Mometasone Furoate 50 Micrograms/Dose Nasal Spray Suspension
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each actuation of the pump delivers a metered dose of 50 micrograms of mometasone furoate (as mometasone furoate monohydrate).
Excipient(s): Contains 0.02 mg benzalkonium chloride per actuation.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Nasal spray, suspension White, homogenous suspension
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension is indicated for use in adults and children 6 years of age and older to treat the symptoms of seasonal allergic or perennial allergic rhinitis.
In patients who have a history of moderate to severe symptoms of seasonal allergic rhinitis, prophylactic treatment with Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension may be initiated up to four weeks prior to the anticipated start of the pollen season.
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension is indicated for the symptomatic treatment of nasal polyps in adults 18 years of age and older.
4.2 Posology and method of administration Posology
Seasonal or perennial allergic rhinitis
The usual recommended dose is two actuations (50 micrograms/actuation) in each nostril once daily (total dose 200 micrograms). Once symptoms are controlled, dose reduction to one actuation in each nostril (total dose 100 micrograms) may be effective for maintenance.
If symptoms are inadequately controlled, the dose may be increased to a maximum daily dose of four actuations in each nostril once daily (total dose 400 micrograms). Dose reduction is recommended following control of symptoms.
Mometasone furoate nasal spray demonstrated a clinically significant onset of action within 12 hours after the first dose in some patients with seasonal allergic rhinitis; however, full benefit of treatment may not be achieved in the first 48 hours. Therefore, the patient should continue regular use to achieve full therapeutic benefit.
Paediatric population
Children between the ages of 6 and 11 years: The usual recommended dose is one actuation (50 micrograms/actuation) in each nostril once daily (total dose 100 micrograms). Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension should not be used in children below age of 6 years because of insufficient data on safety and efficacy (see section 5.1).
Nasal polyposis
The usual recommended starting dose for polyposis is two actuations (50 micrograms/actuation) in each nostril once daily (total daily dose of 200 micrograms). If after 5 to 6 weeks symptoms are inadequately controlled, the dose may be increased to a daily dose of two sprays in each nostril twice daily (total daily dose of 400 micrograms). After effective control of symptoms is maintained, the dose should be lowered to once daily. If no improvement in symptoms is seen after 5 to 6 weeks of twice daily administration, alternative therapies should be considered.
Efficacy and safety studies of mometasone furoate nasal spray for the treatment of nasal polyposis were four months in duration.
Paediatric population
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension should not be used in children below age of 18 years because of insufficient data on safety and efficacy.
Method of administration
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension is intended only for nasal use.
Before each use container should be shaken well. After initial priming of the Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension pump (10 actuations, until a uniform spray is observed), each actuation delivers approximately 100mg of mometasone furoate suspension, containing mometasone furoate monohydrate equivalent to 50 micrograms mometasone furoate. If the spray pump has not been used for 14 days or longer, it should be re-primed with 2 actuations, until a uniform spray is observed, before next use.
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
- Presence of untreated localised infection involving the nasal mucosa.
- Patients who have experienced recent nasal surgery or trauma until healing has occurred.
4.4 Special warnings and precautions for use
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract, or in untreated fungal, bacterial, systemic viral infections or ocular herpes simplex.
As for other nasal steroids, patients using mometasone furoate nasal spray over long-term period should be examined periodically for possible changes in the nasal mucosa. If localised fungal infection of the nose or pharynx develops, discontinuance of mometasone furoate nasal spray therapy or appropriate treatment may be required. Persistence of nasopharyngeal irritation may be an indication for discontinuing mometasone furoate nasal spray.
Patients who are transferred from long-term administration of systemically active corticosteroids to mometasone furoate nasal spray require careful attention. Systemic corticosteroid withdrawal in such patients may result in adrenal insufficiency for a number of months until recovery of HPA axis function. Such transfer may also unmask pre-existing allergic conditions, such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy.
During transfer from systemic corticosteroids to Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension some patients may experience symptoms of withdrawal from systemically active corticosteroids (e.g., joint and/or muscular pain, lassitude, and depression initially).
The safety and efficacy of mometasone furoate nasal spray has not been studied for use in the treatment of unilateral polyps, polyps associated with cystic fibrosis, or polyps that completely obstruct the nasal cavities.
Unilateral polyps that are unusual or irregular in appearance, especially if ulcerating or bleeding, should be further evaluated.
Patients receiving corticosteroids who are potentially immunosuppressed should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and of the importance of obtaining medical advice if such exposure occurs.
Following the use of intranasal corticosteroids, instances of nasal septum perforation or increased intraocular pressure have been reported very rarely.
Systemic effects of nasal corticosteroids may occur, particularly at high doses prescribed for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).
The use of Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension may produce positive results in doping controls.
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspensioncontains benzalkonium chloride which is irritant and may cause nasal irritation. If used for a longer period, the preservative benzalkonium chloride may cause nasal mucosa swelling. In the case of such a reaction (persistently congested nose) medicinal drugs without a preservative should be used if possible. Unless such products are available another pharmaceutical form should be taken. See also section 5.3.
Paediatric population
Safety and efficacy of mometasone furoate nasal spray for the treatment of nasal polyposis in children and adolescents under 18 years have not been studied.
Systemic effects of nasal corticosteroids may occur, particularly at high doses prescribed for prolonged periods. Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses.
It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid if possible, to the lowest dose at which effective control of symptoms is maintained. In addition, consideration should be given to referring the patient to a paediatric specialist.
4.5 Interaction with other medicinal products and other forms of interaction
A clinical interaction study in adults and children was conducted with loratadine. No interactions were observed.
See also section 4.4 (Special warning and precautions for use) regarding use with systemic corticosteroids.
4.6 Fertility, pregnancy and lactation
Pregnancy:
There are no or limited amount of data from the use of intranasal mometasone furoate in pregnant women. Following intranasal administration systemic exposure to mometasone furoate is limited (see section 4.9). Corticosteroids cross the placenta. After systemic use of high dose corticosteroids, effects on the foetus/neonate have been described (intra-uterine growth retardation, adrenocortical suppression, cleft palate) .Animal studies have shown reproduction toxicity and teratogenity after systemic administration (see section 5.3).
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension is not recommended during pregnancy.
Breast-feeding:
It is unknown whether mometasone furoate/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility:
There are no data on the effect of mometasone furoate on human fertility. Fertility was unaffected following mometasone furoate treatment in animal studies.
4.7 Effects on ability to drive and use machines
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Summary of the safety profile
Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension is generally well tolerated and has mainly local adverse reactions.
Tabulated list of adverse reactions
Adverse reactions are categorized by body system and frequency. Frequencies are defined using the following categories: very common (>=1/10), common (>=1/100 to <1/10), uncommon (>=1/1,000 to <1/100), rare (>=1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Respiratory, thoracic and mediastinal disorders
-Common: Epistaxis, throat irritation, nasal irritation, nasal burning and nasal ulceration
General disorders and administration site administration site conditions -Common: Headache
-Rare: Hypersensitivity
-Very rare: Anaphylaxis, angioedema, disturbances in smell and taste Description of selected adverse reactions
Epistaxis was generally self-limiting and mild in severity, and occurred at a higher incidence compared to placebo (5%), but at a comparable or lower incidence when compared to the active control nasal corticosteroids studied (up to 15%). The incidence of all other effects was comparable with that of placebo.
Following the use of intranasal corticosteroids, instances of nasal septum perforation or increased intraocular pressure have been reported very rarely.
Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.
Paediatric population
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
Growth retardation has been reported in children receiving intranasal steroids.
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 reactions via the Yellow Card Scheme: www.mhra.gov.uk/yellowcard.
4.9 Overdose
Because of the negligible (<0.1%) systemic bioavailability of Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension, overdose is unlikely to require any therapy other than observation, followed by initiation of the appropriate prescribed dosage. Inhalation or oral administration of excessive doses of corticosteroids may lead to suppression of HPA axis function.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Decongestants and other nasal preparations for topical use-corticosteroids ATC Code: R01A D09
Mechanism of action
Mometasone furoate is a topical glucocorticosteroid with local antiinflammatory properties.
It is likely that much of the mechanism for the anti-allergic and antiinflammatory effects of mometasone furoate lies in its ability to inhibit the release of mediators of allergic reactions.
Clinical efficacy and safety
In studies utilising nasal antigen challenge, mometasone furoate nasal spray has shown anti-inflammatory activity in both the early- and late- phase allergic responses. This has been demonstrated by decreases (vs placebo) in histamine and eosinophil activity and reductions (vs baseline) in eosinophils, neutrophils, and epithelial cell adhesion proteins.
In 28% of the patients with seasonal allergic rhinitis, mometasone furoate nasal spray demonstrated a clinically significant onset of action within 12 hours after the first dose. The median (50%) onset time of relief was 35.9 hours.
Paediatric population
In a placebo-controlled clinical trial in which paediatric patients (n=49/group) were administered mometasone furoate nasal spray 100 micrograms daily for one year, no reduction in growth velocity was observed.
There are limited data available on the safety and efficacy of Mometasone Furoate 50 micrograms/dose Nasal Spray, suspension in the paediatric population aged 3 to 5 years, and an appropriate dosage range cannot be established.
5.2 Pharmacokinetic properties
Mometasone furoate, administered as an aqueous nasal spray, has a negligible (<0.1%) systemic bioavailability and is generally undetectable in plasma, despite the use of a sensitive assay with a lower quantitation limit of 50pg/ml; thus, there are no relevant pharmacokinetic data for this dosage form. Mometasone furoate suspension is very poorly absorbed from the gastrointestinal tract, and the small amount that may be swallowed and absorbed undergoes extensive first-pass hepatic metabolism prior to excretion in urine and bile.
5.3 Preclinical safety data
No toxicological effects unique to mometasone furoate exposure were demonstrated. All observed effects are typical of this class of compounds and are related to exaggerated pharmacologic effects of glucocorticoids.
Preclinical studies demonstrate that mometasone furoate is devoid of androgenic, antiandrogenic, estrogenic or antiestrogenic activity but, like other glucocorticoids, it exhibits some antiuterotrophic activity and delays vaginal opening in animal models at high oral doses of 56mg/kg/day and 280mg/kg/day.
Like other glucocorticoids, mometasone furoate showed a clastogenic potential in-vitro at high concentrations. However, no mutagenic effects can be expected at therapeutically relevant doses.
In studies of reproductive function, subcutaneous mometasone furoate, at 15 micrograms/kg prolonged gestation and prolonged and difficult labour occurred with a reduction in offspring survival and body weight or body weight gain. There was no effect on fertility.
Like other glucocorticoids, mometasone furoate is a teratogen in rodents and rabbits. Effects noted were umbilical hernia in rats, cleft palate in mice and gallbladder agenesis, umbilical hernia, and flexed front paws in rabbits. There were also reductions in maternal body weight gains, effects on foetal growth (lower foetal body weight and/or delayed ossification) in rats, rabbits and mice, and reduced offspring survival in mice.
The carcinogenicity potential of inhaled mometasone furoate (aerosol with CFC propellant and surfactant) at concentrations of 0.25 to 2.0 micrograms/l was investigated in 24-month studies in mice and rats. Typical glucocorticoid-related effects, including several non-neoplastic lesions, were observed. No statistically significant dose-response relationship was detected for any of the tumour types.
The preclinical data show that benzalkonium chloride could have inhibitory effects on the cilia including irreversible standstill, dependent on the concentration and duration of treatment with this excipient. Also, histopathological changes of the nasal mucosa were induced.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Microcrystalline cellulose (E460) carmellose sodium (E468) Glycerol (E442)
Citric acid monohydrate (E330) Sodium citrate dihydrate (E331) Polysorbate 80 (E433) Benzalkonium chloride Water for injection
6.2 Incompatibilities
Not applicable
6.3 Shelf life
2 years
After first opening of the bottle:
2 months
6.4 Special precautions for storage
Do not freeze
6.5 Nature and contents of container
White high density polyethylene (HDPE) plastic bottle fitted with PE/PP nasal spray pump
Pack sizes:
1 bottle containing 10.0g nasal spray suspension, corresponding to 60 delivered doses 1 bottle containing 17.0g nasal spray suspension, corresponding to 120 delivered doses
1 bottle containing 18.0g nasal spray suspension, corresponding to 140 delivered doses
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Shake well before use.
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Sandoz Limited
Frimley Business Park
Frimley
Camberley
Surrey
GU16 7SR
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 04416/1236
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
27/11/2012
10
DATE OF REVISION OF THE TEXT
18/04/2015