Phenylephrine-SZ (Drops) Instructions for Use

Marketing Authorization Holder

Severnaya Zvezda NAO (Russia)

Manufactured By

Diafarm, JSC (Russia)

Packaging and Quality Control Release

SEVERNAYA ZVEZDA, NAO (Russia)

Contact Information

SEVERNAYA ZVEZDA NAO (Russia)

ATC Code

S01FB01 (Phenylephrine)

Active Substance

Phenylephrine (Rec.INN registered by WHO)

Dosage Form

Phenylephrine-SZ

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

Dosage Form, Packaging, and Composition

Eye drops in the form of a clear solution from colorless to light yellow.

Excipients: disodium edetate dihydrate, citric acid, sodium citrate dihydrate, benzalkonium chloride, sodium metabisulfite, 1M sodium hydroxide solution (for pH adjustment), purified water.

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

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 an alpha-adrenergic agonist that has a pronounced non-selective alpha-adrenergic agonist effect. When used in therapeutic doses, it does not have a significant stimulating effect on the central nervous system.

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

It has a weak effect on beta-adrenergic receptors, including those of the heart (does not have a positive chronotropic or inotropic effect). The drug has a vasoconstrictor effect similar to that of norepinephrine. The vasopressor effect of phenylephrine is weaker than that of norepinephrine but is more prolonged. It causes vasoconstriction within 30-90 seconds after instillation, with a duration 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. Mydriasis persists after instillation of a 2.5% solution for 2 hours. Mydriasis caused by phenylephrine is not accompanied by cycloplegia.

Pharmacokinetics

Absorption and Distribution

Phenylephrine easily penetrates the eye tissues, C_max in plasma is reached within 10-20 minutes after instillation into the eye. Preliminary instillation of local anesthetics may increase the systemic absorption of phenylephrine and prolong mydriasis.

Metabolism and Excretion

Phenylephrine is excreted by the kidneys unchanged (< 20%) or as inactive metabolites.

Indications

The medicinal product Phenylephrine-SZ is indicated for use in adults aged 18 years and older

• Iridocyclitis (to prevent the occurrence of posterior synechiae and reduce 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;
• Conducting a provocative test in patients with a narrow anterior chamber angle profile 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 mucous membrane of the eye);
• Accommodative spasm.

The medicinal product Phenylephrine-SZ is indicated for use in children and adolescents aged 6 to 18 years

• Accommodative spasm.

ICD codes

Dosage Regimen

It is used topically, as instillations into the conjunctival sac.

For iridocyclitis, the drug is used to prevent the development and rupture of already formed posterior synechiae; 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.

For ophthalmoscopy, a single instillation of the drug is used. As a rule, instillation of 1 drop of the drug into the conjunctival sac is sufficient to create mydriasis. Maximum mydriasis is achieved after 15-30 minutes and lasts for 1-3 hours.

If it is necessary to maintain mydriasis for a long time, a repeated instillation of the drug is possible after 1 hour.

For diagnostic procedures, a single instillation of the drug 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 the drug and after pupil dilation is from 3 to 5 mm Hg, then the provocative test is considered positive;
• for differential diagnosis of the type of eyeball injection if 5 minutes after instillation of the drug, 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.

To relieve accommodative spasm in children from 6 years of age and adults, the drug is instilled, 1 drop into each eye at night daily for 4 weeks.

Adverse Reactions

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

Phenylephrine may cause reactive miosis the day after application. Repeated instillations of the drug over a short period of time may lead to less pronounced mydriasis than previously observed.

Due to significant contraction of the pupil dilator muscle, 30-45 minutes after instillation under the influence of phenylephrine, 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.

Tabulated summary of adverse reactions

The frequency of adverse reactions is given in accordance with the following classification: very common (≥1/10), common (≥1/100 but <1/10), uncommon (≥1/1000 but <1/100), rare (≥1/10000 but <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from the available data).

Elderly patients

Reactive miosis the day after application and less pronounced mydriasis after repeated instillations of the drug over a short period of time occur more frequently in elderly patients.

Contraindications

• Hypersensitivity to phenylephrine or to any of the excipients included in the drug;;
• Narrow-angle or angle-closure glaucoma;
• Old age;
• Severe cardiovascular or cerebrovascular diseases;
• Arterial hypertension in combination with coronary artery disease, aortic aneurysm, AV block I-III degree, arrhythmia;
• Tachycardia;
• Impaired tear production;
• Prematurity;
• Children under 6 years of age (for accommodative spasm);
• Hyperthyroidism;
• Hepatic porphyria;
• Congenital glucose-6-phosphate dehydrogenase deficiency;
• Rhinitis.

With caution

Diabetes mellitus (risk of increased blood pressure associated with autonomic regulation disorder).

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

Sickle cell anemia, wearing contact lenses, after surgical interventions (reduced healing due to conjunctival hypoxia).

Use in Pregnancy and Lactation

Pregnancy

The effect of phenylephrine in pregnant women has not been sufficiently studied, so the use of the drug during pregnancy is possible only if the potential benefit to the mother outweighs the possible risk to the fetus.

In animals in late pregnancy, Phenylephrine caused fetal growth retardation and stimulated early onset of labor.

Breastfeeding period

It is not known whether the drug is excreted in breast milk. When prescribing the drug, breastfeeding should be discontinued during treatment.

Pediatric Use

Contraindication: children under 6 years of age (for accommodative spasm);

Special Precautions

Exceeding the recommended dose of the 25 mg/ml solution in patients with eye 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.

Excipients

The drug Phenylephrine-SZ contains the preservative benzalkonium chloride, which may cause eye irritation and discoloration of soft contact lenses. Direct contact of the drug with soft contact lenses should be avoided. Patients using contact lenses should remove the lenses before using the drug and reinsert them no earlier than 15 minutes after instillation. Due to the content of the preservative benzalkonium chloride in the drug, the development of punctate or ulcerative toxic keratopathy is possible with frequent or prolonged use of the drug by patients with dry eye syndrome and concomitant corneal diseases. During the treatment of such patients, monitoring of the corneal condition is required.

Effect on the ability to drive vehicles and operate machinery

After using the drug, due to changes in accommodation and pupil width, a decrease in visual acuity is possible, therefore, until it is restored, it is not recommended to drive vehicles and engage in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms anxiety, nervousness, dizziness, sweating, vomiting, palpitations, weak or shallow breathing.

Treatment if systemic effects of phenylephrine occur, adverse events can be stopped by administering alpha-blockers, for example, 5-10 mg of phentolamine intravenously. The injection can be repeated if necessary.

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.

The use of phenylephrine with MAO inhibitors, as well as within 21 days after their discontinuation, should be carried out with caution, as in this case there is a possibility of an uncontrolled increase in blood pressure.

The vasopressor effect of alpha-adrenergic agonists can also be potentiated with simultaneous use with tricyclic antidepressants, propranolol, reserpine, guanethidine, methyldopa, and m-cholinergic blockers.

Phenylephrine may potentiate the depression of cardiovascular activity during inhalation anesthesia.

Concomitant use with other adrenergic agonists and sympathomimetics may enhance the effect of phenylephrine on the cardiovascular system.

The use of phenylephrine may weaken concomitant antihypertensive therapy and lead to increased blood pressure and tachycardia.

Storage Conditions

The drug should be stored out of the reach of children, in a place protected from light, at a temperature not exceeding 25°C (77°F). Do not freeze.

Shelf Life

The shelf life is 3 years. Do not use after the expiration date printed on the package.

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

Dispensing Status

The drug is dispensed 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.