AVAMYS Nasal spray, suspension Ref.[6858] Active ingredients: Fluticasone Fluticasone furoate

Systemic corticosteroid effects

Systemic effects of nasal corticosteroid may occur, 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. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

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.

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.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Growth retardation

Growth retardation has been reported in children receiving 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 and section 5.1). Therefore, children should be maintained on the lowest possible efficacious dose which delivers adequate symptom control (see section 4.2). It is recommended that the growth 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).

Patients on ritonavir

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

Excipients

This medicinal product contains benzalkonium chloride. Long-term use may cause oedema of the nasal mucosa.

Interaction with CYP3A inhibitors

Fluticasone furoate is rapidly cleared by extensive first pass metabolism mediated by the cytochrome P450 3A4.

Based on data with another glucocorticoid (fluticasone propionate), that is metabolised by CYP3A4, coadministration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate.

Caution is recommended when co-administering fluticasone furoate with potent CYP3A inhibitors including cobicistat-containing products as an increase in the risk of systemic side effects is expected. Coadministration should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side effects, in which case patients should be monitored for systemic corticosteroid side effects. 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 a 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.

Pregnancy

There are no adequate data from the use of fluticasone furoate in pregnant women. In animal studies glucocorticoids have been shown to induce malformations including cleft palate and intra-uterine growth retardation. This is not likely to be relevant for humans given recommended nasal doses which results in minimal systemic exposure (see section 5.2). Fluticasone furoate should be used in pregnancy only if the benefits to the mother outweigh the potential risks to the foetus or child.

Breast-feeding

It is unknown whether nasal administered fluticasone furoate is excreted in human breast milk.

Administration of fluticasone furoate to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

Fertility

There are no fertility data in humans.

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

Summary of the safety profile

The most commonly reported adverse reactions during treatment with fluticasone furoate are epistaxis, nasal ulceration and headache. The most serious undesirable effects are rare reports of hypersensitivity reactions, including anaphylaxis (less than 1 case per 1000 patients).

Tabulated list of adverse reactions

There were over 2700 patients treated with fluticasone furoate in safety and efficacy studies for seasonal and perennial allergic rhinitis. Paediatric exposure to fluticasone furoate in safety and efficacy studies in seasonal and perennial allergic rhinitis included 243 patients 12 to <18 years, 790 patients 6 to <12 years and 241 patients 2 to <6 years.

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.

Description of selected adverse reactions

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 6 weeks) than in short-term use (up to 6 weeks).

Systemic effects

Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods (see section 4.4). Growth retardation has been reported in children receiving nasal corticosteroids.

^** Dyspnoea cases were reported in more than 1% of patients during clinical trials with fluticasone furoate; similar rates were also observed in placebo groups.

Paediatric population

The safety in children under 6 years has not been well established. Frequency, type and severity of adverse reactions observed in the paediatric population are similar to those in the adult population.

Epistaxis

^* 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.

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 in growth velocity was observed compared to placebo (see Clinical efficacy and safety).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the national reporting system listed in Appendix V.

Not applicable.