GlaxoSmithKline Consumer Healthcare (Ireland) Ltd

Flixonase Allergy Relief 50 micrograms per dose Nasal Spray

Each actuation delivers 100mg of suspension containing 50 micrograms of fluticasone propionate.

Excipients: also includes 20 micrograms of Benzalkonium Chloride per spray.

For a full list of excipients, see 6.1.

Nasal spray, suspension

A white, opaque aqueous suspension intended for intranasal administration.

Flixonase Allergy Relief 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 and animal dander.

Flixonase Allergy Relief is for administration by the intranasal route only.

Adults and Children over 12 years of age for the prophylaxis and treatment of allergic rhinitis:

Two sprays into each nostril once a day, preferably in the morning. Once control is achieved the dose should be titrated down to the lowest effective dose of one spray in each nostril once a day (100mcg 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 to the lowest effective dose (see above).

The maximum daily dose should not exceed four sprays into each nostril.

Elderly Patients:

The normal adult dosage is applicable.

Children under 12 years of age:

Treatment should not be initiated without the advice of a physician.

Onset of action in the treatment of allergic rhinitis has been observed as early as 2-4 hours after use, with most users achieving symptomatic relief within 12 hours of treatment. Maximum benefit may require 3-4 days of continuous treatment in some people (see section 5.1 Pharmacodynamic Properties).

When Flixonase Allergy Relief is discontinued, it may be several days before symptoms recur.

Flixonase Allergy Relief is contra-indicated in patients with a hypersensitivity to any of its ingredients.

Consumers will be advised that if improvement is not seen within 7 days of continuous use they should stop treatment and seek the advice of a doctor.

Consumers will be advised that if after 7 days of continuous use, their symptoms have improved but are not adequately controlled then they should seek the advice of a pharmacist or doctor, who may provide additional treatment.

Consumers will be advised not to use Flixonase Allergy Relief for more than 6 months continuously.

Consumers will be advised to seek medical advice before using Flixonase Allergy Relief if:

• they are using another corticosteroid product, such as tablets, creams, ointments, asthma medications, similar nasal sprays or eye/nose drops.

• they have an infection in the nasal passages or sinuses.

• they have recently had an injury or surgery to the nose, or problems with ulceration in the nose.

A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3 A4 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 flucticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side-effects.

Under normal circumstances, very low plasma concentrations of flucticasone 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.

Pregnancy: There is inadequate evidence of safety in human pregnancy. In animal reproduction studies adverse effects typical of potent corticosteroid are only seen at high systemic exposure levels; direct intranasal application ensures minimal systemic exposure.

The use of Fluticasone Propionate Allergy Relief during human pregnancy should be avoided unless thought essential by the doctor. Consumers should be advised to seek a medical opinion before using Flixonase Allergy Relief if they are pregnant or breast-feeding.

None reported.

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 are 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.

There is no data available on the effects of acute or chronic overdosage with Flixonase Allergy Relief. Intranasal administration of fluticasone propionate at 20 times the recommended dose in adults (2mg twice daily) for seven days to healthy human volunteers had no effect on hypothalamic-pituitary-adrenal axis function.

Fluticasone propionate is a glucocorticosteroid, which has potent anti-inflammatory activity by acting via the glucocorticoid receptor. However, when used at up to four times the recommended daily dose on the nasal mucosa, has no detectable systemic activity and causes little or no hypothalamic pituitary adrenal (HPA) axis suppression. 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).

Fluticasone propionate has been shown to significantly reduce inflammatory mediators in both the early and late phase reactions of allergic rhinitis. Placebo-controlled clinical studies have demonstrated that intranasal fluticasone propionate significantly reduces the symptoms of allergic rhinitis.

In addition, comparator studies have shown that intranasal fluticasone propionate is more effective in treating nasal symptoms of allergic rhinitis than anti-histamines, but with a similar beneficial effect on eye symptoms.

As with other aqueous nasal sprays, fluticasone propionate has an immediate 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 use. However, most users experience symptomatic relief within 12 hours of starting treatment. Maximum relief may require 34 days of continuous treatment in some people.

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, (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%).

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 2501000mcg 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.

No clinically relevant findings were observed in preclinical studies.

Glucose (Anhydrous)

Microcrystalline Cellulose and Carboxymethylcellulose (Carmellose) Sodium (Avicel RC591)

Phenylethyl Alcohol

Benzalkonium Chloride

Polysorbate 80

Dilute Hydrochloric Acid

Purified Water

Not applicable.

2 years.

Do not store above 30°C. Do not refrigerate.

Flixonase Allergy Relief is supplied in an amber glass Type I or III (Ph. Eur.) bottle fitted with a metering, atomising pump, nasal adapter and a dust cover.

Each bottle provides approximately 60 metered sprays, when used as recommended.

Shake gently before use.

GlaxoSmithKline Consumer Healthcare (Ireland) Ltd

Stonemasons Way

Rathfarnham

Dublin 16

Ireland

Trading as: Allen & Hanburys

PA 678/95/1

Date of first authorisation: 02 May 2003

Date of last renewal: 02 May 2008

October 2009