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.

What is in this leaflet?

Please read this leaflet carefully before you use AVAMYS.

This leaflet answers some common questions about AVAMYS. 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. Your doctor has weighed the expected benefits of you taking AVAMYS against the risks this medicine could have for you.

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 is AVAMYS used for?

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.

AVAMYS contains the medicine fluticasone furoate. This medicine belongs to a group of medicines known as corticosteroids, frequently called 'steroids'. They are not 'anabolic steroids' which are the steroids sometimes misused by athletes.

AVAMYS works to decrease inflammation caused by allergy (rhinitis).

Your doctor may have prescribed AVAMYS for another reason.

AVAMYS is not addictive.

Before you use AVAMYS

Do not use if:

You must not use AVAMYS if:

  • you have ever had an allergic reaction to fluticasone furoate or any of the ingredients listed toward the end of this leaflet. (See "Ingredients")
  • the expiry date (EXP) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering.

Tell your doctor if:

You must tell your doctor if:

  • you are allergic to foods, dyes, preservatives or any other medicines.
  • you are taking an antiviral medicine called a protease inhibitor (e.g. ritonavir) or a type of medicine used to treat fungal infections (e.g. ketoconazole).
  • you are taking any other medicines, including medicines you buy without a prescription. This includes inhaled, oral or injected steroids.
  • you are breastfeeding, pregnant or trying to become pregnant.

How do I use AVAMYS?

How much to use

Take AVAMYS as directed by your doctor or pharmacist. Don't exceed the recommended dose.

Adults and adolescents 12 years and older:

  • The usual starting dose is 2 sprays in each nostril once a day.
  • 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.
  • 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.

How to use it

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.

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.

Use in children

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

What do I do if I use too much? (Overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 131126) for advice, if you think you or anyone else may have taken too much AVAMYS, even if there are no signs of discomfort or poisoning.

If you are not sure what to do, contact your doctor or pharmacist.

While you are using AVAMYS

Things you must do

Tell your doctor if, for any reason, you have not taken your medicine exactly as directed.

If you forget to use AVAMYS:

  • If you miss a dose, take it when you remember.
  • If it is almost time for your next dose, wait until then. Do not take a double dose to make up for a forgotten dose.

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

Contact your doctor if you experience a change in your vision.

Things you must 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.

Things to be careful of

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.

What are the side effects?

Check with your doctor as soon as possible if you think you are experiencing any side effects or allergic reactions due to taking AVAMYS, even if the problem is not listed below.

Like other medicines, AVAMYS can cause some side effects. If they occur, they are most likely to be minor and temporary. However, some may be serious and need medical attention.

The most commonly reported side-effects are:

  • 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.

Uncommon side effects are:

  • 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.

Tell your doctor immediately if you notice any of the following:

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

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.

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

How do I store AVAMYS?

Keep this medicine where children cannot reach it, such as in a locked cupboard.

Store AVAMYS below 30°C.

Do not refrigerate or freeze.

Always keep the cap on.

Do not leave in a car, on a window sill or in a bathroom.

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

Return any unused or expired medicine to your pharmacist.

Product description

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.

Ingredients

AVAMYS contains the active ingredient fluticasone furoate.

AVAMYS also contains glucose anhydrous, dispersible cellulose, polysorbate 80, benzalkonium chloride, disodium edetate, and purified water.

Supplier

Your AVAMYS is supplied by:

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

Where to go for further information

Pharmaceutical companies are not in a position to give people an individual diagnosis or medical advice. Your doctor or pharmacist is the best person to give you advice on the treatment of your condition.

This leaflet was prepared on 5 October 2018.

The information provided applies only to: AVAMYS

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

AVAMYS: AUST R 131443

© 2018 GSK group of companies or its licensor

Version 8.0

Published by MIMS February 2019

BRAND INFORMATION

Brand name

Avamys

Active ingredient

Fluticasone furoate

Schedule

S4

 

1 Name of Medicine

Fluticasone furoate.

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.

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.

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.

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.

4.3 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.

4.8 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.

4.2 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).

4.7 Effects on Ability to Drive and Use Machines

Fluticasone furoate is unlikely to produce an effect.

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).

7 Medicine Schedule (Poisons Standard)

S4.

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.

Summary Table of Changes