Alleterk® nasal

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ALLETERK® NAZO (ALLERTEC® NAZO)

Composition:

Active substance: mometasone furoate;

One dose contains 50 mcg of mometasone furoate monohydrate (calculated as anhydrous form);

Excipients: benzalkonium chloride solution, glycerin, polysorbate-80, microcrystalline cellulose, sodium carmellose, citric acid monohydrate, sodium citrate, water for injections.

Pharmaceutical form. Nasal spray, metered, suspension.

Main physico-chemical properties: white or almost white viscous suspension.

Pharmacotherapeutic group.

Anti-inflammatory and other locally-acting drugs for nasal cavity disorders. Corticosteroids. ATC code R01AD09.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Mometasone furoate is a synthetic corticosteroid for topical use that exerts a pronounced anti-inflammatory effect.

The primary mechanism of the anti-inflammatory and antiallergic action of mometasone furoate is related to its ability to inhibit the release of mediators of allergic reactions. Mometasone furoate significantly reduces the synthesis/release of leukotrienes from leukocytes of patients with allergic diseases. Mometasone furoate has demonstrated high activity in cell culture studies in suppressing the synthesis/release of IL-1, IL-5, IL-6, and TNFα. It is also a potent inhibitor of leukotriene production and of Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.

In challenge studies involving antigen application to the nasal mucosa, the aqueous nasal spray containing mometasone furoate showed high anti-inflammatory activity both in the early and late phases of the allergic reaction. This was confirmed by a reduction (compared to placebo) in histamine levels and eosinophil activity, as well as a decrease (compared to baseline) in the number of eosinophils, neutrophils, and epithelial adhesion proteins.

A pronounced clinical effect within the first 12 hours of treatment with the aqueous nasal spray containing mometasone furoate was achieved in 28% of patients with seasonal allergic rhinitis. On average, relief occurred within 35.9 hours.

Children

In a placebo-controlled clinical study in which children (n=49/group) received the nasal spray containing mometasone furoate at a dose of 100 mcg once daily, no growth suppression was observed.

Data on the safety and efficacy of the nasal spray containing mometasone furoate in children aged 3 to 5 years are limited; therefore, the appropriate dosage range cannot be established. In a study involving 48 children aged 3 to 5 years who received mometasone furoate at doses of 50, 100, or 200 mcg/day intranasally for 14 days, no significant differences compared to placebo were observed in the mean change in plasma cortisol levels following stimulation with tetracosactide.

Information on the use of the medicinal product in children is provided in the section "Posology and method of administration".

Pharmacokinetics.

Absorption

The systemic bioavailability of mometasone furoate following administration as a nasal spray is < 1% in plasma (based on data obtained using a sensitive method with a lower limit of quantification of 0.25 pg/mL).

Distribution and metabolism

Mometasone furoate suspension is very poorly absorbed from the gastrointestinal tract, and any small amount that may be swallowed and absorbed is completely metabolized during first-pass liver metabolism.

Excretion

Absorbed mometasone furoate is completely metabolized, and metabolites are excreted via bile and urine.

Clinical characteristics.

Indications.

• Treatment of seasonal or perennial allergic rhinitis in adults and children aged 3 years and older.
• Treatment of nasal polyps in patients aged 18 years and older.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Presence of untreated localized infection involving the nasal mucosa, such as herpes simplex.

Due to the inhibitory effect of corticosteroids on wound healing, intranasal corticosteroids should not be administered to patients who have recently undergone nasal surgery or who have experienced nasal trauma until healing has occurred.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of mometasone with CYP3A inhibitors, including medicinal products containing cobicistat, is expected to increase the risk of systemic adverse reactions. Such combinations should be avoided, except when the expected benefit of treatment outweighs the potential risk of systemic corticosteroid-related adverse reactions. In such cases, careful monitoring for the occurrence of systemic adverse reactions associated with corticosteroid use is recommended.

ALLETEK® NASA was used concomitantly with loratadine. No interaction was observed.

Special precautions for use.

Immunosuppression

ALERTIC® NASAL should be used with caution, if necessary, in patients with active or latent respiratory tuberculosis, as well as in those with untreated fungal, bacterial, or systemic viral infections.

Patients receiving corticosteroids may potentially have reduced immune responsiveness and should therefore be warned about the increased risk of contracting certain infectious diseases (such as varicella, measles) and advised to consult a physician if such infections occur.

Local nasal effects

After 12 months of treatment with ALERTIC® NASAL in patients with perennial rhinitis, no signs of nasal mucosal atrophy were observed; furthermore, mometasone furoate contributed to normalization of the histological picture of the nasal mucosa. However, patients using the drug for several months or longer should undergo periodic examinations to detect possible changes in the nasal mucosa. If a localized fungal infection of the nose or pharynx develops, therapy with the drug may need to be discontinued or appropriate treatment initiated. Persistent irritation of the nasal or pharyngeal mucosa may also be an indication for discontinuation of treatment.

Use of the medicinal product is not recommended in case of nasal septum perforation.

In clinical studies, the incidence of epistaxis was higher compared to placebo. Nasal bleeding was generally mild in severity and resolved spontaneously.

Systemic effects of corticosteroids

Systemic effects may occur when inhaled corticosteroids are administered at high doses over prolonged periods. These effects are much less common than with oral corticosteroids and may vary between different patients and different corticosteroid agents. Potential systemic effects 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).

Cases of increased intraocular pressure have been reported after administration of intranasal corticosteroids.

Visual disturbances may occur during treatment with systemic or topical (including intranasal, inhaled, and intraocular) corticosteroids. If a patient experiences blurred vision or other visual disturbances, they should be referred to an ophthalmologist for evaluation of possible causes, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after systemic and topical corticosteroid use.

Particular care is required when switching from systemic corticosteroid therapy to treatment with ALERTIC® NASAL. Discontinuation of systemic corticosteroids in these patients may result in adrenal insufficiency for several months until recovery of the hypothalamic-pituitary-adrenal axis function. If such patients show signs and symptoms of adrenal insufficiency or corticosteroid withdrawal symptoms (e.g., joint and/or muscle pain, fatigue, depression), despite resolution of nasal symptoms, systemic corticosteroid therapy should be reinstated along with other treatments and appropriate measures taken. Such a change in therapy may also unmask pre-existing allergic conditions (such as allergic conjunctivitis, eczema, etc.) that were previously suppressed by systemic corticosteroid therapy.

Use of doses higher than recommended may lead to clinically significant adrenal suppression. If evidence of doses exceeding the recommended levels is present, consideration should be given to the possible need for additional systemic corticosteroid coverage during periods of stress or elective surgery.

Nasal polyps

The safety and efficacy of ALERTIC® NASAL in the treatment of unilateral polyps, polyps associated with cystic fibrosis, or polyps completely obstructing the nasal cavity have not been studied.

Unilateral polyps, particularly if atypical or associated with ulceration or bleeding, should be investigated further.

Effect on growth in children

In children receiving long-term treatment with nasal corticosteroids, regular monitoring of growth is recommended. If growth retardation occurs, therapy should be re-evaluated with the aim of reducing the dose of the nasal corticosteroid to the lowest effective dose that maintains symptom control, if possible. Additionally, referral to a pediatric specialist may be appropriate.

Non-nasal symptoms

Although the medicinal product controls nasal symptoms in most patients, concomitant use of appropriate additional therapy may provide further relief of other symptoms, particularly ocular symptoms.

Excipients

The medicinal product contains 20 µg of benzalkonium chloride per dose. Benzalkonium chloride may cause irritation or swelling inside the nose, especially with prolonged use.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of mometasone furoate in pregnant women are lacking or limited. Reproductive toxicity has been observed in animal studies.

Like other intranasal corticosteroids, ALERTIC® NASAL should be used during pregnancy only if the expected benefit justifies the potential risk to the woman, fetus, or infant. Infants born to mothers who used corticosteroids during pregnancy should be carefully monitored for possible adrenal insufficiency.

Use during lactation

It is unknown whether mometasone furoate passes into breast milk. As with other intranasal corticosteroids, a decision must be made whether to discontinue breastfeeding or to discontinue/abstain from treatment with ALERTIC® NASAL, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the woman.

Fertility

There are no clinical data on the effect of mometasone furoate on fertility. Animal studies have demonstrated reproductive toxicity, but no effect on fertility.

Ability to influence reaction speed when driving or operating machinery.

Unknown.

Method of Administration and Dosage

Dosage

Treatment of seasonal or perennial allergic rhinitis. The recommended prophylactic and therapeutic dose for adults (including elderly patients) and children aged 12 years and older is 2 sprays (50 mcg each) into each nostril once daily (total daily dose – 200 mcg). After achieving therapeutic effect, dose reduction to 1 spray into each nostril once daily (total daily dose – 100 mcg) is advisable for maintenance therapy.

If symptoms are not adequately controlled, the dose may be increased to the maximum daily dose of four sprays into each nostril once daily (total daily dose 400 mcg). Dose reduction is recommended once symptom control is achieved.

For children aged 3–11 years, the recommended therapeutic dose is 1 spray (50 mcg) into each nostril once daily (total daily dose – 100 mcg).

The medicinal product has demonstrated a clinically significant onset of action within 12 hours after the first administration in some patients with seasonal allergic rhinitis. However, full benefit from treatment may not be achieved within the first 48 hours; therefore, patients should continue regular use to achieve full therapeutic effect.

It may be necessary to initiate treatment with ALLELTEK® NASAL several days before the expected onset of the pollen season in patients with a history of moderate to severe seasonal allergic rhinitis symptoms.

Nasal polyps

The usual recommended initial dose is 2 sprays (50 mcg each) into each nostril once daily (total daily dose – 200 mcg). If adequate symptom control is not achieved after 5–6 weeks, the dose may be increased to 2 sprays into each nostril twice daily (total daily dose 400 mcg). The dose should be gradually reduced to the lowest dose that maintains effective symptom control. If no symptom improvement is observed after 5–6 weeks of twice-daily administration, the patient should be re-evaluated and treatment strategy reconsidered.

Studies on the efficacy and safety of ALLELTEK® NASAL in the treatment of nasal polyposis lasted four months.

Administration of nasal spray

Before using a new bottle of the medication, it must be primed. Priming is performed by approximately 10 actuations of the dosing device, which establishes consistent delivery of the medication, ensuring that each spray releases approximately 100 mg of suspension containing 50 mcg of mometasone (one dose). If the nasal spray has not been used for 14 days or longer, re-priming is required by 2 sprays until a full spray is observed before subsequent use.

After the specified number of doses has been used from the bottle or after 2 months from the first use of the bottle, it should be discarded.

Instructions for administration:

1. Shake the bottle vigorously before each use (Fig. 1).

Fig. 1

2. Before each administration, clear the nose of mucus thoroughly.
3. Insert the nozzle into one nostril and close the other nostril with a finger, as shown in Fig. 2. Tilt the head forward and hold the bottle vertically.

Fig. 2

4. Inhale through the nose and press once on the spray nozzle with the fingers.
5. Exhale through the mouth. Repeat step 4 for the second spray into the same nostril.
6. Remove the spray from the nasal passage and continue breathing through the mouth.
7. Repeat steps 3–6 for the second nostril (Fig. 3).

Fig. 3

After using the spray, wipe the spray nozzle with a clean tissue and cover with the protective cap.

It is important to clean the dosing device regularly. Remove the protective cap and spray nozzle, wash them with warm running water, dry thoroughly, and reassemble. Do not attempt to clean the nozzle with a needle or other sharp object, as this may damage the dispenser.

Regular cleaning of the nozzle is very important.

Children.

The safety and efficacy of ALLELTEK® NASAL have not been established for the treatment of seasonal or perennial allergic rhinitis in children under 3 years of age, or for nasal polyps in children under 18 years of age.

Overdose.

Symptoms

Inhalation or oral administration of excessive doses of corticosteroids may lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.

Treatment

Since the systemic bioavailability of the drug is < 1%, it is unlikely that overdose would require any measures other than patient monitoring followed by resumption of the drug at the recommended dose.

Adverse Reactions

During clinical trials in allergic rhinitis, epistaxis (nosebleeds) was self-limiting and mild to moderate in severity. It occurred somewhat more frequently than with placebo (5%) but less frequently than with other intranasal corticosteroids investigated and used as active controls (in some of these, the incidence of epistaxis reached up to 15%). The incidence of other adverse events was comparable to that observed with placebo. In patients with nasal polyps, the overall incidence of adverse reactions was similar to that observed in patients with allergic rhinitis.

Systemic effects of intranasal corticosteroids are more likely to occur with high-dose and long-term use.

The table below lists adverse reactions observed in clinical trials (in more than 1%) in patients with allergic rhinitis or nasal polyposis, as well as during post-marketing use, regardless of the indication. Adverse reactions are listed by primary MedDRA System Organ Class. Within each organ system class, adverse reactions are categorized into frequency groups. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100). The frequency of adverse reactions during the post-marketing period is considered "not known (cannot be estimated from available data)."

Table

*observed with twice-daily administration for the treatment of nasal polyps

†observed infrequently with twice-daily administration for the treatment of nasal polyps

Children

In children, the incidence of adverse reactions, including epistaxis (6%), headache (3%), nasal irritation (2%), and sneezing (2%), was comparable to that observed with placebo.

Reporting of suspected adverse reactions

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

Shelf life.

2 years.

Shelf life after first opening – 2 months.

Storage conditions.

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

Keep out of the reach of children.

Packaging.

60, 120, or 140 doses of suspension in a PET bottle with a metering pump-spray dispenser delivering one dose of the medicinal product, closed with a cap. One bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer.

«Farmea» / Farmea.

Manufacturer's address and location of its operations.

10 rue Bouche Thomas, ZAC d’Orgemont, 49000 Angers, France /
10 rue Bouche Thomas, ZAC d’Orgemont, 49000 Angers, France.

Marketing Authorization Holder.

Pharmaceutical Works «POLPHARMA» S.A. /
Pharmaceutical Works «POLPHARMA» S.A.