MOMETASONE SANDOZ 50 µg/dose Susp pulv nas Fl/17g

Each pump actuation delivers a dose of 50 micrograms of mometasone furoate (as mometasone furoate monohydrate).

Excipient with known effect : each dose of this medicine contains 0,02 mg of benzalkonium chloride per dose.

MOMETASONE SANDOZ 50 micrograms/dose, nasal spray suspension is indicated in adults and children from 3 years of age for the symptomatic treatment of seasonal allergic rhinitis or perennial rhinitis.

MOMETASONE SANDOZ 50 micrograms/dose, nasal spray suspension is indicated for the treatment of nasal polyposis in adults from 18 years of age.

Once the pump is primed, each spray of MOMETASONE SANDOZ delivers approximately 100 mg of mometasone furoate suspension, containing mometasone furoate monohydrate equivalent to 50 micrograms of mometasone furoate.

Dosage

Seasonal allergic rhinitis or perennial rhinitis

Adults (including elderly patients) and children from 12 years of age:

The usually recommended dose is two sprays (50 micrograms/spray) in each nostril once daily (a total dose of 200 micrograms). When symptoms are controlled, reducing the dose to one spray in each nostril (a total dose of 100 micrograms) may be effective as maintenance treatment.

If symptoms are not adequately controlled, the dosage may be increased to a maximum daily dose of four sprays in each nostril once daily (a total dose of 400 micrograms). It is recommended to reduce the dosage when symptoms are controlled.

Children aged 3 to 11 years:

The usually recommended dose is one spray (50 micrograms/spray) in each nostril once daily (a total dose of 100 micrograms).

In some patients with seasonal allergic rhinitis, the first clinically significant effects have been observed within 12 hours of the first dose of MOMETASONE SANDOZ. However, the full benefit of treatment may not be achieved within the first 48 hours. Therefore, the patient should continue to take the treatment regularly to obtain the full therapeutic benefit.

Treatment with MOMETASONE SANDOZ may be initiated a few days before the expected start of the pollen season in patients with a history of moderate to severe seasonal allergic rhinitis symptoms.

Nasal polyposis

The usually recommended initial dose for the treatment of polyposis is two sprays (50 micrograms/spray) in each nostril once daily (a total daily dose of 200 micrograms). If symptoms are not adequately controlled after 5 to 6 weeks, the daily dosage may be increased to two sprays in each nostril, twice daily (a total daily dose of 400 micrograms). The minimum effective dose should be sought. In the absence of symptom improvement after 5 to 6 weeks of twice-daily administration, the patient should be re-examined and the therapeutic approach reassessed.

The efficacy and safety studies of the mometasone furoate nasal spray suspension in the treatment of nasal polyposis were conducted over a period of four months.

Paediatric population

Seasonal allergic rhinitis and perennial rhinitis

The safety and efficacy of MOMETASONE SANDOZ in children under 3 years of age have not been established.

Nasal polyposis

The safety and efficacy of MOMETASONE SANDOZ in children and adolescents under 18 years of age have not been established.

Method of administration

Before administering the first dose, shake the vial well then prime the pump with 10 actuations (until a uniform spray is obtained). If the pump has not been used for 14 days or more, it must be re-primed with 2 actuations until a uniform spray is obtained, before any further use.

Shake the vial well before each use. The vial must be discarded once the number of sprays stated on the vial has been reached or within 2 months after first use.

Hypersensitivity to the active substance, mometasone furoate, or to any of the excipients listed in section Composition.

MOMETASONE SANDOZ must not be used in cases of untreated local infection of the nasal mucosa, such as herpes simplex.

Due to the inhibitory action of corticosteroids on wound healing, patients who have recently undergone surgery or trauma to the nose must not use nasal corticosteroids until healing has occurred.

Immunosuppression

MOMETASONE SANDOZ should be used with caution, or even avoided, in patients with active or latent pulmonary tuberculosis, or untreated fungal, bacterial, systemic or viral infections.

Patients treated with corticosteroids, who may be immunosuppressed, must be warned of the risks in case of exposure to certain infections (for example chickenpox, measles) and of the importance of seeking medical advice if such exposure occurs.

Local effects on the nasal mucosa

In a clinical study conducted in patients with perennial rhinitis, no signs of atrophy of the nasal mucosa were observed after 12 months of treatment with MOMETASONE SANDOZ. Furthermore, mometasone furoate tended to change the appearance of the nasal mucosa towards a state closer to normal appearance.

Nevertheless, patients using MOMETASONE SANDOZ for several months, or even longer, should be examined regularly to detect any changes in the nasal mucosa. If a local nasal or pharyngeal fungal infection occurs, discontinuation of treatment with MOMETASONE SANDOZ or appropriate treatment may be necessary. Persistent nasopharyngeal irritation may require interruption of treatment with MOMETASONE SANDOZ.

The use of MOMETASONE SANDOZ is not recommended in cases of perforation of the nasal septum (see section Adverse effects).

In clinical studies, cases of epistaxis were reported with an incidence higher than placebo. Epistaxis was generally self-resolving and of mild intensity (see section Adverse effects).

Systemic effects of corticosteroids

Systemic effects may occur with nasal corticosteroids, particularly when prescribed at high doses over prolonged periods. The risk of these effects occurring is much lower than with oral corticosteroids and may vary from patient to patient and depending on the different corticosteroid preparations. Potential systemic effects may include Cushing's syndrome, cushingoid symptoms, inhibition of adrenal function, growth retardation in children and adolescents, cataract, glaucoma and, more rarely, various psychological or behavioural disorders including psychomotor hyperactivity, sleep disturbances, anxiety, depression or aggression (particularly in children).

Following administration of intranasal corticosteroids, cases of increased intraocular pressure have been reported (see section Adverse effects).

Patients who are switched from long-term systemic corticosteroid therapy to treatment with MOMETASONE SANDOZ must be carefully monitored. Discontinuation of systemic corticosteroids in these patients may lead to adrenal insufficiency for several months, until function of the HPA axis is restored. If these patients show signs and symptoms of adrenal insufficiency or symptoms related to corticosteroid withdrawal (for example: joint and/or muscle pain, lassitude and depression), systemic corticosteroid therapy must be resumed even though nasal symptoms are relieved, and other therapeutic measures and appropriate measures must be implemented. Such a situation may also unmask pre-existing allergic conditions such as allergic conjunctivitis and eczema that were previously controlled by systemic corticosteroid therapy.

Administration of doses higher than those recommended may lead to clinically significant inhibition of adrenal function. If doses higher than those recommended are necessary, additional systemic corticosteroid treatment during periods of stress or surgery should be considered.

Nasal polyps

The safety and efficacy of MOMETASONE SANDOZ nasal spray suspension have not been studied in the treatment of unilateral polyps, polyps associated with cystic fibrosis, or polyps completely obstructing the nasal cavities.

Unilateral polyps with an unusual or irregular appearance, particularly in cases of ulceration or bleeding, should be thoroughly investigated.

Effect on growth in the paediatric population

Regular monitoring of growth is recommended in children receiving prolonged nasal corticosteroid therapy. If growth slows, treatment should be reassessed in order to reduce, if possible, the nasal corticosteroid dose to the minimum effective dose. In addition, the patient should be referred to a paediatrician.

Extranasal symptoms

Although administration of MOMETASONE SANDOZ controls nasal symptoms in most patients, appropriate additional treatment may relieve other symptoms, particularly ocular symptoms.

Visual disorders

Visual disturbances may occur with systemic or local corticosteroid therapy. In case of blurred vision or any other visual disturbance occurring during corticosteroid therapy, an ophthalmological examination is required to look for possible causes, which may include: cataract, glaucoma, or a rarer lesion such as central serous chorioretinopathy (CSCR), described with the administration of systemic or local corticosteroids.

MOMETASONE SANDOZ contains benzalkonium chloride.

This medicine contains 20 µg of benzalkonium chloride per spray, which may cause oedema of the nasal mucosa, particularly with long-term use.

Concomitant treatment with a CYP3A inhibitor, for example a medicine containing cobicistat, may increase the risk of systemic side effects. The combination should be avoided, unless the benefits outweigh the increased risk of systemic corticosteroid side effects; in that case, patients should be monitored for possible systemic corticosteroid side effects.

A clinical study on interactions with loratadine was carried out. No interaction was observed.

Pregnancy

There are no or limited data on the use of mometasone furoate in pregnant women. Animal studies have shown reproductive toxicity (see section Preclinical safety). Like other nasal corticosteroids, MOMETASONE SANDOZ must not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the mother, the fetus or the infant. Infants born to mothers who received corticosteroids during pregnancy should be closely monitored because of the risk of adrenal insufficiency.

Breast-feeding

There is no data available on the passage of mometasone furoate into breast milk. As with other nasal corticosteroids, a decision must be made either to discontinue breastfeeding or to discontinue/abstain from treatment with MOMETASONE SANDOZ 50 micrograms/dose nasal spray suspension, taking into account the benefit of breastfeeding for the child relative to the benefit of treatment for the woman.

Fertility

There are no clinical data on the effect of mometasone furoate on fertility. Studies conducted in animals have shown reproductive toxicity, but no effect on fertility (see section Preclinical safety).

MOMETASONE SANDOZ has no effect on the ability to drive vehicles and use machines.

Summary of the safety profile

Based on data from clinical studies conducted in allergic rhinitis, the epistaxis reported was generally spontaneously resolving and of mild intensity, and the incidence of cases was higher than that observed with placebo (5 %), but comparable to or lower than that observed with nasal corticosteroids used in the control group (up to 15 %). The incidence of all other adverse reactions was comparable to that observed with placebo. In patients treated for nasal polyposis, the overall incidence of adverse reactions was similar to that observed in patients with allergic rhinitis.

Systemic effects may occur with nasal corticosteroids, particularly when prescribed at high doses for prolonged periods.

Tabulated summary of adverse reactions

Treatment-related adverse reactions (≥ 1 %) reported during clinical studies in patients with allergic rhinitis or nasal polyposis and those reported since marketing regardless of indication are presented in Table 1.

Adverse reactions are listed according to the main MedDRA system organ classes. Within each system organ class, adverse reactions are ranked by frequency. Frequencies were defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100). The frequency of adverse reactions reported since marketing is considered "not known (cannot be estimated from the available data)".

* reported in the treatment of nasal polyposis with a dosage of two doses per day

† reported at an indeterminate frequency in the treatment of nasal polyposis with a dosage of two doses per day

Paediatric population

In children, the incidence of adverse effects reported during clinical studies, for example epistaxis (6 %), headache (3 %), nasal irritation (2 %) and sneezing (2 %), was comparable to that observed with placebo.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: www.signalement-sante.gouv.fr .

Symptoms

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

Management

Since the systemic bioavailability of MOMETASONE SANDOZ 50 micrograms/dose, nasal spray suspension is <1 %, an overdose is unlikely to require treatment other than monitoring. Treatment will be reinstituted at the appropriate prescribed dose.

Pharmacotherapeutic class: Nasal decongestants and other nasal preparations for topical use - corticosteroids, ATC code: R01AD09

Mechanism of action

Mometasone furoate is a topical glucocorticoid that exerts a local anti-inflammatory effect at doses without systemic effect.

It is likely that a large part of the antiallergic and anti-inflammatory mechanism of mometasone furoate lies in its capacity to inhibit the release of mediators of allergic reactions.

Mometasone furoate significantly inhibits the release of leukotrienes by leukocytes extracted from allergic patients. In cell culture in vitro, mometasone furoate strongly inhibits the synthesis and release of IL-1, IL-5, IL-6 and TNFα; it also strongly inhibits the production of leukotrienes. Furthermore, it exerts a very strong inhibition of the production of Th2 cytokines, IL-4 and IL-5, by human CD4+ T lymphocytes.

Pharmacodynamic effects

In studies using an allergen nasal challenge test, an anti-inflammatory action of mometasone furoate nasal spray was demonstrated in both the early and late phases of the allergic response. This activity was demonstrated by the observation of a decrease (compared with placebo) in histamine and eosinophil activity, as well as a decrease (compared with baseline) in eosinophils, neutrophils and epithelial cell adhesion proteins.

In 28 % of patients with seasonal allergic rhinitis, a first significant clinical effect was observed within 12 hours of the first dose of mometasone furoate nasal spray suspension. The median time (50 % of the study population) to obtain first relief was 35,9 hours.

Paediatric population

In a placebo-controlled clinical study in paediatric patients (n=49 subjects per group), mometasone furoate nasal spray was administered at a dose of 100 micrograms per day for one year. No growth retardation was reported.

The available data on the safety and efficacy of mometasone furoate nasal spray in the paediatric population aged 3 to 5 years are limited and an appropriate dosage could not be established.

In a study involving 48 children aged 3 to 5 years receiving 50, 100 or 200 μg/day of intranasal mometasone furoate for 14 days, no significant difference compared with placebo was observed in terms of the mean change in plasma cortisol level in response to the tetracosactide stimulation test.

The European Medicines Agency has granted a waiver of the obligation to submit the results of studies conducted with mometasone furoate nasal spray in all subgroups of the paediatric population in seasonal and perennial allergic rhinitis (see section Dosage and administration for information on paediatric use).

Absorption

Mometasone furoate administered as an aqueous nasal spray has a systemic bioavailability < 1 % in plasma with a sensitive assay method having a lower limit of quantification of 0,25 pg/mL.

Distribution

Not applicable, insofar as absorption of mometasone administered nasally is very low.

Biotransformation

The small amount of mometasone furoate that may be swallowed and absorbed undergoes a significant hepatic first-pass effect.

Elimination

Absorbed mometasone furoate is extensively metabolised and its metabolites are eliminated in the urine and bile.

No toxicological effect linked to a specific exposure to mometasone furoate has been demonstrated. All observed effects are characteristic of this class of products and correspond to an exacerbation of the pharmacological effects of glucocorticoids.

Preclinical studies conducted in animals show that mometasone furoate lacks androgenic, anti-androgenic, estrogenic and anti-estrogenic activity. However, like other glucocorticoids, it exerts, in animal models, some anti-uterotrophic activity and delays vaginal opening when high oral doses of 56 mg/kg/day and 280 mg/kg/day are administered.

Like other glucocorticoids, mometasone furoate has shown in vitro a clastogenic potential at high concentrations. However, no mutagenic effect is expected at the recommended therapeutic doses.

In reproductive function studies, subcutaneous injection of mometasone furoate at a dose of 15 micrograms/kg resulted in prolonged gestation as well as longer and difficult labour with reduced survival and weight or weight development of the offspring. There was no effect on fertility.

Like other glucocorticoids, mometasone furoate is teratogenic in rodents and rabbits. The effects observed were the occurrence of umbilical hernias in rats, cleft palates in mice, and agenesis of the gallbladder, umbilical hernias and flexion of the forelimbs in rabbits.

A decrease in maternal weight gain was also observed, as well as effects on fetal growth (lower fetal weight and/or delayed ossification) in rats, rabbits and mice, together with a decrease in offspring survival in mice.

The carcinogenic potential of inhaled mometasone furoate (in a pressurised vial with CFC propellant gas and surfactant agent) at concentrations ranging between 0,25 and 2,0 micrograms/L was studied for 24 months in mice and rats. Effects characteristic of glucocorticoids, including the occurrence of several non-neoplastic lesions, were observed. It was not possible to establish a statistically significant dose-response relationship for any of the tumour types studied.

Environmental risk assessment studies have shown that mometasone may present a risk to surface waters (see section Disposal and handling).

2 years.

After first opening of the vial: 2 months.

Do not freeze.

This medicine may present a risk to the environment (see section Preclinical safety). Tissues used to wipe and/or blow the nose after treatment with MOMETASONE SANDOZ must be discarded with household waste in order to prevent the unused product from reaching the aquatic environment. Any unused medicinal product or waste must be disposed of in accordance with local regulations.