Brixox

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

Composition:

Active ingredient: oxymetazoline hydrochloride;

1 ml of solution contains 0.5 mg of oxymetazoline hydrochloride;

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

Pharmaceutical form. Nasal spray, metered.

Main physicochemical properties: clear or almost clear solution, colorless to slightly yellowish in hue.

Pharmacotherapeutic group. Decongestants and other agents for local use in nasal cavity disorders. Simple sympathomimetics. Oxymetazoline. ATC code R01A A05.

Pharmacological Properties

Pharmacodynamics

Oxymetazoline – the active substance of the dosed nasal spray – has sympathomimetic and vasoconstrictive effects, thereby reducing nasal mucosal edema and restoring nasal breathing. Reduction of nasal mucosal swelling promotes restoration of sinus aeration and the middle ear cavity through the unblocked Eustachian tube.

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

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

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

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

A double-blind, parallel-group comparative study involving 247 patients demonstrated faster and greater improvement in typical symptoms of acute rhinitis (nasal congestion, rhinorrhea, sneezing, general malaise) (p < 0.05) due to the combined vasoconstrictive, antiviral, anti-inflammatory, and antioxidant effects of oxymetazoline. Thus, treatment with 0.05% oxymetazoline nasal spray significantly reduced the duration of common colds by an average of 2 days, from 6 to 4 days, compared to saline placebo (p < 0.001).

Pharmacokinetics

The effect of oxymetazoline develops within several seconds.

The onset of effect of 0.05% oxymetazoline from 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, parallel-group comparative study with isotonic saline solution involving 247 patients: the mean 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 data from human pharmacokinetic 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 mutagenicity test in bacteria was negative. There are no data on carcinogenicity. Teratogenic effects were not observed in rats and rabbits. Doses exceeding the therapeutic range caused embryolethal effects or led to fetal growth retardation. Lactation was inhibited in rats. There are no data on fertility impairment.

Preclinical studies indicate that benzalkonium chloride, depending on concentration and exposure time, may have an inhibitory effect on 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.
• To restore drainage and nasal breathing in paranasal sinusitis, as well as in eustachitis associated with rhinitis.
• To eliminate swelling prior to diagnostic procedures in the nasal passages.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients.
• Atrophic rhinitis.
• 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;
• tranycypromine-type monoamine oxidase inhibitors;
• agents that increase blood pressure

may lead to elevated arterial pressure. Therefore, combined use should be avoided if possible.

Special precautions for use

The drug should be used only after a careful benefit-risk assessment in the following cases:

• 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;
• when using monoamine oxidase inhibitors (MAO inhibitors) and other drugs that potentially increase blood pressure.

Prolonged use and overdose of the nasal decongestant may lead to reduced drug efficacy (tachyphylaxis). Misuse of this drug may result in:

• reactive hyperemia of the nasal mucosa (rebound effect);
• chronic nasal mucosal edema (drug-induced rhinitis);
• atrophy of the nasal mucosa.

The preservative (benzalkonium chloride) contained in the medicinal product BRIZOKS, nasal spray, metered, may cause nasal mucosal swelling, especially with prolonged use. If such a reaction is suspected (chronically blocked nose), another medicinal product for intranasal administration that does not contain preservatives should be used. If a preservative-free nasal preparation is unavailable, another pharmaceutical form should be used.

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 fetal and neonatal health. Currently, adequate epidemiological data are lacking. Animal studies have shown reproductive toxicity at doses exceeding the therapeutic range.

The drug should be used during pregnancy only with particular caution and after careful benefit-risk assessment. 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. BRIZOKS, nasal spray, metered, should be used during breastfeeding only after a careful benefit-risk assessment. Exceeding the recommended dosage is not recommended, as it may reduce breast milk production.

Ability to affect reaction speed when driving or operating machinery

BRIZOKS, nasal spray, metered, has no effect or has a negligible effect on the ability to drive or operate machinery. However, after prolonged use of the drug at doses exceeding the recommended ones, a systemic effect on the cardiovascular system cannot be ruled out. In such cases, the ability to drive may be reduced.

Dosage and Administration

Adults and children aged 6 years and older

Use 2–3 times daily, one spray into each nostril at a time.

Administer the specified single dose of the medicinal product BRIZOKS, nasal spray, metered, no more than 3 times daily.

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

Administration method

The spray mechanism operates by pressing on the finger support. Before first use, remove the protective cap, hold the nasal spray in hand, and press the pump several times until a consistent aerosol mist is produced. Hold the spray nozzle close to the entrance of each nostril and spray once. After use, clean the spray nozzle and, if necessary, the protective cap. If the medication has not been used for 7 days or longer, press the pump once before reusing.

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 after 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.

Stimulation of the central nervous system may manifest as anxiety, excitement, hallucinations, and seizures.

Depression of the central nervous system 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, apnea, and psychogenic disorders.

In children, overdose often leads to 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 therapy in a hospital setting is indicated. Activated charcoal (adsorbent), sodium sulfate (laxative), or gastric lavage (in case of large amounts of the drug) should be administered immediately, as oxymetazoline may be rapidly absorbed. Vasopressor agents are contraindicated. Non-selective α-blockers may be used as an antidote. If necessary, perform anticonvulsant therapy, artificial ventilation of the lungs, and measures to reduce body temperature.

Side effects

The frequency of side effects is classified as follows:

very common (≥ 1/10);

common (≥ 1/100 to < 1/10);

uncommon (≥ 1/1,000 to < 1/100);

rare (≥ 1/10,000 to < 1/1,000);

very rare (< 1/10,000).

Not known (cannot be estimated from the available data).

Nervous system disorders

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

Cardiovascular system disorders

Rare: palpitations, tachycardia, arterial hypertension.

Very rare: arrhythmias.

Respiratory, thoracic and mediastinal disorders

Common: burning and dryness of nasal mucosa, sneezing.

Uncommon: rebound effect, increased swelling of the mucous membrane, nasal bleeding after discontinuation.

Very rare: apnoea in infants and newborns.

Musculoskeletal and connective tissue disorders

Very rare: cramps (mainly in children).

Immune system disorders

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

Reporting suspected adverse reactions

Reporting suspected adverse reactions after marketing authorization is highly important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and pharmacists, 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. 2 years.

After first opening of the bottle, do not store for more than 6 months.

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 dosing device; 1 bottle per cardboard pack.

Availability category. Over-the-counter.

Manufacturer

Limited Liability Company "Multispray".

Manufacturer's address and place of business

24, Valeriy Petrosov St., lit. "A-2", Kharkiv, Kharkiv region, 61052, Ukraine.

Marketing Authorization Holder

Limited Liability Company "BERKANA+".

Address of the Marketing Authorization Holder. 20/1 Pushkina St., Bohodukhiv, Bohodukhiv district, Kharkiv region, 62103, Ukraine.