Nasofan Aqueous 50 Microgram Nasal Spray
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Nasofan Aqueous 50 microgram Nasal Spray.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 100 microlitre metered spray contains 50 micrograms of fluticasone propionate.
Excipient(s) with known effect:
contains 40 micrograms of benzalkonium chloride per metered spray.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Nasal spray suspension.
The medicinal product consists of a white, opaque aqueous suspension contained within an amber glass multidose bottle fitted with a metering pump.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Nasofan Aqueous 50 microgram Nasal Spray is indicated in adults and children aged 4 years and older for the prophylaxis and treatment of seasonal allergic rhinitis (including hay fever) and perennial rhinitis.
4.2 Posology and method of administration
Posology
Paediatric population
The safety and efficacy of Nasofan Aqueous 50 micrograms Nasal Spray in children aged less than 4 years has not been established.
Adults and children of 12 years of age and over:
Two sprays into each nostril once a day (200 mcg) preferably in the morning is recommended. In some cases two sprays into each nostril twice a day (400 mcg) may be required. Once symptoms are under control a maintenance dose of one spray per nostril once a day (100 mcg) may be used. If symptoms recur the dosage may be increased accordingly. The maximum daily dose should not exceed four sprays into each nostril (400 mcg). The minimum dose at which the effective control of symptoms is maintained should be used.
Elderly patients:
The normal adult dosage is applicable.
Children between ages of 4 and 11:
One spray into each nostril once a day (100 mcg), preferably in the morning, is recommended. In some cases one spray into each nostril twice a day (200 mcg) may be required. The maximum daily dose should not exceed two sprays into each nostril (200 mcg). The minimum dose at which the effective control of symptoms is maintained should be used.
For full therapeutic benefit regular usage is essential. The absence of an immediate effect should be explained to the patient since maximum relief may not be obtained for 3 to 4 days after commencement of treatment.
Method of administration
Nasofan Aqueous 50 microgram Nasal Spray is for administration by the intranasal route only.
Precautions to be taken before handling or administering the medicinal product
Prior to first use Nasofan Aqueous 50 microgram Nasal Spray must be primed by pressing down and releasing the pump six times. If Nasofan Aqueous 50 microgram Nasal Spray has not been used for 7 days it must be reprimed by pressing down and releasing the pump a sufficient number of times until a fine mist is produced.
4.3 Contraindications
Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Local infections: infections of the nasal airways should be appropriately treated but do not constitute a specific contraindication to treatment with Nasofan Aqueous 50 microgram Nasal Spray.
Administration of treatment may be necessary for several days for the full benefit of Nasofan Aqueous 50 microgram Nasal Spray to be achieved.
Upon transferring patients from systemic steroid treatment to Nasofan Aqueous 50 microgram Nasal Spray care must taken if there is any reason to suppose that their adrenal function is impaired.
In most cases Nasofan Aqueous 50 microgram Nasal Spray will control seasonal allergic rhinitis, however in the event of an abnormally heavy challenge of summer allergens appropriate additional therapy may be necessitated in certain instances. Such an instance may particularly be to control eye symptoms.
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). Please refer to section 5.1 and 5.2.
Adrenal suppression may occur to clinically significant levels as a result of treatment with higher than recommended doses of nasal corticosteroids. 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 (see section 5.1 for data on intranasal fluticasone propionate).
Incidences of significant interactions between fluticasone propionate and potent inhibitors of the cytochrome P450 3A4 system (e.g. ketoconazole and protease inhibitors such as ritonavir) may occur. Increased systemic exposure to fluticasone propionate may result (e.g. Cushing’s Syndrome and adrenal suppression have been observed). Therefore concomitant use of fluticasone propionate and ritonavir should be avoided unless the expected benefit exceeds the possible risk of systemic adverse reaction of corticosteroids.
In patients who have tuberculosis, any type of untreated infection, ocular herpes or have had a recent surgical operation or injury to the nose or mouth, the possible benefits of the treatment should be weighed against possible hazards.
Nasofan Aqueous 50 microgram Nasal Spray contains benzalkonium chloride solution which is an irritant that may cause skin reactions. If used for longer periods, 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 taken. It may also cause bronchospasm.
Paediatric population
Some nasal corticosteroids have been reported to produce growth retardation in children when prescribed at licensed doses. It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If slowed growth is observed, a review of the therapy should be performed with a resultant reduction of the dose of nasal corticosteroid, if possible, to the lowest dose at which effective control of symptoms is maintained. Furthermore a referral of the patient to a paediatric specialist should be considered.
4.5 Interaction with other medicinal products and other forms of interaction
Care should be taken when administering fluticasone propionate in patients taking concurrent drugs that are highly potent inhibitors of the cytochrome P450 3A4 system (e.g. protease inhibitors such as ritonavir). In an interaction study in healthy subjects with intranasal fluticasone propionate, ritonavir (a highly potent cytochrome P450 3A4 inhibitor) 100 mg b.i.d. increased the fluticasone propionate plasma concentrations several hundred fold, resulting in markedly reduced serum cortisol concentrations. Cases of Cushing's syndrome and adrenal suppression have been reported. The combination should be avoided unless the benefit outweighs the increased risk of systemic glucocorticoid side-effects. Other inhibitors of cytochrome P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations (see section 4.4).
Paediatric population
Interaction studies have only been performed in adults.
4.6 Fertility, pregnancy and lactation
Pregnancy
There is inadequate evidence of safety in human pregnancy. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development, including cleft palate and intra-uterine growth retardation. There may therefore be a very small risk of such effects in the human foetus. It should be noted, however, that the foetal changes in animals occur after relatively high systemic exposure; direct intranasal application ensures minimal systemic exposure.
As with other drugs the use of Nasofan Aqueous 50 microgram Nasal Spray during human pregnancy requires that the possible benefits of the drug be weighed against the possible hazards.
Breastfeeding
The secretion of fluticasone propionate in human breast milk has not been investigated. Subcutaneous administration of fluticasone propionate to lactating laboratory rats produced measurable plasma levels and evidence of fluticasone propionate in the milk. However, following intranasal administration to primates, no drug was detected in the plasma, and it is therefore unlikely that the drug would be detectable in milk. When Nasofan Aqueous 50 microgram Nasal Spray is used in breast feeding mothers the therapeutic benefits must be weighed against the potential hazards to mother and baby.
4.7 Effects on ability to drive and use machines
Nasofan Aqueous 50 microgram Nasal Spray has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (1/10), common ( 1/100 to <1/10), uncommon ( 1/1000 to <1/100), rare ( 1/10,000 to <1/1000) and very rare (<1/10,000) including isolated reports.
|
System Organ Class |
Adverse Event |
Frequency |
|
Immune system disorders |
Hypersensitivity reactions with the following manifestations: | |
|
Bronchospasm |
Rare | |
|
Anaphylactic reactions |
Rare | |
|
Anaphylactoid reactions |
Rare | |
|
Cutaneous hypersensitivity reactions |
Very rare | |
|
Angioedema (mainly facial and oropharyngeal oedema) |
Very rare | |
|
Nervous system disorders |
Headache, unpleasant taste, unpleasant smell. |
Common |
|
Eye disorders |
Glaucoma, raised intraocular pressure, cataract |
Very rare |
|
These events have been identified from spontaneous reports following prolonged treatment. | ||
|
Respiratory, Thoracic & Mediastinal disorders |
Epistaxis |
Very common |
|
Nasal dryness, nasal irritation, throat dryness, throat irritation. |
Common | |
|
Nasal septal perforation, mucocutaneous ulceration |
Very rare | |
|
Usually in patients who have hadprevious nasal surgery. |
Systemic effects of some nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.
Paediatric population
Some nasal corticosteroids have been reported to produce growth retardation in children when prescribed at licensed doses. It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored.
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
There are no data available on the effects of acute or chronic overdose with Nasofan Aqueous 50 microgram Nasal Spray. Intranasal administration of 2 milligrams fluticasone propionate twice daily for seven days to healthy human volunteers has no effect on hypothalamo-pituitary-adrenal (HPA) axis function.
Inhalation or oral administration of high doses of corticosteroids over a long period 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: R01AD08
Clinical efficacy and safety
Fluticasone propionate causes little or no hypothalamic-pituitary-adrenal axis suppression following intranasal administration.
Following intranasal dosing of fluticasone propionate, (200mcg/day) no significant change in 24h serum cortisol AUC was found compared to placebo (ratio1.01, 90%CI 0.9-1.14).
Paediatric population
In a 1-year randomised, double-blind, placebo-controlled, parallel group growth study in pre-pubescent children aged 3 to 9 years (56 patients receiving intranasal fluticasone propionate and 52 receiving placebo) no statistically significant difference in growth velocity was observed in patients receiving intranasal fluticasone propionate (200 micrograms per day nasal spray) compared to placebo. The estimated growth velocity over one year of treatment was 6.20 cm/year (SE=0.23) in the placebo group and 5.99 cm/year (SE=0.23) in the fluticasone propionate group; the mean difference between treatments in growth velocity after one year was 0.20 cm/year (SE=0.28, 95% CI= -0.35, 0.76). No evidence of clinically relevant changes in HPA axis function or bone mineral density was observed as assessed by 12-hour urinary cortisol excretion and dual-energy x-ray absorptiometry, respectively.
5.2 Pharmacokinetic properties
Absorption
Following intranasal dosing of fluticasone propionate, (200mcg/day) steady-state maximum plasma concentrations were not quantifiable in most subjects (<0.01ng/mL). The highest Cmax observed was 0.017ng/mL. Direct absorption in the nose is negligible due to the low aqueous solubility with the majority of the dose being eventually swallowed. When administered orally the systemic exposure is <1% due to poor absorption and pre-systemic metabolism. The total systemic absorption arising from both nasal and oral absorption of the swallowed dose is therefore negligible.
Distribution
Fluticasone propionate has a large volume of distribution at steady-state (approximately 318L). Plasma protein binding is moderately high (91%).
Biotransformation
Fluticasone propionate is cleared rapidly from the systemic circulation, principally by hepatic metabolism to an inactive carboxylic acid metabolite, by the cytochrome P450 enzyme CYP3A4. Swallowed fluticasone propionate is also subject to extensive first pass metabolism. Care should be taken when co-administering potent CYP3A4 inhibitors such as ketoconazole and ritonavir as there is potential for increased systemic exposure to fluticasone propionate.
Elimination
The elimination rate of intravenous administered fluticasone propionate is linear over the 250—1000mcg dose range and are characterised by a high plasma clearance (CL=1.1L/min). Peak plasma concentrations are reduced by approximately 98% within 3-4 hours and only low plasma concentrations were associated with the 7.8h terminal half-life. The renal clearance of fluticasone propionate is negligible (<0.2%) and less than 5% as the carboxylic acid metabolite. The major route of elimination is the excretion of fluticasone propionate and its metabolites in the bile.
5.3 Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Glucose, anhydrous Dispersible Cellulose Phenylethyl Alcohol
Benzalkonium Chloride solution (40 micrograms per delivered dose) Polysorbate 80 Purified Water
6.2 Incompatibilities
Not applicable.
6.3 Shelf life 3 years.
6.4 Special precautions for storage
Do not store above 25°C
6.5 Nature and contents of container
12 ml or 15ml amber glass bottle [Type III] fitted with an atomising metering pump.
Pack sizes: 60, 120, 150, 240 (2 bottles each containing 120 sprays) and 360 (3 bottles each containing 120) metered sprays.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
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
Norton Healthcare Limited, t/a IVAX Pharmaceuticals UK,
Ridings Point Whistler Drive Castleford
West Yorkshire WF10 5HX UNITED KINGDOM
8. MARKETING AUTHORISATION NUMBER
PL 00530/0745
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12/05/2005 / 11/05/2010
10 DATE OF REVISION OF THE TEXT
12/02/2016