Alfabrim (Drops) Instructions for Use

Marketing Authorization Holder

Micro Labs Limited (India)

ATC Code

S01EA05 (Brimonidine)

Active Substance

Brimonidine (Rec.INN registered by WHO)

Dosage Form

Alfabrim

Eye drops 0.15%: 5 ml dropper bottle

Dosage Form, Packaging, and Composition

Eye drops transparent, colorless or light yellow in color.

Excipients: sodium carmellose 1.69 mg, boric acid 2 mg, sodium tetraborate 0.25 mg, potassium chloride 1.4 mg, sodium chloride 6 mg, calcium chloride dihydrate 0.2 mg, magnesium chloride hexahydrate 0.06 mg, stabilized oxychloro complex (sodium chlorite, sodium chlorate, chlorine dioxide) recalculated as sodium chlorite 0.05 mg, sodium hydroxide q.s. to pH 6.8, purified water up to 1 ml.

5 ml – polymer dropper bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antiglaucoma drug

Pharmacotherapeutic Group

Antiglaucoma agent – selective alpha₂-adrenergic agonist

Pharmacological Action

Brimonidine is a selective α₂-adrenergic agonist.

The maximum reduction in intraocular pressure (IOP) is achieved after 2 hours. The hypotensive effect of brimonidine is provided by reducing the production of aqueous humor and increasing outflow through the uveoscleral pathway.

Pharmacokinetics

After instillation of the eye drops, the maximum plasma concentration of brimonidine is reached within 0.5-2.5 hours, the systemic half-life (T_1/2) is about 2 hours.

Brimonidine is intensively metabolized in the liver.

It is excreted mainly by the kidneys in the form of unchanged brimonidine and its metabolites. About 87% of the radioactively labeled brimonidine is excreted within 120 hours, with 74% of the radioactive label found in the urine.

Indications

• Reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

ICD codes

Dosage Regimen

Topically.

Into the conjunctival sac of the affected eye, 1 drop 3 times a day with an interval between instillations of about 8 hours.

Brimonidine can be used with other ophthalmic drugs to reduce IOP. If two or more drugs are used, a 5-minute break should be taken between instillations.

No dosage adjustment is required in the elderly.

There are no data on the use of brimonidine in patients with renal or hepatic impairment.

Adverse Reactions

The following side effects were identified in clinical studies

With a frequency of 10-20% allergic conjunctivitis, conjunctival hyperemia, eye itching.

With a frequency of 5-9% eye burning, conjunctival folliculosis, increased blood pressure, allergic eye reactions, dry mouth, visual impairment.

With a frequency of 1-4% taste disturbance, allergic reactions, asthenia, blepharitis, blepharoconjunctivitis, blurred vision, bronchitis, cataract, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, dyspepsia, dyspnea, epiphora, eye discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid redness, fatigue, flu-like syndrome, follicular conjunctivitis, foreign body sensation in the eye, gastrointestinal tract disorders, headache, hypercholesterolemia, hypotension, infections (mainly colds and respiratory system infections), sleep disorders, keratitis, eyelid disorders, pharyngitis, photophobia, rash, rhinitis, sinusitis, somnolence, stinging sensation in the eye, superficial punctate keratopathy, increased lacrimation, visual field defects, vitreous detachment, vitreous disorders, vitreous floaters, decreased visual acuity.

With a frequency of <1% corneal erosion, stye, nasal dryness, taste perversion.

In children aged 2-6 years, the most frequent adverse drug reactions were somnolence (50-83%) and decreased activity. In children over 7 years of age (body weight >20 kg), somnolence occurred in 25% of cases. About 16% of children discontinued the drug due to the occurrence of somnolence.

In the post-marketing period, reports of the following adverse reactions have been received, regardless of causality: bradycardia, depression, hypersensitivity, iritis, dry keratoconjunctivitis, miosis, nausea, skin reactions (including erythema, eyelid itching, rash, and vasodilation), syncope, and tachycardia. In children, apnea, bradycardia, coma, hypotension, hypothermia, muscle hypotonia, lethargy, pallor, respiratory depression, and somnolence were identified.

Contraindications

• Hypersensitivity to brimonidine and other components of the drug;
• Concomitant therapy with MAO inhibitors;
• Children under 2 years of age;
• Breastfeeding period.

With caution

Orthostatic hypotension, heart failure, cerebrovascular diseases leading to cerebral circulation insufficiency, renal failure, hepatic failure, depression, Raynaud’s syndrome, obliterating thromboangiitis, children aged 2-7 years.

Use in Pregnancy and Lactation

Preclinical studies have not revealed a teratogenic effect on the fetus. However, it has been established that Brimonidine crosses the placental barrier and is present in small amounts in the fetal plasma. Controlled studies in pregnant women have not been conducted. During pregnancy, Brimonidine should be used only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

Animal studies have shown that Brimonidine passes into breast milk. Breastfeeding should be discontinued during the use of the drug.

Use in Hepatic Impairment

Use with caution in hepatic insufficiency

Use in Renal Impairment

Use with caution in renal insufficiency

Pediatric Use

Contraindicated in children under 2 years of age, use with caution in children aged 2-7 years

Geriatric Use

No dosage adjustment is required in the elderly.

Special Precautions

Brimonidine may exacerbate the course of syndromes accompanied by vascular insufficiency. Brimonidine should be used with caution in patients with depression, impaired cerebral or coronary circulation, Raynaud’s syndrome, orthostatic hypotension, or obliterating thromboangiitis.

Although clinical studies have not found a significant effect of brimonidine on blood pressure, the drug should be used with caution in patients with cardiovascular diseases.

Cases of bacterial keratitis have been described after the use of the drug in multi-dose bottles. These cases occurred due to unintentional contamination of the bottle by patients, most of whom had concomitant corneal diseases or damage to the ocular surface epithelium.

Effect on the ability to drive vehicles and operate machinery

The use of brimonidine may be accompanied by episodes of weakness and drowsiness in some patients. If the patient’s work is associated with potentially hazardous activities, driving vehicles, the patient must be warned in advance about the possible decrease in concentration and speed of psychomotor reactions, and it is recommended to refrain from these activities.

Overdose

In case of accidental ingestion of the drug by adults, the only symptom recorded was a decrease in blood pressure. In children, cases of overdose have been recorded both after instillation and after accidental ingestion.

If symptoms of overdose are detected, symptomatic therapy and ensuring airway patency are necessary. There are no data on the removal of brimonidine by hemodialysis.

Drug Interactions

Due to the possible hypotensive effect of brimonidine, its simultaneous use with antihypertensive agents and cardiac glycosides requires caution.

Brimonidine may enhance the depressant effect on the central nervous system of drugs that depress the central nervous system (including alcohol, barbiturates, narcotic analgesics, sedatives, and anesthetics).

Tricyclic antidepressants may enhance the hypotensive effect of clonidine. The effect of the simultaneous use of tricyclic antidepressants and brimonidine has not been studied. Caution should be exercised when using them concomitantly, as tricyclic antidepressants can disrupt the metabolism of circulating amines.

MAO inhibitors may exacerbate the systemic adverse drug reactions of brimonidine, for example, a decrease in blood pressure.

Storage Conditions

Store in a light-protected place at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

The shelf life is 36 months. The shelf life of the drug after first opening the dropper bottle is 28 days. Do not use after the expiration date printed on the package.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.