Merallis® advance

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MERALYS® ADVANCE

Composition:

Active substance: xylometazoline hydrochloride;

1 ml of solution contains 1 mg or 0.5 mg of xylometazoline hydrochloride;

Excipients: purified sea water, potassium dihydrogen phosphate, sodium hyaluronate, purified water.

Pharmaceutical form. Nasal spray, solution.

Main physicochemical properties. Clear, colorless solution.

Pharmacotherapeutic group. Medicinal products used in nasal disorders. Simple sympathomimetics.

ATC Code R01A A07.

Pharmacological Properties

Pharmacodynamics

Xylometazoline is a sympathomimetic agent acting on α-adrenergic receptors.

Meralis**®** Advance causes constriction of nasal blood vessels, reducing swelling of the nasal mucosa and its paranasal sinuses, thereby improving nasal breathing in cases of nasal and sinus congestion.

The effect of the medicinal product begins within a few minutes after application and lasts up to 12 hours.

The drug does not impair mucociliary function. Meralis**®** Advance has a balanced pH value within the physiological range of the nasal cavity. Hyaluronic acid hydrates the mucous membrane and thus supports its optimal condition for the healing process, if needed.

Pharmacokinetics

After nasal administration, xylometazoline is practically not absorbed, and plasma concentrations are so low that they cannot be detected by current analytical methods. In cases of overdose or prolonged use, the absorbed amount of the drug may occasionally be sufficient to cause systemic effects, particularly involving the central nervous and cardiovascular systems.

Clinical Characteristics

Indications

Symptomatic treatment of nasal congestion due to colds, hay fever, allergic rhinitis, and sinusitis.

For facilitating drainage of secretions in diseases of the nasal accessory sinuses.

Adjunctive therapy in cases of otitis media (to relieve mucosal swelling).

For facilitating rhinoscopy.

Contraindications

Meralis® Advance should not be used in the following cases:

• Hypersensitivity to the active substance xylometazoline hydrochloride or to any of the excipients of the medicinal product;
• Dry inflammation of the nasal mucosa with crust formation (dry rhinitis);
• Concurrent treatment with monoamine oxidase inhibitors (MAOIs); treatment with MAOIs within two weeks prior to starting Meralis® Advance, or concurrent treatment with other medicinal products capable of increasing blood pressure;
• After hypophysectomy or surgical interventions on the dura mater;
• Angle-closure glaucoma;
• Children under 2 years of age — for the 0.05% spray; children under 12 years of age — for the 0.1% spray;
• Pregnancy.

Interaction with Other Medicinal Products and Other Forms of Interaction

Monoamine oxidase inhibitors (MAOIs): xylometazoline may potentiate the effect of monoamine oxidase inhibitors and induce a hypertensive crisis. Do not use xylometazoline in patients taking or who have taken MAOIs within the last two weeks.

Tricyclic and tetracyclic antidepressants: concomitant use of tricyclic or tetracyclic antidepressants and sympathomimetic agents may enhance the sympathomimetic effect of xylometazoline; therefore, simultaneous use is not recommended. Concomitant use with β-blockers may cause bronchospasm or reduction in blood pressure. Due to the potential hypertensive effect of xylometazoline, this medicinal product should not be used in combination with antihypertensive agents (e.g., methyldopa). Complex interactions may also occur with α- and β-blockers, potentially causing hypotension or hypertension, tachycardia or bradycardia.

Special precautions for use

The medicinal product should be prescribed with caution to patients who have experienced severe adverse reactions to adrenergic agents, such as insomnia, dizziness, tremor, cardiac arrhythmia, or increased arterial pressure.

Meralis® Advance should be used with caution and only after careful assessment of the benefit-risk ratio in patients with elevated intraocular pressure, severe cardiovascular disorders (e.g., ischemic heart disease, hypertension), prostate hyperplasia, pheochromocytoma, porphyria, or metabolic disorders (e.g., diabetes mellitus). Do not use in patients receiving or who have received treatment with monoamine oxidase inhibitors (MAOIs) within the previous 2 weeks.

Patients with prolonged QT syndrome who are receiving xylometazoline are at increased risk of serious ventricular arrhythmias.

The recommended dose of the medicinal product should not be exceeded, especially when treating children and elderly patients. Do not use the medicinal product for longer than 5 consecutive days.

Due to the risk of nasal mucosal atrophy, this product should be used in patients with chronic inflammation of the nasal mucosa only under medical supervision.

Prolonged use or overdose of sympathomimetic decongestants may cause reactive hyperemia of the nasal mucosa, leading to airway obstruction, which in turn may lead to repeated or continuous use of the product. This may result in chronic edema (medication-induced rhinitis) and, eventually, atrophy of the nasal mucosa. In mild cases, discontinuation of sympathomimetics should first be considered in one nostril, and after symptoms resolve, in the other nostril, to preserve nasal breathing at least partially.

Rare cases of posterior reversible encephalopathy syndrome (PRES) / reversible cerebral vasoconstrictive syndrome (RCVS) have been reported during use of sympathomimetic agents. Reported symptoms include sudden severe headache, nausea, vomiting, and visual disturbances. Symptoms usually resolve or improve within several days after appropriate treatment. If signs or symptoms of PRES/RCVS develop, the medicinal product should be discontinued immediately and medical advice sought.

Use during pregnancy or breastfeeding

Pregnancy. The medicinal product should not be used during pregnancy due to its potential vasoconstrictive effect.

Breastfeeding. The product should not be used in breastfeeding women, as it is unknown whether it is excreted in breast milk.

Fertility. There are no adequate data on the effect of the product on fertility. Since systemic exposure to xylometazoline hydrochloride is very low, the likelihood of an effect on fertility is extremely small.

Ability to affect reaction speed when driving or operating machinery

With prolonged use of Meralis**®** Advance at high doses, undesirable effects on the cardiovascular system may occur, which could negatively affect the ability to drive or operate machinery.

Method of Administration and Dosage

Before using the medicinal product, the nose should be thoroughly cleaned.

Meralis**®** Advance, 0.05% nasal spray, is prescribed for children aged 2 to 12 years at a dose of 1 spray into each nostril once or twice daily.

Meralis**®** Advance, 0.1% nasal spray, is prescribed for adults and children aged 12 years and older at a dose of 1 spray into each nostril two to three times daily.

The product should not be used for more than 5 days unless otherwise directed by a physician.

Treatment with Meralis**®** Advance may be resumed after a break of several days. Prolonged use of the medicinal product may lead to atrophy of the nasal mucosa. In cases of chronic rhinitis, Meralis**®** Advance may be used under medical supervision due to the risk of developing nasal mucosal atrophy.

Before first use, the product must be primed by spraying 5 times into the air to ensure consistent dosing.

If the bottle has not been used for several days, it is necessary to prime it at least once by spraying into the air to ensure consistent dosing.

For hygienic reasons and to prevent the spread of infection, each spray bottle should be used by only one person.

How to use the spray:

• Clean the nose thoroughly before use;
• Hold the bottle vertically, supporting the bottom with the thumb and placing the nozzle between two fingers;
• Slightly tilt the bottle and insert the nozzle into the nostril;
• Administer the spray by pressing down on the pump while simultaneously inhaling gently through the nose;
• After use, clean and dry the nozzle before replacing the cap.

The last dose is recommended to be administered immediately before bedtime.

Children

Meralis**®** Advance, 0.05% nasal spray, is indicated for the treatment of children aged 2 to 12 years. Meralis**®** Advance, 0.1% nasal spray, is indicated for the treatment of children aged 12 years and older.

Overdose

Symptoms

With nasal administration, systemic effects are unlikely due to local vasoconstriction, which reduces absorption. However, in case of systemic absorption, xylometazoline, as an α2-adrenergic agonist, may exert effects similar to clonidine: a brief increase in arterial blood pressure followed by prolonged hypotension and sedation.

Symptoms of intoxication with imidazole derivatives may be clinically unclear, as periods of stimulation may alternate with periods of depression of the central nervous and cardiovascular systems.

Symptoms of central nervous system stimulation include anxiety, agitation, hallucinations, and seizures.

Symptoms of central nervous system depression include decreased body temperature, lethargy, drowsiness, and coma.

Additional possible symptoms include miosis, mydriasis, sweating, nausea, cyanosis, fever, pallor, central nervous system paralysis, sedation, dry mouth, arrhythmia, tachycardia, bradycardia, cardiac arrest, arterial hypertension, shock-like hypotension, pulmonary edema, respiratory disturbances, and apnea.

Overdose, especially in children, may significantly affect the central nervous system, causing spasms, coma, bradycardia, apnea, and arterial hypertension, which may later shift to arterial hypotension.

Treatment

Severe overdose requires hospitalization. Since hydrochloride xylometazoline is rapidly absorbed, activated charcoal (adsorbent), sodium sulfate (laxative), or gastric lavage (in cases of higher doses) should be administered immediately. Hypotension can be managed with non-selective alpha-blockers. Vasoconstrictors are contraindicated. Antipyretics and anticonvulsants may be used as needed, along with artificial oxygen respiration.

Adverse Reactions

The adverse reactions that may occur during the use of the medicinal product are listed below. Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100 to <1/10); uncommon (≥ 1/1000 to <1/100); rare (≥ 1/10,000 to <1/1000); very rare (<1/10,000), including isolated cases; frequency not known (frequency cannot be estimated from the available data).

Immune system disorders

Uncommon: hypersensitivity reactions, including angioedema, rash, pruritus.

Nervous system disorders

Rare: headache, insomnia, dizziness, fatigue, convulsions (usually in children); very rare: nervousness, somnolence/lethargy (usually in children), hallucinations (particularly in children).

Eye disorders

Uncommon: transient visual disturbances.

Cardiac and vascular disorders

Rare: irregular or rapid heartbeat; very rare: arrhythmia, arterial hypertension.

Respiratory, thoracic and mediastinal disorders

Common: dryness or discomfort of the nasal mucosa, burning sensation in the mucous membranes of the nose and throat, sneezing; uncommon: rebound nasal mucosa swelling after discontinuation of treatment, epistaxis; very rare: apnea in children.

Gastrointestinal disorders

Common: nausea; uncommon: vomiting.

Musculoskeletal and connective tissue disorders

Very rare: convulsions, particularly in children.

General disorders and administration site conditions

Common: burning sensation at the site of application, rebound phenomenon.

Prolonged or frequent use, especially with high doses of xylometazoline, may cause burning sensation or dryness of the mucous membrane and increased swelling of the mucous membrane, which worsens with continued use of the medicinal product (medicamentosa rhinitis). This effect may occur as early as 7 days after treatment initiation, and if treatment continues, it may lead to long-term damage of the mucous membrane with crust formation (dry rhinitis).

Reporting suspected adverse reactions after medicinal product authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years. The shelf life after first opening of the container is not more than 180 days.

Storage conditions. No special storage conditions required. Keep out of reach of children.

Packaging. 10 ml of solution in a bottle with a dosing device; 1 bottle in a cardboard box.

Classification. Over-the-counter (without prescription).

Manufacturer. Jadran-Galenski Laboratorij d.d.

Manufacturer's name and address

Svilno 20, 51000 Rijeka, Croatia