Brimonidine

Pharmacological properties

brimonidine is a relative selective agonist of α2-adrenergic receptors (a topical preparation used to reduce increased intraocular pressure (IOP)). when used in the form of eye drops of 1.5 mg / ml, the maximum effect of IOP reduction is achieved after 2 hours. The hypotensive effect of brimonidine is ensured by reducing the formation and increase of the outflow of intraocular fluid along the uveoscleral tract.

Pharmacokinetics When instilling eye drops C_max achieved after 0.5–2.5 h, T_½ is about 2 hours

The binding of brimonidine to plasma proteins has not been investigated. The drug is metabolized mainly in the liver. Brimonidine and its metabolites are excreted by the kidneys.

Indications

Decreased IOP in patients with open-angle glaucoma or increased eye pressure (both as monotherapy and in combination with other drugs that reduce IOP).

Application

Apply topically. instill in the conjunctival sac of the affected eye 1 drop 3 times a day with an interval between administrations of 8 hours

Alfagan P can be used with other ophthalmic drugs to reduce IOP. If the patient simultaneously applies other eye drops, an interval of at least 5 minutes between instillations should be maintained.

Children. The effectiveness and safety of the use of the drug Alfagan P in children under 2 years of age and children with low body weight (up to 20 kg) has not been proven.

Contraindications

Hypersensitivity to brimonidine tartrate or other components of the drug.

The use of MAO inhibitors and antidepressants that affect noradrenergic transmission (e.g. tricyclic antidepressants and mianserin).

During pregnancy and breastfeeding.

Children under 2 years of age, low body weight (up to 20 kg), since the safety and effectiveness of the drug in these groups of patients have not been studied.

Side effects

Adverse reactions that occurred in patients taking the brimonidine ophthalmic solution (0.1–0.2%) are described in accordance with the meddra classification and are distributed according to organ systems as follows: very often (≥1 / 10); often (from ≥1 / 100 to 1/10); infrequently (from ≥1 / 1000 to 1/100); rarely (from ≥1 / 10,000 to 1/1000); very rarely (1/10 000).

Within each group, adverse reactions are presented in decreasing order of severity.

Clinical research experience. Since clinical trials are conducted under various conditions, the rates of adverse reactions observed during clinical trials of the drug cannot be directly compared with those of another drug and may not reflect the indicators that were identified in the practical use of the drug.

Infectious and parasitic diseases: often - infections (mainly colds and respiratory), rhinitis, infectious sinusitis, sinusitis, pharyngitis, bronchitis, flu syndrome.

Disorders from the circulatory and lymphatic systems: often - hypercholesterolemia.

Violations of the organ of vision: very often - allergic conjunctivitis, conjunctival hyperemia, itching of the eyes; often - burning, conjunctival folliculosis, allergic reactions to the eyes, blurred vision, blepharitis, blepharoconjunctivitis, blurred vision, cataracts, conjunctival edema, conjunctival hemorrhage, conjunctivitis, lacrimation, eye discharge, dry eye, eye irritation , erythema of the eyelids, follicular conjunctivitis, sensation of a foreign body, keratitis, diseases of the eyelids, photophobia, acute pain, superficial spotty keratopathy, lacrimation, loss of the visual field, detachment of the vitreous, glass damage Nogo body floating in the vitreous turbidity, reduced visual acuity, coloring cornea, conjunctiva discoloration; infrequently - corneal erosion, barley.

Violations of the vessels: often - arterial hypotension, hypertension.

Disorders from the respiratory system, chest and mediastinal organs: often - cough, shortness of breath; infrequently - dryness of the nasal mucosa.

Digestive disorders: often - dyspepsia, indigestion, impaired taste, dry mouth.

General disorders and disorders at the place of use: often - asthenia, fatigue.

Disorders from the immune system: often - allergic reactions.

Violations of the nervous system: often - dizziness, headache, drowsiness; infrequently - a violation of taste.

Psychiatric Disorders: Often - Insomnia.

Disorders from the skin and subcutaneous tissues: often - rashes.

Experience of post-registration application. During the post-registration application of the ophthalmic solution of brimonidine tartrate, the following adverse reactions were recorded. Since these reactions came from an unknown number of patients, their frequency is currently impossible to determine. Adverse reactions, which are indicated below, were selected because of their severity, frequency of reports, possible connection with the use of the ophthalmic solution of brimonidine tartrate, or because of a combination of these factors.

Disorders from the cardiovascular system: unknown - arrhythmias (including bradycardia and tachycardia).

Psychiatric Disorders: Unknown - Depression.

Disorders from the immune system: unknown - hypersensitivity, skin reactions (including erythema, itching of the eyelids, skin rash, vasodilation).

Disorders from the organ of vision: unknown - iritis, dry keratoconjunctivitis, myosis, iridocyclitis (anterior uveitis).

Disorders from the nervous system: unknown - syncope, coma.

Digestive disorders: unknown - nausea.

In children who used the brimonidine tartrate ophthalmic solution, the following adverse reactions were recorded.

Disorders from the respiratory system, chest and mediastinal organs: unknown - apnea.

Disorders from the cardiovascular system: unknown - bradycardia.

Vascular disorders: unknown - arterial hypotension.

Disorders from the nervous system: unknown - hypotension, lethargy, drowsiness.

General disorders and disorders at the place of use: unknown - pale skin, hypothermia.

Disorders from the respiratory system, chest and mediastinal organs: unknown - respiratory failure.

special instructions

With caution, the drug should be prescribed to patients with depression, cerebral and coronary insufficiency, Raynauds syndrome, with orthostatic hypotension and thromboangiitis obliterans.

Although during the clinical studies of brimonidine tartrate, the ophthalmic solution showed a slight effect on the blood pressure of patients, it should be used with caution in patients with severe, unstable and uncontrolled forms of cardiovascular disease.

Cases of bacterial keratitis associated with the use of multi-dose containers for ophthalmic products for topical use have been reported. This happened because, in most cases, patients noted concomitant diseases of the cornea or a violation of the integrity of the surface of the eye, and when using containers they accidentally polluted them.

If eye drops are not used correctly or the tip of the dropper bottle comes in contact with the eye or surrounding surfaces, eye drops may become contaminated with common bacteria that can cause eye infections. Serious eye damage and further loss of vision may result from contaminated eye drops.

Immediately after use, close the dropper bottle with a cap. If the drops change color or become cloudy, discontinue use.

It is necessary to strictly monitor the condition of patients with the above conditions, if the patient worsens, the drug should be discontinued.

In the case of eye surgery or the development of an intercurrent state (for example, trauma or infection), you should immediately consult a doctor about the possibility of further use of a dropper bottle for repeated use.

Alfagan P was not studied in patients with hepatic or renal insufficiency, therefore, the drug should be used with caution in such patients.

The effect of dialysis on the pharmacokinetics of brimonidine in patients with renal failure is unknown.

Patients who wear soft contact lenses must be removed before installing Alfagan P. Contact lenses can be worn again after 15 minutes.

In some patients who received brimonidine tartrate 0.2%, allergic reactions from the eyes were noted. If allergic reactions occur, the use of the drug should be discontinued.

Use during pregnancy or lactation. Controlled studies involving pregnant women have not been performed. During pregnancy and lactation, the drug should be used only when the expected benefit to the mother significantly exceeds the potential risk to the fetus or child. If necessary, the use of the drug should stop breast-feeding.

The ability to influence the reaction rate when driving vehicles or other mechanisms. The use of the drug may be accompanied by visual impairment, so the patient should refrain from driving vehicles and other mechanisms until visual acuity is restored. Taking the drug may be accompanied by episodes of weakness and / or drowsiness in some patients. If the patient’s work is associated with potentially dangerous activities, he must be warned in advance about a possible decrease in attention and the speed of psychomotor reactions, it is recommended to refrain from performing this type of activity.

Interactions

When using more than one local ophthalmic agent, the preparations are used with an interval of 5 minutes.

Despite the absence of special studies of the drug’s drug interaction, one should take into account the possibility of enhancing the effect of drugs that depress the central nervous system (alcohol, barbiturates, opium derivatives, sedatives, general anesthetics). Since Alfagan P can lower blood pressure, antihypertensive drugs and cardiac glycosides should be prescribed with caution.

Due to the known decrease in the severity of the hypotensive effect of clonidine (alpha-adrenergic agonist) when combined with tricyclic antidepressants, the possibility of reducing the effectiveness of the drug Alfagan P with concomitant treatment with tricyclic antidepressants cannot be ruled out.

Theoretically, MAO inhibitors can affect the metabolism of brimonidine and potentially lead to an increase in the incidence of systemic adverse reactions, such as arterial hypotension.

Caution is advised to prescribe the drug to patients taking drugs that can affect the metabolism of amines and their distribution in the vascular bed, for example, chlorpromazine, methylphenidate, reserpine.

Overdose

Overdose with topical application (in adults). Received reports of cases of drug overdose are included in the list of adverse reactions.

Systemic overdose with accidental ingestion (in adults). Information about the accidental ingestion of brimonidine into the body of an adult is very limited.The only adverse reaction currently reported was arterial hypotension. It was reported that arterial hypotension was accompanied by reactive hypertension.

Overdose treatment includes supportive and symptomatic therapy, airway management.

Overdose of other α has been reported₂- agonists who caused symptoms such as arterial 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). Symptoms of an overdose of brimonidine, such as apnea, bradycardia, coma, arterial hypotension, hypothermia, hypotension, lethargy, pale skin, respiratory failure, drowsiness, were recorded in newborns, infants, and children receiving brimonidine ophthalmic solution (0.1–0, 2%) as part of the treatment of congenital glaucoma or in case of accidental ingestion of brimonidine.

Some of these symptoms required intensive care with intubation. All patients fully recovered within 6-24 hours.

Storage conditions

At a temperature not exceeding 25 ° c. the shelf life of the drug after the first opening of the dropper bottle is 28 days.