FENEPRIN 10 %

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FENEFRIN 10% (FENEFRIN® 10%)

Composition:

Active substance: phenylephrine hydrochloride; 1 ml of solution contains 100 mg of phenylephrine hydrochloride;

1 ml contains 38 drops;

Excipients: disodium edetate, benzalkonium chloride, diluted hydrochloric acid, water for injections.

Pharmaceutical form. Eye drops, solution.

Main physico-chemical properties: clear, colorless or slightly yellowish solution, free from visible mechanical particles.

Pharmacotherapeutic group. Agents used in ophthalmology. Sympathomimetics, excluding antiglaucoma agents. ATC Code S01FB01.

Pharmacological Properties.

Pharmacodynamics.

Phenylephrine as an ophthalmic agent is used locally in concentrations of 0.06–10.0% to achieve vasoconstrictive effects at concentrations of 0.1–0.25%.

Phenylephrine hydrochloride belongs to the group of alpha-1-sympathomimetic agents with a pronounced antihyperemic effect. The ability of phenylephrine to dilate the pupil is associated with activation of alpha-1 receptors on the iris dilator muscle and is partially responsible for reducing intraocular pressure following administration of phenylephrine hydrochloride at high concentrations (2.5–10%). Vasoconstriction is achieved and manifests as an anti-edematous effect on the nasal mucosa and conjunctiva during hyperemia, even when applying low-concentration phenylephrine solutions. After instillation of a 10% phenylephrine hydrochloride solution, in some cases, paralysis of accommodation and miosis have been observed. However, there is evidence that a 10% solution induces maximal pupil dilation within 20 minutes without causing accommodation paralysis. The mydriatic effect lasts approximately 5 hours. A clear dose- (or concentration-) dependent relationship has been demonstrated regarding the effect on accommodation (or pupil dilation), showing enhanced effects on pupil size and intraocular pressure at concentrations ranging from 0.1% to 10.0%. A 0.125% solution does not affect pupil size or intraocular pressure.

Pharmacokinetics.

The corneal epithelium plays an important role in the metabolism of phenylephrine. After removal of the corneal epithelium, the penetration of phenylephrine and its metabolites increases approximately tenfold, as phenylephrine is poorly lipid-soluble and, at physiological pH levels, behaves as a weak base. Phenylephrine is also partially metabolized in corneal tissues. The intraocular concentration of phenylephrine is significantly reduced due to metabolism when the concentration of the solution instilled into the conjunctival sac is less than 0.1%.

Clinical characteristics.

Indications.

Pupil dilation

Maximum rapid and pronounced dilation of the pupil.

Prevention and treatment

Prevention of uveitis or prevention of synechiae formation in uveitis.

Surgical intervention

Pupil dilation prior to intraocular surgical procedures.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients;
• closed-angle glaucoma, dry nose, vascular aneurysm;
• advanced age, severe cardiovascular or cerebrovascular disorders;
• disruption of the integrity of the eyeball;
• impaired tear production;
• hyperthyroidism, thyrotoxicosis;
• pheochromocytoma;
• metabolic acidosis, hypercapnia, hypoxia;
• prostatic gland diseases with increased risk of urinary retention;
• hepatic porphyria;
• congenital deficiency of glucose-6-phosphate dehydrogenase;
• concomitant use of monoamine oxidase inhibitors (MAOIs) and use within 2 weeks after discontinuation of MAOIs;
• insulin-dependent diabetes mellitus;
• concomitant use with tricyclic antidepressants and antihypertensive medicinal products (including beta-adrenoblockers).

Interaction with other medicinal products and other forms of interaction.

The mydriatic effect of the drug is reduced when other ophthalmic preparations containing miotic agents are used locally. The drug may impair the ability of miotic agents to reduce intraocular pressure. The mydriatic effect of phenylephrine is enhanced by local application of atropine.

Antihypertensive medicinal products (including beta-adrenoblockers) are contraindicated for concomitant use with phenylephrine for local application, as antagonistic effects of many antihypertensive drugs may occur, potentially leading to fatal outcomes.

MAO inhibitors. Concomitant use of phenylephrine during treatment with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of MAOI therapy is contraindicated. Concomitant use with MAOIs or within 21 days after their discontinuation should be performed with caution, as systemic adrenergic effects may develop.

Tricyclic antidepressants are contraindicated for concomitant use with phenylephrine. Vasoconstrictor effects of adrenergic agents may be enhanced by tricyclic antidepressants (risk of cardiac arrhythmia, including several days after discontinuation), propranolol, reserpine, guanethidine, methyldopa, and muscarinic receptor blockers.

Inhalational anaesthesia / halothane. Increased risk of ventricular fibrillation. Phenylephrine should be used with caution during general anaesthesia, as myocardial sensitivity to sympathomimetics is increased and cardiovascular depression may be potentiated during inhalational anaesthesia.

Cardiac glycosides or quinidine. Increased risk of arrhythmia.

Special precautions for use.

A significant increase in blood pressure has been observed after instillation of 10% phenylephrine solution in recommended doses.

"Phenephrin 10%" should be administered with caution to patients with cardiovascular disorders, arterial hypertension, severe cardiac dysfunction, arrhythmias, and severe vascular diseases such as marked atherosclerosis or insulin-dependent diabetes. In cases of conjunctival hyperemia and corneal epithelial damage, absorption may increase, potentially enhancing systemic adverse effects.

Instillation of the agent into the eye following trauma, surgical intervention, or in patients with reduced tear production (during anesthesia) may result in significant systemic absorption of phenylephrine in quantities sufficient to initiate a systemic vasoconstrictive response.

A "rebound" miosis has been observed in elderly patients one day after administration of phenylephrine solution, and repeated application led to reduced pupillary dilation. Due to the pronounced effect of the drug on pupillary dilation, transient appearance of floating pigment spots in the intraocular fluid may occur in elderly patients within 30–45 minutes after instillation of phenylephrine solution into the eye. The anterior chamber angle should be evaluated prior to drug administration to avoid triggering an acute glaucoma attack.

It is prohibited to wear soft contact lenses during treatment, as benzalkonium chloride, which may be retained in the lenses, can cause corneal damage. Patients may wear rigid contact lenses under medical supervision, but must always remove them before applying the medication and refrain from reinserting them for at least 20 minutes after instillation.

Use during pregnancy or breastfeeding.

Pregnancy.

There is no experience with the use of this drug in pregnant women; therefore, the use of "Phenephrin 10%" during pregnancy is contraindicated.

Breastfeeding.

It is unknown whether phenylephrine passes into breast milk; therefore, breastfeeding should be discontinued during treatment with this drug.

Ability to affect reaction speed when driving or operating machinery.

"Phenephrin 10%" causes pupillary dilation and prevents accommodation. It may cause blurred vision. Additionally, there is a risk of photophobia for several hours after instillation. Patients should avoid driving, operating automated systems, or performing hazardous tasks requiring attention, concentration, and motor coordination for several hours after administration of the drug, as it may reduce the speed and effectiveness of reaction.

Method of Administration and Dosage

The medication is intended for adults.

For maximum rapid and pronounced mydriasis, instill one drop of the medication once into the conjunctival sac.

To disrupt synechiae, apply one drop of the medication to the conjunctiva of one or both eyes once daily. The duration of treatment should not exceed 5 days; medical supervision is required during prolonged therapy.

For pupil dilation prior to surgical intervention, administer the medication 30–60 minutes before the surgical procedure.

Dosage for elderly patients

The medication should be prescribed with caution to elderly patients and only after evaluating the possibility of using an alternative agent with a lower concentration of phenylephrine.

Method of Administration

The patient should slightly tilt the head backward, gently pull down the lower eyelid, and carefully squeeze the dropper bottle to instill the drop into the conjunctival sac, ensuring that the tip of the bottle does not touch the eye. The bottle should be closed immediately after instillation.

As with the use of any ophthalmic solution, it is recommended to apply pressure for 1 minute on the lacrimal sac area at the inner corner of the eye immediately after each drop to reduce systemic absorption.

Rigid contact lenses should be removed before instillation of eye drops. They may be reinserted 20 minutes after instillation. Soft contact lenses must not be worn during the treatment period.

If more than one ophthalmic medication is used, the interval between administrations should be at least 5 minutes. Ophthalmic ointments should be applied last.

Children. The medication is not intended for use in children.

Overdose

Symptoms: headache, elevated arterial blood pressure, palpitations, vomiting, panic fear, anxiety, excitement, tremor, initial tachycardia followed by reflex bradycardia due to stimulation of the aortic nerve, intracerebral hemorrhage, loss of consciousness, weakness, fatigue, seizures, pallor of the facial skin, paroxysm, syncope, ventricular fibrillation, and dyspeptic symptoms.

The toxic oral dose is 3 mg/kg body weight in children and 300 mg/kg body weight in adults.

Treatment is symptomatic. In cases of acute overdose, administer activated charcoal or gastric lavage. In cases of overdose following instillation into the conjunctival sac, immediately rinse the eye with water.

In cases of reflex bradycardia, administer atropine (in children, dose of 0.01–0.02 mg/kg body weight).

In cases of life-threatening elevation of arterial blood pressure, administer phentolamine, a peripheral alpha-receptor antagonist.

Side effects

Eye-related.

The drug may cause reactive hyperemia following the decline of vasoconstrictive effect and may induce burning sensation in the conjunctival sac, blurred vision, allergic reactions, irritation, photophobia, discomfort, lacrimation, increased intraocular pressure, and reactive miosis the day after administration.

Cardiovascular system: tachycardia, palpitations, cardiac arrhythmia, arterial hypertension, ventricular arrhythmia, reflex bradycardia, coronary artery occlusion, pulmonary artery embolism.

General symptoms: headache, excitation, loss of consciousness, syncope, dizziness, tremor, paresthesia, insomnia, pallor of the facial skin, weakness, dyspnea, and dyspeptic symptoms.

Paralysis of the ciliary muscle lasting several hours may occur. In some cases, the drug may cause accommodation disturbances up to three diopters. The drug may increase blood pressure, usually to a mild degree. Occasionally, strong pressor responses have been reported, accompanied by rapid heartbeat, tachycardia, cardiac rhythm disturbances, and severe headaches. These general effects occurred mainly in patients with conjunctival hyperemia, hemorrhages into the conjunctival sac, and epithelial defects of the cornea or conjunctiva.

Prolonged use may lead to severe redness and thickening of the cornea due to edema. Continuous use may cause pupillary constriction in elderly patients.

Occasionally, after prolonged use, xerosis (epithelial keratinization) of the conjunctiva and obstruction of the lacrimal duct may develop.

"Phenephrine 10%" may even exacerbate narrowing of the anterior chamber angle, triggering an attack of glaucoma. If "Phenephrine 10%" is administered in patients with glaucoma, additional medications such as pilocarpine should be used to reduce intraocular pressure.

Shelf life. 2 years.

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

Storage conditions.

Store in a place protected from light and inaccessible to children, at a temperature not exceeding 25 °C. Do not freeze. After first opening, store for no more than 28 days.

Packaging.

10 ml in a plastic dropper bottle closed with a cap featuring a tamper-evident seal.

One dropper bottle together with the instruction for medical use is packaged in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

LLC "Unimed Pharma" / "UNIMED PHARMA Ltd".

Manufacturer's address and location of business activity.

11 Orieskova St., 821 05, Bratislava, Slovak Republic /
Orieskova 11, 821 05 Bratislava, Slovak Republic.