NASONEX 50 µg nasal powder spray bottle/140doses

Mometasone furoate (in monohydrate form)............................................50 micrograms/dose.

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

NASONEX nasal spray is indicated in adults and children from 3 years of age for the symptomatic treatment of seasonal allergic rhinitis or perennial rhinitis.

NASONEX nasal spray is indicated for the treatment of nasal polyposis in adults from 18 years of age.

Once the pump is primed, each spray of NASONEX nasal spray 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, a reduction of the dose to one spray in each nostril (a total dose of 100 micrograms) may be effective as maintenance treatment. If symptoms are not sufficiently 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 a day (i.e. 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 NASONEX nasal spray. However, the full therapeutic benefit 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 NASONEX nasal spray may be initiated a few days before the expected onset 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 a day (i.e. a total daily dose of 200 micrograms). If symptoms are not sufficiently controlled after 5 to 6 weeks, the daily dosage may be increased to two sprays in each nostril, twice a day (i.e. 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 management reassessed.

The efficacy and safety studies of NASONEX nasal spray 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 NASONEX nasal spray in children under 3 years of age have not been established.

Nasal polyposis

The safety and efficacy of NASONEX nasal spray in children and adolescents under 18 years of age have not been established.

Method of administration

Before administering the first dose, shake the bottle well, then prime the pump with 10 sprays (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 sprays 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.

NASONEX nasal spray 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 nasal surgery or trauma must not use nasal corticosteroids until healing has occurred.

Immunosuppression

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

Patients treated with corticosteroids, who may be immunosuppressed, must be warned of the risks on exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs.

Local effects on the nasal mucosa

In a clinical study conducted in patients with perennial rhinitis, no sign of nasal mucosal atrophy was observed after 12 months of treatment with NASONEX nasal spray. Moreover, mometasone furoate tended to restore the appearance of the nasal mucosa to a state closer to that of a normal mucosa. Nevertheless, patients using NASONEX nasal spray for several months, or even longer, should be examined regularly in order to detect any possible changes in the nasal mucosa. If a local nasal or pharyngeal fungal infection occurs, discontinuation of treatment with NASONEX nasal spray or appropriate treatment may be necessary. Persistent nasopharyngeal irritation may require interruption of treatment with NASONEX nasal spray.

The use of Nasonex 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).

NASONEX nasal spray contains benzalkonium chloride. Benzalkonium chloride may cause irritation or swelling inside the nose, especially if used over a long period.

Systemic effects of corticosteroids

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

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

Visual disturbances may occur during systemic or local corticosteroid therapy (notably by nasal, inhaled and intra-ocular route). In case of blurred vision or appearance of any other visual symptom during corticosteroid therapy, an ophthalmological examination is required to look for visual disorders, notably cataract, glaucoma, or a rarer lesion such as central serous chorioretinopathy, described with the administration of corticosteroids by systemic or local route.

Patients transferring from long-term systemic corticosteroid therapy to treatment with NASONEX nasal spray should be closely 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 present signs and symptoms of adrenal insufficiency or symptoms related to corticosteroid withdrawal (for example: joint and/or muscle pain, fatigue and depression), systemic corticosteroid therapy should be resumed despite the fact that nasal symptoms are relieved, and other therapeutic measures as well as appropriate measures should be put in place. 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 recommended may result in clinically significant adrenal function suppression. If doses higher than recommended are used, systemic corticosteroid supplementation should be considered during periods of stress or during elective surgery.

Nasal polyps

The safety and efficacy of NASONEX nasal spray 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 NASONEX nasal spray controls nasal symptoms in most patients, appropriate additional treatment may help relieve other symptoms, particularly ocular symptoms.

(See section Warnings and precautionsregarding the use of systemic corticosteroids)

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

Concomitant administration of CYP3A inhibitors, including products containing cobicistat, is expected to increase the risk of systemic side effects. The combination should be avoided, unless the benefits outweigh the increased risk of systemic side effects of corticosteroids; in this case, patients should be monitored for possible systemic side effects of corticosteroids.

Pregnancy

There are no or limited data on the use of mometasone furoate in pregnant women. Studies performed in animals have shown reproductive toxicity (see section Preclinical safety). Like other nasal corticosteroids, NASONEX nasal spray should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the mother, the foetus 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 NASONEX nasal spray, 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).

Unknown.

Summary of the safety profile

Based on data from clinical studies conducted in allergic rhinitis, the epistaxis reported was generally self-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 effects was comparable to that observed with placebo. In patients treated for nasal polyposis, the overall incidence of adverse effects 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 effects (≥ 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 effects are listed by the main MedDRA System Organ Classes. Within each System Organ Class, adverse effects 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 effects 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: https://signalement.social-sante.gouv.fr/.

Symptoms

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

Management

Since the systemic bioavailability of NASONEX nasal spray is < 1 %, an overdose is unlikely to require treatment other than monitoring, followed by taking the appropriate prescribed dosage.

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 much of the mechanism of the antiallergic and anti-inflammatory effects 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 exerts strong inhibition of the synthesis and release of IL-1, IL-5, IL-6 and TNFα ; it also exerts strong inhibition of leukotriene production. In addition, it exerts very strong inhibition of the production of Th2 cytokines, IL-4 and IL-5, by human CD4+ T lymphocytes.

Pharmacodynamic effects

In studies using a nasal allergen challenge test, an anti-inflammatory action of NASONEX 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 following the first dose of NASONEX nasal spray. The median time (50% of patients) to obtain first relief was 35,9 hours.

Paediatric population

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

The data available on the safety and efficacy of NASONEX 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 mometasone furoate intranasally for 14 days, no significant difference compared with placebo was observed in terms of 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 NASONEX nasal spray and other associated brand names 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 of < 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 is devoid of androgenic, anti-androgenic, oestrogenic or anti-oestrogenic activity. However, like other glucocorticoids, it exerts, in animal models, a certain anti-uterotrophic activity and delays vaginal opening when high doses of 56 mg/kg/day and 280 mg/kg/day are administered orally.

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 studies on reproductive function, subcutaneous injection of mometasone furoate at a dose of 15 micrograms/kg resulted in prolonged gestation as well as longer and more difficult labour, with reduced survival and reduced or altered weight gain 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, effects on foetal growth (lower foetal weight and/or delayed ossification) in rats, rabbits and mice, as well as a decrease in offspring survival in mice, were also observed.

The carcinogenic potential of inhaled mometasone furoate (in a pressurised container with CFC propellant and surfactant agent) at concentrations between 0,25 and 2,0 micrograms/l was studied for 24 months in mice and rats. The characteristic effects 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.

3 years

To be used within 2 months after first use.

Store at a temperature not exceeding 25°C.

Do not freeze.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

• Indication(s) appearing in the marketing authorisation at the date of publication of this decree