Nazehaler

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NASEHALE

Composition:

Active substance: mometasone furoate;

1 spray dose contains 50 mcg of mometasone furoate (as mometasone furoate monohydrate);
Excipients: benzalkonium chloride; microcrystalline cellulose and sodium carmellose mixture, citric acid monohydrate, polysorbate 80, glycerin, sodium citrate, water for injections.

Pharmaceutical form. Nasal spray, suspension.

Main physicochemical properties: homogeneous redispersible suspension, white to almost white in color.

Pharmacotherapeutic group.
Anti-inflammatory and other agents for local use in nasal cavity disorders. Corticosteroids. ATC code R01AD09.

Pharmacological Properties.

Pharmacodynamics.

Mometasone furoate is a synthetic corticosteroid for topical use that exerts a pronounced anti-inflammatory effect. The local anti-inflammatory action of mometasone furoate occurs at doses that do not produce systemic effects.

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 suffering from allergic diseases. Mometasone furoate has demonstrated 10-fold greater activity in cell culture than other steroids, including beclomethasone dipropionate, betamethasone, hydrocortisone, and dexamethasone, in suppressing the synthesis/release of IL-1, IL-5, IL-6, and TNFα. It is also a potent inhibitor of Th2 cytokine production, specifically IL-4 and IL-5, from human CD4+ T-cells. Mometasone furoate is also 6 times more active than beclomethasone dipropionate and betamethasone in inhibiting IL-5 production. In challenge studies involving antigen application to the nasal mucosa, mometasone furoate nasal spray demonstrated high anti-inflammatory activity in both the early and late phases of the allergic response. 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 cell adhesion proteins.

Pronounced clinical effect within the first 12 hours of using mometasone furoate aqueous nasal spray was achieved in 28% of patients with seasonal allergic rhinitis. On average (50%), symptom relief occurred within 35.9 hours. In addition, mometasone furoate demonstrated significant efficacy in alleviating ocular symptoms (redness, tearing, itching) in patients with seasonal allergic rhinitis.

In studies involving patients with nasal polyps, mometasone furoate demonstrated significant clinical efficacy in relieving nasal congestion, reducing polyp size, and restoring the sense of smell compared to placebo.

In clinical studies involving patients aged 12 years and older, mometasone furoate administered at 200 mcg twice daily demonstrated high efficacy in alleviating symptoms of rhinosinusitis compared to placebo. Over 15 days of treatment, rhinosinusitis symptoms were assessed using a symptom severity scale (MSS – Major Symptom Score) (facial pain, pressure in the nasal sinuses, pain on palpation, sinus pain, rhinorrhea, postnasal drip, and nasal congestion). The efficacy of amoxicillin administered at 500 mg three times daily did not significantly differ from placebo in alleviating rhinosinusitis symptoms on the MSS scale. During the post-treatment follow-up period, the number of relapses in the mometasone furoate group was low and comparable to that in the amoxicillin and placebo groups. Treatment duration for acute rhinosinusitis exceeding 15 days was not evaluated.

Pharmacokinetics.

The systemic bioavailability of mometasone furoate following intranasal administration is < 1% in plasma (based on data obtained using a sensitive assay method with a lower limit of quantification of 0.25 pg/mL). Mometasone furoate suspension is very poorly absorbed from the gastrointestinal tract, and any small amount that may be swallowed and absorbed undergoes extensive first-pass metabolism prior to excretion, which occurs predominantly in the form of metabolites via bile and to a lesser extent via urine.

Clinical Characteristics.

Indications.

Treatment of seasonal or perennial allergic rhinitis in adults and children aged 3 years and older. Prophylactic treatment of moderate to severe allergic rhinitis should be initiated 4 weeks before the start of the pollen season. As an adjunctive therapeutic agent in antibiotic treatment of acute episodes of sinusitis in adults (including elderly) and children aged 12 years and older.

Treatment of symptoms of acute rhinosinusitis without signs of severe bacterial infection in adults and children aged 12 years and older.

Treatment of nasal polyps and associated symptoms, including nasal congestion and loss of smell, in patients aged 18 years and older.

Contraindications.

Hypersensitivity to the active substance mometasone furoate or to any of the excipients.

The medicinal product should not be used in the presence of untreated localized infection of the nasal mucosa, such as herpes simplex.

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

Interaction with other medicinal products and other forms of interaction.

Concomitant therapy with CYP3A inhibitors, including medicinal products containing cobicistat, is expected to increase the risk of systemic adverse effects. Concomitant use should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse effects; in such cases, patients should be monitored for the occurrence of systemic corticosteroid adverse effects.

Mometasone furoate has been used concomitantly with a non-sedating oral antihistamine (loratadine). The pharmacokinetic parameters and safety profile remained unchanged for both medicinal products.

Special precautions for use.

Immunosuppression.

The medicinal product NAZEHALER should be used with caution or not used at all in patients with active or inactive tuberculosis infection of the respiratory tract or in patients with untreated fungal, bacterial, or systemic viral infections. Patients receiving corticosteroids with potentially suppressed immunity should be warned about the risk of contracting certain infections (e.g., varicella, measles) and the importance of seeking medical advice if such infections occur.

Candida infection.

Localized infections of the nose and throat caused by Candida albicans have occurred following intranasal administration of mometasone furoate. If such an infection develops, treatment with mometasone furoate should be discontinued and, if necessary, appropriate local or systemic therapy should be initiated.

Nasal septum perforation.

Cases of nasal septum perforation have been observed in patients following intranasal administration of corticosteroids, including mometasone furoate. As with any prolonged local treatment of the nasal cavity, patients using mometasone furoate for several months or longer should be periodically examined for possible changes in the nasal mucosa.

Local nasal effects.

After 12 months of treatment with mometasone furoate in a study of patients with perennial rhinitis, no signs of atrophy of the nasal mucosa were observed; furthermore, mometasone furoate tended to restore the nasal mucosa to a normal histological phenotype. Nevertheless, patients using mometasone furoate for several months or longer should be periodically examined for possible changes in the nasal mucosa. If a localized fungal infection of the nose or throat develops, discontinuation of NAZEHALER and appropriate treatment may be required. Persistent irritation of the nasopharynx may be an indication for discontinuing mometasone furoate.

NAZEHALER is not recommended in cases of nasal septum perforation (see section "Special precautions for use").

Nasal bleeding.

Nasal bleeding was observed more frequently in patients with allergic rhinitis and in patients with chronic rhinosinusitis with nasal polyps receiving mometasone furoate than in those receiving placebo (see section "Adverse reactions").

Systemic effects of corticosteroids.

Hypercorticism and adrenal suppression may occur if intranasal corticosteroids, including mometasone furoate, are used at doses higher than recommended (see section "Dosage and administration") or in patients at risk of developing such effects. If such changes occur, the dose of mometasone furoate should be gradually reduced or tapered according to established procedures for discontinuing oral corticosteroid therapy. These effects are much less likely than with oral corticosteroids and may vary between individual patients and depending on the type of corticosteroid. Potential systemic effects may include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma, and, less commonly, various psychological or behavioral effects, including psychomotor hyperactivity, sleep disturbances, anxiety, depression, or aggression (particularly in children).

Cases of increased intraocular pressure have been reported after administration of intranasal corticosteroids (see section "Special precautions for use"). Visual disturbances may occur with systemic and local (including intranasal, inhaled, and intraocular) use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, referral to an ophthalmologist should be considered to evaluate possible causes of visual disturbances, which may include cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which has been reported after systemic and local corticosteroid use.

Patients transferred from prolonged systemic corticosteroid therapy to the intranasal spray NAZEHALER require special attention. Systemic withdrawal of corticosteroids in such patients may lead to adrenal insufficiency over several months until hypothalamic-pituitary-adrenal (HPA) axis function recovers. If these patients develop signs and symptoms of adrenal insufficiency or withdrawal symptoms (e.g., joint and/or muscle pain, fatigue, and depression initially), despite improvement in nasal symptoms, systemic corticosteroid therapy should be reinstated, and other therapeutic approaches and appropriate treatment measures should be implemented. Such a transition may also unmask existing allergic conditions, such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy. Treatment with doses higher than recommended may lead to clinically significant suppression of adrenal function. If there is evidence of use of doses higher than recommended, additional systemic corticosteroid therapy should be considered during periods of stress or elective surgery.

Impaired wound healing.

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

Nasal polyps.

The safety and efficacy of the intranasal spray NAZEHALER for the treatment of unilateral polyps, polyps associated with cystic fibrosis, or polyps completely obstructing the nasal cavity have not been studied. Unilateral polyps of unusual or irregular appearance, especially if ulcerated or bleeding, should be further investigated.

Use in the pediatric population.

The safety and efficacy of mometasone furoate for the prevention of nasal symptoms of seasonal allergic rhinitis have been established in pediatric patients aged 12 years and older. Use of mometasone furoate for this indication is supported by evidence from controlled studies involving adults and children aged 12 years and older. The safety and efficacy of mometasone furoate for the treatment of chronic rhinosinusitis with nasal polyps in pediatric patients under 18 years of age have not been established. Efficacy was not demonstrated in one 4-month study conducted to evaluate the safety and efficacy of mometasone furoate in the treatment of chronic rhinosinusitis with nasal polyps in children aged 6 to 17 years. The primary objective of the study was to assess safety. Overall, 127 patients with chronic rhinosinusitis with nasal polyps were randomized to receive placebo or mometasone furoate 100 mcg once or twice daily (patients aged 6 to 11 years) or 200 mcg once or twice daily (patients aged 12 to 17 years). Results of this study do not support the efficacy of mometasone furoate in the treatment of chronic rhinosinusitis with nasal polyps in children. Adverse reactions reported in this study were similar to those reported in patients aged 18 years and older with chronic rhinosinusitis with nasal polyps.

Effect on children's growth.

Controlled clinical studies have shown that intranasal corticosteroids may cause a reduction in growth velocity in children. This effect has been observed in the absence of laboratory evidence of suppression of the hypothalamic-pituitary-adrenal (HPA) axis, indicating that growth velocity is a more sensitive indicator of systemic corticosteroid effects in pediatric patients than some HPA axis function tests commonly used. The long-term consequences of this reduced growth velocity associated with intranasal corticosteroids, including the impact on adult final height, are unknown. The potential for "catch-up" growth after discontinuation of intranasal corticosteroid therapy has not been adequately studied. Growth in children receiving intranasal corticosteroids, including mometasone furoate, should be monitored regularly (e.g., using stadiometry). The potential impact of long-term treatment on growth should be weighed against the clinical benefits obtained and the availability of safe and effective non-corticosteroid treatment alternatives. To minimize systemic effects of intranasal corticosteroids, including mometasone furoate, the lowest effective dose should be used for each patient.

Symptoms unrelated to the nose.

Although the intranasal spray NAZEHALER controls nasal symptoms in most patients, concomitant use of appropriate additional therapy may provide additional relief of other symptoms, particularly those affecting the eyes.

Important information about excipients.

The intranasal spray NAZEHALER contains benzalkonium chloride. Benzalkonium chloride may cause irritation or swelling inside the nose, especially with prolonged use.

Use during pregnancy or breastfeeding.

Pregnancy.

Mometasone is minimally systemically absorbed after intranasal administration, and it is not expected that use of the medicinal product by the mother would affect the fetus. Observational data on the use of mometasone furoate in pregnant women are insufficient to assess any associated risk of major congenital malformations, miscarriage, or other adverse outcomes for the mother or fetus. Systemic corticosteroids (administered subcutaneously, subcutaneously/dermally/orally, and dermally/orally) have been shown to have teratogenic effects in animals.

Breastfeeding.

Studies in pregnant women or women who are breastfeeding have not been conducted. However, mometasone furoate is minimally systemically absorbed by the mother after intranasal administration, and breastfeeding is not expected to result in exposure of the infant to mometasone. Corticosteroid preparations should not be used in pregnant women or women who are breastfeeding unless clearly necessary.

Ability to affect reaction speed when driving or operating machinery.

Unknown.

Method of Administration and Dosage

Before using a new NASEHALER bottle, it must be calibrated. Calibration is performed by approximately 10 actuations of the dosing device, which establishes a consistent delivery of the medication, ensuring that each actuation releases approximately 100 mg of suspension containing 50 µg of mometasone (one dose). If the nasal spray has not been used for 14 days or longer, re-priming is required before the next use by two actuations until a full spray is observed. Do not puncture the nozzle before starting use. The bottle should be shaken vigorously before each use. If the nozzle becomes clogged, remove the plastic cap, gently detach the nozzle, wash it with warm running water, dry it thoroughly, and reattach it.

Do not attempt to clean the nozzle with a needle or any other sharp object, as this may damage the dispenser.

Regular cleaning of the nozzle is very important.

Before each use, the nose should be cleared thoroughly of mucus.

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 µg each) into each nostril once daily (total daily dose – 200 µg). After achieving the therapeutic effect, the dose should be reduced to 1 spray into each nostril once daily for maintenance therapy (total daily dose – 100 µg).

If symptoms are not adequately controlled with the recommended therapeutic dose, the daily dose may be increased to the maximum: 4 sprays into each nostril once daily (total daily dose – 400 µg). After symptom relief is achieved, the dose should be reduced. The medication has demonstrated a clinically significant onset of action within 12 hours after the first dose 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 the full therapeutic effect. For children aged 3–11 years, the recommended therapeutic dose is 1 spray (50 µg) into each nostril once daily (total daily dose – 100 µg).

Adjunctive treatment of acute sinusitis episodes. For adults (including elderly patients) and children aged 12 years and older, the recommended therapeutic dose is 2 sprays (50 µg each) into each nostril twice daily (total daily dose – 400 µg).

If symptoms are not adequately controlled with the recommended therapeutic dose, the daily dose may be increased to 4 sprays into each nostril twice daily (total daily dose – 800 µg). After symptom relief is achieved, dose reduction is recommended.

Acute rhinosinusitis. For adults and children aged 12 years and older, the recommended therapeutic dose is 2 sprays (50 µg each) into each nostril twice daily (total daily dose – 400 µg).

Nasal polyps. For patients aged 18 years and older (including elderly patients), the recommended dose is 2 sprays (50 µg each) into each nostril twice daily (total daily dose – 400 µg). After achieving the clinical effect, the dose should be reduced to 2 sprays into each nostril once daily (total daily dose – 200 µg).

Elderly patients.
In patients aged 64 to 86 years with allergic rhinitis or chronic rhinosinusitis with nasal polyps, no differences in safety and/or efficacy of mometasone furoate were observed compared to younger adult patients.

Children.

Seasonal allergic rhinitis and perennial rhinitis. The safety and efficacy of mometasone furoate nasal spray in children under 3 years of age have not been established.

Nasal polyposis. The safety and efficacy of mometasone furoate nasal spray in children and adolescents under 18 years of age have not been established.

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 mometasone furoate is < 1% (based on results from a sensitive assay with a lower limit of quantification of 0.25 pg/mL), it is unlikely that any measures beyond patient monitoring and subsequent administration of the medication at the recommended dose will be required in case of overdose.

Adverse Reactions

Short description of the safety profile.

Nasal bleeding was generally self-limiting and mild to moderate in severity, occurring at a higher frequency compared to placebo (5%), but at a comparable or lower frequency than that reported with the studied control intranasal corticosteroids (up to 15%), as observed in clinical trials of allergic rhinitis. The incidence of all other adverse effects was similar to that of placebo. In patients receiving treatment for nasal polyps, the overall incidence of adverse effects was similar to that observed in patients with allergic rhinitis.

Systemic effects of intranasal corticosteroids may be possible, particularly when high doses are used over prolonged periods.

Tabulated list of adverse reactions.

Treatment-related adverse reactions (≥ 1%) reported in clinical trials in patients with allergic rhinitis or nasal polyps, and post-marketing reports, regardless of indication, are presented in the table below. All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), and frequency not known (cannot be estimated from available data).

Treatment-related adverse reactions are listed by system organ class and frequency.

* for twice-daily dosing in nasal polyps.

† reported with atypical frequency for twice-daily dosing in the treatment of nasal polyps. Pediatric patients.

In the pediatric population, the frequency of adverse effects observed in clinical trials, such as epistaxis (6%), headache (3%), nasal irritation (2%), and sneezing (2%), was comparable to placebo.

The following clinically significant adverse reactions are described in other sections

• Epistaxis, nasal ulcers, Candida albicans infection, impaired wound healing (see section "Special precautions for use");
• Glaucoma and cataract (see section "Special precautions for use");
• Immunosuppression and risk of infections (see section "Special precautions for use");
• Hypercortisolism and adrenal suppression, including growth suppression (see sections "Special precautions for use").

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows ongoing monitoring of the benefit-risk balance of this medicinal product. Healthcare and pharmacy professionals, 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.

Storage conditions.

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

Do not freeze. Keep out of reach of children.

Packaging.

18 g (140 doses) of suspension in a bottle with a metered pump-spray and cap. One bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Cipla Ltd.

Manufacturer's address and location of manufacturing site.

Unit III, Plot No. 9, 10 and 15, Indore Special Economic Zone, Phase II, Pithampur, District Dhar, IN-454 775, India.