Irifrin^® (Drops) Instructions for Use

Marketing Authorization Holder

Sentiss Pharma, Pvt. Ltd. (India)

ATC Code

S01FB01 (Phenylephrine)

Active Substance

Phenylephrine (Rec.INN registered by WHO)

Dosage Forms

	Irifrin®	Eye drops 2.5%: 5 ml dropper bottle
		Eye drops 10%: 5 ml bottle or dropper bottle

Dosage Form, Packaging, and Composition

Eye drops as a clear solution from colorless to light yellow.

Excipients: benzalkonium chloride – 0.1 mg, disodium edetate – 1 mg, hypromellose – 3 mg, sodium metabisulfite – 2 mg, citric acid – 1.16 mg, sodium citrate dihydrate – 7.5 mg, water for injections – q.s.

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

Eye drops 10% as a clear solution from colorless to light yellow.

Excipients: benzalkonium chloride – 0.1 mg, disodium edetate – 1 mg, sodium hydroxide – 0.24 mg, sodium phosphate dibasic dihydrate – 0.24 mg, sodium phosphate monobasic anhydrous – 1.1 mg, sodium metabisulfite – 3 mg, citric acid – 2 mg, sodium citrate dihydrate – 2 mg, water for injections – q.s.

5 ml – dark glass bottles (1) with dropper – cardboard boxes.
5 ml – plastic dropper bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Topical alpha-adrenergic agonist for use in ophthalmology

Pharmacotherapeutic Group

Agents used in ophthalmology; mydriatic and cycloplegic agents; sympathomimetics, except antiglaucoma drugs

Pharmacological Action

Phenylephrine is a sympathomimetic. It has pronounced alpha-adrenergic activity and, when used in usual doses, does not have a significant stimulating effect on the CNS.

When used topically in ophthalmology, it causes pupil dilation, improves the outflow of intraocular fluid, and constricts conjunctival vessels.

Phenylephrine has a pronounced stimulating effect on postsynaptic α-adrenergic receptors and has a very weak effect on myocardial β-adrenergic receptors. The drug has a vasoconstrictor effect similar to that of norepinephrine, while it has virtually no chronotropic and inotropic effects on the heart. The vasopressor effect of phenylephrine is less pronounced than that of norepinephrine but is more prolonged. It causes vasoconstriction within 30-90 seconds after instillation, with a duration of action of 2-6 hours.

After instillation, Phenylephrine contracts the pupil dilator and the smooth muscles of the conjunctival arterioles, thereby causing pupil dilation. Mydriasis occurs within 10-60 minutes after a single instillation. It continues after instillation of the 2.5% solution and persists for 2 hours, and for the 10% solution – for 3-7 hours. Mydriasis caused by phenylephrine is not accompanied by cycloplegia.

Pharmacokinetics

Phenylephrine easily penetrates into the eye tissues, C_max in plasma occurs 10-20 minutes after topical application. Preliminary instillation of local anesthetics may increase systemic absorption and prolong mydriasis. Phenylephrine is excreted in the urine unchanged (<20%) or as inactive metabolites.

Indications

• Iridocyclitis (for the prevention of posterior synechiae and reduction of exudation from the iris);
• Diagnostic pupil dilation during ophthalmoscopy and other diagnostic procedures necessary to monitor the condition of the posterior segment of the eye, during laser interventions on the fundus and vitreoretinal surgery;
• Conducting a provocative test in patients with a narrow anterior chamber angle and suspected angle-closure glaucoma;
• Differential diagnosis of superficial and deep injection of the eyeball;
• Red eye syndrome (to reduce hyperemia and irritation of the eye mucosa);
• Prevention of asthenopia and accommodation disorders in patients with high visual load;
• Treatment of false myopia (accommodation disorders) and prevention of the progression of true myopia in patients with high visual load;
• For pupil dilation in ophthalmic surgery, in the treatment of glaucomatocyclitic crises (the 10% solution of the drug is used).

ICD codes

Dosage Regimen

When performing ophthalmoscopy, 2.5% eye drops are used once as instillations. As a rule, the introduction of 1 drop of 2.5% phenylephrine into the conjunctival sac is sufficient to create mydriasis. Maximum mydriasis is achieved after 15-30 minutes and remains at a sufficient level for 1-3 hours. If it is necessary to maintain mydriasis for a long time, repeated instillation of phenylephrine is possible after 1 hour.

In adults and children over 12 years of agewith insufficient pupil dilation, as well as in patients with a rigid iris (pronounced pigmentation) for diagnostic pupil dilation, the use of 10% eye drops in the same dose is possible.

For relieving accommodation spasm, adults and children over 6 years of age are prescribed 2.5% eye drops, 1 drop in each eye at night daily for 4 weeks.

In case of persistent accommodation spasm, the use of 10% eye drops is possible in adults and children over 12 years of age – 1 drop in each eye at night daily for 2 weeks.

For diagnostic procedures, a single instillation of phenylephrine 2.5% eye drops is used:

• As a provocative test in patients with a narrow anterior chamber angle profile and suspected angle-closure glaucoma. If the difference between intraocular pressure values before instillation of Irifrin^® and after pupil dilation is from 3 to 5 mm Hg, the provocative test is considered positive;
• For differential diagnosis of the type of eyeball injection – if 5 minutes after instillation, constriction of the eyeball vessels is noted, then the injection is classified as superficial; if redness of the eye persists, it is necessary to carefully examine the patient for the presence of iridocyclitis or scleritis, as this indicates dilation of deeper vessels.

For iridocyclitis, Phenylephrine is used as 2.5% or 10% eye drops to prevent the development and rupture of already formed posterior synechiae and to reduce exudation into the anterior chamber of the eye. For this purpose, 1 drop of the drug is instilled into the conjunctival sac of the affected eye(s) 2-3 times/day.

In glaucomatocyclitic crises, the vasoconstrictor effect of phenylephrine contributes to a decrease in intraocular pressure, which is most pronounced when using 10% eye drops. To relieve glaucomatocyclitic crises, Phenylephrine 10% eye drops are instilled 2-3 times/day.

When preparing for surgical interventions, 30-60 minutes before surgery, a single instillation of phenylephrine 10% eye drops is performed to achieve mydriasis. After opening the membranes of the eyeball, repeated instillation of the drug is not allowed.

10% eye drops are not used for irrigation, soaking tampons during surgery, or for subconjunctival administration.

Adverse Reactions

Local reactions

From the organ of vision conjunctivitis, periorbital edema.

In some cases, patients note a burning sensation at the beginning of use, blurred vision, irritation, discomfort, lacrimation, increased intraocular pressure.

Phenylephrine may cause reactive miosis the day after application. Repeated instillations of the drug at this time may produce less pronounced mydriasis than the day before. This effect is more common in elderly patients.

Due to significant contraction of the pupil dilator under the influence of phenylephrine, 30-45 minutes after instillation, pigment particles from the pigment layer of the iris may be detected in the aqueous humor of the anterior chamber. The suspension in the aqueous humor must be differentiated from manifestations of anterior uveitis or from the entry of blood cells into the aqueous humor of the anterior chamber.

Systemic reactions

From the skin contact dermatitis.

From the cardiovascular system palpitations, tachycardia, arrhythmia (including ventricular), increased blood pressure, ventricular arrhythmia, reflex bradycardia, coronary artery occlusion, pulmonary embolism. In rare cases, after topical application of a 10% phenylephrine solution, serious disorders of the cardiovascular system may develop, including myocardial infarction, vascular collapse, and intracranial hemorrhage.

Contraindications

• Hypersensitivity to the drug;
• Narrow-angle or angle-closure glaucoma;
• The drug is contraindicated in elderly patients with serious disorders of the cardiovascular or cerebrovascular system;
• It is contraindicated to use the drug for additional pupil dilation during surgical operations in patients with impaired integrity of the eyeball, as well as with impaired tear production;
• The 10% solution of the drug is contraindicated in children under 12 years of age and in patients with arterial aneurysm;
• The 2.5% solution of the drug is contraindicated in premature infants;
• Hyperthyroidism;
• Hepatic porphyria;
• Congenital deficiency of glucose-6-phosphate dehydrogenase.

Use in Pregnancy and Lactation

Since the effect of phenylephrine during pregnancy and lactation has not been sufficiently studied, the use of the drug in these patients is possible only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus or breastfed infant.

Use in Hepatic Impairment

The use of the drug is contraindicated in hepatic porphyria.

Pediatric Use

Contraindications: children under 12 years of age (10% eye drops); premature infants (2.5% eye drops).

Geriatric Use

Contraindicated in elderly patients with serious disorders of the cardiovascular system and cerebral circulation.

Special Precautions

In patients with diabetes – increased risk of increased blood pressure associated with autonomic regulation impairment.

In elderly patients – increased risk of reactive miosis.

Concomitant use with MAO inhibitors (including within 21 days after their discontinuation).

Exceeding the recommended dose of 2.5% eye drops in patients with injuries, diseases of the eye or its appendages, in the postoperative period, or with reduced tear production (anesthesia) may lead to increased absorption of phenylephrine and the development of systemic side effects.

Due to the fact that it causes conjunctival hypoxia – in patients with sickle cell anemia, when wearing contact lenses, after surgical interventions (slowing of healing).

Drug Interactions

The mydriatic effect of phenylephrine is enhanced when used in combination with the topical application of atropine. Due to the enhancement of the vasopressor effect, tachycardia may develop.

Use Phenylephrine 2.5% or 10% eye drops with caution simultaneously with MAO inhibitors or within 21 days after discontinuation, as there is a risk of uncontrolled increase in blood pressure.

The vasopressor effect of adrenomimetic agents may also be potentiated when used concomitantly with tricyclic antidepressants, propranolol, reserpine, guanethidine, methyldopa, and m-cholinoblockers.

The use of phenylephrine in the form of 10% eye drops in combination with the systemic use of beta-blockers may lead to acute arterial hypertension.

May potentiate the depressant effect on the activity of the cardiovascular system during inhalation anesthesia.

Concomitant use with sympathomimetics may enhance the cardiovascular effects of phenylephrine.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.