Otrinaze

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

Composition:

Active substance: fluticasone propionate;

1 dose of the medicinal product contains fluticasone propionate 50 mcg;

Excipients: glucose anhydrous, microcrystalline cellulose, sodium carboxymethylcellulose, phenethyl alcohol, benzalkonium chloride, polysorbate 80, hydrochloric acid diluted, and purified water.

Pharmaceutical form. Aqueous nasal spray, metered.

Main physico-chemical characteristics: white, opaque suspension, free from any visible foreign particles.

Pharmacotherapeutic group. Medicinal products for respiratory system disorders. Medicines for treatment of nasal diseases. Anti-inflammatory and other products for local nasal use. Glucocorticosteroids, fluticasone. ATC code R01AD08.

Pharmacological properties.

Pharmacodynamics.

Fluticasone propionate exerts a pronounced anti-inflammatory effect, but its systemic activity is minimal when administered intranasally. Fluticasone propionate does not suppress or suppresses only to a very slight extent the hypothalamic-pituitary-adrenal function. After intranasal administration of fluticasone propionate (at a dose of 200 μg/day) over 24 hours, no significant change in plasma cortisol AUC is observed compared to placebo.

Pharmacokinetics.

After intranasal administration of fluticasone propionate (200 μg/day), Cmax in plasma is not detectable in most patients (less than 0.01 ng/mL). Direct absorption of the drug from the nasal cavity is negligible. Total systemic absorption of the drug, including the portion of the dose that is swallowed, is also minimal.

Fluticasone propionate has a large volume of distribution—approximately 318 L. Plasma protein binding is moderately high—91%.

Fluticasone propionate is rapidly cleared from systemic circulation, primarily via hepatic metabolism into an inactive carboxylic acid metabolite by cytochrome P450 CYP3A4. Caution should be exercised when co-administering with strong CYP3A4 inhibitors, such as ketoconazole and ritonavir, due to the potential for increased systemic exposure to fluticasone propionate.

The main route of elimination is excretion via the intestine, primarily as unchanged, unabsorbed substance. Renal clearance of fluticasone propionate is very low (less than 0.2%).

Clinical characteristics.

Indications.

Prophylaxis and treatment of allergic rhinitis, including hay fever and allergic rhinitis caused by inhaled allergens such as house dust mites and animal dander.

Symptomatic relief of sneezing, nasal itching and rhinorrhea, eye itching and tearing, nasal congestion and associated sinus discomfort.

Contraindications.

Hypersensitivity to any component of the medicinal product. Concomitant use with medicinal products for the treatment of HIV (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Under normal conditions, intranasal administration results in very low plasma concentrations of fluticasone propionate due to extensive first-pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the liver and intestine. Therefore, the likelihood of clinically significant drug interactions mediated by fluticasone propionate is very low.

Concomitant use with CYP3A inhibitors, including agents containing cobicistat, may increase the risk of systemic adverse effects. Concomitant use should be avoided, except when the benefit outweighs the risk of systemic corticosteroid side effects. If concomitant use is necessary, systemic corticosteroid adverse effects should be monitored.

Data from a clinical interaction study in healthy volunteers showed that concomitant administration of fluticasone propionate with ritonavir (a strong inhibitor of cytochrome P450 3A4) may lead to a significant increase in plasma concentrations of fluticasone propionate, resulting in a substantial reduction in serum cortisol levels. During post-marketing use, reports have been received of clinically significant interactions in patients treated with intranasal or inhaled fluticasone propionate and ritonavir, leading to systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, except when the benefit outweighs the risk of systemic corticosteroid effects.

Clinical studies have shown that concomitant administration of fluticasone propionate with other P450 3A4 inhibitors results in negligible (erythromycin) or mild (ketoconazole) increases in plasma concentrations of fluticasone propionate, without causing a noticeable reduction in serum cortisol levels.

However, concomitant use with strong inhibitors of cytochrome P450 3A4 (e.g., ketoconazole) should be undertaken with caution due to the potential for increased systemic effects of fluticasone propionate.

Special precautions for use.

Treatment should be discontinued or a doctor should be consulted if there is no improvement within 7 days. A physician should also be consulted if symptoms have decreased but adequate control has not been achieved.

Adults and children aged 12 years and older should not use the drug continuously for longer than 6 months without consulting a doctor.

Children aged 4 to 11 years should not use the drug continuously for longer than 2 months without consulting a doctor.

Growth retardation has been observed in children receiving intranasal corticosteroids. Children should be prescribed the lowest possible dose of fluticasone propionate for the shortest duration needed to achieve adequate symptom control.

The full therapeutic effect of Otrenase may take several days of treatment to be achieved.

In most cases of seasonal allergic rhinitis, treatment with Otrenase nasal spray alone is sufficient. However, in severe cases (e.g., during periods of high allergen concentration in summer), additional appropriate therapy may be required.

Consult a doctor before using this medication if:

• you are concurrently using other corticosteroids in the form of tablets, creams, ointments, similar nasal sprays, or eye/nasal drops; or anti-asthma medications;
• you have fever or nasal or sinus infection;
• you have recently experienced nasal trauma, nasal surgery, or developed nasal ulcers.

Infectious-inflammatory conditions of the nasal passages require appropriate treatment but are not a specific contraindication for Otrenase use.

Caution is advised when switching patients from systemic corticosteroid therapy to Otrenase, especially if there is reason to suspect impaired adrenal function.

Treatment with intranasal corticosteroids at doses higher than recommended may cause clinically significant suppression of adrenal function. If doses above the recommended levels are used, consider the need for additional systemic corticosteroids during periods of stress or surgical procedures.

There have also been reports of increased risk of systemic effects when fluticasone propionate is used concomitantly with other potent CYP3A inhibitors (see section "Interaction with other medicinal products and other forms of interaction").

Systemic effects of intranasal corticosteroids have been reported, particularly with long-term use of high doses. These effects are less likely than with oral corticosteroids and may vary between individual patients and different corticosteroid agents. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma, and, less frequently, a range of psychological or behavioral effects such as psychomotor hyperactivity, sleep disturbances, anxiety, depression, or aggression (particularly in children).

Visual disturbances may occur during treatment with systemic or topical corticosteroid medications. If a patient experiences symptoms such as blurred vision or other visual disturbances, they should consult an ophthalmologist to determine possible causes, including cataract, glaucoma, or central serous chorioretinopathy (CSC).

Contains benzalkonium chloride, which may cause bronchospasm.

Use during pregnancy or breastfeeding.

Fluticasone propionate should be used during pregnancy or breastfeeding only if the expected benefit to the woman outweighs the potential risk to the fetus/infant.

Ability to affect reaction speed when driving or operating machinery.

Effect is unlikely.

Dosage and Administration

Otrinaze is intended for intranasal use only.

Adults and children aged 12 years and older:

2 sprays into each nostril once daily, preferably in the morning.

In some cases, 2 sprays into each nostril twice daily may be indicated. When symptoms are under control, a maintenance dose should be used: 1 spray into each nostril once daily. If symptoms recur, the dose may be increased accordingly. The maximum daily dose (4 sprays into each nostril) should not be exceeded.

Children aged 4 to 11 years:

The recommended dose is 1 spray into each nostril once daily, preferably in the morning. The maximum daily dose (1 spray into each nostril) must not be exceeded.

Children under 4 years of age:

Do not use in children under 4 years of age.

Elderly patients:

Adult dosage recommendations apply.

To achieve full therapeutic effect, the medication must be used regularly. Maximum therapeutic effect is achieved within 3–4 days after the start of treatment, which explains the absence of immediate therapeutic response.

Shake the bottle gently before use.

Before first use, the bottle must be primed by pressing the pump until a fine mist appears.

Children.

Do not use in children under 4 years of age.

Overdose.

Symptoms of acute or chronic overdose have not been reported. Intranasal administration of 2 mg of fluticasone propionate twice daily for 7 days in healthy volunteers did not affect hypothalamic-pituitary-adrenal (HPA) axis function. Prolonged use of doses exceeding the recommended levels may lead to temporary suppression of adrenal function. Treatment with fluticasone propionate in such patients should be continued at doses sufficient to control symptoms; adrenal function recovers within several days, which can be verified by measuring plasma cortisol levels.

Adverse reactions.

The adverse effects listed below are classified by system organ class and frequency of occurrence. The frequency categories are defined as follows:

Very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1000 and < 1/100), rare (≥ 1/10000 and < 1/1000), very rare (< 1/10000), including isolated cases.

Immune system

Very rare: hypersensitivity reactions, anaphylaxis/anaphylactic reactions, bronchospasm, skin rash, facial or lingual swelling.

Nervous system

Common: headache, unpleasant taste and smell.

Eye organs

Very rare: glaucoma, increased intraocular pressure, cataract.

Respiratory system and thoracic organs

Very common: epistaxis (nasal bleeding).

Common: nasal dryness, nasal irritation, throat dryness, throat irritation.

Very rare: nasal septum perforation, nasal ulcers.

Systemic effects may occur with the use of intranasal corticosteroids, especially when high doses are used over prolonged periods.

Shelf life. 3 years.

Storage conditions.

Store below 30 °C. Shake well before use.

Keep out of reach and sight of children.

Packaging. A dark glass bottle with a metering device, nasal adapter and cap, packed in a cardboard box. Each bottle contains 60 doses.

Prescription status.

Over-the-counter (non-prescription).

Manufacturer.

Glaxo Wellcome S.A., Spain.

Glaxo Wellcome S.A., Spain.

Manufacturer's address and place of business.

Glaxo Wellcome S.A., Avenida de Extremadura 3, Pol. Ind. Allendeduero, 09400 Aranda de Duero, Burgos, Spain.

Glaxo Wellcome S.A., Avenida de Extremadura 3, Pol. Ind. Allendeduero, 09400 Aranda de Duero, Burgos, Spain.