M-spray

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT M-SPRAY (M-SPRAY)

Composition:

Active substance: mometasone furoate;

One dose of nasal spray suspension contains an amount of mometasone furoate monohydrate equivalent to 50 mcg of anhydrous mometasone furoate;

Excipients: benzalkonium chloride solution (corresponds to benzalkonium chloride); glycerin; polysorbate-80 (E 433); microcrystalline cellulose (E 460) and sodium carmellose; citric acid monohydrate (E 330); sodium citrate (E 331); purified water.

Pharmaceutical form. Metered nasal spray.

Main physicochemical properties: viscous suspension of white or almost white color.

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, exerting 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 suppress the release of mediators involved in 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 a 10-fold greater activity than other corticosteroids, 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 application to the nasal mucosa, the aqueous nasal spray M-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.

A pronounced clinical effect within the first 12 hours of using M-SPRAY 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, M-SPRAY demonstrated significant efficacy in reducing ocular symptoms (redness, tearing, itching) in patients with seasonal allergic rhinitis.

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

In studies involving patients aged 12 years and older, the medicinal product M-SPRAY at a dose of 200 mcg twice daily demonstrated high efficacy in alleviating symptoms of rhinosinusitis compared to placebo. Over a 15-day treatment period, rhinosinusitis symptoms were assessed using the Major Symptom Score (MSS) scale (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 alleviating rhinosinusitis symptoms on the MSS scale. During the follow-up period after treatment completion, the recurrence rate in the M-SPRAY group was low and comparable to the amoxicillin and placebo groups. 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 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, with excretion occurring 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 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 or to any of the excipients.

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 reactions. Concomitant use should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse reactions; in such cases, patients should be monitored for the occurrence of systemic corticosteroid adverse effects.

In a clinical study, M-SPRAY 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 medication should not be used in the presence of untreated local infection involving the nasal mucosa.

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

M-SPRAY should be used with caution or not used at all in patients with active or latent tuberculosis infection of the respiratory tract, as well as in those with untreated fungal, bacterial, systemic viral infections, or herpes simplex infection affecting the eyes.

As with any long-term therapy, patients using this medication for several months should be periodically examined for possible changes in the nasal mucosa. In clinical studies, no signs of nasal mucosal atrophy were observed after 12 months of treatment with M-SPRAY; moreover, mometasone furoate contributed to the normalization of the histological appearance of the nasal mucosa.

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

There is no evidence of suppression of hypothalamic-pituitary-adrenal (HPA) axis function during long-term treatment with M-SPRAY. However, prolonged use of intranasal corticosteroids (including M-SPRAY) may potentially affect adrenal cortex function and, in certain cases, lead to hypercorticism in corticosteroid-sensitive patients. Patients transitioning to M-SPRAY therapy after prolonged systemic corticosteroid treatment should be closely monitored, as adrenal insufficiency may occur.

The safety and efficacy of M-SPRAY 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 rare, especially when associated with ulceration or bleeding, should be investigated further.

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), as well as the need to consult a physician if such exposure occurs.

The safety and efficacy of M-SPRAY 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 M-SPRAY, some patients may experience corticosteroid withdrawal symptoms despite improvement in nasal symptoms. Such patients should be specifically reassured about the importance of continuing M-SPRAY treatment.

When changing therapy, previously masked allergic conditions may also become apparent.

The use of high doses of glucocorticosteroids or their prolonged use may cause systemic effects, such as growth suppression in children. The long-term effects of intranasal or inhaled steroids in children are not fully understood. Generally, physicians should carefully monitor the growth of any child receiving long-term glucocorticosteroid therapy. In a study of 49 children who used M-SPRAY for one year at a dose of 100 mcg per day, no growth suppression was observed.

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

Visual disturbances may occur with both systemic and local corticosteroid use (including intranasal, inhaled, and intraocular administration). If symptoms such as blurred vision or other visual disturbances occur, the patient should be referred to an ophthalmologist to evaluate possible causes, including cataract, glaucoma, or rare conditions such as central serous chorioretinopathy, which have been reported after both systemic and local corticosteroid use.

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 pain, dental pain, orbital or periorbital swelling/edema, or worsening condition after initial improvement.

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

Use during pregnancy or breastfeeding

Pregnancy

There is a lack of or limited data on the use of mometasone furoate in pregnant women. Animal studies have shown reproductive toxicity (see section "Pharmacological properties"). As with other intranasal corticosteroid medications, M-SPRAY should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the mother, fetus, or infant.

Newborns whose mothers received corticosteroids during pregnancy should be carefully monitored for signs of adrenal insufficiency.

Breastfeeding

It is unknown whether mometasone furoate is excreted in human breast milk. As with other intranasal corticosteroid medications, a decision should be made whether to discontinue breastfeeding or to discontinue/abstain from M-SPRAY therapy, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the mother.

Fertility

There are no clinical data on the effect of mometasone furoate on fertility. Animal studies have shown reproductive toxicity but did not demonstrate effects on fertility (see section "Pharmacological properties").

Ability to affect reaction rate when driving or operating machinery

Unknown.

Method of administration and dosage

Before using a new bottle of the medication, it should be primed. Priming is performed by approximately 10 actuations of the dosing device, which establishes consistent delivery of the medication, with each actuation 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, re-priming is required by 2 actuations until full spray is observed. Do not puncture the nozzle before initial 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 remove the nozzle, rinse it with warm running water, dry it, and reattach it. Do not attempt to clear the nozzle with a needle or other sharp object, as this may damage the dispenser.

Regular cleaning of the nozzle is very important.

Before each use, the nose should be thoroughly cleared 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 therapeutic effect, the maintenance dose should be reduced to 1 spray in each nostrip once daily (total daily dose – 100 mcg).

If symptom relief is not achieved 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, dose reduction is recommended.

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 may not be achieved within the first 48 hours; therefore, patients should continue regular use to achieve full therapeutic 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 symptom relief is not achieved with the recommended therapeutic dose, the daily dose may be increased to 4 sprays in each nostril twice daily (total daily dose – 800 mcg). After symptom relief, dose reduction is recommended.

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 effect, the dose should be reduced to 2 sprays in each nostril once daily (total daily dose – 200 mcg).

Children

In placebo-controlled clinical studies in children who received M-SPRAY at a daily dose of 100 mcg for one year, no growth suppression was observed.

The safety and efficacy of M-SPRAY 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 the hypothalamic-pituitary-adrenal (HPA) axis.

Adverse reactions

Treatment-related adverse reactions associated with M-SPRAY observed in clinical trials in patients with allergic rhinitis are listed in Table 1.

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

In children, the incidence of adverse reactions was comparable 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 reactions was similar to that with placebo and comparable to the number observed in patients with allergic rhinitis.

Treatment-related adverse reactions observed with M-SPRAY in clinical studies in more than 1% of patients are listed in Table 2.

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

In patients with acute rhinosinusitis, the overall number of adverse reactions was comparable to that with placebo and similar to the number 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, nosebleeds, occurred at approximately the same frequency in the placebo group (2.6%) and the M-SPRAY group (2.9% and 3.7%, respectively).

Systemic effects of nasal corticosteroids may occur, particularly with prolonged use of high doses.

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

Blurred vision has been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua

Shelf life. 2 years.

After first opening, remains suitable for 2 months.

Storage conditions.

No special storage requirements.

Keep out of reach of children.

Packaging. 16 g (120 doses) or 18 g (140 doses) of suspension in a 20 ml high-density polyethylene bottle with a metered spray pump and a nasal applicator with cap. One bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer.

FARMEA.

Manufacturer's address and address of the site of manufacturing activity.

10 rue Boucher de Perthes, ZAC d'Orgeval, ANGERS, 49000, France.