Consumer medicine information

Avamys Nasal Spray

Fluticasone furoate

BRAND INFORMATION

Brand name

Avamys

Active ingredient

Fluticasone furoate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Avamys Nasal Spray.

SUMMARY CMI

AVAMYS Nasal Spray

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 AVAMYS?

AVAMYS contains the active ingredient Fluticasone furoate. AVAMYS is used to treat symptoms of allergic rhinitis including stuffy, runny or itchy nose, sneezing, and watery, itchy or red eyes.

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

2. What should I know before I use AVAMYS?

Do not use if you have ever had an allergic reaction to AVAMYS 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 AVAMYS? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with AVAMYS 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 AVAMYS?

  • Adults and adolescents 12 years and older - The usual starting dose is 2 sprays in each nostril once a day (55 micrograms fluticasone furoate). Once symptoms are controlled you may be able to decrease your dose to 1 spray in each nostril once a day.
  • Children (2 to 11 years): The usual starting dose is 1 spray in each nostril once a day (27.5 micrograms fluticasone furoate).

More instructions can be found in Section 4. How do I use AVAMYS? in the full CMI.

5. What should I know while using AVAMYS?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using AVAMYS.
  • Tell your doctor, if you are taking any other 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 are allergic to foods, dyes, preservatives or any other medicines.
Things you should not do
  • Do not stop using AVAMYS or change the dose without first checking with your doctor.
  • Do not use AVAMYS in or near the eyes.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use AVAMYS to treat any other complaints unless your doctor says to.
Driving or using machines
  • Be careful driving or operating machinery until you know how AVAMYS affects you.
  • AVAMYS is unlikely to affect your ability to drive or use machinery.
Looking after your medicine
  • Store your AVAMYS below 30°C, protected from direct sunlight. Always keep the cap on.
  • Do not freeze.

For more information, see Section 5. What should I know while using AVAMYS? 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. AVAMYS 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

AVAMYS Nasal Spray

Active ingredient(s): Fluticasone furoate


Consumer Medicine Information (CMI)

This leaflet provides important information about using AVAMYS. 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 AVAMYS.

Where to find information in this leaflet:

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

1. Why am I using AVAMYS?

AVAMYS contains the active ingredient fluticasone furoate. AVAMYS belongs to a group of medicines known as corticosteroids, frequently called 'steroids'. AVAMYS works to decrease inflammation caused by allergy (rhinitis).

AVAMYS is used to treat symptoms of allergic rhinitis including stuffy, runny or itchy nose, sneezing, and watery, itchy or red eyes. The effects are usually felt within the first day, although some people will not feel the effects until several days after first taking it.

Your doctor may have prescribed AVAMYS for another reason.

AVAMYS is not addictive.

2. What should I know before I use AVAMYS?

Warnings

Do not use AVAMYS if:

  • you are allergic to fluticasone furoate, or any of the ingredients listed at the end of this leaflet.
  • 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
  • you are allergic to foods, dyes, or any other medicine.
  • you take any medicines for any other condition.

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 AVAMYS 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 AVAMYS 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 AVAMYS.

4. How do I use AVAMYS?

How much to take

Adults and adolescents 12 years and older:

  • The usual starting dose is 2 sprays in each nostril once a day (55 micrograms fluticasone furoate).
  • Once symptoms are controlled you may be able to decrease your dose to 1 spray in each nostril once a day.

Children (2 to 11 years):

  • The usual starting dose is 1 spray in each nostril once a day (27.5 micrograms fluticasone furoate).
  • If symptoms are severe, your doctor may increase the dose to 2 sprays in each nostril once a day until symptoms are under control. It may then be possible for the dose to be reduced to 1 spray in each nostril once a day.
    Follow the instructions provided and use AVAMYS until your doctor tells you to stop.

When to take AVAMYS

  • See the instruction leaflet inside the pack for information on how to use AVAMYS.
  • Shake well before use.
  • AVAMYS is sprayed into the nose as a fine mist. It has virtually no taste.
  • AVAMYS is not for use in the eyes.
  • Use AVAMYS once a day and at the same time each day. This will treat your symptoms throughout the day and night.

If you forget to use AVAMYS

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.

Otherwise, your doctor may think that it was not working as it should and change your treatment unnecessarily.

How long to use it for

Your doctor will tell you how long to use AVAMYS.

Do not stop using AVAMYS, or change the dose without first checking with your doctor.

If you use too much AVAMYS

If you think that you or anyone else have used too much AVAMYS, 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 AVAMYS?

Things you should do

  • Tell your doctor or pharmacist that you are using AVAMYS 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.
  • Use AVAMYS only in your nose.

Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Call your doctor straight away if you experience:

  • Wheezing, swelling of the lips/mouth, difficulty in breathing, hayfever, lumpy rash (hives) or fainting. These could be a symptom of an allergic reaction.

Remind any doctor, dentist or pharmacist you visit that you are using AVAMYS.

Things you should not do

  • Do not use AVAMYS in or near the eyes.
  • Do not give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Do not use AVAMYS to treat any other complaints unless your doctor says to.

Use in children

AVAMYS is not recommended for use in children below 2 years of age.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how AVAMYS affects you.

AVAMYS is unlikely to affect your ability to drive or use machinery.

Looking after your medicine

Store your AVAMYS below 30°C.

Protect from direct sunlight.

Do not freeze.

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

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

Always keep the cap on.

Keep AVAMYS in its pack until it is time to use it.

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.

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
  • nose bleeds.
  • nasal ulceration - which may cause irritation or discomfort in your nose. You may also get streaks of blood when you blow your nose.
  • headache.
  • Pain, burning, irritation, soreness or dryness in the inside of the nose.
  • Slowing of growth in children has also been observed, however the frequency of this occurring cannot be estimated from the available data.
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
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 AVAMYS contains

Active ingredient
(main ingredient)
fluticasone furoate
Other ingredients
(inactive ingredients)
glucose anhydrous, dispersible cellulose, polysorbate 80, benzalkonium chloride, disodium edetate, and purified water.
Potential allergensN/A

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

What AVAMYS looks like

AVAMYS nasal spray is a white suspension contained in an amber glass bottle, fitted with a pump. The bottle is in an off-white plastic casing with a light blue cap and side-button. The casing has a window for viewing the bottle contents. The bottle contains either 30 or 120 sprays.

Each spray delivers approximately 27.5 micrograms fluticasone furoate.

AUST R 131443.

Who distributes AVAMYS

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

This leaflet was prepared in November 2022.

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

© 2022 GSK group of companies or its licensor

Version 9.0

Published by MIMS February 2023

BRAND INFORMATION

Brand name

Avamys

Active ingredient

Fluticasone furoate

Schedule

S4

 

1 Name of Medicine

Fluticasone furoate.

2 Qualitative and Quantitative Composition

Avamys Nasal Spray is a white suspension of micronised fluticasone furoate for topical administration to the nasal mucosa by means of a metering atomising spray pump. Each spray of the suspension delivers approximately 27.5 micrograms of micronised fluticasone furoate as an ex-device dose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension spray.

4 Clinical Particulars

4.1 Therapeutic Indications

For the treatment of seasonal allergic rhinitis and perennial allergic rhinitis in adults and children of ages 2 years and older.

4.2 Dose and Method of Administration

Fluticasone furoate Nasal Spray is for administration by the intranasal route only.
For full therapeutic benefit regular usage is recommended. Onset of action has been observed as early as 8 hours after administration. It may take several days of treatment to achieve maximum benefit. An absence of an immediate effect should be explained to the patient.
Patients should be instructed that the device must be primed: before first use, and; if the cap is left off; if the device does not seem to be working; if the nasal spray has not been used for 30 days or more.
In order to prime the device the nasal spray needs to be shaken vigorously for about 10 seconds with the cap on. This is important as fluticasone furoate is a thick suspension that becomes liquid when vigorously shaken. It will only spray when it becomes liquid.
The patient must then press the button firmly all the way in, approximately 6 times until a fine mist is seen (to ensure a full dose is delivered).
Once primed the patient must shake the nasal spray vigorously each time before use.
The cap must be replaced after use to keep the nozzle clean and to prevent the need for re-priming.
Patients must follow the step-by-step instructions in the instruction leaflet for use and handling.

For seasonal allergic rhinitis and perennial allergic rhinitis.

Adults and adolescents (12 years and over). The recommended starting dosage is 2 sprays (27.5 micrograms of fluticasone furoate per spray) in each nostril once daily (total daily dose, 110 micrograms).
Once adequate control of symptoms is achieved, dose reduction to one spray in each nostril once daily (total daily dose, 55 micrograms) may be effective for maintenance.
Children (2 to 11 years of age). The recommended starting dosage is 1 spray (27.5 micrograms of fluticasone furoate per spray) in each nostril once daily (total daily dose, 55 micrograms).
Patients not adequately responding to 1 spray in each nostril once daily (total daily dose, 55 micrograms) may use 2 sprays in each nostril once daily (total daily dose, 110 micrograms). Once adequate control of symptoms is achieved, dose reduction to 1 spray in each nostril once daily (total daily dose, 55 micrograms) is recommended.
Children under 2 years of age. There is no experience in children under the age of 2 years.
Special patient groups.

Elderly patients.

No dosage adjustment required. (See Section 5.2 Pharmacokinetic Properties, Special patient populations).

Renal patients.

No dosage adjustment required. (See Section 5.2 Pharmacokinetic Properties, Special patient populations).

Patients with hepatic impairment.

No dosage adjustment is required at the indicated dosage in patients with hepatic impairment (see Section 5.2 Pharmacokinetic Properties, Special patient populations).

4.3 Contraindications

Avamys is contraindicated in patients with a history of hypersensitivity to any components of the preparations (see Section 2 Qualitative and Quantitative Composition; Section 6.1 List of Excipients).

4.4 Special Warnings and Precautions for Use

As with all intranasal corticosteroids, the total systemic burden of corticosteroids should be considered whenever other forms of corticosteroids are prescribed concurrently.

Local infection.

Infection of the nasal airways should be appropriately treated but does not constitute a contraindication to treatment with Avamys. After nasal surgery, healing must have occurred before use.
Nasopharyngeal candidiasis can occur in patients treated with intranasal steroids, as a class effect. Special care should be taken when treating patients who may be susceptible to candida infections (e.g. diabetics).

Systemic effects/adrenocortical function.

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. Intranasal steroid products are designed to deliver drug directly to the nasal mucosa in order to minimise overall systemic glucocorticoid exposure and side effects.
Topical corticosteroids may be absorbed in amounts that can have systemic effects. Use of excessive doses may cause suppression of HPA function, reduction in bone density and retardation of growth rate in adolescents and children.
The lowest dose of Avamys 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 furoate is low (estimated at 0.50%) when given as Avamys 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.

Ocular effects.

As with other intranasal corticosteroids, physicians should be alert for evidence of systemic effects including ocular changes. Rare instances of glaucoma and increased intra-ocular pressure have been reported following administration of intranasal corticosteroids, as a class effect. Therefore, close monitoring is warranted in patients with a history of increased intraocular pressure, glaucoma and/or cataracts.
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).

Paediatric use.

Growth retardation has been reported in children receiving some nasal corticosteroids at licensed doses. A reduction in growth velocity has been observed in children treated with fluticasone furoate 110 micrograms daily for one year (see Section 4.8 Adverse Effects (Undesirable Effects); Section 5.1 Pharmacodynamic Properties). Therefore, children should be maintained on the lowest dose which delivers adequate symptom control (see Section 4.2 Dose and Method of Administration).
The potential growth effects of treatment should be weighed against the clinical benefits and availability of safe and effective non-corticosteroid alternatives.
It is recommended that the height of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. If growth is slowed, therapy should be reviewed with the aim of reducing the dose of nasal corticosteroid if possible, to the lowest dose at which effective control of symptoms is maintained. In addition, consideration should be given to referring the patient to a paediatric specialist.

Use in the elderly.

No dosage adjustment required (see Section 5.2 Pharmacokinetic Properties, Special patient populations).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Fluticasone furoate is rapidly cleared by extensive first pass metabolism mediated by the cytochrome P450 3A4. In a drug interaction study of intranasal fluticasone furoate with the potent CYP3A4 inhibitor ketoconazole there were more subjects with measurable fluticasone furoate concentrations in the ketoconazole group (6 of the 20 subjects) compared to placebo (1 out of 20 subjects). This small increase in exposure did not result in statistically significant difference in 24 hour serum cortisol levels between the two groups.
The enzyme induction and inhibition data suggest that there is no theoretical basis for anticipating metabolic interactions between fluticasone furoate and the cytochrome P450 mediated metabolism of other compounds at clinically relevant intranasal doses. Therefore, no clinical studies have been conducted to investigate interactions of fluticasone furoate on other drugs (see Section 5.2 Pharmacokinetic Properties).
Based on data with another glucocorticoid metabolised by CYP3A4, co-administration with ritonavir is not recommended because of the potential risk of increased systemic exposure to fluticasone furoate.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There were no effects on mating performance or fertility of male or female rats in which systemic exposure to fluticasone furoate was achieved by inhalational administration.
(Category B3)
There is insufficient evidence of safety of fluticasone furoate 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. Following intranasal administration of fluticasone furoate at the maximum recommended human dose (110 micrograms per day), plasma concentrations were typically non-quantifiable (see Section 5.2 Pharmacokinetic Properties). Fetal exposure and therefore potential for reproductive toxicity is expected to be very low. As with other compounds of this class, the use of Avamys during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.
The excretion of fluticasone furoate into human breast milk has not been investigated. Related drugs are known to be excreted in the milk of lactating rats. However, plasma levels in patients following intranasal application of fluticasone furoate at recommended doses are low and therefore the amount of fluticasone ingested by the newborn is likely to be very small.

4.7 Effects on Ability to Drive and Use Machines

Fluticasone furoate is unlikely to produce an effect.

4.8 Adverse Effects (Undesirable Effects)

Avamys nasal spray was well tolerated in adult, adolescent and paediatric subjects 2 years of age and older with seasonal allergic rhinitis and/or perennial allergic rhinitis over two and six week treatment periods. The compound was also well tolerated in longer term use over a period of 12 weeks in paediatric subjects and over a period of one year in adult and adolescent subjects.

Adverse events.

A summary of the adverse events occurring at an incidence of ≥ 3% and more frequently in the fluticasone furoate than placebo group in the adult and adolescents perennial allergic rhinitis long-term safety study (FFR102123) is provided in Table 1.

Adverse reactions.

Data from large clinical trials were used to determine the frequency of adverse reactions. The following convention has been used for the classification of frequency: very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1000 and < 1/100; rare ≥ 1/10,000 and < 1/1000; very rare < 1/10,000.

Respiratory, thoracic and mediastinal disorders.

Very common: Epistaxis.
Epistaxis was generally mild to moderate in intensity. In adults and adolescents, the incidence of epistaxis was higher in longer term use (more than six weeks) than in short term use (up to six weeks). In paediatric clinical studies of up to 12 weeks duration the incidence of epistaxis was similar between fluticasone furoate and placebo.
Common: Nasal ulceration.
Children. Not known: Growth retardation.
In a one-year clinical study assessing growth in pre-pubescent children receiving 110 micrograms of fluticasone furoate once daily, an average treatment difference of -0.27 cm per year (95% confidence interval: -0.48, -0.06 cm) in growth velocity was observed compared to placebo (see Section 5.1 Pharmacodynamic Properties, Clinical trials).

Post marketing data.

Immune system disorders.

Rare: Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria.

Nervous system disorders.

Common: Headache.

Respiratory, thoracic and mediastinal disorders.

Uncommon: Rhinalgia, nasal discomfort (including nasal burning, nasal irritation, and nasal soreness), nasal dryness.
Very rare: Nasal septum perforation.

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

In a bioavailability study, intranasal doses of up to 2640 micrograms per day were administered over three days with no adverse systemic effects observed. (See Section 4.4 Special Warnings and Precautions for Use).
Acute overdose is unlikely to require any therapy other than observation.
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 furoate is a synthetic trifluorinated corticosteroid that possesses a very high affinity for the glucocorticoid receptor and when administered intranasally, has a potent anti-inflammatory action in the airway.

Clinical trials.

Seasonal and perennial allergic rhinitis in adults and adolescents (12 years and over).

Five randomised, double blind, parallel group, placebo controlled trials have investigated the safety and efficacy of Avamys nasal spray 110 micrograms once daily in adults and adolescents 12 years of age and older with symptoms of seasonal or perennial allergic rhinitis. The five trials include one 2 week dose ranging trial in patients with seasonal allergic rhinitis (FFR20001), three 2 week efficacy trials in patients with seasonal allergic rhinitis (FFR30003, FFR103184, FFR104861) and one 4 week efficacy trial in patients with perennial allergic rhinitis (FFR30002).
The primary efficacy variable for all studies was based on the daily assessment of four nasal symptoms (rhinorrhoea, nasal congestion, nasal itching and sneezing) using a four point (0 [none] to 3 [severe]) categorical scoring scale, with the maximum score being 12, called the total nasal symptom score (TNSS). The reflective TNSS (rTNSS) requires the patient to record symptom severity over the previous 12 hours; the instantaneous TNSS (iTNSS) requires the patient to record symptom severity at the time immediately prior to the next dose. Morning and evening rTNSS scores were averaged over the treatment period and the difference in placebo in the change from baseline rTNSS was the primary efficacy variable.
Additional key secondary efficacy variables were assessed, including mean change from baseline over the entire treatment period in AM pre-dose iTNSS, mean change from baseline over the entire treatment period in daily reflective total ocular symptom score (rTOSS) (applicable to the seasonal allergic rhinitis trials only, excluding FFR20001) and the patients' perception of overall response to therapy. The total ocular symptom score (TOSS) was calculated on the daily assessment of three ocular symptoms (itching/burning, tearing/watering, and redness) using a four point (0 [none] to 3 [severe]) categorical scoring scale, with the maximum score being 9.
In the four seasonal allergic rhinitis trials, Avamys nasal spray 110 micrograms once daily significantly improved nasal symptoms (comprising rhinorrhea, nasal congestion, sneezing and nasal itching) and ocular symptoms (comprising itching/burning, tearing/watering and redness of the eyes) compared with placebo (see Table 2). The improvement was maintained over the full 24 hours after once daily administration as evaluated by AM pre-dose iTNSS (treatment effect ranged from -0.902 to -1.898, p < 0.001 across the four studies). Similar improvement was observed for AM rTNSS and PM rTNSS and AM rTOSS and PM rTOSS suggesting consistent day time and night time relief of nasal and ocular symptoms.
Onset of action was experienced as early as eight hours after initial administration. Significant improvement in symptoms was observed in the first 24 hours in all studies, and continued to improve over several days.
Avamys nasal spray significantly improved the patients' perception of overall response to therapy. Additionally, the patients' quality of life (assessed by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)), was significantly improved from baseline with Avamys nasal spray compared to placebo (Minimum Important Difference in all studies = improvement of at least -0.5 over placebo; treatment difference ranged from -0.572 to -1.000, p < 0.001, across the four studies).
In the perennial allergic rhinitis trial, Avamys nasal spray 110 micrograms once daily significantly improved nasal symptoms compared to placebo (mean change from baseline in daily rTNSS, LS mean difference = -0.706, p = 0.005, 95% CI -1.20, -0.21). The improvement in nasal symptoms was maintained over the full 24 hours after once daily administration. The patients' perception of overall response to therapy was significantly improved compared to placebo. Although numerical improvements in overall RQLQ scores with Avamys nasal spray 110 microgram were noted, these were not statistically significant when compared to placebo.
In a two year study designed to assess the ocular safety of Avamys (110 micrograms once daily intranasal spray), adults and adolescents with perennial allergic rhinitis received either Avamys nasal spray (n = 367) or placebo (n = 181). The primary outcomes [time to increase in posterior subcapsular opacity (≥ 0.3 units from baseline in Lens Opacities Classification System, Version III (LOCS III grade, a visual comparison classification system)) and time to increase in intraocular pressure (IOP; ≥ 7 mmHg from baseline)] were not statistically significant between the two groups. Increases in posterior subcapsular opacity (≥ 0.3 units from baseline) were more frequent in subjects treated with Avamys nasal spray 110 micrograms [14 (4%)] versus placebo [4 (2%)] and were transient in nature for ten subjects in the Avamys nasal spray group and two subjects in the placebo group. Increases in IOP (≥ 7 mmHg from baseline) were more frequent in subjects treated with Avamys nasal spray 110 micrograms: 7 (2%) for Avamys nasal spray 110 micrograms once daily and 1 (< 1%) for placebo. These events were transient in nature for four subjects in the Avamys nasal spray group and one placebo subject; for two additional subjects in the fluticasone furoate group the finding occurred at the final visit and it could not be determined whether the event was transient or not. At weeks 52 and 104, 95% of subjects in both treatment groups had posterior subcapsular opacity values within ± 0.1 of baseline values for each eye and, at week 104, ≤ 1% of subjects in both treatment groups had ≥ 0.3 increase from baseline in posterior subcapsular opacity. At weeks 52 and 104, the majority of subjects (> 95%) had IOP values of within ± 5 mmHg of the baseline value. Increases in posterior subcapsular opacity or IOP were not accompanied by any adverse events of cataracts or glaucoma.

Seasonal and perennial allergic rhinitis in children (2 to 11 years of age).

The paediatric dose is based on assessment of the efficacy data across the allergic rhinitis population in children.
Two randomised, double blind, parallel group, placebo controlled trials have investigated the safety and efficacy of Avamys nasal spray 55 micrograms and 110 micrograms once daily in the treatment of children 2 to < 12 years of age with symptoms of seasonal or perennial allergic rhinitis.
In the seasonal allergic rhinitis trial (FFR100010) of two weeks duration, Avamys nasal spray 110 micrograms once daily was effective on primary (daily rTNSS, LS mean difference = -0.616, p = 0.025, 95% CI -1.15, -0.08) and all secondary nasal endpoints, except the individual reflective score for rhinorrhea. No significant differences were observed between Avamys nasal spray 55 micrograms and placebo on any endpoint.
In the perennial allergic rhinitis trial (FFR30008) of twelve weeks duration, with the primary endpoint assessed over the first 4 weeks, Avamys nasal spray 55 micrograms once daily was effective on daily rTNSS (LS mean difference = -0.754, p = 0.003, 95% CI -1.24, -0.27). Although there was a trend towards improvement in rTNSS with Avamys nasal spray 110 micrograms this did not reach statistical significance (LS mean difference = -0.452, p = 0.073, 95% CI -0.95, 0.04).
The above efficacy results are based on children 6 to < 12 years of age. Efficacy in children 2 to < 6 years of age was supported by a numerical decrease in the rTNSS.
A randomised, double blind, parallel group, multicenter, one year placebo controlled clinical growth study (FFR101782) evaluated the effect of Avamys nasal spray nasal spray 110 micrograms daily on growth velocity in 474 prepubescent children (5 to 7.5 years of age for girls and 5 to 8.5 years of age for boys) with stadiometry. Mean growth velocity over the 52 week treatment period was lower in the patients receiving Avamys nasal spray (5.19 cm/year) compared to placebo (5.46 cm/year). The mean treatment difference was -0.27 cm per year [95% CI -0.48 to -0.06].
At baseline, mean daily 24 hour rTNSS as reported by subjects in the placebo group was similar to rTNSS reported by the Avamys nasal spray group (6.099 and 6.118, respectively). Daily 24 hour rTNSS decreased in both the placebo and Avamys nasal spray groups over 1-52 weeks of treatment. This reduction in nasal symptom scores was consistently equal or greater for the Avamys nasal spray treated group (mean change from baseline -1.23) over treatment weeks 1-52 compared with the placebo treated group (mean change from baseline -0.99). Study treatment compliance based on daily e-diary recordings was high and similar between the treatment groups, and was supported by changes in nasal spray device weights.
These findings may have been due to several factors including the naturally occurring increase and decrease in frequency and severity of the symptoms of PAR; the subjective nature of symptom ratings; variations in the maturity of the patients; the need for parental assistance in rating symptoms; and the availability of the study supplied loratadine syrup. Mean loratadine syrup rescue medication use was approximately 0.5 teaspoon per day for both treatment groups over the 52 week treatment period. There was little change from baseline in the percentage of rescue free days for both treatment groups (-2.23%, placebo; -2.96%, Avamys nasal spray).

5.2 Pharmacokinetic Properties

Absorption.

Fluticasone furoate undergoes extensive first pass metabolism and incomplete absorption in the liver and gut resulting in negligible systemic exposure. The intranasal dosing of 110 microgram once daily does not typically result in measurable plasma concentrations (< 10 picograms/mL). Fluticasone furoate has a low (0.50%) systemic bioavailability at intranasal doses of up to 2640 microgram per day.

Distribution.

The plasma protein binding of fluticasone furoate is greater than 99%. Fluticasone furoate is widely distributed with volume of distribution at steady-state of, on average, 608 L.

Metabolism.

Fluticasone furoate is rapidly cleared (total plasma clearance of 58.7 L/h) from systemic circulation principally by hepatic metabolism to an inactive 17-beta-carboxylic metabolite by the cytochrome P450 enzyme CYP3A4. The principal route of metabolism was hydrolysis of the S-fluoromethyl carbothioate function to form the 17-beta-carboxylic acid metabolite. In vivo studies have revealed no evidence of cleavage of the furoate moiety to form fluticasone.

Excretion.

Elimination was primarily via the faecal route following oral and intravenous administration indicative of excretion of fluticasone furoate and its metabolites via the bile. Following intravenous administration, the elimination phase half-life averaged 15.1 hours. Urinary excretion accounted for approximately 1% and 2% of the orally and intravenously administered dose, respectively.

Special patient populations.

Elderly.

Only a small number of elderly subjects (n = 23/872; 2.6%) provided pharmacokinetic data. There was no evidence for a higher incidence of subjects with quantifiable fluticasone furoate concentrations in the elderly, when compared to the younger subjects.

Children.

Fluticasone furoate is typically not quantifiable (< 10 picograms/mL) following intranasal dosing of 110 micrograms once daily. Quantifiable levels were observed in < 16% of paediatric patients following intranasal dosing of 110 micrograms once daily and only < 7% of paediatric patients following 55 micrograms once daily. There was no evidence for a higher incidence of quantifiable levels of fluticasone furoate in younger children (less than 6 years of age).

Renal impairment.

Fluticasone furoate is not detectable in urine from healthy volunteers after intranasal dosing. Less than 1% of dose related material is excreted in urine and, therefore, renal impairment would not be expected to affect the pharmacokinetics of fluticasone furoate.

Hepatic impairment.

There are no data on intranasal fluticasone furoate in subjects with hepatic impairment. Data are available following inhaled administration of fluticasone furoate (as fluticasone furoate or fluticasone furoate/vilanterol) to subjects with hepatic impairment that are also applicable for intranasal dosing. A study of a single 400 microgram dose of oral inhaled fluticasone furoate in patients with moderate hepatic impairment (Child-Pugh B) resulted in increased Cmax (42%) and AUC(0-∞) (172%) compared to healthy subjects. Following repeat dosing of orally inhaled fluticasone furoate/vilanterol for 7 days, there was an increase in fluticasone furoate systemic exposure (up to 3-fold as measured by AUC(0-24)) in subjects with hepatic impairment (Child-Pugh A, B or C) compared with healthy subjects. The increase in fluticasone furoate systemic exposure (fluticasone furoate/vilanterol 200/25 micrograms) in subjects with moderate hepatic impairment (Child-Pugh B) was associated with an average 34% reduction in serum cortisol compared with healthy subjects. In subjects with severe hepatic impairment (Child-Pugh C) that received a lower dose of 100/12.5 micrograms there was no reduction in serum cortisol. Based on these findings the average predicted exposure for 110 micrograms of intranasal fluticasone furoate in this patient population would not be expected to result in clinically significant suppression of cortisol.

5.3 Preclinical Safety Data

Genotoxicity.

There was no evidence of a genotoxicity potential of fluticasone furoate in a standard battery of genotoxicity assays.

Carcinogenicity.

No evidence of a tumorigenic effect was observed in two year inhalational studies of fluticasone furoate in mice receiving doses of up to 18.8 microgram/kg/day or in rats receiving up to 8.6 microgram/kg/day. These doses were approximately 8.5 and 4-fold the human adult dose based on mg/kg, respectively.

6 Pharmaceutical Particulars

6.1 List of Excipients

Avamys Nasal Spray also contains the following excipients: Glucose Anhydrous, Dispersible Cellulose, Polysorbate 80, Benzalkonium Chloride, Disodium Edetate, and Purified Water.

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

Store below 30°C. Do not refrigerate or freeze.

6.5 Nature and Contents of Container

Avamys Nasal Spray is a white suspension contained in an amber glass bottle fitted with a metering atomising spray pump. This inner pack is incorporated within a predominantly off- white plastic device with a blue side actuated lever and a lid which contains a stopper. Each spray of the suspension delivers approximately 27.5 micrograms of micronised fluticasone furoate as an ex-device dose.
Avamys Nasal Spray is available in 120, 60 and 30 spray packs.
Not all pack sizes are being distributed in Australia.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Description.

Fluticasone furoate is practically insoluble or insoluble in water, and slightly soluble in acetone, dimethylsulphoxide and ethanol.
Chemical Name: Androsta-1,4-diene-17-carbothioic acid, 6,9-difluoro-17-[(2-furanylcarbonyl)oxy]-11-hydroxy-16-methyl-3-oxo-, S- (fluoromethyl) ester, (6α,11β,16α,17α)- (9Cl).
Molecular Formula: C27H29F3O6S.

Chemical structure.


CAS number.

397864-44-7.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes