Alfagan^® R (Drops) Instructions for Use

Marketing Authorization Holder

AbbVie, LLC (Russia)

Manufactured By

Allergan Sales, LLC (USA)

ATC Code

S01EA05 (Brimonidine)

Active Substance

Brimonidine (Rec.INN registered by WHO)

Dosage Form

Alfagan® R

Eye drops 0.15%: 5 ml, 10 ml, or 15 ml dropper bottle

Dosage Form, Packaging, and Composition

Eye drops in the form of a transparent yellowish-green solution.

Excipients: stabilized oxychloro complex [sodium chlorite, sodium chlorate, chlorine dioxide], carmellose sodium, sodium chloride, potassium chloride, calcium chloride dihydrate, magnesium chloride hexahydrate, boric acid, sodium borate decahydrate, hydrochloric acid or sodium hydroxide, purified water.

5 ml – polyethylene dropper bottles (1) – cardboard boxes.
10 ml – polyethylene dropper bottles (1) – cardboard boxes.
15 ml – polyethylene dropper bottles (1) – cardboard boxes.

Clinical-Pharmacological Group

Antiglaucoma drug

Pharmacotherapeutic Group

Drugs used in ophthalmology; antiglaucoma drugs and miotic agents; sympathomimetics for the treatment of glaucoma

Pharmacological Action

Brimonidine is a selective alpha₂-adrenergic agonist that has a stimulating effect on alpha₂-adrenergic receptors. When used in the form of 0.15% eye drops, the maximum reduction in intraocular pressure (IOP) is achieved after 2 hours. The hypotensive effect of brimonidine is provided by reducing the production and increasing the outflow of intraocular fluid through the uveoscleral pathway.

Pharmacokinetics

Upon instillation of eye drops, C_max in blood plasma is reached in 0.5-2.5 hours, T_1/2 is about 2 hours. The systemic absorption of brimonidine is slow.

The drug is metabolized mainly in the liver. Brimonidine and its metabolites are excreted by the kidneys.

Indications

• open-angle glaucoma;
• ocular hypertension (in monotherapy or in combination with other IOP-lowering drugs).

ICD codes

Dosage Regimen

Instill one drop into the conjunctival sac of the affected eye(s) three times daily.

Maintain an interval of approximately 8 hours between administrations.

For concomitant therapy with other topical ophthalmic agents, administer Alfagan^® R last.

If using more than two topical ophthalmic drugs, observe a minimum 5-minute interval between instillations of each medication.

Do not allow the dropper tip to contact the eye, eyelids, or any other surface to prevent contamination of the solution.

Discard the opened bottle 28 days after first use, even if solution remains.

Administer the drug exactly as prescribed; do not alter the dosage frequency or discontinue use without consulting a physician.

Adverse Reactions

The frequency of side effects identified during studies was assessed as follows: very common (>10%), common (>1% and <10%); uncommon (>0.1% and <1%), rare (>0.01% and <0.1%).

The following side effects were identified in clinical studies of Alfagan^® R

From the organ of vision very common – allergic conjunctivitis, conjunctival hyperemia, itching of the eye mucosa and eyelid skin; common – burning sensation, conjunctival folliculosis or follicular conjunctivitis, local allergic reactions from the eyes (including keratoconjunctivitis), blepharitis, blepharoconjunctivitis, blurred vision, cataract, conjunctival edema, conjunctival hemorrhage, conjunctivitis, lacrimation retention, mucous discharge from the eyes, dryness and irritation of the eye mucosa, pain, eyelid edema, eyelid redness, foreign body sensation in the eyes, keratitis, eyelid lesions, photosensitivity, superficial punctate keratopathy, lacrimation, visual field loss, vitreous body functional disorders, vitreous hemorrhage, vitreous floaters and decreased visual acuity; uncommon – corneal erosion, stye;

From the CNS common – headache, drowsiness, insomnia, dizziness.

From the cardiovascular system common – increased BP; uncommon – decreased BP.

From the respiratory system common – bronchitis, cough, dyspnea; uncommon – dryness of the nasal mucosa, apnea.

From the GI tract common – gastrointestinal disorders – dyspepsia, dry mouth.

From the skin and subcutaneous tissue common – rash.

Infectious and parasitic diseases common – flu-like syndrome, infectious disease (chills and respiratory infection), rhinitis, sinusitis, including infectious.

Laboratory parameters common – hypercholesterolemia.

Others common – general allergic reactions, asthenia, fatigue; uncommon – taste perversion.

In children, the following were noted: apnea, bradycardia, decreased BP, hypothermia, muscle hypotonia.

During the post-marketing period, additional reports of the following side effects were received

From the organ of vision frequency unknown – iritis, dry keratoconjunctivitis, miosis;

From the CNS depression;

From the cardiovascular system bradycardia, tachycardia.

From the GI tract nausea.

From the skin and subcutaneous tissue local skin reactions (erythema, eyelid itching, facial edema, rash and vasodilation of the vessels of the eyelids and face).

Contraindications

• Hypersensitivity to brimonidine and other components of the drug;
• Concomitant therapy with MAO inhibitors;
• Children under 2 years of age, low body weight (under 20 kg);
• Breastfeeding period.

With caution: orthostatic hypotension, heart failure, cerebrovascular diseases leading to cerebral circulation insufficiency, renal failure (creatinine clearance below 40 ml/min), hepatic failure, depression, Raynaud’s syndrome, obliterating thromboangiitis, children aged 2 to 7 years.

Use in Pregnancy and Lactation

Preclinical studies did not reveal any effect on reproductive function. However, it has been established that Brimonidine crosses the placental barrier and is present in small amounts in the fetal blood plasma. No damaging effect on the fetus has been established.

No controlled studies have been conducted in pregnant women. During pregnancy, Alfagan^® R should be used with extreme caution, only in cases where the expected benefit to the mother significantly outweighs the possible risk to the fetus.

Animal studies have established that brimonidine tartrate passes into breast milk. Breastfeeding should be discontinued during the use of the drug.

Use in Hepatic Impairment

With caution: hepatic failure.

Use in Renal Impairment

With caution: renal failure (creatinine clearance below 40 ml/min).

Pediatric Use

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

Special Precautions

Effect on the ability to drive vehicles and mechanisms

Taking Alfagan^® R 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, they must be warned in advance about a possible decrease in concentration and speed of psychomotor reactions, and it is recommended to refrain from these activities.

Overdose

There are no reports of drug overdose.

In case of accidental ingestion of the drug, the following symptoms are possible: CNS depression, drowsiness, depression and loss of consciousness, decreased BP, bradycardia, decreased body temperature, cyanosis of the skin, apnea.

If symptoms of overdose are detected, symptomatic therapy and airway patency control are necessary.

Drug Interactions

No studies on the drug interaction of Alfagan^® R have been conducted, but when used concomitantly, the possibility of enhancing the effect of drugs that depress the CNS (alcohol, barbiturates, opiates, sedatives, general anesthetics) should be taken into account. Given the ability of alpha-adrenergic agonist drugs to reduce BP and heart rate, antihypertensive drugs and cardiac glycosides should be used concomitantly with caution.

Due to the known decrease in the severity of the hypotensive effect of clonidine (an alpha₂-adrenergic agonist) when used concomitantly with tricyclic antidepressants, a possible decrease in the effectiveness of Alfagan^® R during concomitant treatment with tricyclic antidepressants cannot be excluded.

Alfagan^® R should be used with caution with tricyclic antidepressants, which can affect the metabolism of amines and their distribution in the vascular bed.

Storage Conditions

At a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

The shelf life of the drug after first opening the dropper bottle is 28 days.

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.