1 Name of Medicine
Mometasone furoate.
2 Qualitative and Quantitative Composition
Nasonex Allergy Aqueous Nasal Spray delivers in each actuation approximately 100 mg of mometasone furoate monohydrate suspension, containing mometasone furoate monohydrate equivalent to mometasone furoate 50 microgram.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Nasonex Allergy Aqueous Nasal Spray is a metered-dose, manual pump spray unit.
4.1 Therapeutic Indications
Nasonex Allergy Aqueous Nasal Spray is indicated for the prophylaxis or treatment of allergic rhinitis for up to six months in adults and children 12 years of age and over.
4.2 Dose and Method of Administration
Do not exceed the recommended dosage. For intranasal use only.
The effect of Nasonex Allergy Aqueous Nasal Spray is not immediate. Full therapeutic benefit takes a few days to develop. Dosage should be administered as directed and not be taken by the patients at will for symptomatic relief.
In patients who have a history of moderate to severe symptoms of seasonal allergic rhinitis, prophylactic treatment with Nasonex Allergy is recommended two to four weeks prior to the anticipated start of the pollen season.
Adults (including geriatric patients) and adolescents 12 years of age and over.
The usual recommended dose for prophylaxis and treatment of allergic rhinitis is two sprays (50 microgram/spray) in each nostril once daily (total daily dose 200 microgram). Once symptoms are controlled, reducing the dose to one spray in each nostril (total daily dose 100 microgram) may be effective for maintenance.
After the first dose of mometasone furoate nasal spray, clinically significant improvement of symptoms was achieved within 12 hours in 28% of a group of patients (n = 190) with seasonal allergic rhinitis (median = 36 hours). However, the 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.
Instructions to patients.
Shake container well before each use. Do not pierce the nasal applicator. After the initial priming of the Nasonex Allergy Aqueous Nasal Spray pump (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 microgram of mometasone furoate. If the spray pump has not been used for 14 days or longer, it should be reprimed with 2 actuations, until uniform spray is observed, before the next use.
Cleaning your nasal spray.
It is important to clean your nasal spray regularly, otherwise it may not work properly. Remove the dust cap and gently pull off the nozzle. Wash the nozzle and dust cap in warm water and then rinse under a running tap. Do not try to unblock the nasal applicator by inserting a pin or other sharp objects as this will damage the applicator and cause you not to get the right dose of medicine. Allow to dry in a warm place. Push the nozzle back onto the bottle and replace the dust cap. The spray will need to be re-primed with 2 sprays when first used after cleaning.4.3 Contraindications
Use in children under 12 years of age.
Use for longer than six months without the advice of a doctor or pharmacist.
Patients with known hypersensitivity to mometasone furoate or any of the excipients.
Severe nasal infection, especially candidiasis.
Persons with haemorrhagic diathesis or with a history of recurrent nasal bleeding.
4.4 Special Warnings and Precautions for Use
Improvement should be seen within seven days of starting treatment. Treatment should be reassessed if there is no improvement within seven days of continuous use, or if symptoms have improved but are not adequately controlled after seven days of continuous use.
If signs or symptoms of eye pain and/or visual disturbance develop, discontinuance of mometasone nasal spray use or appropriate treatment may be required.
Nasonex Allergy Aqueous 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.
Following 12 months of treatment with mometasone furoate nasal spray, there was no evidence of atrophy of the nasal mucosa. Mometasone furoate tended to reverse the nasal mucosa closer to a normal histological phenotype. As with any long-term treatment, patients using Nasonex Allergy Aqueous 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, discontinuance of Nasonex Allergy Aqueous Nasal Spray therapy or appropriate treatment may be required. Persistence of nasopharyngeal irritation may be an indication for discontinuing Nasonex Allergy Aqueous Nasal Spray.
Nasonex Allergy Aqueous 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.
Topical corticosteroids may be absorbed in amounts that can have systemic effects. Use of excessive doses may suppress HPA function. Physicians should be alert for evidence of systemic effects, especially in chronically treated patients.
However, there is no evidence of hypothalamic pituitary adrenal (HPA) axis suppression following prolonged treatment with mometasone furoate aqueous nasal spray. Patients who are transferred from long-term administration of systemically active corticosteroids to mometasone furoate aqueous 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 aqueous 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 aqueous nasal spray therapy. Such transfer may also unmask pre-existing allergic conditions such as allergic conjunctivitis and eczema, previously suppressed by systemic corticosteroid therapy.
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 aerosolised corticosteroids, instances of nasal septum perforation or increased intraocular pressure have been reported very rarely.
Visual disturbance may be reported with systemic and topical (including, intranasal, inhaled and intraocular) corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes of visual disturbances which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Use in the elderly.
See Section 4.2 Dose and Method of Administration; Section 4.8 Adverse Effects (Undesirable Effects); Section 5.1 Pharmacodynamic Properties.
Paediatric use.
Nasonex Allergy Aqueous Nasal Spray should not be used in children under 12 years of age.
Controlled clinical trials have shown that intranasal corticosteroids may cause a reduction in growth velocity in children. This effect has been observed in the absence of laboratory evidence of hypothalamic pituitary adrenal (HPA) axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for 'catch up' growth following discontinuation of treatment with intranasal corticosteroids has not been adequately studied.
The growth of children receiving intranasal corticosteroids should be monitored routinely (e.g. via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits and the availability of safe and effective noncorticosteroid alternatives. To minimise the systemic effects of intranasal corticosteroids, each patient should be titrated to his/her lowest effective dose.
However, no reduction in growth velocity was observed in a placebo controlled clinical trial in which paediatric patients were administered mometasone furoate aqueous nasal spray 100 microgram daily for one year. The effects of treatment for periods of greater than one year have not been studied.
Effects on laboratory tests.
None identified.4.5 Interactions with Other Medicines and Other Forms of Interactions
There have been no formal interaction studies performed.
Mometasone furoate via MFNS has been administered concomitantly with loratadine with no effect on plasma concentrations of loratadine or its major metabolite. In these studies, mometasone furoate plasma concentrations were not detectable using an assay with a LLOQ of 50 picogram/mL. The combination therapy was well tolerated (Reference 40).
Mometasone furoate is metabolized by CYP3A4.
Coadministration with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, ritonavir, cobicistat-containing products) may lead to increased plasma concentrations of corticosteroids and potentially increase the risk for systemic corticosteroid side-effects. Consider the benefit of coadministration versus the potential risk of systemic corticosteroid effects, in which case patients should be monitored for systemic corticosteroid side-effects.
4.6 Fertility, Pregnancy and Lactation
Effects on fertility.
As with other corticosteroids, at exposure levels associated with marked signs of systemic corticosteroid toxicity, mometasone furoate had progestogenic effects on the female reproductive tract and mammary glands. However, fertility was unimpaired in a reproductive toxicity study carried out in rats.
(Category B3)
In animal studies, small quantities of mometasone furoate were found to cross the placental barrier. Like other corticosteroids, at doses associated with signs of systemic toxicity, mometasone furoate reduced foetal growth and was teratogenic in mice, rats and rabbits after subcutaneous or topical application. Higher doses had progestogenic effects in pregnant rats, associated with prolonged gestation, dystocia and reduced pup survival.
There are no adequate or well controlled studies in pregnant women. Low levels of systemic mometasone have been measured following nasal administration of Nasonex Allergy Aqueous Nasal Spray.
As with other nasal corticosteroid preparations, Nasonex Allergy Aqueous Nasal Spray should be used in pregnant women only if the potential benefit justifies the potential risk to the mother or foetus. Infants born of mothers who received corticosteroids during pregnancy should be observed carefully for hypoadrenalism.
After oral administration, small quantities of mometasone furoate and/or its metabolites were transferred into the milk of lactating rats. There are no data on the extent of passage of mometasone furoate and/or its metabolites into the breast milk of women using mometasone furoate nasal spray. As with other nasal corticosteroid preparation, Nasonex Allergy should be used by lactating mother only if the potential benefit justifies any potential risk to the infant.4.7 Effects on Ability to Drive and Use Machines
The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.
4.8 Adverse Effects (Undesirable Effects)
Treatment related local adverse events reported in clinical studies include headache (8%), epistaxis (i.e. frank bleeding, blood tinged mucus and blood flecks) (8% vs placebo 5%), nasal burning (2% vs placebo 3%), and nasal irritation (2% vs placebo 2%) and nasal ulceration, which are typically observed with the use of a corticosteroid nasal spray. Epistaxis was generally self limiting and mild in severity, and occurred at a comparable or lower incidence compared to other active control nasal corticoids used in clinical studies (up to 15%). The incidence of all other effects was comparable with that of placebo.
In the elderly, the more common adverse events were epistaxis (12% vs placebo 5%), headache (9% vs placebo 6%) and pharyngitis (4% vs placebo 2%).
Rarely, immediate hypersensitivity reactions (e.g. bronchospasm, dyspnea) 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.
Post-market experience.
The following additional adverse reactions have been reported in post-marketing use with Nasonex: vision blurred.
Reporting suspected adverse effects.
Reporting suspected adverse reactions after registration 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 at http://www.tga.gov.au/reporting-problems.4.9 Overdose
Because the systemic bioavailability of Nasonex Allergy Aqueous Nasal Spray is low and has been estimated as < 1%, overdose is unlikely to require any therapy other than observation. Treatment can be reinitiated at the usual recommended dose.
Inhalation or oral administration of excessive doses of corticosteroids may lead to suppression of hypothalamic pituitary adrenal (HPA) axis function.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).
5 Pharmacological Properties
5.1 Pharmacodynamic Properties
Mechanism of action.
Mometasone furoate is a topical glucocorticosteroid with local anti-inflammatory properties at doses that are not systemically active.
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.
Clinical trials.
The clinical program evaluated the efficacy and safety of mometasone furoate nasal spray in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in adults and children aged 12 years and older. Five phase I clinical studies evaluated the systemic safety and local tolerability of mometasone furoate. Other clinical studies included:
One phase II dose ranging study conducted to determine the optimum dose for the phase III program; and
seven phase III studies designed to assess the safety and efficacy of mometasone furoate nasal spray in treating seasonal allergic rhinitis for 28 days (including two studies which evaluated the prophylactic efficacy of mometasone furoate in preventing the symptoms of seasonal allergic rhinitis, and two which evaluated inflammatory response markers following nasal provocation with allergens); and
five phase III studies designed to assess the safety and efficacy of mometasone furoate in the treatment of perennial allergic rhinitis for 12 weeks. Four studies investigated the long-term safety and maintenance of therapeutic effect of mometasone furoate over 52 weeks; one perennial allergic rhinitis study was conducted in the elderly population; and three open label perennial allergic rhinitis studies included a "variable-dose group" in which the dose of mometasone furoate varied from 100 to 400 microgram daily depending on symptoms.
During the course of the phase II/III clinical program, 3120 patients (12 years of age and older) were treated with mometasone furoate nasal spray. The majority (65%) of patients was treated with 200 microgram once daily. The remainder received mometasone furoate in a dose ranging from 50 microgram to 800 microgram once daily. A total of 712 patients were treated with mometasone furoate for at least 6 months and 350 patients were treated for 12 months or longer.
The results of the efficacy studies demonstrated that mometasone furoate nasal spray 200 microgram/day was consistently superior to placebo in relieving the symptoms of seasonal allergic rhinitis and perennial allergic rhinitis and was of comparable efficacy to other commonly used topical corticosteroid sprays. In the case of seasonal allergic rhinitis it is also superior to placebo in the prophylaxis of symptoms. In the long-term studies in perennial allergic rhinitis there was no evidence of any diminution of its efficacy over time.
After the first dose of mometasone furoate nasal spray, clinically significant improvement of symptoms was achieved within 12 hours in 28% of a group of patients (n = 190) with seasonal allergic rhinitis (median = 36 hours). However, the 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.
5.2 Pharmacokinetic Properties
Absorption.
Systemic bioavailability of mometasone furoate was investigated in 24 healthy volunteers following intranasal administration of 400 microgram of the suspension. Mometasone was detectable in plasma (at sporadic time points) in only 4 of the 24 subjects, despite the use of a sensitive assay with a limit of quantitation of 50 picogram/mL. Thus, there were no relevant pharmacokinetic data for this dosage form.
Systemic absorption of mometasone furoate suspension administered as aqueous nasal spray, 200 microgram single dose, was measured using a sensitive assay with a lower quantitation limit of 0.25 picogram/mL. Mean Cmax was 5.77 picogram/mL (CV% 32) and mean AUC(0-12 hr) 29.6 picogram.hr/mL (CV% 37). When compared with dose adjusted PK data for IV mometasone administration from earlier studies with a quantitation limit of 50 picogram/mL and longer sampling duration, the estimated relative systemic (or 'absolute') bioavailability is < 1%. The bioavailability of mometasone following intranasal administration is low.
Systemic effects were not detected in adults, adolescents or children following the administration of mometasone furoate aqueous nasal spray.
Mometasone furoate suspension is very poorly absorbed from the gastrointestinal tract.
Distribution.
No data available.
Metabolism.
Mometasone furoate undergoes extensive first pass metabolism.
Excretion.
Mometasone furoate is excreted in the urine and bile.
5.3 Preclinical Safety Data
Genotoxicity.
Mometasone furoate is not considered to be genotoxic. There was no evidence of mutagenicity in in vitro tests which included tests for reverse mutation in Salmonella typhimurium and Escherichia coli and forward gene mutation in a mouse lymphoma cell line. Limited evidence of clastogenicity was obtained in Chinese hamster ovary cells, although this finding was not confirmed in a second assay in Chinese hamster lung cells in vitro, nor in vivo assays including a chromosomal aberration assay in mouse spermatogonia, a mouse micronucleus assay or in a rat bone marrow clastogenicity assay. Mometasone furoate did not cause DNA damage in rat liver cells.
Carcinogenicity.
No data available.6 Pharmaceutical Particulars
6.1 List of Excipients
Dispersible cellulose, glycerol, citric acid - anhydrous, sodium citrate, polysorbate 80 and purified water with benzalkonium chloride 0.2 mg/g as preservative. Nasonex Allergy Aqueous Nasal Spray does not contain fluorocarbon propellants.
6.2 Incompatibilities
Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
6.3 Shelf Life
In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.
6.4 Special Precautions for Storage
Store below 25°C. Do not freeze.
6.5 Nature and Contents of Container
Nasonex Allergy Aqueous Nasal Spray.
Metered atomising pump unit containing mometasone furoate (as the monohydrate) 50 microgram/actuation; 40, 65 and 140 metered doses.
6.6 Special Precautions for Disposal
In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.
6.7 Physicochemical Properties
Chemical structure.
Mometasone furoate monohydrate is 9,21-dichloro-11β,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione 17-(2-furoate) monohydrate. The empirical formula is C27H30Cl2O6.H2O. MW = 539.45.
CAS number.
83919-23-7 (mometasone furoate anhydrous).7 Medicine Schedule (Poisons Standard)
S2 Pharmacy Medicine.
Summary Table of Changes
