Mometasone Furoate 50 Micrograms/Actuation Nasal Spray Suspension
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Mometasone Furoate 50 micrograms/actuation Nasal Spray, Suspension.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each actuation (0.1 ml) of the pump delivers a metered dose of 50 micrograms Mometasone Furoate (as the monohydrate). The total weight of one actuation is 100 mg.
Excipient with known effect: contains 20 micrograms benzalkonium chloride per actuation).
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Nasal Spray, Suspension.
White to off-white opaque suspension. pH: between 4.3. and 4.9
Osmolality: between 270 and 330 mOsm/Kg
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Mometasone Furoate Nasal Spray is indicated in adults and children aged 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 Nasal Spray may be initiated up to four weeks prior to the anticipated start of the pollen season.
Mometasone furoate nasal spray is indicated for the treatment of nasal polyps in adults aged 18 years and older.
4.2 Posology and method of administration
Posology
Paediatric population
The safety and efficacy of Mometasone Furoate Nasal Spray in children aged less than six years have not yet been established.
Seasonal or Perennial Allergic Rhinitis
Adults (including geriatric patients) and children aged 12 years and older: 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.
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 Nasal Spray should not be used in children below 6 years of age because of insufficient data on safety and efficacy (see section 5.1).
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.
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). The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. 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.
Method of administration
Precautions to be taken before handling or administering Mometasone Furoate Nasal Spray
Prior to administration of the first dose, shake container well and actuate pump 10 times (until a uniform spray is obtained). If pump is not used for 14 days or longer, reprime the pump with 2 actuations until a uniform spray is observed. Shake container well before each use. The bottle should be discarded after the labelled number of actuations or within 2 months of first use.
After initial priming of the Mometasone Furoate Nasal Spray pump, each actuation delivers approximately 100 mg of mometasone furoate suspension, containing mometasone furoate monohydrate equivalent to 50 micrograms mometasone furoate into each nostril.
4.3 Contraindications
Hypersensitivity to the active substance or to any or the excipients listed in section 6.1.
Mometasone Furoate Nasal Spray should not be used in the presence of untreated localised infection involving the nasal mucosa.
Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal surgery or trauma should not use a nasal corticosteroid until healing has occurred.
4.4 Special warnings and precautions for use
Mometasone furoate nasal spray 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.
Following 12 months of treatment with mometasone furoate nasal spray there was no evidence of atrophy of the nasal mucosa; also, mometasone furoate tended to reverse the nasal mucosa closer to a normal histologic phenotype. As with any long-term treatment, patients using mometasone furoate nasal spray over several months or longer should be examined periodically for possible changes in the nasal mucosa. If localised fungal infection of the nose or pharynx develops, discontinuation 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.
Although mometasone furoate will control the nasal symptoms in most patients, the concomitant use of appropriate additional therapy may provide additional relief of other symptoms, particularly ocular symptoms.
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. If these patients exhibit signs and symptoms of adrenal insufficiency, systemic corticosteroid administration should be resumed and other modes of therapy and appropriate measures instituted.
During transfer from systemic corticosteroids to mometasone furoate nasal spray some patients may experience symptoms of withdrawal from systemically active corticosteroids (e.g., joint and/or muscular pain, lassitude and depression initially), despite relief from nasal symptoms and will require encouragement to continue mometasone furoate nasal spray therapy. Such transfer may also unmask pre-existing allergic conditions, such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy.
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 (see section 4.8).
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).
Treatment with higher than recommended doses may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.
Mometasone furoate nasal spray contains benzalkonium chloride, which is an irritant that 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) then preservative-free medicinal products for nasal use should be used if possible; however if such preservative-free medicinal products are not available another pharmaceutical form should be used. See 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 of age have not been studied.
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
(See 4.4 Special warnings and special precautions for use with systemic corticosteroids)
A clinical interaction study was conducted with loratadine. No interactions were observed.
Paediatric population
Interaction studies have only been performed in adults.
4.6 Fertility, pregnancy and lactation
There are no adequate or well-controlled studies in pregnant women. As with other nasal corticosteroid preparations, mometasone furoate nasal spray should not be used in pregnancy or lactation unless the potential benefit to the mother justifies any potential risk to the mother, fetus or infant. Infants born of mothers who received corticosteroids during pregnancy should be observed carefully for hypoadrenalism.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed.
4.8 Undesirable effects
Treatment-related adverse events reported in clinical studies for allergic rhinitis in adult and adolescent patients are shown below (Table 1).
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)
Table 1:Allergic Rhinitis-Treatment Related Undesirable Effects for mometasone furoate nasal spray
|
Respiratory, thoracic and mediastinal disorders Common |
Epistaxis, pharyngitis, nasal burning, nasal irritation, nasal ulceration |
|
General disorders and administration site conditions | |
|
Common |
Headache |
Epistaxis was generally self-limiting and mild in severity, it 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.
In patients treated for nasal polyposis, the overall incidence of adverse events was comparable to placebo and similar to that observed for patients with allergic rhinitis. Treatment-related adverse events reported in >1% of patients in clinical studies for polyposis are shown below (Table 2).
Table 2: Polyposis-Treatment Related Undesirable Effects >1% for mometasone furoate nasal spray
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 Upper respiratory tract infection Epistaxis |
common common |
uncommon very common |
|
Gastrointestinal disorders Throat irritation |
--- |
common |
|
General disorders and administration site conditions Headache |
common |
common |
In patients treated for acute rhinosinusitis, the incidence of epistaxis for mometasone furoate was 3.3% vs. 2.6% for placebo and similar to that observed for patients treated with allergic rhinitis.
Rarely, immediate hypersensitivity reactions, including bronchospasm and dyspnoea, may occur after intranasal administration of mometasone furoate monohydrate. Very rarely, anaphylaxis and angioedema have been reported.
Disturbances of taste and smell have been reported very rarely.
As with other intranasal corticosteroids very rare cases of nasal septum perforation have been reported.
Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.
Rare cases of glaucoma, increased intraocular pressure (see section 4.4) and/or cataracts have been reported with the use of intranasal corticosteroids.
Paediatric population
In the paediatric population, the incidence of adverse events, e.g., epistaxis (6%), headache (3%), nasal irritation (2%) and sneezing (2%) was comparable to placebo.
When used at high doses for long periods of time, corticosteroid nasal sprays may cause certain side effects such as growth retardation in children (see section 4.4).
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 at: www.mhra.gov .uk/yellowcard.
4.9 Overdose
Because of the negligible (<0.1%) systemic bioavailability of mometasone furoate, 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
Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory properties at doses that are not systemically active.
It is likely that much of the mechanism for the anti-allergic and anti-inflammatory effects of mometasone furoate lies in its ability to inhibit the release of mediators of allergic reactions. Mometasone furoate inhibits the release of leukotrienes from leucocytes of allergic patients.
In cell culture, mometasone furoate demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6 and TNFa; it is also a potent inhibitor of leukotriene production. In addition, it is an extremely potent inhibitor of the production of the Th2 cytokines, IL-4 and IL-5, from human CD4+ T-cells.
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.
In two trials with 1954 patients, mometasone furoate nasal spray 200 microgram administered twice daily demonstrated significant improvement in symptoms associated with acute rhinosinusitis compared to placebo as evaluated by the Major Symptom Score (MSS) composite of symptoms (facial pain/pressure/tenderness, sinus headache, rhinorrhea, post nasal drip and nasal congestion/stuffiness) during a 15-day treatment period (P02683 p < 0.001; P02692 p = 0.038). A 500 mg three times a day amoxicillin arm was not significantly different from placebo in reducing these symptoms of acute rhinosinusitis as evaluated by the MSS. The SNOT-20 HRQL showed a significant level of benefit at the 200 mcg twice daily dose of mometasone furoate vs. placebo (p=0.047). Treatment duration beyond 15 days was not evaluated in acute rhinosinusitis.
In a placebo-controlled clinical trial in which paediatric patients (n=49/group) were administered mometasone furoate 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 in the paediatric population aged 3 to 5 years, and an appropriate dosage range cannot be established. In a study involving 48 children aged 3 to 5 years treated with intranasal mometasone furoate 50, 100 or 200 micrograms/day for 14 days, there was no significant differences from placebo in the mean change in plasma cortisol level in response to the tetracosactrin stimulation test.
5.2 Pharmacokinetic properties
Mometasone furoate, administered as an aqueous nasal spray, has negligible (<0.1%) systemic bioavailability and is generally undetectable in plasma, despite the use of a sensitive assay with a lower quantitation limit of 50 pg/ml. 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 have been demonstrated. All observed effects are typical of this class of compound and are related to exaggerated pharmacological effects of glucocorticoids.
Preclinical studies demonstrated 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 56 mg/kg/day and 280 mg/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 fetal growth (lower fetal 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 and carmellose sodium (Avicel RC - 591) Glycerol
Sodium citrate dihydrate Citric acid monohydrate Polysorbate 80 Benzalkonium chloride Water for Injection
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
Use within 8 weeks of first use.
6.4 Special precautions for storage
Do not store above 25°C. Do not freeze.
6.5 Nature and contents of container
Mometasone Furoate Nasal Spray is contained in a white, high density polyethylene bottle, that contains 10 g (60 actuations) or 18 g (120 or 140 actuations) of product formulation, supplied with a metered-dose, manual polypropylene spray pump and actuator.
Pack sizes : 10g, 1 bottle containing 60 actuations
18g, 1 bottle containing 120 actuations 18g, 1 bottle containing 140 actuations
Multipack: 2 bottles, each containing 140 actuations (280 actuations in total)
Multipack: 3 bottles, each containing 140 actuations (420 actuations in total)
Not all pack sizes may be marketed
6.6 Special precautions for disposal
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Teva UK Limited Brampton Road,
Hampden Park,
Eastbourne,
East Sussex BN22 9AG UNITED KINGDOM
8 MARKETING AUTHORISATION NUMBER(S)
PL 00289/1748
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10 DATE OF REVISION OF THE TEXT
30/06/2015