FLUTIFORM

What it is

Flutiform is a pressurised metered dose inhaler containing fluticasone propionate and formoterol fumarate dihydrate. The inhaler is a white to off-white liquid suspension inside a pressurised metal canister. Flutiform is available in three strengths: 50 micrograms fluticasone propionate with 5 micrograms formoterol fumarate dihydrate per actuation; 125 micrograms fluticasone propionate with 5 micrograms formoterol fumarate dihydrate per actuation; and 250 micrograms fluticasone propionate with 10 micrograms formoterol fumarate dihydrate per actuation. Fluticasone propionate is a synthetic trifluorinated glucocorticoid with potent anti-inflammatory activity in the lungs when administered by inhalation, and reduces the symptoms, improves lung function and prevents exacerbations of asthma, with fewer adverse effects than when corticosteroids are administered systemically. Formoterol fumarate is a potent long-acting, selective beta-2 adrenergic receptor agonist that acts locally in the lungs as a bronchodilator, with onset of bronchodilation occurring rapidly within one to three minutes and a duration of effect of at least twelve hours.

Approved indications

— Regular maintenance treatment of asthma where the use of a combination product (an inhaled corticosteroid and a long-acting beta-2 agonist) is appropriate, including patients not adequately controlled with inhaled corticosteroids and inhaled short-acting beta-2 agonist on an 'as required' basis.

Dosing overview

Flutiform is for administration by the inhaled route in patients with asthma from the age of 12 years and older. The recommended dose for adults and children aged 12 years and above is two inhalations of Flutiform 50/5 micrograms or Flutiform 125/5 micrograms twice daily; if asthma remains poorly controlled on the 50/5 strength, the dose can be increased to two inhalations of Flutiform 125/5 micrograms twice daily. For adults only, the recommended dose is two inhalations of Flutiform 250/10 micrograms twice daily; if asthma remains poorly controlled on Flutiform 125/5 micrograms, the dose can be increased to two inhalations of Flutiform 250/10 micrograms twice daily. For patients currently receiving medium to high doses of inhaled corticosteroid therapy whose disease severity clearly warrants treatment with two maintenance therapies, the recommended starting dose is two inhalations twice daily of Flutiform 125/5 micrograms. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained.

Key safety warnings

Flutiform should not be used to treat acute asthma symptoms, for which a fast and short-acting bronchodilator is required. Serious asthma-related adverse events and exacerbations may occur during treatment with Flutiform, and patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Flutiform. Sudden and progressive deterioration in the control of asthma is potentially life-threatening and these patients require urgent medical assessment. Cardiovascular effects such as increases in systolic blood pressure and heart rate may occasionally be seen with all sympathomimetic drugs, especially at higher than therapeutic doses, and Flutiform should be used with caution in patients with pre-existing cardiovascular disease including prolongation of the QTc interval. Flutiform should be used with caution in patients with a history of thyrotoxicosis, phaeochromocytoma, diabetes mellitus, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium, hypertrophic obstructive cardiomyopathy, idiopathic sub-valvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, cardiac arrhythmias or severe heart failure. With sufficient doses, all inhaled steroids can have adverse effects; possible systemic effects include Cushing's syndrome, Cushingoid features, depression of the hypothalamic-pituitary adrenal (HPA) axis, reduction of bone mineral density, cataract, glaucoma and retardation of growth rate in children and adolescents. Prolonged treatment with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Visual disturbance may be reported with systemic and topical corticosteroid use, and 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).

Contraindications

Flutiform is contraindicated in patients with hypersensitivity to any of the active substances or to the excipients.

Regulatory history

Flutiform was first registered on the Australian Register of Therapeutic Goods on 14 June 2013, with three strengths registered: fluticasone propionate 50 micrograms with formoterol fumarate 5 micrograms, fluticasone propionate 125 micrograms with formoterol fumarate 5 micrograms, and fluticasone propionate 250 micrograms with formoterol fumarate 10 micrograms. The TGA approved Flutiform for regular treatment of asthma where the use of a combination product is appropriate on 4 February 2013. The TGA found the chemistry, quality control, and drug substance aspects of Flutiform acceptable, with the application being for a fixed combination of previously approved drug substances.