Genemist 27.5 _g Nasal spray suspension

Adults and adolescents (12 years and over): Treatment of the symptoms of seasonal allergic rhinitis: In patients with seasonal allergic rhinitis, GENEMIST nasal spray is indicated in the treatment of nasal symptoms (rhinorrhoea, nasal congestion, nasal itching and sneezing) and ocular symptoms (itching/burning, tearing/watering, and redness of the eye). Treatment of the symptoms of perennial allergic rhinitis: In patients with perennial allergic rhinitis, GENEMIST nasal spray is indicated in the treatment of nasal symptoms (rhinorrhoea, nasal congestion, nasal itching and sneezing).

Children (2 to 11 years): Treatment of the symptoms of seasonal allergic rhinitis: In patients with seasonal allergic rhinitis, GENEMIST nasal spray is indicated in the treatment of nasal symptoms (rhinorrhoea, nasal congestion, nasal itching and sneezing). Treatment of the symptoms of perennial allergic rhinitis: In patients with perennial allergic rhinitis, GENEMIST nasal spray is indicated in the treatment of nasal symptoms (rhinorrhoea, nasal congestion, nasal itching and sneezing).

Posology For full therapeutic benefit regular scheduled usage is recommended. Onset of action has been observed as early as 8 hours after initial administration. It may take several days of treatment to achieve maximum benefit. An absence of an immediate effect should be explained to the patient.

Seasonal allergic rhinitis and perennial allergic rhinitis:

Adults and adolescents (12 years and over): The recommended starting dosage is two sprays (27,5 u03bcg of fluticasone furoate per spray) in each nostril once daily (total daily dose: 110 u03bcg). Once adequate control of symptoms is achieved, dose reduction to one spray in each nostril (total daily dose: 55 u03bcg) may be effective for maintenance.

Children (2 to 11 years of age): The recommended starting dosage is one spray (27,5 u03bcg of fluticasone furoate per spray) in each nostril once daily (total daily dose: 55 u03bcg). Patients not adequately responding to one spray in each nostril once daily (total daily dose: 55 u03bcg) may use two sprays in each nostril once daily (total daily dose: 110 u03bcg). Once adequate control of symptoms is achieved, dose reduction to one spray in each nostril once daily (total daily dose: 55 u03bcg) is recommended.

Children under 2 years of age: There is no experience in children under the age of 2 years.

Elderly patients: The normal adult dosage is applicable.

Renal patients: The normal adult dosage is applicable.

Hepatic patients: No dose adjustment is required in patients with hepatic impairment (see section 5.2).

Method of administration: GENEMIST nasal spray is for administration by the intranasal route only. Shake the nasal spray before use. Patients should be instructed that the device must be primed before first use and re-primed if the cap is left off or the device does not seem to be working. 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.

Hypersensitivity to fluticasone furoate or to any of the excipients of GENEMIST nasal spray listed in section 6.1.

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 u03bcg 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 u03bcg 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 practitioners 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 u22651/10, common u22651/100 and <1/10, uncommon u22651/1 000 and <1/100, rare u22651/10 000 and <1/1 000, very rare <1/10 000, not known (cannot be estimated from the available data).

Clinical trial data: Respiratory, thoracic and mediastinal disorders Very common Epistaxis Common Nasal ulceration Musculoskeletal and connective tissue disorders Not known Growth retardation in children Eye disorders Not known Vision blurred (see section 4.4)

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 u03bcg 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 u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

In a bioavailability study, intranasal doses of up to 2 640 u03bcg per day were administered over three days with no adverse systemic effects observed. Acute overdose is unlikely to require any therapy other than observation.