The Fflux study is an open-label, randomised, controlled, non-inferiority trial, comparing the effectiveness of switching 225 adult patients with asthma, who were controlled on Seretide® Evohaler® 250/25 µg. Patients either remained on Seretide® Evohaler® 250/25 µg, or were switched to flutiform 250/10 µg.

For phase II of the trial, 116 patients controlled on flutiform 250/10 µg either remained on flutiform 250/10 µg, or were stepped down to flutiform 125/5 µg.

 

 

Patients who stepped across from Seretide Evohaler 250/25 µg to flutiform 250/10 µg experienced: 

Non-inferior asthma control*1

(according to ACQ7 questionnaire) 

  

Significantly higher odds of being more controlled1#

(according to GINA Criteria3)

odds ratio [95% CI] 2.04 [1.16, 3.59], p = 0.01

 

Controlled patients who stepped down to flutiform 125/5 µg:

 

Continued to benefit from good asthma control**2

 


Non-inferiority limit on the ACQ7 (7 item asthma control questionnaire) was set at 0.3
* (mean difference [95% CI] -0.11 [-0.31,0.09])
** (mean difference [95% CI] 0.01 [-0.20,0.22])

                                                                                                                                              

References 

  1. Kemppinen A, Gardener E, Thomas V et al. J Thorac Dis 2016; 8(Suppl 5):AB038.
  2. Kemppinen A, Gardener E,Thomas V et al. J Thorac Dis 2016; 8(Suppl 5):AB039.
  3. GINA (Global Initiative for Asthma). Pocket Guide for Asthma Management and Prevention (for Adults and Children Older than 5 Years). A Pocket Guide for Physicians and Nurses. Updated 2016.

flutiform®(fluticasone propionate and formoterol fumarate) pressurised inhalation suspension
Prescribing Information United Kingdom.
Please read the Summary of Product Characteristics before prescribing.
Presentation Pressurised inhalation suspension, in a pressurised metered dose inhaler (pMDI), containing fluticasone propionate and formoterol fumarate dihydrate at strengths of 50 μg/5 μg, 125 μg/5 μg or 250 μg/10 μg per actuation. Indications Regular treatment of asthma where the use of a combination product (inhaled corticosteroid and long-acting β2-agonist) is appropriate: For patients not adequately controlled with inhaled corticosteroids and ‘as required’ inhaled short-acting β2-agonist (SABA), or for patients already adequately controlled on both an inhaled corticosteroid and a long-acting β2-agonist (LABA). flutiform 50 μg/5 μg and 125 μg/5 μg per actuation are indicated for use in adults and adolescents 12 years and above. flutiform 250 μg/10 μg per actuation is only indicated for use in adults. Dosage and administration For inhalation use. The patient should be shown how to use the inhaler correctly by a physician or other healthcare professional. Patients should be given the strength of flutiform containing the appropriate fluticasone propionate dose for their disease severity (note that flutiform 50 μg/5 μg per actuation is not appropriate in patients with severe asthma). The appropriate strength should be taken as two inhalations, twice-daily (normally in the morning and evening) and used every day, even when asymptomatic. flutiform should not be used in children under 12 years. Prescribers should be aware that in asthmatics, fluticasone propionate is as effective as some other inhaled steroids when administered at approximately half the total daily microgram dose. Total daily dose can be increased if asthma remains poorly controlled by administering a higher strength inhaler. Appropriate doses of the β2-agonist and inhaled corticosteroid (ICS) in separate inhalers, or the ICS alone, should be prescribed if a patient requires doses outside the recommended dose regimens. Patients should be assessed regularly and once asthma is controlled, treatment should be reviewed and stepped down to the lowest effective dose, or an ICS alone. It is extremely important to regularly review patients as their treatment is stepped down. ICSs alone are first line treatment for most patients. flutiform is not intended for initial treatment of mild asthma. For patients with severe asthma the ICS therapy should be established before prescribing a fixed-dose combination product. Patients on flutiform must not use an additional LABA. An inhaled SABA should be taken for immediate relief of asthma symptoms arising between doses. The AeroChamber Plus® spacer device is recommended in patients who find it difficult to use inhalers; re-titration should always follow the introduction of a spacer device. Patients should be advised to contact their prescriber when the flutiform dose counter is getting near zero. Contra-indications Hypersensitivity to the active substances or to any of the excipients. Precautions and warnings flutiform should not be used for the first treatment of asthma, to treat acute asthma symptoms or for prophylaxis of exercise-induced asthma. It should not be initiated during an exacerbation, during significantly worsening or acutely deteriorating asthma, and should not be stopped abruptly. Patients should use their flutiform maintenance treatment as prescribed, even when asymptomatic. If a patient experiences serious asthma-related adverse events or exacerbations, they should continue treatment but also seek medical advice. Patients should be reviewed as soon as possible if there is any indication of deteriorating asthma control. In the case of sudden and progressive deterioration, which is potentially life-threatening, an urgent medical assessment should be carried out. Use with caution in patients with: pulmonary tuberculosis; quiescent tuberculosis; fungal, viral or other infections of the airway; thyrotoxicosis; pheochromocytoma; diabetes mellitus (consider additional blood sugar controls); uncorrected hypokalaemia; predisposition to low levels of serum potassium; impaired adrenal function (monitor HPA axis function regularly) ; hypertrophic obstructive cardiomyopathy; idiopathic subvalvular aortic stenosis; severe hypertension; aneurysm or other severe cardiovascular disorders. There is risk of potentially serious hypokalaemia with high doses of β2-agonists or concomitant treatment with β2-agonists and drugs that can induce or potentiate a hypokalaemic effect. Particular caution is recommended in unstable or acute severe asthma and other conditions when the likelihood for hypokalemia adverse effects is increased. Monitoring of serum potassium levels is recommended during these circumstances. Formoterol may induce prolongation of the QTc interval. Caution must be observed when treating patients with existing prolongation of QTc interval. flutiform shodiscontinued immediately if there is evidence of paradoxical bronchospasm. Systemic effects with an ICS may occur, particularly at high doses for prolonged periods or when combined with potent CYP3A4 inhibitors, but are less likely than with oral corticosteroids. Use of a spacer device may also cause an increased systemic exposure. Increased exposure can be expected in patients with severe hepatic impairment. Prolonged treatment with high doses of corticosteroids may result in adrenal suppression and acute adrenal crisis, particularly in adolescents and children or potentially as a result of trauma, surgery, infection or rapid dose reduction. Patients should be advised that flutiform contains a small amount of ethanol; however this negligible amount does not pose a risk to patients. flutiform is not recommended in children under 12 years of age. Interactions Caution is advised in long-term co-administration with strong CYP3A4 inhibitors (e.g. ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nelfinavir, saquinavir, ketoconazole and telithromycin); co-administration should be avoided if possible. Ritonavir in particular should be avoided, unless the benefits outweigh the risks of systemic side-effects. Caution is advised with use of non-potassium sparing diuretics (e.g. loop or thiazide), xanthine derivatives, glucocorticosteroids, L-Dopa, L-thyroxine, oxytocin, alcohol or other adrenergic drugs. There is an increased risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons. Hypokalaemia may increase the risk of arrhythmias in patients being treated with digitalis glycosides. Concomitant use of β-adrenergic drugs can have a potentially additive effect. Caution should be taken when using formoterol fumarate with drugs known to prolong the uld be QTc interval, such as tricyclic antidepressants or MAOIs (and for two weeks following their discontinuation), as well antipsychotics (including phenothiazines), quinidine, disopyramide, procainamide and antihistamines. Concomitant use of an MAOI or a similar agent, such as furazolidone or procarbazine, may precipitate hypertensive reactions. β-blockers and formoterol fumarate may inhibit the effect of each other. β-blockers may produce severe bronchospasm in asthma patients, and they should not normally be treated with β-blockers including those that are used as eye drops to treat glaucoma. Under certain circumstances, as e.g. as prophylaxis after myocardial infarction, cardioselective β blockers could be considered with caution. Pregnancy and lactation flutiform is not recommended during pregnancy. It should only be considered if benefits to the mother outweigh risks to the foetus. It is not known whether fluticasone propionate or formoterol are excreted in breast milk; a risk to the breast feeding infant cannot be excluded. A decision should be made on whether to discontinue breastfeeding or discontinue/abstain from flutiform. Side-effects Potentially serious side-effects: hyperglycaemia; depression; aggression; behavioural changes (predominantly in children); paradoxical bronchospasm; agitation; vertigo; palpitations; ventricular extrasystoles; angina pectoris; tachycardia; hypertension; dyspnoea; peripheral oedema; Cushings Syndrome; adrenal suppression; growth retardation; cataract and glaucoma; hypersensitivity reactions and QTc interval prolongation. Please consult the SPC for details of non-serious side-effects and those reported for the individual molecules. Legal category POM Package quantities and price One inhaler containing 120 actuations 50 μg/5 μg - £14.40 125 μg/5 μg - £28.00 250 μg/10 μg - £45.56 Marketing Authorisation numbers PL 16950/0167 PL 16950/0168 PL16950/0169 Marketing Authorisation holder Napp Pharmaceuticals Limited, Cambridge Science Park, Milton Road, Cambridge CB4 0GW, UK. Tel: 01223 424444. Member of the Napp Pharmaceutical Group For medical information enquiries, please contact medicalinformationuk@napp.co.uk Date of preparation July 2015 Date effective August 2015UK/FLUT-15085
Adverse events should be reported.
Reporting forms and information can be found at
www.mhra.gov.uk/yellowcard.
Adverse events should also be reported
to Napp Pharmaceuticals Limited on
01223 424444.
® FLUTIFORM is a registered trade mark of Jagotec AG, and is used under licence.
® The ‘lung’ device (logo) is a registered trade mark of Mundipharma AG
® AEROCHAMBER and AEROCHAMBER PLUS are registered trademarks of Trudell Medical International.
© 2012 Napp Pharmaceuticals Limited.
® SERETIDE and EVOHALER are registered trade marks of Glaxo Group Limited.
UK/FLUT-16060Date of preparation: October 2016