Instructions Brimogen eye drops 2mg/ml 5ml No. 1
Composition
active ingredient: brimonidine tartrate;
1 ml of solution contains brimonidine tartrate 2 mg, equivalent to 1.32 mg of brimonidine;
Excipients: benzalkonium chloride; polyvinyl alcohol; sodium chloride; sodium citrate; citric acid, monohydrate; 1 M sodium hydroxide solution/ 25% hydrochloric acid solution (for pH adjustment); water for injections.
Dosage form
Eye drops, solution.
Main physicochemical properties: the solution is clear, slightly yellow, no more colored than the GY3 standard, without visible particles.
Pharmacotherapeutic group
Antiglaucoma and miotic agents. ATX code S01E A05.
Pharmacological properties
Pharmacodynamics.
Brimonidine is an α-2-adrenergic receptor agonist. Brimonidine has a 1000-fold greater affinity for α-2-adrenergic receptors than for α-1-adrenergic receptors. As a result, brimonidine results in the absence of mydriasis and vasoconstriction in microvessels associated with human retinal xenografts.
Brimonidine tartrate, after administration into the conjunctival sac, reduces intraocular pressure, with minimal effect on the cardiovascular system and respiratory system.
Limited data on the use of the drug in patients with bronchial asthma have not confirmed the occurrence of adverse reactions.
Brimonidine has a rapid onset of action, with peak hypotensive effect occurring 2 hours after administration. In two clinical trials conducted over a period of one year, brimonidine reduced intraocular pressure by approximately 4–6 mm Hg.
Based on fluorophotometric studies in animals and volunteers, brimonidine tartrate appears to have a dual mechanism of action. Brimonidine is believed to reduce intraocular pressure by reducing aqueous humor synthesis and increasing uveoscleral outflow.
Clinical studies confirm that brimonidine can be effectively combined with topical beta-blockers. Short-term clinical studies also confirm that brimonidine has a significant clinical additive effect in combination with travoprost (6 weeks) and latanoprost (3 months).
Pharmacokinetics.
After 10 days of instillation of a 0.2% solution into the conjunctival sac twice daily, low plasma concentrations of brimonidine were observed (Cmax averaged 0.06 ng/mL).
After repeated administration of the drug (2 times a day for 10 days), a small accumulation of the drug in the blood was observed. The area under the plasma concentration-time curve for 12 hours at steady state (AUC0-12h) was 0.31 ng h/ml compared to 0.23 ng h/ml after the first dose. The average half-life from the general circulation after topical application of the drug was approximately 3 hours.
The binding of brimonidine to plasma proteins after topical administration is approximately 29%.
Brimonidine binds reversibly to melanin in ocular tissues in vitro and in vivo. After two weeks of ocular administration, brimonidine concentrations in the iris, ciliary body, and choroid/retinal membranes 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 not known. However, biomicroscopic examination of patients treated with brimonidine tartrate eye drops for up to 1 year did not reveal any significant adverse ocular effects. No significant ocular toxicity was observed in monkeys treated with brimonidine tartrate at doses approximately 4 times the recommended dose.
Brimonidine is well absorbed from the gastrointestinal tract in humans and is rapidly eliminated after oral administration. A significant portion of the dose (approximately 75%) is excreted in the urine as metabolites within 5 days; no unchanged drug has been demonstrated in the urine. In vitro studies using animal and human liver indicate that its metabolism is primarily mediated by aldehyde oxidase and cytochrome P450. Systemic elimination is thought to be primarily mediated by hepatic metabolism.
Kinetic profile.
No significant deviations from the proportional relationship between brimonidine dose, maximum plasma concentration Cmax and AUC were detected after a single administration of the drug at a concentration of 0.08%, 0.2% and 0.5%, respectively.
Elderly patients.
The Cmax, AUC, and half-life of brimonidine after a single dose are similar in elderly patients (65 years and older) and younger patients, indicating that age does not affect its systemic absorption and elimination.
Clinical studies lasting 3 months in elderly patients confirmed that the overall effect of brimonidine was very small.
Indication
Reduction of elevated intraocular pressure in patients with open-angle glaucoma or elevated intraocular pressure:
as monotherapy in cases where topical beta-blockers are contraindicated;
as part of combination therapy with other drugs that reduce intraocular pressure, if the pressure reduction with the use of these drugs is insufficient.
Contraindication
Hypersensitivity to brimonidine tartrate or to any of the other ingredients of the drug.
Childhood.
Taking monoamine oxidase inhibitors (MAOIs), antidepressants that affect noradrenergic transmission (e.g. tricyclic antidepressants, mianserin).
Interaction with other medicinal products and other types of interactions
The drug is contraindicated in patients undergoing treatment with MAO inhibitors and in patients taking antidepressants that affect noradrenergic transmission (i.e. tricyclic antidepressants and mianserin).
Although specific drug interaction studies with brimonidine have not been conducted, the possibility of an increased effect of drugs that depress the central nervous system (CNS) (alcohol, barbiturates, opiates, sedatives or anesthetics) should be considered.
The drug should be prescribed with caution to patients taking medications that may affect the metabolism of amines and their distribution in the vascular bed (e.g. chlorpromazine, methylphenidate, reserpine).
After the use of brimonidine, a decrease in blood pressure was observed in some patients, which was not clinically significant. Hypotensive drugs and cardiac glycosides should be prescribed with caution.
Caution should be exercised when using brimonidine concomitantly with antihypertensive drugs and/or cardiac glycosides. Caution is recommended at the beginning of treatment (or when increasing the dose of the drug) during combination therapy with systemic agents (regardless of their pharmaceutical form) that may cause interaction with alpha-adrenoceptor agonists or affect their efficacy, i.e. adrenoceptor agonists or antagonists (e.g. isoprenaline, prazosin).
Application features
The drug should be used with caution in patients with acute or unstable and uncontrolled circulatory disease. In some patients (12.7%) during clinical studies, cases of ocular hypersensitivity reactions were recorded after taking brimonidine.
If allergic reactions occur, use of brimonidine should be discontinued.
Delayed ocular hypersensitivity reactions have been reported following the use of brimonidine, some of which have been associated with increased intraocular pressure.
The drug should be used with caution in patients with depression, cerebrovascular and coronary insufficiency, Raynaud's syndrome, orthostatic hypotension, and thromboangiitis obliterans.
The effect of the drug on patients with hepatic or renal insufficiency has not been studied, therefore caution should be exercised when using the drug in patients with relevant diseases.
The preservative in the medicine, benzalkonium chloride, may cause eye irritation, so avoid contact with soft contact lenses. Contact lenses should be removed before instilling the medicine and wait at least 15 minutes before reinserting them. The substance may cause discoloration of soft contact lenses.
Use during pregnancy or breastfeeding
Brimonidine tartrate has not been studied in pregnant women. During pregnancy or breastfeeding, the drug should be used only if the expected benefit to the woman significantly outweighs the potential risk to the fetus or child.
If necessary, use of the drug should be discontinued.
Ability to influence reaction speed when driving vehicles or other mechanisms
Brimonidine may cause fatigue and/or drowsiness, which may affect the ability to drive and use machines. Brimonidine may also cause blurred vision and/or blurred vision, which may impair the ability to drive and use machines, especially at night or in dim light. The patient should wait until these symptoms have resolved before driving or using machines.
Method of administration and doses
Use in adults, including elderly patients.
It is recommended to apply 1 drop of the drug in the affected eye(s) 2 times a day with an interval of approximately 12 hours. For elderly patients, dose adjustment is not required.
As with any other eye drops, to reduce the likelihood of brimonidine entering the bloodstream and lymphatic system, it is recommended to press and hold the lacrimal sac at the inner corner of the eye for 1 minute immediately after instillation of the drug (punctal compression). This action should be performed immediately after each drop.
When using more than one topical ophthalmic medicinal product, it is recommended to leave an interval of at least 5-15 minutes between their use.
Use in renal and hepatic impairment.
No studies have been conducted on the use of the drug in patients with impaired liver or kidney function.
Children.
The safety and effectiveness of brimonidine in children have not been established.
Overdose
The reports received usually mentioned cases that had already been described as side effects.
Systemic overdose due to accidental ingestion (adults).
There are limited data on accidental oral administration of brimonidine in adult patients. The only adverse event reported was a decrease in blood pressure. Rebound hypertension occurred after a recorded episode of decreased blood pressure.
Treatment of oral overdose includes supportive and symptomatic treatment; it is necessary to ensure the patient's airway is patent.
Overdose with other alpha-2-agonists has been reported, causing symptoms such as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmia, miosis, apnea, hypotension, hypothermia, respiratory failure and convulsions.
Overdose with topical application and systemic overdose with accidental ingestion (in children).
Serious side effects have been reported after accidental use of the drug by children.
Symptoms of brimonidine overdose, including apnea, bradycardia, coma, hypotension, hypothermia, hypotension, lethargy, pale skin, respiratory failure, and drowsiness, have been observed in neonates, infants, and children receiving brimonidine ophthalmic solution (0.1–0.2%) as part of the treatment of congenital glaucoma or in the event of accidental ingestion of brimonidine.
Some of these symptoms required intensive care with intubation. All patients recovered fully within 6–24 hours.
Side effects
The most common adverse reactions (in 22–25% of patients) are dry mouth, conjunctival hyperemia, and burning/stinging sensation in the eyes. These symptoms are usually transient and do not require discontinuation of treatment.
Symptoms of ocular allergic reactions occurred in 12.7% of patients in clinical trials (11.5% of patients discontinued the study). These reactions occurred in most cases between months 3 and 9 of treatment.
Within each grouping below, undesirable effects are presented in order of decreasing seriousness. The frequency of side effects is classified as follows: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (< 1/100); rare (> 1/1000 to < 1/100); very rare (< 1/10000); not known (frequency cannot be estimated from the available data).
On the part of the immune system: infrequently - systemic allergic reactions.
On the part of the psyche: infrequently - depression; very rarely - insomnia.
From the nervous system: very often - headache, drowsiness; often - dizziness, taste disturbance; very rarely - loss of consciousness.
On the part of the organs of vision: very often - eye irritation (conjunctival hyperemia, burning and tingling sensation, itching, conjunctival folliculosis, foreign body sensation), decreased visual acuity - allergic inflammation of the eyelids and conjunctivitis, allergic inflammation of the conjunctiva, allergic reactions in the eye area and follicular conjunctivitis; often - local irritation (swelling and redness of the eyelids, inflammation of the eyelid margins, swelling of the conjunctiva and the presence of discharge from the conjunctival sac, eye pain and tearing), photosensitivity, damage and discoloration of the corneal epithelium, dry eyes, conjunctival discoloration, visual impairment, conjunctivitis; very rarely - inflammation of the iris, constriction of the pupils.
Cardiac disorders: not known – arrhythmia (including bradycardia and tachycardia).
Vascular disorders: very rarely - hypertension, arterial hypotension.
Respiratory, thoracic and mediastinal disorders: common: upper respiratory tract symptoms; uncommon: dry nasal mucosa; rare: shortness of breath.
From the gastrointestinal tract: very often - dryness of the oral mucosa; often - gastrointestinal disorders.
General disorders and administration site conditions: very common - fatigue; common - weakness (asthenia).
The following adverse reactions have been observed during post-marketing use of brimonidine tartrate eye drops solution. The reports are based on voluntary reports from an unknown number of patients, therefore it is not possible to estimate their frequency.
On the part of the organs of vision: inflammation of the iris and ciliary body (inflammation of the choroid of the anterior segment of the eye); itching of the eyelids.
Skin and subcutaneous tissue disorders: skin reactions including erythema, facial swelling, itching, rash and dilation of blood vessels (vasodilation).
In newborns and infants in whom brimonidine was used as part of the treatment of congenital glaucoma, symptoms of its overdose, such as loss of consciousness, lethargy, drowsiness, decreased blood pressure, lethargy, bradycardia, hypothermia, cyanosis, pallor, respiratory arrest and apnea, were observed.
Expiration date
2 years.
The shelf life after first opening the bottle is 28 days.
Storage conditions
Store at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
5 ml in a bottle with a dropper and cap; 1 or 3 or 6 bottles in a cardboard box.
Vacation category
According to the recipe.
Producer
Manufacturer responsible for the release of the series:
Pharmaselect International Betelgeuse GmbH.
Ernst-Melchior-Gasse 20, 1020 Vienna, Austria.
Phone/Fax: +43 178603860/+43 1786038620 Email: regulatory@pharmaselect.com
