Consumer medicine information

Flixonase Allergy & Hayfever 24 Hour

Fluticasone propionate

BRAND INFORMATION

Brand name

Flixonase Allergy & Hayfever 24 Hour

Active ingredient

Fluticasone propionate

Schedule

S2

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Flixonase Allergy & Hayfever 24 Hour.

What is in this leaflet?

Please read this leaflet carefully before you use FLIXONASE ALLERGY & HAYFEVER 24 HOUR.

This leaflet answers some common questions about FLIXONASE ALLERGY & HAYFEVER 24 HOUR. It does not contain all of the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What FLIXONASE ALLERGY & HAYFEVER 24 HOUR is used for

FLIXONASE ALLERGY & HAYFEVER 24 HOUR contains a corticosteroid called fluticasone propionate, which treats inflamed tissue. The tiny amounts sprayed into your nose help to reduce swelling and irritation.

FLIXONASE ALLERGY & HAYFEVER 24 HOUR is used to prevent and treat seasonal allergic rhinitis (e.g. hayfever) and perennial rhinitis in adults aged 18 years and over.

Use only on medical advice in adolescents aged 12 - 17 years.

Do not use in children under 12 years of age.

When you have rhinitis, the inside of your nose becomes swollen and itchy. This usually occurs during spring and summer when it is caused by breathing pollens from grasses or trees. This condition is called hayfever.

Some people get problems all the year round and this is called perennial rhinitis. It is often due to house dust mites or animals such as cats or dogs.

When you spray FLIXONASE ALLERGY 24 HOUR into your nose it helps to relieve the itching, sneezing and blocked or runny nose.

Ask your pharmacist or doctor if you have any questions or if you aren't sure why FLIXONASE ALLERGY & HAYFEVER 24 HOUR has been recommended for you.

FLIXONASE ALLERGY & HAYFEVER 24 HOUR is not addictive.

Before you use FLIXONASE ALLERGY & HAYFEVER 24 HOUR

When you must not use it

  • Do not use FLIXONASE ALLERGY & HAYFEVER 24 HOUR if you have ever had an allergic reaction to fluticasone propionate, an allergic reaction to any other corticosteroid or any of the ingredients listed at the end of this leaflet.
  • Read the side effects section to find out the symptoms of an allergic reaction.
  • Do not use FLIXONASE ALLERGY & HAYFEVER 24 HOUR after the expiry date (EXP) printed on the pack.
  • If you use it after the expiry date has passed, it may not work as well.
  • Do not use FLIXONASE ALLERGY & HAYFEVER 24 HOUR if the packaging is torn or shows signs of tampering.
    If you're not sure whether you should be using FLIXONASE ALLERGY & HAYFEVER 24 HOUR, talk to your pharmacist or doctor.

Before you start to use it

You must tell your Pharmacist or doctor if You:

  • Are pregnant or planning to become pregnant
  • Are breastfeeding
  • Have recently had nasal ulcers, injury or surgery to your nose
  • Have a tendency to nose bleeds
  • Have or have recently suffered from a nasal infection in or around the nose
  • Have a high temperature, cold or have been diagnosed with a sinus infection.
  • Are taking ritinovir (used to treat HIV)
  • Are using ketoconozole (used to treat infections)
  • Are using other corticosteroids which may include some eczema creams, asthma inhalers, tablets, injections, nasal sprays and eye or nose drops.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop Some medicines may affect the way other medicines work. Your doctor or pharmacist will be able to tell you what to do when using FLIXONASE ALLERGY & HAYFEVER 24 HOUR with other medicines.

How to use FLIXONASE ALLERGY & HAYFEVER 24 HOUR

How much to use

If your FLIXONASE ALLERGY & HAYFEVER 24 HOUR is new and you have not used it before, or if you have not used it for one week or more, you should activate six sprays into the air before use.

For adults aged 18 and over, the usual dose is two sprays into each nostril once daily, preferably in the morning.

FLIXONASE Allergy & Hayfever 24 Hour quickly starts to reduce inflammation and swelling in your nose, although it may take a few days to significantly improve symptoms.

Therefore to prevent the onset of symptoms, start to use FLIXONASE Allergy & Hayfever 24 Hour a few days before expected exposure to one of your 'usual' triggers.

It may take a few days for this medicine to work and it is VERY IMPORTANT THAT YOU USE IT REGULARLY. If you stop the treatment when you feel better your symptoms may return as the medication wears off.

If your symptoms include watery eyes and they trouble you, advise your doctor or pharmacist.

Once your symptoms have improved you may be able to halve the dose to one spray into each nostril once a day. If symptoms get worse again, the dosage may be increased to two sprays into each nostril once a day. Try to use the lowest dose to control your symptoms.

Do not use a larger dose or use your nasal spray more often than recommended in the instruction leaflet. Do not use more than 2 sprays in each nostril daily.

If after 7 days your symptoms have not improved, stop using the spray and speak to your doctor.

If after 7 days your symptoms have improved but not enough, speak to your doctor or pharmacist for advice.

Use only on medical advice in adolescents aged 12 - 17 years.

Do not use in children under 12 years of age.

Intranasal corticosteroids may cause children to grow more slowly.

Do not use for more than 6 months continuously without the advice of a doctor.

If you use too much (overdose)

If you or someone else accidentally uses too much FLIXONASE Allergy & Hayfever 24 Hour on one occasion, there is nothing to worry about. However, if you use too much of it over a long time (months or years) you may start to get unwanted side effects inside your nose and body.

Discuss any worries you may have about this with your doctor or pharmacist.

In case of overdose or poisoning contact a doctor or a Poisons Information Centre (telephone Australia 131126; New Zealand 0800 764 766).

Using the spray

  1. Shake the bottle and remove the cap. Prime the bottle by pumping the spray a few times until a fine mist is produced.
  2. Blow your nose gently.
  3. Close one nostril as shown and put the nozzle in the other nostril. Tilt your head forward slightly and keep the bottle upright.
  4. Start to breathe in slowly through your nose. While you are breathing in squirt a spray of fine mist into your nostril by pressing down firmly on the collar with your fingers.
  5. Breathe out through your mouth. Repeat step 4 to take a second spray in the same nostril.
  6. Remove the nozzle from this nostril and breathe out through your mouth.
  7. Repeat steps 3 to 6 for the other nostril.

AFTER USING THE SPRAY WIPE THE NOZZLE CAREFULLY WITH A CLEAN TISSUE OR HANDKERCHIEF, AND REPLACE THE CAP.

Discard 3 months after first use.

How long to use the spray

Your pharmacist or doctor will tell you how long to use your FLIXONASE ALLERGY 24 HOUR FLUTICASONE for.

Do not use the spray for more than 6 months without the advice of your doctor or pharmacist.

If you forget to use the spray

If you miss a dose, just use the next one when it is due.

While you are using FLIXONASE ALLERGY & HAYFEVER 24 HOUR

Things you must do

Tell your doctor or pharmacist that you are using FLIXONASE ALLERGY & HAYFEVER 24 HOUR if you are about to be started on any new medicines.

Tell your pharmacist or doctor if, for any reason, you have not used your medicine exactly as recommended.

Use FLIXONASE ALLERGY & HAYFEVER 24 HOUR only in your nose.

Things you must not do

Do not give this medicine to anyone else, even if his or her symptoms seem similar to yours.

Do not use FLIXONASE ALLERGY & HAYFEVER 24 HOUR to treat any other conditions unless advised by your doctor to do so.

Side effects

Check with your pharmacist or doctor as soon as possible if you have any problems while using FLIXONASE ALLERGY & HAYFEVER 24 HOUR, even if you do not think the problems are related to the medicine or are not listed in this leaflet.

See your doctor or pharmacist if:

  • You develop signs or symptoms of a nasal or sinus infection such as fever, pain or swelling, or discoloured nasal discharge.

Like other medicines, FLIXONASE ALLERGY & HAYFEVER 24 HOUR can cause some side effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and may need medical attention.

The most commonly reported side-effects are:

  • dry or irritated nose or throat
  • nosebleeds
  • bad taste or smell
  • headache
  • sores in the nose

If any of these side effects persist, or are troublesome, see your doctor.

Stop using your spray and contact your doctor immediately if:

  • You get new changes to your vision, including blurred vision, that develop after starting this product. There have been rare reports of eye problems such as cataracts, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) in people who have used large amounts of corticosteroids over a period of several years.
  • You develop small holes (perforations) in the ridge inside the nose that separates the nostrils.
  • You experience an allergic reaction.

If you think you are having an allergic reaction to FLIXONASE ALLERGY & HAYFEVER 24 HOUR, TELL YOUR DOCTOR IMMEDIATELY or go to the emergency department at your nearest hospital.

Symptoms of an allergic reaction include skin rashes and itching, sometimes with breathing problems or swelling of the lips, tongue, throat or face.

This is not a complete list of all possible side effects. Others may occur in some people and there may be some side effects not yet known.

Tell your pharmacist or doctor if you notice anything else that is making you feel unwell, even if it is not on this list.

Ask your doctor or pharmacist if you don't understand anything in this list.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using FLIXONASE ALLERGY & HAYFEVER 24 HOUR

Storage

Keep this medicine where young children cannot reach it.

Keep FLIXONASE ALLERGY & HAYFEVER 24 HOUR below 30°C.

Protect it from frost and light.

Do not freeze.

Do not store it, or any other medicine, in a bathroom or near a sink. Heat and dampness can destroy some medicines.

Keep your FLIXONASE ALLERGY & HAYFEVER 24 HOUR in its pack until it is time to take it. If you take the product out of its packaging it may not keep well.

Disposal

If your doctor tells you to stop using FLIXONASE ALLERGY & HAYFEVER 24 HOUR, or the Product has passed its expiry date, ask your pharmacist what to do with any FLIXONASE ALLERGY & HAYFEVER 24 HOUR left over.

Discard 3 months after first use.

Product description

What Flixonase Allergy & Hayfever 24 Hour looks like

FLIXONASE ALLERGY & HAYFEVER 24 HOUR is contained in a brown glass bottle fitted with a metering pump, a nasal adaptor and a dust cover containing around 60 or 120 sprays.

All pack sizes may not be marketed.

Ingredients

FLIXONASE ALLERGY & HAYFEVER 24 HOUR contains the active ingredient fluticasone propionate. It also contains the following inactive ingredients:

Dispersible cellulose, sodium carboxymethylcellulose, anhydrous glucose, polysorbate 80, hydrochloric acid (to adjust pH), purified water, benzalkonium chloride, phenethyl alcohol.

Manufacturer/Distributor/Supplier

FLIXONASE Allergy & Hayfever is supplied by:

GlaxoSmithKline Consumer Healthcare,
82 Hughes Avenue
Ermington NSW 2115 Australia & Auckland, New Zealand.

Freecall
1800 028 533 (Australia only)
0800 540 144 (New Zealand only)

FLIXONASE Allergy & Hayfever 24 Hour has an Australian Registration number of AUST R 72724.

Trademarks are owned by or licensed to the GSK group of companies

This leaflet was prepared in January 2019.

Published by MIMS October 2019

BRAND INFORMATION

Brand name

Flixonase Allergy & Hayfever 24 Hour

Active ingredient

Fluticasone propionate

Schedule

S2

 

1 Name of Medicine

Fluticasone propionate.

2 Qualitative and Quantitative Composition

Active ingredients: Flixonase Allergy & Hayfever 24 Hour nasal spray (0.05% w/w) is an aqueous suspension of microfine fluticasone propionate for topical administration to the nasal mucosa by means of a metering, atomising spray pump. Each 100 mg of spray delivered by the nasal adaptor contains 50 microgram of fluticasone propionate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Aqueous suspension of microfine fluticasone propionate. Each 100 mg of spray contains 50 micrograms of fluticasone propionate. Nasal spray, suspension.

4 Clinical Particulars

4.1 Therapeutic Indications

Flixonase Allergy & Hayfever 24 Hour nasal spray is indicated for the prophylaxis and treatment of allergic rhinitis for up to 6 months in adults 18 years and over.

4.2 Dose and Method of Administration

Flixonase Allergy & Hayfever 24 Hour is for administration by the intranasal route only.

Adults 18 years and over.

For the prophylaxis and treatment of seasonal allergic rhinitis and perennial rhinitis.

The recommended dose is two sprays into each nostril once a day (200 microgram per 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 microgram per day).
Although some beneficial effects may be seen within 24 hours, for full therapeutic benefit daily 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.
The maximum daily dose should not exceed four sprays (200 microgram) into each nostril.
Prophylaxis of allergic rhinitis requires treatment before contact with allergen.
For full therapeutic benefit regular usage is essential.

4.3 Contraindications

Fluticasone propionate aqueous nasal spray is contraindicated in patients with a hypersensitivity to any of its ingredients, or a history of allergic reaction to other corticosteroid medicines.

4.4 Special Warnings and Precautions for Use

Identified precautions.

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 fluticasone propionate aqueous nasal spray.
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 have been reported, 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.
Reduced growth velocity has been observed in children treated with intranasal corticosteroids.
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 postmarketing 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 Section 4.5 Interactions with Other Medicines and Other Forms of 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, particularly to control eye symptoms.
Rare instances of glaucoma and increased intraocular pressure have been reported following administration of intranasal corticosteroids, as a class effect.
Candidiasis of the throat can occur in patients treated with intranasal steroids. Special care should be taken when treating patients who may be susceptible to candida infections (e.g. diabetics).
Because of the inhibitory effect of these drugs on wound healing, patients with recent nasal septal ulcers, nasal surgery or nasal trauma should not use intranasal corticosteroids until healing has occurred.

Visual disturbance.

Visual disturbance may be reported with systemic and topical 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 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.

Adrenocortical function.

Intranasal steroid products are designed to deliver drug directly to the nasal mucosa in order to minimise overall systemic glucocorticoid exposure and side effects. However systemic effects such as HPA axis suppression, reduction of bone density and retardation of growth rate in children may occur with intranasal steroids, particularly at high doses prescribed for prolonged periods of time.
The lowest dose of Flixonase Allergy & Hayfever 24 Hour nasal spray that causes suppression of the HPA axis or effects on bone mineral density or growth retardation has not yet been established. However, the systemic bioavailability of fluticasone propionate is low (estimated at 1.26% using high doses), when given as Flixonase Allergy & Hayfever 24 Hour nasal spray, and this limits the potential for such systemic side effects. Measurement of serum cortisol and 24 hour urinary cortisol in the clinical studies in adults did not suggest any HPA axis suppression with recommended doses. Studies of effects on the HPA axis in children have not been conducted.

Use in hepatic impairment.

No data is available.

Use in renal impairment.

No data is available.

Use in the elderly.

The normal adult dosage is applicable.

Paediatric use.

Adolescents 12-17 years.

Use only on medical advice.
Do not use in children under 12 years of age.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

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 postmarketing 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 coadministering potent cytochrome P450 3A4 inhibitors (e.g. ketoconazole), as there is potential for increased systemic exposure to fluticasone propionate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category B3)
The use of intranasal fluticasone propionate during pregnancy requires that the benefits be weighed against possible risks associated with the product or with any alternate therapy.
There is insufficient evidence of safety of fluticasone propionate in human pregnancy. Systemically absorbed corticosteroids are known to induce foetotoxic and teratogenic effects in rodent studies. However, equivalent effects have not been reported when these compounds have been given to humans during pregnancy. Reproductive toxicity studies with fluticasone propionate in mice and rats have shown the expected foetotoxic and teratogenic effects at subcutaneous doses of 100 to 150 microgram/kg/day and above. As with previous compounds of this class, these effects are unlikely to be relevant to human therapy. Direct intranasal application ensures minimal systemic exposure.
The use of Flixonase Allergy & Hayfever 24 Hour nasal spray during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus. Medical advice should be sought before use if pregnant.
 The use of intranasal fluticasone propionate during lactation requires that the benefits be weighed against possible risks associated with the product or with any alternate therapy.
The excretion of fluticasone propionate into human breast milk has not been investigated. Subcutaneous administration of titrated drug to lactating rats resulted in measurable radioactivity in both plasma and milk (levels in milk were 3-7 times plasma levels) 1-8 hours postdosing. However, plasma levels in patients following intranasal application of fluticasone propionate at recommended doses are low and the amount of fluticasone ingested by the newborn is estimated to be very small as a consequence of very low maternal plasma concentration.
Medical advice should be sought before use if breastfeeding.

4.7 Effects on Ability to Drive and Use Machines

Fluticasone propionate is unlikely to affect the ability to drive or use machinery.

4.8 Adverse Effects (Undesirable Effects)

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 www.tga.gov.au/reporting-problems.
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.

Eye disorders.

Very rare: glaucoma, raised intraocular pressure, cataract.
Not known: vision blurred.

Respiratory, thoracic and mediastinal disorders.

Very common: epistaxis.
Common: nasal dryness, nasal irritation, throat dryness, throat irritation.
Very rare: nasal septal perforation, nasal ulcer.

4.9 Overdose

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. Intranasal administration of 2400 microgram fluticasone per day (i.e. 12 times the recommended dose) for four days to healthy human volunteers caused a small degree of suppression of adrenal steroid production.
Suppression of adrenal steroid production may give rise to typical signs and symptoms of Cushing's disease, such as buffalo hump, puffiness of face, hypertension and elevated blood glucose. If such a condition were to occur, care should be taken to wean the patient slowly off the steroid due to the probability of adrenal impairment. Recovery from impaired adrenocortical function caused by prolonged steroid therapy is usually slow and has been known to last up to 12 months.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Fluticasone propionate is a glucocorticosteroid which has potent anti-inflammatory activity by acting via the glucocorticoid receptor. When used topically on the nasal mucosa at recommended doses has little or no detectable systemic activity.
Fluticasone propionate causes little or no hypothalamic pituitary adrenal (HPA) axis suppression following intranasal administration. Following intranasal dosing of fluticasone propionate at the recommended dose (200 microgram/day) no significant change in 24 hour serum cortisol AUC was found compared to placebo (ratio 1.01, 90% CI 0.9-1.14). After intranasal administration of high dose fluticasone propionate (2400 microgram/day, i.e. 12 times the recommended dose) a small change in 24 hour serum cortisol AUC was found compared to placebo (ratio 0.79, 90% CI 0.71-0.89).
The effects of BKC on nasal mucosa and ciliary function have been examined, and no damaging effects have been observed in clinical studies of up to 1 year duration.

Pharmacodynamic effects.

Fluticasone propionate has been shown to significantly reduce inflammatory mediators in both the early and late phase reactions of allergic rhinitis.

Clinical trials.

Rhinitis.

Clinical trials aimed to establish the efficacy of fluticasone propionate aqueous nasal spray (FPANS) 200 microgram once daily (od) in adults with seasonal or perennial rhinitis. To determine that these dosages were optimal for treating adults and to compare the efficacy of FPANS 200 microgram od with that of the standard therapy, beclomethasone dipropionate aqueous nasal spray (BDPANS) 200 microgram was used twice daily (bd). Clinical trial data is available from over 4,000 patients. Efficacy determination included daily symptom assessments.
Dose ranging studies showed FPANS to be significantly superior to placebo in the relief of symptoms of rhinitis, even at very low doses (25 microgram twice daily), although higher doses (e.g. 200 microgram daily) provided significant improvements more rapidly.
Once daily doses of 200 microgram FPANS have been shown to be efficacious in patients with seasonal rhinitis. For the relief of adult perennial rhinitis, 200 microgram once daily was as effective as 100 microgram twice daily.

Sinus pain and pressure.

In patients with allergic rhinitis, fluticasone propionate aqueous nasal spray has also been shown to be of benefit for the management of associated sinus pain and pressure.
Two 14 days, randomised, double blind, parallel group clinical studies were performed in 401 adult and adolescent patients aged ≥ 12 years. Both studies compared Flixonase Allergy & Hayfever 24 Hour nasal spray 200 microgram once daily, administered as two 50 microgram sprays per nostril, with placebo. The primary endpoint for both studies was the mean change from baseline in the patient rated sinus pain and pressure score at week 2. In both studies, Flixonase Allergy & Hayfever 24 Hour nasal spray provided significantly greater improvement compared with placebo for the primary endpoint (p < 0.05). The magnitude of the improvement was 10 points compared to placebo and approximately 35 points from baseline (baseline score for this symptom was 75 on a 0-100 scale). The sinus pain and pressure score was also significantly decreased in the Flixonase Allergy & Hayfever 24 Hour nasal spray treated group over the entire 2 week study period (p < 0.05).
Treatment with Flixonase Allergy & Hayfever 24 Hour nasal spray provided significantly greater improvement in symptoms of nasal congestion during week 1, 2 and overall during the 2 week study period (p < 0.05). The overall improvement in congestion compared to placebo was 10 points and approximately 37 points from baseline (baseline score for this symptom was 78 on a 0-100 scale).

5.2 Pharmacokinetic Properties

The data for paediatric pharmacokinetics show consistency with the adult findings.

Absorption.

Following intranasal dosing of fluticasone propionate, (200 microgram/day) steady-state maximum plasma concentrations were not quantifiable in most subjects (< 0.01 nanogram/mL). The highest Cmax observed was 0.017 nanogram/mL. Following the recommended dose of 200 microgram/day, the bioavailability could not be quantified in most subjects and the highest reported value was 1%. The amount of direct absorption in the nose is unknown but appears to be low 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 presystemic metabolism. The total systemic absorption arising from both nasal and oral absorption of the swallowed dose is therefore negligible. The absolute bioavailability of intranasal fluticasone propionate at high doses (2400 microgram/day, i.e. 12 times the recommended dose) is estimated as 1.26% (90% CI 0.85, 1.86).

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 coadministering 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 microgram dose range and are characterized by a high plasma clearance (CL = 1.1 L/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.

5.3 Preclinical Safety Data

Genotoxicity.

Fluticasone propionate has no mutagenic effect in vivo or in vitro, no tumorigenic potential in rodents and is nonirritant and nonsensitising in animal models. There was no evidence of a mutagenic potential in a standard battery of mutagenicity assays.

Carcinogenicity.

No evidence of a tumorigenic effect was observed in either a 2 year study in rats receiving doses of fluticasone propionate up to 57 microgram/kg/day by inhalation or in an 18 month study in mice receiving oral doses of fluticasone propionate up to 1 mg/kg/day.

6 Pharmaceutical Particulars

6.1 List of Excipients

Flixonase Allergy & Hayfever 24 Hour nasal spray also contains the following excipients: anhydrous glucose, cellulose - dispersible, sodium carboxymethylcellulose, phenethyl alcohol, benzalkonium chloride solution, polysorbate 80, hydrochloric acid, water - purified.
Fluticasone propionate aqueous nasal spray contains the antimicrobial preservatives benzalkonium chloride (BKC) and phenethyl alcohol.
Contains no sugar, lactose or gluten.

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

Flixonase Allergy & Hayfever 24 Hour nasal spray should be stored below 30°C. Protect from light. Do not freeze.

6.5 Nature and Contents of Container

Fluticasone propionate aqueous nasal spray is supplied in a polypropylene bottle fitted with a metering, atomising pump, nasal adaptor and a dust cover. It contains approximately 60 or 120 metered sprays, when used as recommended.
Not all packs may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

S-fluoromethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxy- androsta-1,4-diene-17β-carbothioate.

Chemical structure.


CAS number.

Fluticasone propionate: 80474-14-2.

Molecular formula.

C25H31F3O5S.

7 Medicine Schedule (Poisons Standard)

S2 (Pharmacy Medicine).

Summary Table of Changes