Nasonex®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NASENEK® (NASONEX®)

Composition:

Active substance: 1 dose of spray contains mometasone furoate monohydrate (micronized) equivalent to 50 mcg of mometasone furoate (anhydrous);

Excipients: microcrystalline cellulose and sodium carboxymethylcellulose (dispersed cellulose); glycerin; citric acid, monohydrate; sodium citrate, dihydrate; polysorbate 80; benzalkonium chloride solution; purified water.

Pharmaceutical form. Nasal spray, metered.

Main physicochemical properties: white or almost white opaque suspension.

Pharmacotherapeutic group. Anti-inflammatory and other drugs 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 activity 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 and release of leukotrienes from leukocytes of patients suffering from allergic diseases. In cell culture studies, mometasone furoate demonstrated 10-fold greater activity than other steroids—including beclomethasone dipropionate, betamethasone, hydrocortisone, and dexamethasone—in suppressing the synthesis and 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 provocation of the nasal mucosa, the aqueous nasal spray Nasonex® 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.

A pronounced clinical effect within the first 12 hours of treatment with the aqueous nasal spray Nasonex® was achieved in 28% of patients with seasonal allergic rhinitis. On average (50%), symptom relief occurred within 35.9 hours. In addition, Nasonex® demonstrated significant efficacy in reducing ocular symptoms (redness, tearing, itching) in patients with seasonal allergic rhinitis.

In clinical studies involving patients with nasal polyps, Nasonex® 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, Nasonex® at a dose of 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, tenderness upon palpation, pain in the sinus area, rhinorrhea, postnasal drip, and nasal congestion). The efficacy of amoxicillin 500 mg three times daily did not significantly differ from placebo in reducing rhinosinusitis symptoms on the MSS scale. During the follow-up period after treatment completion, the recurrence rate in the Nasonex® group was low and comparable to that in the amoxicillin and placebo groups. The treatment duration for acute rhinosinusitis exceeding 15 days was not evaluated.

Pharmacokinetics

The bioavailability of mometasone furoate following administration as a nasal spray is <1% in plasma (based on data obtained using a sensitive assay 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, primarily 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 2 years and older. Prophylactic treatment of moderate to severe allergic rhinitis should be initiated 4 weeks before the anticipated start of 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 or to any of the excipients.

Interaction with other medicinal products and other forms of interaction.

Concomitant therapy with CYP3A inhibitors, including 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.

In a clinical study, Nasonex® was administered concomitantly with a non-sedating oral antihistamine (loratadine). The pharmacokinetic parameters and safety profile remained unchanged for both medicinal products.

Special precautions for use.

The drug should not be used in the presence of untreated local infection involving the nasal mucosa.

Since corticosteroids may impair wound healing, nasal corticosteroids should not be administered to patients who have recently undergone nasal surgery or who have experienced nasal trauma until healing has occurred.

Nasonex® should be used with caution or not used at all in patients with active or latent tuberculosis of the respiratory tract, as well as in those with untreated fungal, bacterial, systemic viral infections, or herpes simplex infection with ocular involvement.

As with any prolonged therapy, patients using the drug for several months or longer should be periodically examined for possible changes in the nasal mucosa. In clinical studies, no signs of atrophy of the nasal mucosa were observed after 12 months of treatment with Nasonex®; furthermore, mometasone furoate contributed to the normalization of the histological picture of the nasal mucosa.

If a local fungal infection of the nose or pharynx develops, discontinuation of treatment or initiation of appropriate antifungal therapy may be required. Persistent irritation of the nasal or pharyngeal mucosa may also be an indication for discontinuation of therapy.

There is no evidence of suppression of hypothalamic-pituitary-adrenal (HPA) axis function during long-term treatment with Nasonex®. However, prolonged use of intranasal corticosteroids (including Nasonex®) may potentially affect adrenal cortex function and lead to hypercorticism in corticosteroid-sensitive patients or in certain individual cases. Patients who are being switched to Nasonex® after prolonged systemic corticosteroid therapy should be closely monitored, as they may develop adrenal insufficiency.

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

Unilateral polyps, which are unusual and rarely occur, particularly if associated with ulceration or bleeding, should be further investigated.

Patients receiving corticosteroids may have potentially reduced immune responsiveness and should be warned about the increased risk of infection upon exposure to certain infectious diseases (e.g., varicella, measles), and advised to consult a physician if such exposure occurs.

The safety and efficacy of Nasonex® in the treatment of nasal polyps in children and adolescents under 18 years of age have not been studied.

When switching from systemic corticosteroid therapy to treatment with Nasonex®, some patients may experience symptoms of corticosteroid withdrawal, despite improvement in nasal symptoms. Such patients should be specifically reassured about the benefits of continuing treatment with Nasonex®.

Changing therapy may also unmask allergic conditions that were previously suppressed by systemic corticosteroid treatment.

Prolonged or high-dose use of glucocorticosteroids may result in systemic effects, such as growth suppression in children. The long-term effects of intranasal/inhaled steroids in children are not fully understood. Physicians should carefully monitor the growth of children receiving long-term glucocorticosteroid therapy. In a study of 49 children treated with Nasonex® at a dose of 100 mcg daily for one year, no growth suppression was observed.

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

Visual disturbances, including cataracts, glaucoma, and rare conditions such as central serous chorioretinopathy, have been reported with both systemic and local corticosteroid use (including intranasal, inhaled, and intraocular administration). If symptoms such as blurred vision or other visual disturbances occur, patients should be referred to an ophthalmologist for evaluation.

Acute rhinosinusitis: Patients should be advised to seek immediate medical attention if signs or symptoms of severe bacterial infection develop, such as fever, severe unilateral facial or dental pain, orbital or periorbital swelling/edema, or worsening condition after initial improvement.

The safety and efficacy of Nasonex® in the treatment of rhinosinusitis symptoms in children under 12 years of age have not been studied.

Use during pregnancy or breastfeeding.

Systemic (subcutaneously administered) corticosteroids have been shown to be teratogenic in animal studies. Clinical studies in pregnant women or women who are breastfeeding have not been conducted.

Corticosteroid medications should not be used during pregnancy or breastfeeding unless clearly necessary.

Effect on ability to drive or operate machinery.

Not known.

Method of administration and dosage.

Before using a new bottle of the drug, it must be primed. Priming is performed by approximately 10 actuations of the pump, which ensures consistent delivery of the medication, with each spray releasing approximately 100 mg of suspension containing 50 mcg of mometasone (1 dose). If the nasal spray has not been used for 14 days or longer, it must be re-primed by 2 actuations until a full spray is observed. Do not pierce the nozzle before use.

The bottle should be shaken vigorously before each use.

If the nozzle becomes blocked, remove the plastic cap by gently pressing the white ring, carefully detach the nozzle, rinse it under warm running water, dry it thoroughly, and reattach it. Do not attempt to clear the nozzle with a needle or other sharp object, as this may damage the pump.

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) and children aged 12 years and older is 2 sprays (50 mcg each) in each nostril once daily (total daily dose – 200 mcg). After achieving the therapeutic effect, the maintenance dose should be reduced to 1 spray in each nostril once daily (total daily dose – 100 mcg).

If symptoms are not adequately controlled with the recommended therapeutic dose, the daily dose may be increased to the maximum: 4 sprays in each nostril once daily (total daily dose – 400 mcg). After symptom relief, the dose should be reduced.

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

For children aged 2–11 years, the recommended therapeutic dose is 1 spray (50 mcg) in each nostril once daily (total daily dose – 100 mcg).

Adjunctive treatment of acute sinusitis episodes: The recommended therapeutic dose for adults (including elderly) and children aged 12 years and older is 2 sprays (50 mcg each) in each nostril twice daily (total daily dose – 400 mcg).

If symptoms are not adequately controlled with the recommended dose, the daily dose may be increased to 4 sprays in each nostril twice daily (total daily dose – 800 mcg). After symptom relief, the dose should be reduced.

Acute rhinosinusitis: The recommended therapeutic dose for adults and children aged 12 years and older is 2 sprays (50 mcg each) in each nostril twice daily (total daily dose – 400 mcg).

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

Children.

In placebo-controlled clinical trials in children receiving Nasonex® at a daily dose of 100 mcg for one year, no growth suppression was observed.

The safety and efficacy of Nasonex® in the treatment of nasal polyps in children and adolescents under 18 years of age, rhinosinusitis symptoms in children under 12 years of age, and seasonal or perennial allergic rhinitis in children under 2 years of age have not been studied.

Overdose.

Overdose is unlikely to require any therapy other than observation.

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

Adverse reactions.

Treatment-related adverse reactions observed in clinical studies with Nasonex® in patients with allergic rhinitis are listed in Table 1.

Nasal bleeding resolved spontaneously and was mild, occurring somewhat more frequently than with placebo (5%), but less frequently than with other intranasal corticosteroids studied and used as active control (in some of these, the incidence of nasal bleeding reached up to 15%). The incidence of other adverse events was comparable to that observed with placebo.

In children, the incidence of adverse events was similar to that with placebo, for example, nasal bleeding (6%), headache (3%), nasal irritation (2%), and sneezing (2%).

In patients with nasal polyps, the overall number of adverse events was comparable to that with placebo and similar to the number observed in patients with allergic rhinitis.

Treatment-related adverse reactions observed in clinical trials in more than 1% of patients treated with Nasonex® are listed in Table 2.

After intranasal administration of mometasone furoate, hypersensitivity reactions, including bronchospasm and dyspnea, may occasionally occur. Very rarely, anaphylactic reactions, angioneurotic edema, or disturbances of smell and taste have been reported.

In patients with acute rhinosinusitis, the overall incidence of adverse events was comparable to that with placebo and similar to the incidence observed in patients with other indications. Treatment-related adverse reactions observed in clinical trials in more than 2 % of patients are listed in Table 3.

The most common adverse reaction, nasal bleeding, occurred at approximately the same frequency in the placebo group (2.6%) and in the Nasonex® treatment groups (2.9% and 3.7%, respectively).

Systemic effects of intranasal corticosteroids may occur, particularly with high doses used over prolonged periods.

Cases of glaucoma/increased intraocular pressure have been reported with the use of intranasal corticosteroids.

Cases of blurred vision have been reported.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25°C, in a place inaccessible to children. Do not freeze.

Packaging.

18 g (140 doses) of suspension in a polyethylene bottle with a metering pump-sprayer, closed with a cap. One bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Organon Heist bv, Belgium.

Manufacturer's address and place of business.

Industriepark 30, 2220, Heist-op-den-Berg, Belgium.