Flonase 24 hour (Flixonase)

Fluticasone propionate (50mcg per actuation) Aqueous Nasal Spray

Qualitative and Quantitative Composition

Flixonase (Flonase) 24 hour (0.05% w/w) is a white, opaque, aqueous suspension of microfine fluticasone propionate for topical administration to the nasal mucosa by means of a metering, atomising spray pump. Each 100mg of spray delivered by the nasal actuator contains 50 micrograms of fluticasone propionate.

Nasal spray, suspension

Flixonase (Flonase) 24 hour is indicated for the short term (3-6 months) prevention and treatment of seasonal allergic rhinitis including hayfever. Fluticasone propionate has potent anti-inflammatory activity but when used topically on the nasal mucosa has no detectable systemic activity.

Flixonase (Flonase) 24 hour is for administration by the intranasal route only.

Two sprays into each nostril once a day, preferably in the morning. The maximum daily dose should not exceed two sprays into each nostril.

The normal adult dosage is applicable.

For full therapeutic benefit regular usage is essential. The absence of an immediate effect should be explained to the patient as maximum relief may not be obtained until after 3 to 4 days of treatment.

Do not use continuously for more than 6 months without consulting your doctor.

Flixonase (Flonase) 24 hour is contra-indicated in patients with a hypersensitivity to any of its ingredients.

Local infection: Infections of the nasal airways should be appropriately treated but do not constitute a specific contra-indication to treatment with Flixonase (Flonase) 24 hour.

The full benefit of Flixonase (Flonase) 24 hour may not be achieved until treatment has been administered for several days.

Care must be taken while transferring patients from systemic steroid treatment to Flixonase (Flonase) 24 hour if there is any reason to suppose that their adrenal function is impaired.

Although Flixonase (Flonase) 24 hour will control seasonal allergic rhinitis in most cases, an abnormally heavy challenge of summer allergens may in certain instances necessitate appropriate additional therapy, particularly to control eye symptoms.

There is inadequate evidence of safety 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.

However, as with other medicines the use of Flixonase (Flonase) 24 hour during human pregnancy requires that the benefits be weighed against the possible risks associated with the product or with any alternative therapy.

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 low.

None reported.

Due to very low plasma concentrations achieved after intranasal dosing, clinically significant drug interactions are unlikely. Care should be taken when co-administering known strong CYP3A4 inhibitors (eg. ketoconazole, ritonavir) as there is a potential for increased systemic exposure to fluticasone propionate.

As with other nasal sprays, dryness and irritation of the nose and throat, unpleasant taste and smell, headache and epistaxis have been reported.

Hypersensitivity reactions including skin rash and oedema of the face or tongue have been reported. There have also been rare reports of anaphylaxis/anaphylactic reactions and bronchospasm.

Extremely rare cases of nasal septal perforation have been reported following the use of intranasal corticosteroids.

There are no data available on the effects of acute or chronic overdosage with Flixonase (Flonase) 24 hour. Intranasal administration of 2mg fluticasone propionate twice daily for seven days to healthy human volunteers had no effect on hypothalamic-pituitary-adrenal axis function.

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).

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.

Fluticasone propionate has a large volume of distribution at steady-state (approximately 318L). Plasma protein binding is moderately high (91%).

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 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 7.8h 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.

Toxicology has shown only those 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, reproductive toxicology studies or teratology studies.

Fluticasone propionate is devoid of mutagenic activity in vitro and in vivo and showed no tumorigenic potential in rodents. It is both non irritant and non sensitising in animal models.

Shake gently before use.

Dextrose (anhydrous)
Microcrystalline cellulose
Carboxymethylcellulose sodium
Phenylethyl alcohol
Benzalkonium chloride
Polysorbate 80
Dilute hydrochloric acid
Purified water

24 months

Storage conditions:

Store below 25°C.

Package quantities:

Flixonase (Flonase) 24 hour is supplied in an amber glass bottle fitted with a metering, atomising pump, nasal adaptor and a dust cover. Each bottle provides approximately 120 metered sprays, when used as recommended.

Medicines classification

Pharmacist Only Medicine

Date of Preparation

Date: 21 March 2001

Flixonase is a trade mark of the Glaxo Wellcome Group of Companies.