.
Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action. Brimonidine is thought to lower IOP by reducing aqueous humor production and increasing uveoscleral outflow.
Studies show that brimonidine is effective in combination with topical beta-blockers. Short-term studies also suggest that brimonidine has a clinically significant additive effect when combined with travoprost (6 weeks) and latanoprost (3 months).
Pharmacokinetics
After instillation of a 0.2% solution of brimonidine twice daily for 10 days, its concentration in the blood plasma was low (mean Cmax was 0.06 ng/ml). After multiple administration (twice daily for 10 days), insignificant accumulation of the drug in the blood was observed. The area under the pharmacokinetic curve after 12 hours at steady state (AUC 0-12 h) was 0.31 ng×h/ml compared to 0.23 ng×h/ml after the first dose. After topical application, the mean half-life from the systemic circulation was approximately 3 hours.
The binding of brimonidine to plasma proteins after topical administration is approximately 29%.
Brimonidine reversibly binds to melanin in ocular tissues, both in vitro and in vivo. After 2 weeks of instillation into the eyes, brimonidine concentrations in the iris, ciliary body, and choroid were 3-17 times higher than after a single dose. No accumulation was observed in the absence of melanin. The significance of melanin binding is unknown.
No significant ocular adverse reactions were observed in biomicroscopic examinations of the eyes of patients treated with brimonidine for one year, and no significant ocular toxicity was observed in a one-year visual safety study in monkeys administered approximately four times the recommended dose of brimonidine tartrate.
After oral administration, brimonidine is well absorbed and rapidly excreted. The majority of the dose (approximately 75%) is excreted as metabolites in the urine within 5 days; unchanged brimonidine is not detected in the urine.
In vitro studies using animal and human liver indicate that metabolism is primarily mediated by aldehyde oxidase and cytochrome P450. Therefore, systemic elimination is primarily due to hepatic metabolism.
After single administration of brimonidine at doses of 0.08%, 0.2%, and 0.5%, there was no significant dose-proportional variation in plasma Cmax and AUC.
Elderly patients.
After a single dose of brimonidine, plasma Cmax, AUC, and half-life in elderly patients (65 years and older) were not different from those in younger patients. This suggests that age does not affect systemic absorption and elimination. In a study involving elderly patients, systemic exposure to brimonidine was very low.
Indication
Alfa-Brion is used to reduce elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension:
− as monotherapy - when therapy with topical beta-blockers is contraindicated;
− as part of complex therapy with other drugs that lower intraocular pressure — when the target IOP is not achieved with one drug.
Contraindication
Hypersensitivity to the active substance or to the excipients of the medicinal product.
Concomitant use with monoamine oxidase inhibitors (MAOIs) and antidepressants that affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin).
Do not use in children under 2 years of age.
Interaction with other medicinal products and other types of interactions
Alpha-Brion is contraindicated in patients receiving monoamine oxidase inhibitors (MAOIs) and in patients taking antidepressants that affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin) (see section "Contraindications").
Although specific drug interactions of brimonidine have not been studied, the possibility of an enhanced effect should be considered when using central nervous system depressants (alcohol, barbiturates, opiates, sedatives and anesthetics).
There are no data on plasma catecholamine levels following administration of brimonidine. However, brimonidine should be administered with caution to patients taking drugs that affect the metabolism and uptake of circulating amines (e.g. chlorpromazine, methylphenidate, reserpine).
After the use of brimonidine, clinically insignificant decreases in blood pressure were observed in some patients. It is recommended to use caution when prescribing brimonidine and antihypertensive agents and/or cardiac glycosides simultaneously.
It is recommended to be cautious when prescribing (or changing the dose) concomitant systemic agents (regardless of their dosage form) that may interact with alpha-adrenergic agonists or affect their efficacy (e.g., adrenergic receptor agonists or antagonists - isoprenaline, prazosin).
Application features
Pediatric population
Children aged 2 years and older, especially those aged 2 to 7 years and/or weighing ≤ 20 kg, should be treated with caution and under close supervision, given the high frequency and severity of drowsiness (see section 4.8).
Cardiac disorders
Caution should be exercised when treating patients with severe or unstable and uncontrolled cardiovascular disease.
Vision impairment
Ocular allergic reactions have been observed in some patients (12.7%) in clinical trials following the use of brimonidine (see section 4.8). Brimonidine should be discontinued if allergic reactions occur.
Delayed ocular hypersensitivity reactions have been reported with brimonidine 0.2%, some associated with increased IOP.
Vascular disorders
Alfa-Brion should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's syndrome, orthostatic hypotension, or thromboangiitis obliterans.
Liver and kidney failure
The effects of brimonidine in patients with hepatic or renal impairment have not been studied - caution should be exercised when treating such patients.
Benzalkonium chloride
The preservative benzalkonium chloride in the composition of the drug may cause eye irritation, dry eye symptoms, and affect the tear film and corneal surface. Before use, contact lenses should be removed and wait at least 15 minutes after instillation before reinserting them.
Benzalkonium chloride is known to discolour soft contact lenses. Contact of the medicinal product with soft contact lenses should be avoided.
Alfa-Brion should be used with caution in patients with dry eye syndrome and if corneal damage is possible. Patients should be monitored during prolonged treatment.
Use during pregnancy or breastfeeding
Pregnancy. The safety of brimonidine during pregnancy has not been established. In animal studies, brimonidine tartrate did not cause teratogenic effects. Brimonidine tartrate has been shown to cause increased preimplantation loss and reduced postnatal growth in rabbits at plasma levels higher than those achieved during human therapy. Alfa-Brion should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. For information on how to reduce systemic absorption, see section 4.2.
Breastfeeding. It is not known whether brimonidine is excreted in human milk. Brimonidine tartrate is excreted in the milk of rats. Alfa-Brion should not be used by women who are breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Alfa-Brion may cause fatigue and/or drowsiness, which may impair the ability to drive or operate machinery. Alfa-Brion may cause blurred vision and impaired vision, which may impair the ability to drive or operate machinery, especially at night or in poor lighting. The patient should wait until these symptoms have resolved before driving or operating machinery.
Method of administration and doses.
Dosage
Recommended dose for adults (including the elderly)
The recommended dose is 1 drop in the affected eye(s) twice daily, approximately 12 hours apart. No dose adjustment is required in elderly patients.
Use in renal and hepatic failure
The effect of brimonidine has not been studied in patients with hepatic or renal impairment (see section 4.4).
As with any eye drops, to reduce the potential for systemic absorption of the drug, it is recommended to apply pressure to the area of the lacrimal sac near the medial canthus (punctal occlusion) for 1 minute. This should be done immediately after instillation of each drop. This reduces systemic side effects and increases local activity. To prevent contamination of the eyes or eye drops, do not allow the dropper tip to come into contact with any surface.
If more than one topical ophthalmic drug is to be used, the different drugs should be instilled 5–15 minutes apart.
Children.
Clinical studies involving adolescents (12 to 17 years of age) have not been conducted.
Alfa-Brion is not recommended for use in children under 12 years of age and is contraindicated in children under 2 years of age (see sections "Contraindications", "Special instructions for use" and "Adverse reactions"). It is known that severe adverse reactions can occur in newborns. The safety and efficacy of brimonidine in children aged 2 to 12 years have not been established.
Overdose
Overdose in ophthalmic use (adults)
All phenomena observed in known cases of overdose have already been described as adverse reactions.
Systemic overdose due to accidental ingestion (adults)
There is very limited information available regarding accidental ingestion of brimonidine in adults. The only adverse event reported to date was hypotension. It has been reported that the episode of hypotension was accompanied by rebound hypertension.
Treatment of oral overdose includes supportive and symptomatic therapy; it is necessary to ensure the patient's airway is patent.
Overdose of other oral alpha-2-agonists is known to cause symptoms such as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnea, hypotension, hypothermia, respiratory depression and convulsions.
Pediatric population
Serious adverse events have been reported in children following accidental ingestion of brimonidine. Symptoms of central nervous system depression have been observed, typically transient coma or low level of consciousness, lethargy, drowsiness, hypotension, bradycardia, hypothermia, pallor, respiratory depression, and apnea, sometimes requiring intensive care with intubation. All patients have been reported to recover fully within 6–24 hours.
Adverse reactions
The most common adverse reactions of brimonidine are dry mouth, ocular hyperemia, and burning/tingling, which occur in 22–25% of patients. They are usually transient and do not require discontinuation of treatment.
In clinical trials, symptoms of ocular allergic reactions occurred in 12.7% of patients (11.5% of patients discontinued brimonidine for this reason). These reactions occurred mostly between months 3 and 9 of treatment.
Adverse reactions are listed below by system organ class and frequency. Within each grouping, the frequency of reactions is presented in order of decreasing seriousness. The following terminology is used to define the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100,
On the part of the immune system
Uncommon: systemic allergic reactions.
From the psyche
Uncommon: depression.
Very rare: insomnia.
From the nervous system
Very common: headache, drowsiness.
Common: dizziness, taste disturbance.
Very rare: syncope.
From the organs of vision
Very common: eye irritation (hyperemia, inflammation and burning, itching, foreign body sensation, conjunctival follicles), blurred vision, allergic blepharitis, allergic blepharoconjunctivitis, allergic conjunctivitis, ocular allergic reaction and follicular conjunctivitis.
Common: local irritation (hyperemia and edema of the eyelids, blepharitis, conjunctival edema and discharge from the eyes, eye pain and tearing), photophobia, corneal erosion and discoloration, dry eyes, conjunctival pallor, visual impairment, conjunctivitis.
Very rare: iritis, miosis.
From the heart
Uncommon: tachycardia/arrhythmias (including bradycardia and tachycardia).
From the vascular system
Very rare: hypertension, hypotension.
Respiratory, thoracic and mediastinal disorders
Common: respiratory symptoms.
Uncommon: nasal dryness.
Rare: shortness of breath.
Gastrointestinal tract
Very common: dry mouth.
Common: gastrointestinal disorders.
General disorders and administration site conditions
Very common: fatigue.
Common: asthenia.
The following adverse reactions have been identified during post-marketing use of brimonidine in clinical practice. As these reactions were reported voluntarily and the patient population is unknown, it is not possible to estimate their frequency.
On the part of the organs of vision: iridocyclitis (anterior uveitis), itching of the eyelids.
Skin and subcutaneous tissue disorders: skin reactions including erythema, facial edema, pruritus, rash, and vasodilation.
In a study of children aged 2 to 7 years with glaucoma inadequately controlled with beta-blockers, a high prevalence of somnolence (55%) was observed when brimonidine was used as adjunctive therapy. In 8% of children, the adverse reaction was severe and led to discontinuation of treatment in 13% of cases. The incidence of somnolence decreased with increasing age (it was lowest in children aged 7 years - 25%), but was more weight-dependent, increasing in children weighing ≤ 20 kg (63%) compared to children weighing > 20 kg (25%) (see section "Special instructions for use").
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the link: https://aisf.dec.gov.ua/.
Expiration date
2 years.
The shelf life of the drug after first opening the bottle is 28 days.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
5 ml per bottle; 1 bottle per pack.
Release category: By prescription.
Producer
JSC "Farmak".
Location of the manufacturer and its business address
Ukraine, 04080, Kyiv, Kyrylivska St., 74.
