Oxirif

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OXYRIF (OXYRIF)

Composition:

Active substance: oxymetazoline;

1 ml of solution contains oxymetazoline hydrochloride 0.5 mg;

Excipients: citric acid monohydrate; sodium citrate; glycerin; benzalkonium chloride solution; purified water.

Pharmaceutical form. Nasal spray, metered.

Main physicochemical properties: almost transparent, colorless to slightly yellowish solution.

Pharmacotherapeutic group. Anti-edematous and other preparations for local use in nasal cavity diseases. Sympathomimetics, single preparations.

ATC code R01A A05.

Pharmacological Properties

Pharmacodynamics

The active ingredient of the metered nasal spray has sympathomimetic and vasoconstrictor effects, thereby reducing mucosal edema. The medicinal product relieves nasal mucosal swelling and restores nasal breathing. This promotes re-aeration of the paranasal sinuses and the middle ear cavity via the unblocked Eustachian tube.

Antiviral effects of solutions containing oxymetazoline have been demonstrated in studies using virus-infected cultured cells (therapeutic approach). This mechanism of action was confirmed by inhibition of the activity of viruses causing common colds, using a plaque reduction assay, determination of residual infectivity (virus titration), and zpE inhibition test.

Anti-inflammatory and antioxidant effects of oxymetazoline have been demonstrated in various studies. Oxymetazoline significantly affects the formation of lipid mediators from arachidonic acid in stimulated ex vivo alveolar macrophages. In particular, oxymetazoline induces inhibition of 5-lipoxygenase enzyme activity, thereby suppressing the production of pro-inflammatory signaling molecules (LTB4), while simultaneously increasing the synthesis of anti-inflammatory messenger substances (PGE2, 15-HETE). Oxymetazoline also inhibits inducible nitric oxide synthase (iNOS) in long-term cultured alveolar macrophages.

Oxymetazoline significantly reduces oxidative stress induced by ultraviolet carbon particles in primary alveolar macrophages. Oxymetazoline also inhibits iron/ascorbate-induced lipid peroxidation in microsomes (antioxidant effect).

Immunomodulatory effects of oxymetazoline have been demonstrated in human peripheral blood mononuclear cells. In this context, oxymetazoline significantly reduces inflammation by decreasing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Furthermore, oxymetazoline suppresses the immunostimulatory properties of dendritic cells.

A double-blind, comparative study with parallel groups involving 247 patients demonstrated faster and greater improvement in typical symptoms of acute rhinitis (nasal congestion, rhinorrhea, sneezing, general malaise) (p < 0.05), attributable to the combined vasoconstrictive, antiviral, anti-inflammatory, and antioxidant effects of oxymetazoline. Thus, treatment with 0.05% oxymetazoline nasal spray, compared to physiological saline, significantly reduced the duration of common colds from an average of 6 days to 4 days (p < 0.001).

Pharmacokinetics

The effect of oxymetazoline begins within a few seconds.

The effect of oxymetazoline in the form of a 0.05% nasal spray was measured in an open-label observational study. It occurred on average within 20.6 seconds. This finding was confirmed in a double-blind, comparative, parallel-group study involving 247 patients using isotonic saline: onset of effect was observed on average within 25 seconds.

The effect lasts up to 12 hours.

Occasionally, the amount of absorbed oxymetazoline after intranasal administration may be sufficient to produce systemic effects, for example, on the central nervous system or the cardiovascular system.

Further pharmacokinetic data from human studies are not available.

Safety Preclinical Data

Repeated-dose toxicity studies of intranasal oxymetazoline in dogs revealed no risks to human health. The in vitro bacterial mutagenicity test was negative. Data on carcinogenicity are not available. No teratogenic effects were observed in rats and rabbits. Doses exceeding the therapeutic range caused embryolethal effects or fetal growth retardation. Lactation was suppressed in rats. There are no data on fertility impairment.

Preclinical studies indicate that benzalkonium chloride, depending on concentration and duration of exposure, may inhibit ciliary motility, leading to irreversible ciliary arrest, as well as histopathological changes in the nasal mucosa.

Clinical Characteristics

Indications

• Acute rhinitis;
• Allergic rhinitis;
• Spastic vasomotor rhinitis.

For restoration of drainage and nasal breathing in paranasal sinusitis, as well as in eustachitis associated with rhinitis.

To reduce swelling prior to diagnostic procedures in the nasal passages.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients;
• Atrophic rhinitis.

Do not use after transsphenoidal hypophysectomy or other surgical interventions involving the dura mater;

• Children under 6 years of age.

Interaction with other medicinal products and other forms of interaction

Concomitant use of oxymetazoline and:

• Tricyclic antidepressants;
• Monoamine oxidase (MAO) inhibitors of the tranilcypramine type;
• Medicinal products that increase blood pressure, may lead to increased arterial pressure. Therefore, such combined use should be avoided.

Special precautions for use

The medicinal product should be used only after a careful assessment of benefit/ risk in the following conditions:

• elevated intraocular pressure, particularly in narrow-angle glaucoma;
• severe cardiovascular disorders (e.g., ischemic heart disease) and hypertension;
• pheochromocytoma;
• metabolic disorders (e.g., hyperthyroidism, diabetes mellitus);
• benign prostatic hyperplasia;
• porphyria;
• concomitant use of monoamine oxidase inhibitors (MAO inhibitors) and other agents that may potentially increase blood pressure.

Prolonged use or overdose of the nasal decongestant may lead to reduced effectiveness of the drug. Misuse of this product may result in:

• reactive hyperemia of the nasal mucosa (rebound effect);
• chronic swelling of the nasal mucosa (medication-induced rhinitis);
• atrophy of the nasal mucosa.

The preservative benzalkonium chloride contained in the medicinal product may cause swelling of the nasal mucosa, particularly with prolonged use. If such a reaction is suspected (chronically blocked nose), an alternative intranasal medicinal product without preservatives should be selected. If a preservative-free nasal product is unavailable, use of another pharmaceutical form is recommended.

Use during pregnancy or breastfeeding

Pregnancy. Data from a limited number of pregnant women exposed to this medicinal product during the first trimester do not indicate adverse effects of oxymetazoline on pregnancy or on the health of the fetus and newborn. Currently, adequate epidemiological data are lacking. Animal studies have shown reproductive toxicity at doses exceeding the therapeutic range.

During pregnancy, the medicinal product should be used with particular caution, taking into account the benefit/ risk ratio. Exceeding the recommended dosage is not recommended, as overdose may impair fetal blood supply.

Breastfeeding. It is unknown whether oxymetazoline passes into human breast milk. Oxirif, nasal spray, metered, should be used during breastfeeding only after a careful benefit/ risk assessment. The recommended dosage should not be exceeded, as it may reduce breast milk production.

Ability to influence reaction speed when driving vehicles or operating machinery

Oxirif, nasal spray, metered, has no effect or has a negligible effect on the ability to drive vehicles or operate machinery. However, after prolonged use of the medicinal product in doses exceeding the recommended, a systemic effect on the cardiovascular system cannot be excluded. In such cases, the ability to drive vehicles may be impaired.

Dosage and Administration

Adults and children aged 6 years and older

Administer 1 spray into each nostril 2–3 times per day.

Do not exceed the indicated single dose more than 3 times daily.

Do not use the medication for longer than 7 days. Do not exceed the recommended doses.

Method of administration

The spray mechanism operates by pressing the finger rest. Before first use, remove the protective cap, hold the bottle in hand, and press the pump several times until a consistent aerosol mist is produced. Hold the spray nozzle close to the nostril and administer one spray into each nasal passage. After use, clean the spray nozzle and, if necessary, the protective cap.

Children. Do not use the medication in children under 6 years of age.

Overdose

Overdose may occur following nasal or accidental oral administration. The clinical picture of intoxication with imidazole derivatives may be variable, as periods of hyperactivity may alternate with periods of depression of the central nervous, cardiovascular, and respiratory systems.

Central nervous system stimulation may manifest as anxiety, excitation, hallucinations, and seizures.

Central nervous system depression may manifest as decreased body temperature, lethargy, drowsiness, and coma.

Other symptoms may include miosis, mydriasis, fever, sweating, pallor, cyanosis, palpitations, tachycardia, bradycardia, cardiac arrhythmia, cardiac arrest, arterial hypertension, shock hypotension, nausea and vomiting, respiratory depression, and apnea, as well as psychogenic disorders.

In children, overdose often results in predominant central nervous system effects, including seizures and coma, bradycardia, apnea, and arterial hypertension, which may follow an initial hypotensive phase.

In cases of severe overdose, intensive in-hospital therapy is indicated. Activated charcoal (adsorbent), sodium sulfate (laxative), or gastric lavage (in cases of ingestion of large quantities of the drug) should be administered immediately, as oxymetazoline may be rapidly absorbed. Vasopressors are contraindicated. Non-selective α-blockers may be used as antidotes. If necessary, anticonvulsant therapy, lung ventilation, and measures to reduce body temperature should be implemented.

Side effects

The frequency of adverse reactions is classified as follows:

very common (≥ 1/10),

common (from ≥ 1/100 to < 1/10),

uncommon (from ≥ 1/1000 to < 1/100),

rare (from ≥ 1/10,000 to < 1/1000),

very rare (< 1/10,000),

not known (cannot be estimated from available data).

Disorders of the nervous system

Very rare: restlessness, insomnia, fatigue (drowsiness, sedative effect), headache, hallucinations (especially in children).

Cardiovascular system disorders

Rare: palpitations, tachycardia, arterial hypertension.

Very rare: arrhythmia.

Respiratory, thoracic and mediastinal disorders

Common: burning or dryness of nasal mucosa, sneezing.

Uncommon: rebound effect, increased swelling of mucous membrane, epistaxis after discontinuation of use.

Very rare: apnea in infants and newborns.

Musculoskeletal and connective tissue disorders

Very rare: convulsions (mainly in children).

Immune system disorders

Uncommon: hypersensitivity reactions (angioedema, rash, pruritus).

Shelf life.

2 years.

Shelf life after first opening – 6 months.

Do not use after the expiry date.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 ml in polymer bottles with nasal spray, № 1 in a pack.

Supply category.

Over-the-counter.

Manufacturer.

PJSC "CHIMPHARMPLANT "CHERVONA ZIRKA".

Manufacturer's location and address of its business activity.

Ukraine, 61010, Kharkiv region, Kharkiv city, Gordienkovskaya street, building 1.