GENEMIST Nasal spray, suspension Ref.[115274] Active ingredients: Fluticasone furoate

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

Fluticasone furoate has a negligible (0,50%) systemic bioavailability at intranasal doses of up to 24 times the recommended adult daily dose (2 640 μg per day). Systemic effects of nasal corticosteroid may occur, particularly at high doses prescribed for prolonged periods. These effects are less likely to occur than with oral corticosteroids and may vary between patients and different corticosteroids.

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 once daily was not associated with 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 are maintained.

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 μg daily for one year (see section 4.8). Therefore, children should be maintained on the lowest dose which delivers adequate symptom control (see section 4.2). 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.

Medical practioners should be alert to the risk that potential systemic steroid effects including ocular changes, such as central serous chorioretinopathy may occur. GENEMIST contains benzalkonium chloride (see section 6.1). Long-term use may cause oedema of the nasal mucosa.

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

Based on data with another glucocorticoid metabolised by CYP3A4, co-administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate.

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 medicines.

Safety and efficacy of GENEMIST in pregnancy and lactation has not been established.

There are no fertility data in humans.

Based on the pharmacology of fluticasone furoate and other intranasally administered steroids, there is no reason to expect an effect on ability to drive or to operate machinery with GENEMIST.

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 ≥1/1 000 and <1/100, rare ≥1/10 000 and <1/1 000, very rare <1/10 000, not known (cannot be estimated from the available data).

Clinical trial data:

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). 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 μg of GENEMIST once daily, an average treatment difference of -0,27 cm per year in growth velocity was observed compared to placebo.

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 of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of GENEMIST is important. It allows continued monitoring of the benefit/risk balance of GENEMIST. Health care providers are asked to report any suspected adverse reactions to: SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8.

Not applicable.