Aqueous Nasal Spray, suspension Fluticasone propionate 50 mcg per actuation
Indications
Flixonase Allergy & Hayfever 24 Hour is indicated for the prophylaxis and treatment of allergic rhinitis including hay fever and that caused by other airborne allergens such as house dust mite, mould spores and animal dander. During treatment Flixonase Allergy & Hayfever 24 Hour provides symptomatic relief of sneezing, itchy and runny nose, congestion including associated sinus discomfort and pressure around the nose and eyes. Flixonase Allergy & Hayfever 24 Hour also provides relief of ocular symptoms associated with allergic rhinitis.
Flixonase Allergy & Hayfever 24 Hour is for administration by the intranasal route only.
Adults and children 12 years and over: For the prophylaxis and treatment of allergic rhinitis:-
The recommended dose is two sprays into each nostril once a day, preferably in the morning. Once control is achieved the dose should be titrated down to one spray in each nostril once a day (100 micrograms per day). In some cases two sprays into each nostril twice daily may be required for short periods to achieve control of symptoms, after which the dose should be titrated down.
The maximum daily dose should not exceed four sprays into each nostril.
Onset of action in the treatment of allergic rhinitis has been observed in some patients as early as 2-4 hours after use, with most users achieving symptomatic relief within 12 hours of treatment. Prophylaxis of allergic rhinitis requires treatment before contact with allergen.
For full therapeutic benefit regular usage is recommended.
Maximum benefit may require 3-4 days of continuous treatment in some people (Pharmacodynamic Properties).
Children under 12 years of age:-
Treatment should not be initiated without the advice of a physician.
The normal adult dosage is applicable.
FLIXONASE Allergy & Hayfever 24 Hour is contra-indicated in patients with a hypersensitivity to fluticasone propionate or any other of the ingredients.
If improvement is not seen within 7 days of continuous use treatment should be stopped and the advice of a doctor sought. If after 7 days of continuous use, symptoms have improved but are not adequately controlled then the advice of a pharmacist or doctor should be sought. The nasal spray should not be used for more than 6 months continuously without consulting a doctor. Local infection: Infections of the nasal airways should be appropriately treated but do not constitute a specific contraindication to treatment with intranasal fluticasone propionate. Care must be taken when withdrawing patients from systemic steroid treatment, and commencing therapy with intranasal fluticasone propionate, particularly if there is any reason to suspect that their adrenal function is impaired. 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. Medical advice should be sought before using Flixonase Allergy & Hayfever 24 Hour in the case of:
Concomitant use of other corticosteroid products, such as tablets, creams, ointments, asthma medications, similar nasal sprays or eye/nose drops. Fever or an infection in the nasal passages or sinuses. Recent injury or surgery to the nose, or problems with ulceration in the nose. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects (see Interactions). The full benefit of fluticasone propionate aqueous nasal spray may not be achieved until treatment has been administered for several days. Although fluticasone propionate aqueous nasal spray will control seasonal allergic rhinitis in most cases, an abnormally heavy challenge of summer allergens may in certain instances necessitate appropriate additional therapy.
Use in Pregnancy & Lactation
As with other drugs, the use of intranasal fluticasone propionate during pregnancy and lactation requires that the benefits be weighed against possible risks associated with the product or with any alternative therapy.
Pregnancy
(Category B3)
There is inadequate evidence of the safety of fluticasone propionate in human pregnancy. In animal reproduction studies, adverse effects typical of potent corticosteroids are only seen at high systemic exposure levels; direct intranasal application ensures minimal systemic exposure. The use of Flixonase Allergy & Hayfever 24 Hour should be avoided during pregnancy unless thought essential by the doctor. Medical advice should be sought before use if pregnant.
Lactation
Medical advice should be sought before use if breast-feeding. The excretion of fluticasone propionate into human breast milk has not been investigated. When measurable plasma levels were obtained in lactating laboratory rats following subcutaneous administration, there was evidence of fluticasone propionate in the breast milk. However, plasma levels in patients following intranasal application of fluticasone propionate at recommended doses are likely to be very low.
Effects on ability to drive and use machines
Fluticasone propionate is unlikely to produce an effect.
Under normal circumstances, very low plasma concentrations of fluticasone propionate are achieved after intranasal dosing, due to extensive first pass metabolism and high systemic clearance mediated by cytochrome P450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely. A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations. During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing's syndrome and adrenal suppression. Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects. Studies have shown that 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. Nevertheless, care is advised when co-administering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole), as there is potential for increased systemic exposure to fluticasone propionate.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>=1/10), common (>=1/100 and <1/10), uncommon (>=1/1000 and <1/100), rare (>=1/10,000 and <1/1000) and very rare (<1/10,000) including isolated reports. Very common, common and uncommon events were generally determined from clinical trial data. Rare and very rare events were generally determined from spontaneous data. In assigning adverse event frequencies, the background rates in placebo groups were not taken into account, since these rates were generally comparable to those in the active treatment group.
Immune system disorders
Very rare:Hypersensitivity reactions, anaphylaxis/anaphylactic reactions, bronchospasm, skin rash, oedema of the face or tongue.
Nervous system disorders
Common:Headache, unpleasant taste, unpleasant smell. As with other nasal sprays, unpleasant taste and smell and headache have been reported.
Eye disorders
Very rare:Glaucoma, raised intraocular pressure, cataract. A very small number of spontaneous reports have been identified following prolonged treatment. However, clinical trials of up to one year duration have shown that intranasal fluticasone propionate is not associated with an increased incidence of ocular events including cataract, increased intraocular pressure or glaucoma.
Respiratory, thoracic and mediastinal disorders
Very common:Epistaxis. Common:Nasal dryness, nasal irritation, throat dryness, throat irritation. Very rare:Nasal septal perforation. As with other nasal sprays, dryness and irritation of the nose and throat, and epistaxis have been reported. Nasal septal perforation has also been reported following the use of intranasal corticosteroids.
Administration of doses higher than those recommended over a long period of time may lead to temporary suppression of adrenal function.
There are no data from patients available on the effects of acute or chronic overdosage with intranasal fluticasone propionate. In healthy volunteers, intranasal administration of 2 mg fluticasone propionate twice daily for seven days had no effect on hypothalamic-pituitary-adrenal (HPA) axis function (this equates to 20 times the recommended dose).
ATC Code
R01A D08
Mechanism of Action
Fluticasone propionate is a glucocorticosteroid which has potent anti- inflammatory activity by acting via the glucocorticoid receptor. It has no detectable systemic activity and causes little or no hypothalamic pituitary adrenal (HPA) axis suppression. Following intranasal dosing of fluticasone propionate (200 mcg/day) no significant change in 24h serum cortisol AUC was found compared to placebo (ratio 1.01,90%CI 0.9-1.14).
Pharmacodynamic Effects
Fluticasone propionate has been shown to significantly reduce inflammatory mediators in both the early and late phase reactions of allergic rhinitis. As with other aqueous nasal sprays, Flixonase Allergy & Hayfever 24 Hour has an immediate soothing and cooling lavage effect in the nose, and onset of action has been observed in clinical trials to be as early as 2-4 hours after first use. Symptom relief (particularly of nasal congestion) is sustained for 24 hours following once daily administration of 200 mcg doses. Quality of life studies have shown fluticasone propionate, when compared with placebo and antihistamine, to improve patient's routine functioning, including physical and social functioning, and sense of well-being as exemplified by effects on indicators of emotional health, mental health, and energy. In addition, patients receiving fluticasone propionate report superior impact (as compared to placebo and antihistamine) on work and school attendance and performance, and home and leisure/recreation activities affected as a result of symptoms of allergic rhinitis.
Absorption
Following intranasal dosing of fluticasone propionate, (200 mcg/day) steady- state maximum plasma concentrations were not quantifiable in most subjects (<0.01 ng/ml). The highest Cmax observed was 0.017 ng/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 318 L). Plasma protein binding is moderately high (91%).
Metabolism
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 250-1000 mcg dose range and are characterized 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 7.8 h 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.
Pre-clinical Information
Toxicology studies in animals, including reproductive and development toxicology studies, have shown class effects typical of a potent corticosteroid, and these only at doses greatly in excess of those proposed for therapeutic use. No novel effects were identified in repeat dose toxicity tests. Fluticasone propionate is devoid of mutagenic activity in vitro and in vivo and showed no tumorigenic potential in rodents. It is both non irritating and non sensitising in animal models.
Chemical Structure
Shelf-Life
Three years.
Storage
Do not store above 30degC
PHARMACY MEDICINE
FLIXONASE ALLERGY & HAYFEVER 24 HOUR is supplied in a plastic bottle fitted with a metering, atomising pump, nasal adaptor and a dust cover. Each bottle provides approximately 120 metered sprays, when used as recommended.
Instructions for Use/Handling:
Shake gently before use.
List of Excipients:
Dextrose (anhydrous) Microcrystalline cellulose Carboxymethylcellulose sodium Phenylethyl alcohol Benzalkonium chloride Polysorbate 80 Dilute hydrochloric acid Purified water
GlaxoSmithKline (NZ) Ltd trading as GlaxoSmithKline Consumer Healthcare Auckland, New Zealand Telephone: (09) 367 2970
July 2012 Issue: 19 FLIXONASE(r) is a registered trade mark of the GlaxoSmithKline group of companies.