AVAMYS 27.5 micrograms/spray nasal spray suspension

Section 4.8: Splitting of pack to include just specific UK reporting details due to Brexit preparations
Section 7: Change of MAH address

Section 4.8 – addition of Nasal septum perforation to adverse event table with a frequency classification of very rare

Description of change to SPC:

Section 4.2 – amendment to hepatic impairment dose recommendations

Section 4.4 – typographical change

Section 4.5 – typographical change

Section 4.8 – typographical change

Section 5.2 – amendment to hepatic impairment information

Section 4.8 - Undesirable effects,
Section 5.1 - Pharmacodynamic properties,
Section 6.1 - List of excipients

AVAMYS 27.5 micrograms/spray nasal spray suspension

Summary of Changes further to the approval on 17/12/2012 of the MA Renewal (EMEA/H/C/770/R/0014) with updates to the SPC, PIL and Labelling regarding:

·             Warnings & Precaution, Adverse Reactions, Clinical Studies and GPL: Possible side effects – Details: Addition of findings from a one-year paediatric growth study.

·             Warnings & Precaution and Clinical Studies – Details: Addition of findings from a two-year ocular safety study in adults/adolescents.

SPC UPDATES

Minor editorial updates to sections 1, 2, 4.2, 4.3, 4.9, 5.1 and 5.2

4.1     Therapeutic indications

Indication updated to specify minimum age of 6 years (previously 11 years), i.e. to read:

Avamys is indicated in adults, adolescents and children (6 years and over)

4.2       Posology and method of administration

Section updated and rearranged under two sub-headings ‘Posology’ and ‘Method of administration’.

Under the sub-headings ‘Posology/Children under 6 years of age’, revised the wording to read:

The safety and efficacy of Avamys in children under the age of 6 years has not been established. Currently available data are described in section 5.1 and 5.2 but no recommendation on a posology can be made.

Under the sub-headings ‘Posology/Hepatic Impairment’ added the warning:

Caution should be exercised when dosing patients with severe hepatic impairment as patients with hepatic impairment may be more at risk of systemic adverse reactions associated with corticosteroids.

4.4       Special warnings and precautions for use

The following statements were deleted:

As with other intranasal corticosteroids, physicians should be alert to potential systemic steroid effects including ocular changes (see Pharmacodynamic properties).

Avamys contains benzalkonium chloride. It may cause irritation of the nasal mucosa.

The following new sub-headings were added ‘Systemic corticosteroid effects’, ‘Eye disorders’, ‘Growth retardation’, ‘Patients on ritonavir’, and ‘Patients with hepatic impairment’, and the relevant paragraphs have been moved under these.

4.5       Interaction with other medicinal products and other forms of interaction

Added the sub-heading ‘Interaction with CYP3A4 inhibitors’; no changes to text.

4.6       Fertility, pregnancy and lactation

Section updated and rearranged under three sub-headings ‘Pregnancy’, ‘Breast-feeding’ and ‘Fertility’, with the following text added under ‘Fertility’:

There are no fertility data in humans.

4.7       Effects on ability to drive and use machines

Updated the statement to read:

Avamys has no or negligible influence on the ability to drive and use machines.

5.1       Pharmacodynamic properties

Added the description ‘nasal preparations’ to the Pharmacotherapeutic group

6.4       Special precautions for storage

Added the following instructions:

Store upright.

Always keep the cap on.

6.5       Nature and contents of container

Updated the description to remove details on the plastic device, and added the description of the volume of the product, to read:

14.2 ml suspension in a Type I amber bottle (glass) fitted with a metering spray pump.

SPC UPDATES

4.4       Special warnings and precautions for use

The following warning was added regarding a reduction in growth rate in children and the potential systemic steroid effects including ocular changes

A reduction in growth velocity has been observed in children treated with fluticasone furoate 110 micrograms daily for one year (see Undesirable Effects and Pharmacodynamic properties). Therefore, children should be maintained on the lowest possible efficacious dose which delivers adequate symptom control (see Posology and method of administration). As with other intranasal corticosteroids, physicians should be alert to potential systemic steroid effects including ocular changes (see Pharmacodynamic properties).

4.8       Undesirable effects

Added the following undesirable effects with the frequency ‘not known’:

Transient ocular changes

Growth retardation

Regarding the undesirable effect ‘Growth retardation’ the following explanatory note was added

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 in growth velocity was observed compared to placebo (see Clinical experience).

5.1       Pharmacodynamic properties

Under the subheading ‘Perennial Allergic Rhinitis in adults and adolescents’, the following was added:

In a two-year study designed to assess the ocular safety of fluticasone furoate (110 micrograms once daily intranasal spray), adults and adolescents with perennial allergic rhinitis received either fluticasone furoate (n=367) or placebo (n=181). The primary outcomes [time to increase in posterior subcapsular opacity (³0.3 from baseline in Lens Opacities Classification System, Version III (LOCS III grade)) and time to increase in intraocular pressure (IOP; ³7 mmHg from baseline)] were not statistically significant between the two groups. Increases in posterior subscapsular opacity (³0.3 from baseline) were more frequent in subjects treated with fluticasone furoate 110 micrograms [14 (4%)] versus placebo [4 (2%)] and were transient in nature for ten subjects in the fluticasone furoate group and two subjects in the placebo group. Increases in IOP (³7 mmHg from baseline) were more frequent in subjects treated with fluticasone furoate 110 micrograms: 7 (2%) for fluticasone furoate 110 micrograms once daily and 1 (<1%) for placebo. These events were transient in nature for six subjects in the fluticasone furoate group and one placebo subject. 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 ³0.3 increase from baseline in posterior subcapsular opacity.  At weeks 52 and 104, the majority of subjects (>95%) had IOP values of within ± 5mmHg of the baseline value.  Increases in posterior subcapsular opacity or IOP were not accompanied by any adverse events of cataracts or glaucoma.

Under the subheading ‘Seasonal and perennial allergic rhinitis in children’ replaced the following statement regarding growth rate:

Results from a placebo-controlled knemometry study of fluticasone furoate nasal spray 110 micrograms once daily revealed no clinically relevant effects on short-term lower leg growth rate in children (6 to 11 years).

With the following:

A randomised, double-blind, parallel-group, multicenter, one-year placebo-controlled clinical growth study evaluated the effect of fluticasone furoate 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 fluticasone furoate (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].

Section 4.8 - Undesirable effects

4.8       Undesirable effects

Data from large clinical trials were used to determine the frequency of adverse reactions.

The following convention has been used for the classification of frequencies: Very common ≥1/10; Common ≥1/100 to <1/10; Uncommon ≥1/1000 to <1/100; Rare ≥1/10,000 to <1/1000; Very rare <1/10,000.

*Epistaxis was generally mild to moderate in intensity. In adults and adolescents, the incidence of epistaxis was higher in longer-term use (more than 6 weeks) than in short-term use (up to 6 weeks). In paediatric clinical studies of up to 12 weeks duration the incidence of epistaxis was similar between patients receiving fluticasone furoate and patients receiving placebo.

Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.

SUMMARY OF CHANGES (IN RED) TO

SUMMARY OF PRODUCT CHARACTERISTICS

AVAMYS 27.5 micrograms/spray

nasal spray suspension

4.2     Posology and method of administration

Avamys nasal spray is for administration by the intranasal route only.

For full therapeutic benefit regular, scheduled usage is recommended. Onset of action has been observed as early as 8 hours after initial administration. However, it may take several days of treatment to achieve maximum benefit, and the patient should be informed that their symptoms will improve with continuous regular use (see section 5.1). The duration of treatment should be restricted to the period that corresponds to allergenic exposure.

Adults and Adolescents (12 years and over)

The recommended starting dose is two spray actuations (27.5 micrograms of fluticasone furoate per spray actuation) in each nostril once daily (total daily dose, 110 micrograms).

Once adequate control of symptoms is achieved, dose reduction to one spray actuation in each nostril (total daily dose 55 micrograms) may be effective for maintenance.

The dose should be titrated to the lowest dose at which effective control of symptoms is maintained.

Children (6 to 11 years of age)

The recommended starting dose is one spray actuation (27.5 micrograms of fluticasone furoate per spray actuation) in each nostril once daily (total daily dose, 55 micrograms).

Patients not adequately responding to one spray actuation in each nostril once daily (total daily dose, 55 micrograms) may use two spray actuations in each nostril once daily (total daily dose, 110 micrograms).

Once adequate control of symptoms is achieved, dose reduction to one spray actuation in each nostril once daily (total daily dose, 55 micrograms) is recommended.

Children under 6 years of age: The experience in children under the age of 6 years is limited (see section 5.1 and 5.2). Safety and efficacy in this group has not been well established.

Elderly Patients: No dose adjustment is required in this population (see section 5.2).

Renal Impaired Patients: No dose adjustment is required in this population (see section 5.2).

Hepatic Impaired Patients: No dose adjustment is required in mild to moderate hepatic impairment. There are no data in patients with severe hepatic impairment (see section 4.4 and 5.2).

The intranasal device should be shaken before use. The device is primed by pressing the mist release button for at least six spray actuations (until a fine mist is seen), whilst holding the device upright. Re-priming (approximately 6 sprays until a fine mist is seen) is only necessary if the cap is left off for 5 days or the intranasal device has not been used for 30 days or more.

The device should be cleaned after each use and the cap replaced.

4.4     Special warnings and precautions for use

Avamys undergoes extensive first-pass metabolism, therefore the systemic exposure of intranasal fluticasone furoate in patients with severe liver disease is likely to be increased. This may result in a higher frequency of systemic adverse events (see section 4.2 and 5.2). Caution is advised when treating these patients.

Ritonavir

Concomitant administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate (see section 4.5).

Systemic effects of nasal corticosteroid may occur, particularly at high doses prescribed for prolonged periods. These effects vary between patients and different corticosteroids (see section 5.2).

Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. If there is evidence for higher than recommended doses being used, then additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. Fluticasone furoate 110 micrograms once daily was not associated with hypothalamic-pituitary-adrenal (HPA) axis suppression in adult, adolescent or paediatric subjects. However the dose of intranasal fluticasone furoate should be reduced to the lowest dose at which effective control of the symptoms of rhinitis is maintained. As with all intranasal corticosteroids, the total systemic burden of corticosteroids should be considered whenever other forms of corticosteroid treatment are prescribed concurrently.

Growth retardation has been reported in children receiving some nasal corticosteroids at licensed doses. 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 (see section 5.1).

If there is any reason to believe that adrenal function is impaired, care must be taken when transferring patients from systemic steroid treatment to fluticasone furoate.

Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma and/or cataracts.

Avamys contains benzalkonium chloride. It may cause irritation of the nasal mucosa.

4.8     Undesirable effects

Data from large clinical trials were used to determine the frequency of adverse reactions.

The following convention has been used for the classification of frequencies: Very common ≥1/10; Common ≥1/100 to <1/10; Uncommon ≥1/1000 to <1/100; Rare ≥1/10,000 to <1/1000; Very rare <1/10,000.

Epistaxis was generally mild to moderate in intensity. In adults and adolescents, the incidence of epistaxis was higher in longer-term use (more than 6 weeks) than in short-term use (up to 6 weeks). In paediatric clinical studies of up to 12 weeks duration the incidence of epistaxis was similar between patients receiving fluticasone furoate and patients receiving placebo.

Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods.