Nazoxil

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT NAZOKSYL (Nazoxyl)

Composition:

Active substance: xylometazoline hydrochloride;

1 ml of solution contains 1 mg of xylometazoline hydrochloride;

Excipients: benzalkonium chloride; disodium edetate; sorbitol non-crystallizing solution (E 420); hypromellose; sodium chloride; sodium dihydrogen phosphate dihydrate; disodium phosphate dodecahydrate; purified water.

Pharmaceutical form. Nasal spray, metered dose solution.

Main physicochemical properties: clear, colorless or slightly yellow liquid, practically odorless.

Pharmacotherapeutic group.

Agents used in nasal disorders. Anti-edematous and other agents for local treatment of nasal disorders. Simple sympathomimetics. ATC code R01A A07.

Pharmacological properties.

Pharmacodynamics.

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

When applied intranasally, xylometazoline causes vasoconstriction of the blood vessels in the nasal mucosa and paranasal sinuses, thereby reducing swelling and hyperemia of the nasal and nasopharyngeal mucosa. It also decreases associated excessive mucus secretion and facilitates clearance of blocked nasal secretions, promoting nasal decongestion and easing nasal breathing.

The decongestant effect lasts up to 12 hours.

The medicinal product is well tolerated, including by patients with sensitive mucosa, and does not impair mucociliary function.

Pharmacokinetics.

When applied locally, the drug is practically not absorbed, and plasma concentrations of xylometazoline are so low that they are practically undetectable (plasma concentration is close to the limit of detection).

Clinical characteristics.

Indications.

Used for symptomatic treatment of nasal congestion due to colds, hay fever, other allergic rhinitis, and sinusitis.

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

Used as an adjunctive therapy in otitis media (to reduce mucosal swelling).

For facilitating rhinoscopy.

Contraindications.

• Hypersensitivity to xylometazoline or to any other component of the medicinal product;
• Closed-angle glaucoma;
• Transsphenoidal hypophysectomy and surgical interventions with exposure of the meninges in medical history;
• Dry rhinitis (rhinitis sicca) or atrophic rhinitis;
• Hyperthyroidism.

Concomitant use with monoamine oxidase inhibitors (MAOIs) is contraindicated, as well as within two weeks after discontinuation of MAOI therapy.

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 receiving MAOIs or who have received MAOIs within the previous two weeks.

Tricyclic and tetracyclic antidepressants: concomitant use of tricyclic or tetracyclic antidepressants and sympathomimetic agents may enhance the sympathomimetic effect of xylometazoline; therefore, concomitant use of these agents is not recommended.

When used concomitantly with β-blockers, xylometazoline may cause bronchospasm or decreased blood pressure.

Special precautions for use

The medicinal product should not be used for more than 7 consecutive days. Prolonged or excessive use may lead to recurrence of nasal congestion and/or atrophy of the nasal mucosa.

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

Repeated or chronic use of this medicinal product may lead to rebound congestion and narrowing of the upper airways. This may manifest as chronic hyperemia of the nasal mucosa (which in the future may lead to atrophic rhinitis). In moderate cases, treatment may be temporarily discontinued in one nostril or, alternatively, in both nostrils until symptom intensity decreases, in order to maintain nasal patency.

Xylometazoline, like other sympathomimetics, should be used with caution in patients who exhibit strong reactions to adrenergic agents, such as insomnia, dizziness, tremor, cardiac arrhythmia, or increased blood pressure. Patients with long QT interval syndrome who receive xylometazoline are at increased risk of developing severe ventricular arrhythmias.

The product should be prescribed with caution to patients with cardiovascular disorders, arterial hypertension, diabetes mellitus, pheochromocytoma, porphyria, or benign prostatic hyperplasia.

The recommended dose should not be exceeded, especially when treating children or elderly patients.

The medicinal product contains benzalkonium chloride, which may cause irritation of the nasal mucosa, particularly with prolonged use.

The formulation includes an excipient (a moisturizing component) — non-crystallizing sorbitol solution — which helps reduce symptoms of nasal mucosal dryness.

The medicinal product has a balanced pH value within the physiological range typical for the nasal cavity.

Use during pregnancy or breastfeeding

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

Lactation. There is no evidence of any adverse effect on the infant. It is unknown whether xylometazoline is excreted in breast milk; therefore, caution is advised. Women who are breastfeeding should use this product only under medical supervision.

Fertility. There are no adequate data regarding the effect of NAZOKSIL 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

Generally, the medicinal product has no or negligible influence on the ability to drive or operate machinery. However, with prolonged use at high doses, undesirable effects on the cardiovascular system may occur, which could negatively affect the ability to drive or operate machinery.

Dosage and Administration

The medicinal product NAZOKSIL is intended for use in adults and children aged 12 years and older at a dose of 1 spray into each nostril, up to 3 times daily. Do not use more than 3 sprays per nostril per day. The duration of treatment depends on the course of the disease and should not exceed 7 consecutive days.

The spray dispenser ensures accurate dosing and proper distribution of the solution over the nasal mucosal surface. Each spray delivers 0.14 mL of solution, equivalent to 0.14 mg of xylometazoline.

Before first use, prime the spray pump by pressing it several times until a fine mist is released into the air. After priming, the dispenser will be ready for use.

How to use the spray:

• Thoroughly clear the nasal passages before using the spray;
• Hold the bottle vertically, supporting the base with the thumb and positioning the nozzle between the other fingers;
• Gently tilt the bottle and insert the nozzle into one nostril;
• Administer 1 spray while simultaneously inhaling gently through the nose;
• After use, before replacing the cap on the spray nozzle, clean and dry the nozzle;
• To prevent contamination, the bottle should be used by only one person.

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

Children

This medicinal product must not be used in children under 12 years of age.

Overdose

Symptoms

With nasal administration, systemic effects are unlikely due to local vasoconstriction, which reduces absorption. However, in the event of systemic absorption, xylometazoline, as an α2-adrenergic agonist, may exert effects similar to clonidine: transient increase in blood pressure followed by a more 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, ataxia, bradycardia, cardiac arrest, arterial hypertension, shock-like hypotension, pulmonary edema, respiratory disturbances, and apnea. Gastrointestinal symptoms such as nausea and vomiting may also occur.

Overdose, especially in children, may lead to significant effects on the central nervous system, causing seizures, coma, bradycardia, apnea, and arterial hypertension, which may later shift to arterial hypotension.

Severe symptoms after accidental ingestion have not been observed; however, in newborns (2 weeks of age), administration of 1 drop of 0.1% solution into each nostril may lead to coma.

Treatment

Severe overdose requires hospital treatment. Since xylometazoline hydrochloride 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. If necessary, antipyretics and anticonvulsants should be used, along with artificial oxygen ventilation. There are no specific antidotes; atropine may be used in cases of bradycardia.

Adverse Reactions

Immune system disorders:

Uncommon (≥1/1,000 to <1/100): hypersensitivity reactions, including angioedema, rash, itching.

Nervous system disorders:

Rare (≥1/10,000 to <1/1,000): headache, insomnia, fatigue, convulsions (usually in children).

Very rare (<1/10,000): nervousness, drowsiness/lethargy (usually in children).

Eye disorders:

Uncommon (≥1/1,000 to <1/100): transient (transient) visual disturbances.

Cardiovascular system disorders:

Uncommon (≥1/1,000 to <1/100): palpitations, tachycardia.

Very rare (<1/10,000): arrhythmia, arterial hypertension.

Respiratory, thoracic and mediastinal disorders:

Common (≥1/100 to <1/10): dryness or discomfort of the nasal mucosa.

Uncommon (≥1/1,000 to <1/100): epistaxis (nosebleed).

Gastrointestinal disorders:

Common (≥1/100 to <1/10): nausea.

General disorders and administration site conditions:

Common (≥1/100 to <1/10): burning sensation at the site of application, drug-induced rhinitis.

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

If any adverse reactions occur, treatment should be discontinued and medical advice should be sought.

Reporting of suspected adverse reactions

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

Shelf life. 2 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of the reach of children.

Packaging. 10 ml of solution in a polymer bottle with a spray pump; 1 bottle per cardboard box.

Availability category. Over-the-counter (without prescription).

Manufacturer. LLC "Micropharm".

Manufacturer's address and place of business.

20 Shevchenko St., Kharkiv, Ukraine, 61013