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Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS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 (100 mg) contains 50 micrograms of mometasone furoate (as
the monohydrate) as delivered dose (ex actuator).
Excipient with known effect: This medicinal product contains 20 micrograms of benzalkonium chloride per actuation.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Nasal Spray, Suspension.
White to off-white coloured homogeneous re-dispersible suspension with pH about 4.20 to 5 and osmolality 270-330 milliosmole / kg
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Mometasone furoate 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 nasal spray, suspension may be initiated up to four weeks prior to the anticipated start of the pollen season.
Mometasone furoate nasal spray, suspension is indicated for the treatment of symptoms of nasal polyposis in adults 18 years of age and older.
4.2 Posology and method of administration
Posology
Seasonal or Perennial Allergic Rhinitis
Adults (including geriatric patients) and children 12 years of age 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.
Mometasone furoate nasal spray, suspension 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).
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 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 fuorate nasal spray should not be used in children below age of 18 years because of insufficient data on safety and efficacy.
Method of administration
After initial priming of the Mometasone furoate nasal spray, suspension pump (usually 10 actuations, until a uniform spray is observed), each actuation delivers approximately 100 mg 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 reprimed with 2 actuations, until a uniform spray is observed, before next use.
The bottle should be discarded after the labelled number of actuations or within 2 months of first use.
4.3 Contraindications
Hypersensitivity to any ingredients of Mometasone furoate nasal spray, suspension.
Mometasone furoate nasal spray, suspension 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, 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.
Following 12 months of treatment with Mometasone furoate nasal spray, suspension 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, suspension 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, discontinuance of Mometasone furoate nasal spray, suspension therapy or appropriate treatment may be required. Persistence of nasopharyngeal irritation may be an indication for discontinuing Mometasone furoate nasal spray, suspension.
Although Mometasone furoate nasal spray, suspension 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.
There is no evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression following prolonged treatment with Mometasone nasal spray, suspension. However, patients who are transferred from long-term administration of systemically active corticosteroids to Mometasone furoate nasal spray, suspension 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, suspension 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, suspension 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, suspension 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.
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.
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 behavioral effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).
Paediatric population
Safety and efficacy of Mometasone furoate nasal spray, suspension for the treatment of nasal polyposis in children and adolescents under 18 years of age 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 the licensed dose.
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.
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).
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).
Paediatric population
A clinical interaction study in adults and children was conducted with loratadine. No interactions were observed.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no adequate or well-controlled studies in pregnant women. As with other nasal corticosteroid preparations, Mometasone furoate nasal spray, suspension should not be used in pregnancy
Infants born of mothers who received corticosteroids during pregnancy should be observed carefully for hypoadrenalism.
Breastfeeding
Mometasone furoate nasal spray, suspension should not be used in lactation unless the potential benefit to the mother justifies any potential risk to the mother, foetus or infant.
No fertility studies have been conducted with Mometasone furoate nasal spray.
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).
|
Table 1: Allergic Rhinitis -Treatment Related Undesirable Effects for Mometasone furoate nasal spray, suspension | |
|
very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1000 to < 1/100); rare (> 1/10,000 to < 1/1000); very rare (< 1/10,000); Not known (cannot be estimated from the available data) | |
|
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, 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.
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.
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 for Mometasone furoate nasal spray, suspension
very common (>1/10); common (> 1/100 to < 1/10); uncommon (>
|
1/1000to< 1/100); rare (> 1/10,000to < 1/1000); very rare (< 1/10,000); Not known (cannot be estimated from the available data) | ||
|
(200 mcg once a day) |
(200 mcg twice a day) | |
|
Respiratory, thoracic and mediastinal disorders | ||
|
Upper respiratory tract infection |
common |
uncommon |
|
Epistaxis |
common |
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 nasal spray, suspension 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 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 and/or cataracts have been reported with the use of intranasal corticosteroids.
Paediatric population
Growth retardation has been reported in children receiving nasal corticosteroids at licensed doses.
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 Yellow Card Scheme website: www.mhra.gov.uk/yellowcard
4.9 Overdose
Because of the negligible 0.1%) systemic bioavailability of Mometasone furoate 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 anti-inflammatory properties at doses that are not systemically active.
Pharmacodynamic effects
It is likely that much of the mechanism for the anti-inflammatory effects of mometasone furoate lies in its ability to inhibit the release of mediators of allergic reactions. Mometasone furoate significantly 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, suspension 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.
Clinical efficacy and safety
In 28% of the patients with seasonal allergic rhinitis, Mometasone furoate nasal spray, suspension 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, suspension 200 mcg 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 the 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 100 micrograms daily for one year, no reduction in growth velocity was observed.
Paediatric population
There are limited data available on the safety and efficacy of Mometasone furoate nasal spray, suspension 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 pg/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 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 50 pg/ml; thus, there are no relevant pharmacokinetic data for this dosage form. Mometasone furoate nasal spray, 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 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 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
Glycerol
Microcrystalline cellulose Carmellose sodium Citric acid monohydrate Polysorbate 80 Benzalkonium chloride Sodium citrate dihydrate Water for injection
Incompatibilities
6.2
Not applicable.
6.3 Shelf life
2 years
After first use: 2 months
6.4 Special precautions for storage
Do not store above 25°C. Do not freeze. Store in the original container.
6.5 Nature and contents of container
Mometasone Furoate 50 pg Nasal Spray is packed in 20 ml white opaque HDPE vial with a net fill weight of 18.0 g, providing 140 actuations. Each bottle is fitted with a white metered-dose atomising pump, white nasal adaptor and a translucent dust cap for nozzle, packed in a carton.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Cipla (EU) Limited Hillbrow House, Hillbrow Road,
Esher, Surrey, KT10 9NW,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 36390/0075
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
21/12/2012
10 DATE OF REVISION OF THE TEXT
17/02/2015