Briglau eco
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BRIGLAU ECO (BRIGLAU ECO)
Composition:
Active substance: brimonidine tartrate;
1 ml of solution contains brimonidine tartrate 2 mg;
Excipients: polyvinyl alcohol 40-88; sodium citrate; citric acid monohydrate; sodium chloride; hydrochloric acid diluted, 10 % solution; sodium hydroxide, 10 % solution; water for injections.
Pharmaceutical form. Eye drops, solution.
Main physicochemical properties: clear, yellow-green colored solution.
Pharmacotherapeutic group. Anti-glaucoma and miotic agents. ATC code S01E A05.
Pharmacological Properties
Pharmacodynamics
Brimonidine is an α-2 adrenergic receptor agonist. Brimonidine has an affinity for α-2 adrenergic receptors approximately 1000 times greater than its affinity for α-1 adrenergic receptors. As a result, brimonidine does not cause pupillary dilation or capillary constriction in human retinal xenografts.
In humans, brimonidine tartrate administered into the conjunctival sac reduces intraocular pressure with minimal effects on the cardiovascular and respiratory systems.
Limited data on the use of the drug in patients with bronchial asthma did not confirm the occurrence of adverse effects.
Brimonidine has a rapid onset of action, and its maximum hypotensive effect occurs approximately 2 hours after administration. In two clinical studies conducted over one year, brimonidine reduced intraocular pressure by about 4–6 mm Hg.
Fluorophotometric studies in animals and humans indicate that brimonidine tartrate has a dual mechanism of action. Brimonidine likely reduces intraocular pressure by decreasing aqueous humor production and enhancing uveoscleral outflow.
Clinical studies confirm that brimonidine can be effectively combined with topically applied beta-adrenergic blockers. Short-term clinical studies also confirm that brimonidine exerts a significant clinical additive effect when combined with travoprost (6 weeks) and latanoprost (3 months).
Pharmacokinetics
After 10 days of twice-daily administration of a 0.2% solution into the conjunctival sac, low plasma concentrations of brimonidine were observed (mean Cmax was approximately 0.06 ng/mL).
Following repeated administration (twice daily for 10 days), a slight accumulation of the drug in the blood was recorded. The area under the plasma concentration-time curve over 12 hours at steady state (AUC0–12 h) was 0.31 ng·h/mL compared to 0.23 ng·h/mL after the first dose. The mean elimination half-life from systemic circulation after topical administration was approximately 3 hours.
After topical administration, brimonidine is approximately 29% bound to plasma proteins.
In vitro and in vivo, brimonidine reversibly binds to melanin in ocular tissues. After 2 weeks of topical application, brimonidine concentrations in the iris, ciliary body, and choroid/retina were 3–17 times higher than after a single dose. No accumulation of the drug was observed in the absence of melanin.
The significance of melanin binding in humans has not been studied. However, no adverse ophthalmological effects have been confirmed in biomicroscopic examinations of eyes in patients treated with brimonidine for up to 1 year. Signs of toxic effects on the visual organs were also not confirmed in animal studies where brimonidine tartrate was administered at doses four times higher than the recommended human doses over one year.
After oral administration in humans, brimonidine is rapidly absorbed from the gastrointestinal tract and then rapidly eliminated from the body. A significant portion of the dose (approximately 75%) is excreted as metabolites in urine within 5 days; unchanged drug was not detected in urine. In vitro studies using liver tissue from animals and humans indicate that brimonidine metabolism occurs mainly via aldehyde oxidase and cytochrome P450. Therefore, the primary route of elimination of the drug from systemic circulation is hepatic metabolism.
Kinetic Profile
No significant deviations from dose proportionality were observed between brimonidine dose, maximum plasma concentration (Cmax), and AUC after single administration of the drug at concentrations of 0.08%, 0.2%, and 0.5%, respectively.
Geriatric Patients
Cmax, AUC, and elimination half-life of brimonidine after a single dose are similar in elderly patients (aged 65 years and older) and younger patients. Observational data indicate no age-related differences in systemic absorption or elimination of the drug.
Clinical studies lasting 3 months (involving elderly patients) confirmed that the overall systemic impact of brimonidine was very minimal.
Clinical Characteristics
Indications
For lowering elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension:
- As monotherapy, when topical beta-blockers are contraindicated.
- As part of combination therapy with other medicinal products that reduce intraocular pressure, when pressure reduction with these agents is insufficient.
Contraindications
Hypersensitivity to brimonidine tartrate or to any of the excipients of the medicinal product.
Paediatric age (under 18 years).
Contraindicated in patients receiving monoamine oxidase inhibitors (MAO inhibitors) or antidepressants affecting noradrenergic transmission (e.g., tricyclic antidepressants and mianserin).
Interaction with other medicinal products and other forms of interaction
Brimoptol ECO 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 no specific studies on drug interactions with Brimoptol ECO have been conducted, potential enhancement of the effect of central nervous system depressants (alcohol, barbiturates, opioid derivatives, sedatives, general anesthetics) should be considered.
There are no data on plasma catecholamine levels after administration of brimonidine. However, caution is advised when prescribing the drug to patients receiving medicinal products that may affect amine metabolism and their distribution in the vascular bed, such as chlorpromazine, methylphenidate, and reserpine.
Reduction in systemic blood pressure has been observed in some patients after administration of brimonidine, although this reduction was not clinically significant. Antihypertensive agents and cardiac glycosides should be used with caution.
Caution is also required when initiating (or changing the dose of) systemic agents (regardless of pharmaceutical form) that may interact with α-adrenergic receptors or affect their function, i.e., adrenergic agonists or antagonists (e.g., isoprenaline, prazosin).
Special precautions for use
Cardiac disorders
Caution should be exercised when administering the medicinal product to patients with severe, unstable, or uncontrolled cardiovascular diseases.
Visual disturbances
In some patients (12.7%) during clinical trials, ocular hypersensitivity reactions were observed after administration of brimonidine.
If allergic reactions occur, brimonidine should be discontinued. Delayed hypersensitivity reactions involving the eyes have been reported with brimonidine use, some of which included reactions associated with increased intraocular pressure.
Vascular disorders
Briaglu EKO should be prescribed with caution to patients with depression, cerebral and coronary insufficiency, Raynaud's syndrome, orthostatic hypotension, and thromboangiitis obliterans.
Hepatic and renal impairment
Studies on the use of the drug in patients with hepatic or renal impairment have not been conducted; therefore, caution is required when administering brimonidine to such patients.
Use during pregnancy or breastfeeding
Pregnancy
Controlled studies in pregnant women have not been conducted. In animal studies, brimonidine tartrate did not produce teratogenic effects. In rabbits, brimonidine tartrate at plasma levels higher than those achieved during human therapy caused an increase in preimplantation loss and postnatal growth reduction. During pregnancy or breastfeeding, the medicinal product Briaglu EKO should be used only if the expected benefit to the mother clearly outweighs the potential risk to the fetus or infant.
Breastfeeding
It is unknown whether brimonidine passes into human breast milk. The compound is excreted in the milk of lactating rats. Briaglu EKO should not be used during breastfeeding.
Ability to influence reaction speed while driving or operating machinery
Brimonidine may cause fatigue and drowsiness, which may impair the ability to drive or operate machinery. Brimonidine may also cause disturbances in visual acuity and blurred vision, which may interfere with the ability to drive or operate machinery, especially at night or in dim light. Patients should wait until these symptoms have subsided before driving or operating machinery.
Dosage and Administration
Use in adults, including elderly patients
The recommended dose is 1 drop of brimonidine in the affected eye (eyes) twice daily with an interval of approximately 12 hours. Dose adjustment is not required for elderly patients. To reduce systemic absorption, it is recommended to press and hold the lacrimal sac at the inner corner of the eye (punctal occlusion) for 1 minute immediately after instillation.
If more than one ophthalmic medicinal product for local use is being administered, an interval of at least 5–15 minutes between applications is recommended.
Use in renal and hepatic impairment
Studies on the use of brimonidine in patients with hepatic or renal dysfunction have not been conducted.
Children
The efficacy and safety of brimonidine in children have not been established; therefore, the medicinal product should not be used in children.
Overdose
Overdose following ocular administration (adults)
In reported cases of overdose, symptoms consistent with known adverse effects have been observed.
Systemic overdose due to accidental oral ingestion (adults)
Data on accidental oral ingestion of brimonidine in adult patients are limited. The only reported adverse effect was a decrease in arterial blood pressure. Following the episode of hypotension, a "rebound" hypertension occurred. Management of oral overdose includes supportive therapy and symptomatic treatment; maintaining airway patency is essential.
Cases of overdose with other alpha-2 agonists have been reported, causing symptoms such as arterial hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmia, miosis, apnea, hypotonia, hypothermia, respiratory failure, and seizures. Treatment is symptomatic.
Overdose following topical administration and systemic overdose due to accidental oral ingestion in children
Symptoms of brimonidine overdose, particularly central nervous system depression such as coma or impaired consciousness, lethargy, somnolence, hypotonia, bradycardia, hypothermia, pallor, respiratory insufficiency, and apnea, have been reported in neonates, infants, and children following the use of brimonidine ophthalmic solution (0.1–0.2%) as part of treatment for congenital glaucoma or following accidental ingestion of brimonidine. Some patients required hospitalization and resuscitation measures including intubation.
All children fully recovered within 6–24 hours.
Adverse Reactions
The most commonly observed adverse effects (occurring in 22–25% of patients) are dryness of the oral mucosa, conjunctival hyperemia, and a burning/stinging sensation in the eyes. The above-mentioned symptoms are usually temporary and do not require discontinuation of treatment.
Ocular allergic reactions occurred in 12.7% of patients participating in clinical studies (leading to study discontinuation in 11.5% of patients). These reactions mostly occurred between the 3rd and 9th months of treatment.
Within each frequency category, adverse effects are listed in descending order of severity. The frequency of adverse effects is classified as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).
Immune system disorders
Uncommon: general allergic reactions.
Psychiatric disorders
Uncommon: depression.
Very rare: insomnia.
Nervous system disorders
Very common: headache, drowsiness.
Common: dizziness, taste disturbances.
Very rare: loss of consciousness.
Eye disorders
Very common: eye irritation (conjunctival hyperemia, burning and stinging sensation, itching, conjunctival folliculosis, foreign body sensation), reduced visual acuity — eyelid dermatitis, allergic conjunctivitis, allergic conjunctival inflammation, ocular allergic reactions, and follicular conjunctivitis.
Common: local irritation (eyelid swelling and redness, eyelid margin inflammation, conjunctival swelling and discharge from the conjunctival sac, eye pain, and lacrimation), photophobia, corneal epithelial damage and color changes, dry eyes, conjunctival hypopigmentation, visual disturbances, conjunctivitis.
Very rare: iritis, miosis.
Cardiac disorders
Frequency not known: palpitations/arrhythmia (including bradycardia and tachycardia).
Vascular disorders
Very rare: arterial hypotension, arterial hypertension.
Respiratory, thoracic and mediastinal disorders
Common: upper respiratory tract symptoms.
Uncommon: dryness of the nasal mucosa.
Rare: dyspnea.
Gastrointestinal disorders
Very common: dryness of the oral mucosa.
Common: gastrointestinal disorders.
General disorders and administration site conditions
Very common: fatigue.
Common: weakness (asthenia).
The following adverse effects have been observed in clinical practice during the post-marketing period with ophthalmic solutions containing brimonidine tartrate. As these data are derived from spontaneous reports, the number of affected patients is unknown, and therefore the frequency of these reactions cannot be estimated.
Eye disorders
Iritis and cyclitis (anterior segment uveitis); eyelid pruritus.
Skin and subcutaneous tissue disorders
Skin reactions including erythema, facial swelling, pruritus, rash, and vasodilation.
In neonates and infants treated with brimonidine as part of therapy for congenital glaucoma, symptoms of overdose such as loss of consciousness, lethargy, drowsiness, hypotension, hypotonia, bradycardia, hypothermia, cyanosis, pallor, respiratory depression, and apnea have been observed.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after drug authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.
Shelf life
2 years. Do not use the medicinal product after the expiry date stated on the packaging. The shelf life after first opening is 90 days.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 °C.
Keep out of reach of children.
Packaging
5 ml of solution in a polyethylene dropper bottle with a cap and tamper-evident ring.
1 or 3 bottles per cardboard box.
Prescription status
Prescription only.
Manufacturer
Rafarm S.A.
Rafarm S.A.
Manufacturer’s location and address of place of business
Thesi Pousi Xatzi Agiou Louka, Paiania, 190 02, Greece
Thesi Pousi Xatzi Agiou Louka, Paiania, 190 02, Greece
Marketing Authorization Holder
Pharmaceutical Works “POLPHARMA” S.A.
Pharmaceutical Works “POLPHARMA” S.A.
Marketing Authorization Holder’s location and address of place of business
19, Pelplinska Str., 83-200 Starogard Gdanski, Poland
19, Pelplinska Str., 83-200 Starogard Gdanski, Poland