Consumer medicine information

Flixonase Nasule Drops

Fluticasone propionate

BRAND INFORMATION

Brand name

Flixonase Nasule Drops

Active ingredient

Fluticasone propionate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Flixonase Nasule Drops.

SUMMARY CMI

Flixonase Nasule Drops

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Flixonase Nasule Drops?

Flixonase Nasule Drops contains the active ingredient Fluticasone propionate. Flixonase Nasule Drops are used to treat inflamed tissue in the nose.

For more information, see Section 1. Why am I using Flixonase Nasule Drops? in the full CMI.

2. What should I know before I use Flixonase Nasule Drops?

Do not use if you have ever had an allergic reaction to Flixonase Nasule Drops or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Flixonase Nasule Drops? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Flixonase Nasule Drops and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Flixonase Nasule Drops?

5. What should I know while using Flixonase Nasule Drops?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Flixonase Nasule Drops.
  • Tell your doctor if you become pregnant or are trying to become pregnant.
  • Tell your doctor if, for any reason, you have not used your medicine exactly as prescribed.
  • Tell your doctor if you experience a change in your vision.
Things you should not do
  • Do not stop using Flixonase Nasule Drops or change the dose without first checking with your doctor.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use Flixonase Nasule Drops to treat any other complaints unless your doctor says to.
Driving or using machines
  • Flixonase Nasule Drops is unlikely to affect your ability to drive.
Looking after your medicine
  • Store your Flixonase Nasule Drops upright, below 30°C.
  • Protect the drops from direct sunlight. Keep your product in its pack until it is time to use the drops.
  • Do not freeze.

For more information, see Section 5. What should I know while using Flixonase Nasule Drops? in the full CMI

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention. Flixonase Nasule Drops can cause allergic reactions which may be severe. If you develop symptoms of an allergic reaction, call your doctor straight away or go straight to the Emergency Department at your nearest hospital. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Flixonase Nasule Drops

Active ingredient: Fluticasone propionate


Consumer Medicine Information (CMI)

This leaflet provides important information about using Flixonase Nasule Drops. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Flixonase Nasule Drops.

Where to find information in this leaflet:

1. Why am I using Flixonase Nasule Drops?
2. What should I know before I use Flixonase Nasule Drops?
3. What if I am taking other medicines?
4. How do I use Flixonase Nasule Drops?
5. What should I know while using Flixonase Nasule Drops?
6. Are there any side effects?
7. Product details

1. Why am I using Flixonase Nasule Drops?

Flixonase Nasule Drops contain a steroid called fluticasone propionate which, treats inflamed tissue.

Flixonase Nasule Drops work by shrinking swelling inside your nose. This makes breathing easier. You may not feel the maximum benefit for a few weeks.

Inflamed tissue inside the nose can form grape-like swellings called 'polyps'. They cause nasal blockage and discomfort. Flixonase Nasule Drops are used to relieve the symptoms caused by nasal polyps by shrinking them. Flixonase Nasule Drops have not been studied in patients under 16 years of age.

Your doctor may have prescribed Flixonase Nasule Drops for another reason.

Ask your doctor if you have any questions or if you aren't sure why Flixonase Nasule Drops has been prescribed for you.

2. What should I know before I use Flixonase Nasule Drops?

Warnings

Do not use Flixonase Nasule Drops if:

  • you are allergic to fluticasone propionate, or any of the ingredients listed at the end of this leaflet
  • Always check the ingredients to make sure you can use this medicine
  • you are pregnant, trying to become pregnant or breastfeeding, unless your doctor says you should
  • the expiry date (EXP) printed on the pack has passed
  • the packaging is torn or shows signs of tampering

Check with your doctor if you:

  • have any other medical conditions
  • have an infection in your nose or sinuses
  • have had nasal surgery
  • have been treated with steroid injections or taken steroid tablets
  • are allergic to foods, dyes, or any other medicine
  • take any medicines for any other condition
  • are diabetic
  • have a disease or are taking medication that could compromise your immune system
  • have ever had thrush in your mouth

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Flixonase Nasule Drops and affect how it works.

For example, medicines like ketoconazole, used to treat fungal infection, and ritonavir used to treat HIV infection, may affect how Flixonase Nasule Drops works. If you are taking these medicines, consult your doctor or pharmacist who will advise on what you should do.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Flixonase Nasal Drops.

4. How do I use Flixonase Nasule Drops?

How much to use

  • In patients over 16 years of age, the normal dose is one container (400 micrograms contained in 400 microlitres).
  • Follow the instructions provided and use Flixonase Nasule Drops until your doctor tells you to stop. Don't exceed the recommended dose.

When to use Flixonase Nasule Drops

  • Flixonase Nasule Drops should be used once or twice every day unless your doctor tells you otherwise.

How to use Flixonase Nasule Drops

The medicine should be divided equally between both affected nostrils.

Your doctor will advise you what to do if only one nostril is affected.

You may not feel the maximum benefit from your medicine straight away, but it is important that you continue to use the drops regularly.

Your doctor will assess your polyps regularly to decide on the best treatment.

To use Flixonase Nasule Drops, follow the steps below.

Note: It may be easier if someone else puts the drops in for you.

  1. Gently blow each nostril, in turn, to clear.
  2. Open the foil pack by tearing off one side.
  3. Detach one container and return the remaining containers, in the foil, to the carton.
  4. It is important to ensure that the contents of your Nasule are well mixed before use.
  5. While holding the container horizontally by the larger tab, flick the other end a few times and shake. Repeat this process several times until the entire contents of the container are completely mixed.
  6. Hold the lower tab of the container securely. Twist and remove the top and discard the drops.
  7. To ensure the medicine treats the affected area, ideally you should position yourself as follows (see also the diagrams inside the pack):
(a) Move into one of the following positions: kneeling, sitting, or standing. Bend forward until your head is at knee level.
OR
(b) Lie on your back on a bed with your head supported but tilted backwards over the edge. Gently insert the opened nozzle of the container into one nostril. Squeeze the container to deliver 6 drops. This is approximately half the dose.
NOTE: It is not always easy to count the drops. Make sure you hold the container by the dimpled sides. When the container is held just inside the nostril, squeeze until the dimpled sides meet. This delivers about half the dose.
  1. Transfer the container to the other nostril and squeeze it to deliver the remaining drops.
  2. Keep your head in this position for at least 1 minute. If you are lying down, rest your head to one side. After about half a minute rest your head to the other side, for a similar time.

How long to use Flixonase Nasule Drops

Flixonase Nasule Drops help control nasal polyps but are not a cure. Continue to use Flixonase Nasule Drops regularly for as long as your doctor tells you to.

If you forget to use Flixonase Nasule Drops

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, use the product as soon as you remember, then go back to using the product as you would normally

Do not take a double dose to make up for the dose you missed.

If you use too much Flixonase Nasule Drops

If you think that you have used too much Flixonase Nasule Drops, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Flixonase Nasule Drops?

Things you should do

  • Tell your doctor or pharmacist that you are using Flixonase Nasule Drops if you are about to be started on any new medicines.
  • Tell your doctor if you become pregnant or are trying to become pregnant.
  • Tell your doctor if, for any reason, you have not used your medicine exactly as prescribed.
  • Tell your doctor if you experience a change in your vision.
  • Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.
  • Use Flixonase Nasule Drops only in your nose.

Call your doctor straight away if you:

  • think you may be having an allergic reaction

Remind any doctor, dentist or pharmacist you visit that you are using Flixonase Nasule Drops.

Things you should not do

  • Do not stop using Flixonase Nasule Drops or change the dose without first checking with your doctor.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use Flixonase Nasule Drops to treat any other complaints unless your doctor says to.
  • Avoid getting the drops in your eyes. Rinse the eyes with water if you do.
  • Do not stop using this medicine suddenly.

Driving or using machines

Flixonase Nasule Drops is unlikely to affect your ability to drive.

Looking after your medicine

  • Store your Flixonase Nasule Drops upright, below 30°C.
  • Protect the drops from direct sunlight.
  • Do not freeze the drops.

Do not store the drops, or any other medicine, in a bathroom or near a sink.

Do not leave the drops in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep your product in its pack until it is time to use the drops.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a half metres above the ground is a good place to store medicines.

Condensation may form on the inside of the foil pack during storage, but it is not a cause for concern.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • sneezing
  • irritation or dryness in the nose or throat
  • bad taste or smell
  • nose bleed
  • difficulty in breathing
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Eyes
  • cloudy lens in the eye (cataract), increased pressure of the eye that causes problems with vision (glaucoma). These eye problems occurred in people who used Flixonase Nasule Drops for a long time.
Nose
  • breakdown of tissue inside the nose (nasal septal perforation)
  • sores in the nose
Allergic Reaction:
  • wheezing
  • swelling of the lips/mouth
  • difficulty in breathing
  • hay fever
  • lumpy rash ("hives")
  • fainting
Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Flixonase Nasule Drops contains

Active ingredient
(main ingredient)
fluticasone propionate
Other ingredients
(inactive ingredients)
Polysorbate 20, sorbitan monolaurate, dibasic sodium phosphate, monobasic sodium phosphate, water for injection
Potential allergensN/A

Do not take this medicine if you are allergic to any of these ingredients.

What Flixonase Nasule Drops looks like

Flixonase Nasule Drops come in individual polyethylene 'bubbles', in strips of 7 units. Each 'bubble' holds a single dose of 400 micrograms of fluticasone propionate, in a volume of 400 microlitres. The complete strip of 7 is wrapped in foil. Packs contain 4 foil-wrapped strips, each of seven units.

(AUST R 71294)

Who distributes Flixonase Nasule Drops

GlaxoSmithKline Australia Pty Ltd
Level 4, 436 Johnston Street,
Abbotsford, Victoria 3067
Australia

Trade marks are owned by or licensed to the GSK group of companies.

© 2022 GSK group of companies or its licensor.

This leaflet was prepared in November 2022.

Version 7.0

Published by MIMS March 2023

BRAND INFORMATION

Brand name

Flixonase Nasule Drops

Active ingredient

Fluticasone propionate

Schedule

S4

 

1 Name of Medicine

Fluticasone propionate.

2 Qualitative and Quantitative Composition

Each ampoule of Flixonase Nasule Drops contains 400 microgram of fluticasone propionate in 400 microL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Nasal drops.
White opaque, freely dispersed suspension free from any visible foreign matter.

4 Clinical Particulars

4.1 Therapeutic Indications

Flixonase Nasule Drops are indicated for the treatment of mild to moderate nasal polyps and associated symptoms of nasal obstruction in adults and adolescents over 16 years of age.

4.2 Dose and Method of Administration

For full therapeutic benefit regular usage is essential. Nasal polyps require regular medical assessment to monitor severity of the condition. The drops should be administered in a ‘head down’ position (see Section 4.2 Dose and Method of Administration, Instructions for use).

Adults and adolescents over 16 years old.

The contents of one container (400 microgram in 400 microL) to be instilled once or twice daily. The dose should be divided evenly between both affected nostrils.
Unilateral polyposis rarely occurs, and could be indicative of other conditions. Diagnosis should be confirmed by a specialist, and management individualised by them.

Elderly.

The normal adult dosage is applicable.

Children.

There are insufficient data at present to recommend the use of fluticasone propionate for the treatment of nasal polyps in children.

Instructions for use.

Gently blow each nostril, in turn, to clear. Open the foil pack by tearing off one side. Detach one Nasule and return the remaining containers, in the foil pack, to the carton. It is important to ensure that the contents of the container are well mixed before use. While holding the container horizontally by the larger tab, 'flick' the other end a few times and shake. Repeat this process several times until the entire contents of the container are completely mixed.
Hold the top of the container and flick or shake downwards with a quick motion. This will remove any liquid from the neck of the container. Hold then lower tab of the container securely and twist to remove the top.
The drops should be administered with the patient in the 'head down' position to ensure the medicine best reaches the affected area, as shown in the 'Instructions for use' leaflet inside the pack.
Flixonase Nasule Drops are for administration by the intranasal route only. Contact with the eyes should be avoided.
One Nasule holds enough drops for use in both nostrils.
Discard containers after use.

4.3 Contraindications

Flixonase Nasule Drops are contraindicated in patients with a history of hypersensitivity to any components of the preparation.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Local infection. Infection of the nasal airways should be appropriately treated but does not constitute a contraindication to treatment with Flixonase Nasule Drops. After nasal surgery, healing must have occurred before use.
Care must be taken when withdrawing patients from systemic steroid treatment, and commencing therapy with Flixonase Nasule Drops, particularly if there is any reason to suspect that their adrenal function is impaired.
Systemic effects with 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.
The full benefit of Flixonase Nasule Drops may not be achieved until treatment has been administered for several weeks.
Rare instances of glaucoma and increased intra-ocular pressure have been reported following administration of intranasal corticosteroids, as a class effect. If a patient presents with a change in vision, 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).
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).
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.

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 hypothalamic-pituitary-adrenal (HPA) axis suppression, reduction of bone density and retardation of growth in adolescents may occur with intranasal steroids, particularly at high doses prescribed for prolonged periods of time.
The lowest dose of Flixonase that causes suppression of the HPA axis, effects on bone mineral density or growth retardation has not yet been established. However, the systemic bioavailability of fluticasone propionate is low (estimated at 0.06%) when given as Flixonase Nasal Drops and this limits the potential for systemic side effects. Measurement of serum cortisol concentrations in the clinical studies did not suggest any HPA axis suppression with recommended doses.

Use in the elderly.

There are no special precautions for use in the elderly.

Paediatric use.

No data available.

Effects on laboratory tests.

Interactions with laboratory tests have not been established.

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 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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

A fertility study in rats showed decreased mean fetal weight, retardation of ossification, and decreased postnatal viability at the dose of 50 microgram/kg/day subcutaneous (SC) fluticasone propionate.
(Category B3)
There is insufficient evidence of safety of fluticasone propionate in human pregnancy. Systemically absorbed corticosteroids are known to induce fetotoxic 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 fetotoxic and teratogenic effects at SC 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. As with other drugs, the use of Flixonase Nasule Drops during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
The excretion of fluticasone propionate into human breast milk has not been investigated. Subcutaneous administration of tritiated 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 post-dosing. 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. As with other drugs, the use of Flixonase Nasule Drops during lactation requires that the benefits be weighed against possible risks associated with the product or with any alternative therapy.

4.7 Effects on Ability to Drive and Use Machines

Fluticasone propionate is unlikely to produce an effect.

4.8 Adverse Effects (Undesirable Effects)

Table 1 lists the drug related adverse events reported during the randomised treatment phase of the pivotal comparator trials (FLTB3045 and FLTB3046). These adverse events were considered by the investigator to be almost certainly, probably or possibly related to the study drug or of unknown or missing causality.
As with other intranasal products, dryness and irritation of the nose and throat may occur.
Unpleasant taste or smell, epistaxis and hypersensitivity reactions, including skin rash and oedema of the face and tongue, have been reported.
Following the use of intranasal corticosteroids there have been rare reports of anaphylaxis/ anaphylactoid reactions and bronchospasm. Cases of nasal septal perforation and nasal ulcers are very rare. There have also been very rare reports of glaucoma, raised intraocular pressure and cataract.

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.

4.9 Overdose

There are no data available from patients on the effects of acute or chronic overdosage with Flixonase Nasule Drops. In healthy volunteers, intranasal administration of 2 mg fluticasone propionate twice daily for seven days had no effect on HPA axis function. Administration of doses higher than those recommended over a long period of time may lead to temporary suppression of adrenal function. In these patients, treatment with fluticasone propionate should be continued at a reduced dose sufficient to control symptoms; adrenal function generally recovers in a few days and can be verified by measuring plasma cortisol.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Fluticasone propionate has potent anti-inflammatory activity but when used topically on the nasal mucosa has no detectable systemic activity. Fluticasone propionate causes little or no HPA axis suppression following intranasal or topical (dermal) administration and only causes overt HPA axis suppression after very high oral doses (10 mg four times a day, i.e. 40 mg daily, and above).

Clinical trials.

The clinical trials program evaluated the efficacy and safety of fluticasone propionate (FP) nasal drops in the treatment of nasal polyposis in patients ≥ 16 years old with mild to moderate polyps. Two main trials were conducted. Both studies were placebo controlled and consisted of 12 weeks randomised treatment followed by 12 weeks open treatment.
The first trial (FLTB3045) was double blind and compared 400 microgram fluticasone propionate once daily (od) with placebo for 12 weeks. A total of 104 patients were randomised to treatment, after which all received 400 microgram fluticasone propionate od for a further 12 weeks. Six patients (5 from the placebo group) were withdrawn from the randomised phase, while there were no withdrawals during the open label phase. At the end of the treatment period 27% of patients in the FP group showed a reduction in polyp size compared to 16% in the placebo group. This difference was not statistically significant. However, Peak Nasal Inspiratory Flow (PNIF) showed a significant improvement during FP treatment, as did all associated symptoms of rhinitis. The improvement in PNIF is particularly important as relief of nasal obstruction is a main benefit that patients require from treatment with topical steroids.
A second study (FLTB3046) compared 400 microgram fluticasone propionate once daily (od) and twice daily (bd) with placebo over 12 weeks, after which most received 400 microgram fluticasone propionate od for a further 12 weeks. A total of 142 patients were randomised to treatment, with 16 patients withdrawn after randomisation (10 from the placebo group). 107 patients entered the open label phase. At the end of the 12 week treatment period, 15% of patients in the placebo group showed an improvement in polyp size, 24% in the FP 400 microgram od group, and 41% in the 400 microgram bd group. The difference in improvement between FP 400 microgram bd and placebo was statistically significant. In addition, both doses of FP showed a significant improvement in PNIF, an improvement in the clinical assessment of nasal blockage and rhinitis and a reduction in nasal discomfort. FP 400 microgram bd showed greater improvements than 400 microgram od for all symptoms.
In both studies, serum cortisol concentrations were measured at baseline and at the end of the randomised phase to assess effects of treatment on the HPA axis. No significant differences were observed between the fluticasone and placebo groups.
Once daily (400 microgram/day) and twice daily (800 microgram/day) dosing has not been studied beyond 24 and 12 weeks respectively.

5.2 Pharmacokinetic Properties

Absorption.

After recommended doses of intranasal fluticasone propionate plasma levels are low. Systemic bioavailability for the nasal drop formula is extremely low (mean value 0.06%).
Following intravenous administration the pharmacokinetics of fluticasone propionate are proportional to the dose, and can be described by three exponentials.
Absolute oral bioavailability is negligible (< 1%) due to a combination of incomplete absorption from the gastrointestinal tract and extensive first pass metabolism.

Distribution.

Fluticasone propionate is extensively distributed within the body (Vss is approximately 300 litre). Plasma protein binding is 91%. After intravenous administration, fluticasone propionate has a very high clearance (estimated Cl 1.1 litre/min) indicating extensive hepatic extraction.
Peak plasma concentrations are reduced by approximately 98% within 3-4 hours and only low plasma concentrations are associated with the terminal half life, which is approximately 8 hours.

Metabolism.

Fluticasone propionate is extensively metabolised by CYP3A4 enzyme to an inactive carboxylic derivative.

Excretion.

Following oral administration of fluticasone propionate, 87-100% of the dose is excreted in the faeces as parent compound or as metabolites.

Other.

As fluticasone propionate is given at very low doses, any effect on co-administered drug is unlikely.
The data for paediatric pharmacokinetics show consistency with the adult findings.

5.3 Preclinical Safety Data

Genotoxicity.

Fluticasone propionate has no mutagenic effect in vivo or in vitro, no tumorigenic potential in rodents and is non-irritant and non-sensitising in animal models.

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. There was no evidence of a mutagenic potential in a standard battery of mutagenicity assays.

6 Pharmaceutical Particulars

6.1 List of Excipients

Flixonase Nasule Drops also contain the following excipients: polysorbate 20, sorbitan monolaurate, dibasic sodium phosphate, monobasic sodium phosphate, sodium chloride, water for injections.

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 Nasule Drops should be stored below 30°C.
Condensation may form on the inside of the foil pack during storage, but it is not a cause for concern.
Store upright. Protect from direct sunlight. Do not freeze.

6.5 Nature and Contents of Container

Flixonase Nasule Drops are packed as strips of seven polyethylene ampoules (Nasules) within foil wrapping. The Nasules are available in cartons containing 4 x strips of seven units.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Special Precautions for Storage

Flixonase Nasule Drops should be stored below 30°C.
Condensation may form on the inside of the foil pack during storage, but it is not a cause for concern.
Store upright. Protect from direct sunlight. Do not freeze.

6.7 Physicochemical Properties

The chemical name of fluticasone propionate is S-Fluoromethyl 6α, 9α-difluoro-11β-hydroxy- 16α-methyl-3-oxo-17 α-propionyloxy-androsta-1, 4-diene-17β-carbothioate.
The molecular formula of fluticasone propionate is C25H31F3O5S.

Chemical structure.


CAS number.

80474-14-2.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes