Fostair: new beclometasone/ formoterol CFC-free …

1 30 Prescriber 19 June productsCurrent guidance on the man-agement of chronic asthmarecommends that a long-actingbeta2-agonist (LABA) should beintroduced for patients alreadytreated with an inhaled steroid,for whom symptom controlremains unsatisfactory (Step 3).1 There is no difference in efficacybetween using a fixed-dose com-bined inhaler or separate inhalersto administer a LABA and aninhaled are now three combina-tions of a steroid with a LABA:Symbicort Turbohaler (budes-onide/ formoterol ), SeretideAccuhaler and Evohaler (fluticas-one/salmeterol) and fostair ( beclometasone dipropionate/for-moterol).

2 The technologyFostair is a CFC-free metered-doseinhaler (MDI) containing 100 gbeclometasone dipropionate and6 g formoterol per actuation. Thesteroid is delivered as a fine-parti-cle aerosol and has higherbioavailability than that of a CFCMDI: 100 g beclometasone inFostair is equivalent to 250 g froman MDI delivering a is licensed for the regu-lar treatment of asthma where useof a combination product (inhaledcorticosteroid and LABA) is appro-priate, iepatients not adequatelycontrolled with inhaled cortico-steroids and as-needed inhaledshort-acting beta2-agonist orpatients already adequately con-trolled on both inhaled corticos-teroids and recommended dose is oneor two actuations twice daily, to amaximum of four per day.

3 Fostairis not recommended for peopleunder trialsFostair has been compared withfluticasone/salmeterol 125/25 g(n=228)2and budesonide/for-moterol 200/6 g (n=219)3inpatients with moderate to severeasthma. All drugs were adminis-tered as two puffs twice daily(total daily doses are listed inTable 1). Both trials included patientswith forced expiratory volume inone second (FEV1) 50-80 per centFostair: new beclometasone / formoterol CFC-free combinationSteve Chaplin MSc, MRPharmS andPhilip IndMA, FRCPKEY POINTSlFostair is a CFC-free MDI containingbeclometasone dipropionate 100 g and formoterol 6 g per actuationldosage: one or two puffs twice daily.

4 120doses, for the treatment of chronic asthmain adults and is introduced at Step 3 of the BTS/SIGN managementguidelinelbeclometasone is delivered as a fine aerosol that is not bioequivalent toa standard MDI: 100 g beclometasone in fostair is equivalent to 250 gfrom a CFC MDIlin two 12-week trials in patients with stable moderate to severe asthma, fostair was not inferior to fluticasone/salmeterol (Seretide) or budes-onide/ formoterol (Symbicort) at equivalent doseslthe adverse effects of fostair are typical of its component drugslFostair is cheaper than alternative inhaled steroid/long-acting beta2-agonist combinationsFostair is the firstbeclometasone/formoterolcombination for the treat-ment of asthma.

5 Here, SteveChaplin describes the clini-cal trial data relating to itsefficacy and safety, and DrInd comments on its place intherapy. productsFostair ( beclometasone / formoterol )400 g*24 gfluticasone/salmeterol500 g100 gbudesonide/formoterol800 g24 g* equivalent to 1000 g beclometasone from a non-CFC free MDI delivering a non-fine aerosolSteroidLABAT able daily doses of inhaled steroids and LABAs in fostair clinical trialsFigure morning PEF: fostair vsfluticasone/salmeterol (top)2and vsbudes-onide/ formoterol ,3showing no significant difference between treatments**0246810123002001000 MorningPEF(litresperminute)Baseline24681 012 Weeks345340335330325320315310305300 MorningPEF(litresperminute)

6 **p< vsbaselinebeclometasone/ formoterol fluticasone/salmeterolbeclometasone/form oterol budesonide/ formoterol 32 Prescriber 19 June 2008predicted and persistent symp-toms despite treatment with up to1000 g beclometasone dipropi-onate or equivalent (mean base-line dose approximately730-810 g per day). Patients whoexperienced an exacerbation orincreased peak expiratory flow(PEF) during a two-week run-inperiod were studies were designed toassess the noninferiority of Fostaircompared with the comparatorand were of 12 weeks primary end-point in bothwas the mean morning predosePEF during the last two weeks both studies, fostair was notinferior to the comparator prod-uct.

7 Mean PEFs over 12 weeks areillustrated in Figure 1. There werealso no differences betweenFostair and the comparator treat-ments in secondary end-pointsincluding symptom improvement,days free of symptoms and use ofrescue salbutamol during the lasttwo weeks. There were no significant dif-ferences in the frequency of exac-erbations throughout the effectsThe adverse effects associated withFostair are typical of its compo-nent were no sig-nificant differences betweentreatments in the two British Thoracic Society, ScottishIntercollegiates Network.

8 Britishguideline on the management ofasthma. Revised edition May 2008( ;accessed ).2. Papi A, Paggiaro P, Nicolini G, etal. Beclomethasone/ formoterol vsfluticasone/salmeterol inhaled com-bination in moderate to severeasthma. Allergy2007;62 Papi A, Paggiaro PL, Nicolini G, etal. Beclomethasone/ formoterol ver-sus budesonide/ formoterol combina-tion therapy in asthma. Eur Respir J2007;29 Trinity-Chiesi Summary of ProductCharacteristics. November 2007( % ; ).By Steve Chaplin, a pharmacist whospecialises in writing on 19 June 200833 New productsPlace in therapyAddition of a LABA to an inhaledsteroid is probably the best evidence-based step in the asthma guidelines(step 3 of the British ThoracicSociety guidelines).

9 Combination ofan inhaled steroid and a LABA in asingle inhaler is logical: both com-ponents are administered twicedaily, they have complementaryeffects, the combination preventsdeliberate, or inadvertent, inhaledsteroid noncompliance, it is conve-nient for the patient and doctor, andis cost-saving. The launch of fostair brings athird inhaled steroid/LABA com-bination product after Seretide(fluticasone/salmeterol) andSymbicort(budesonide/for-moterol). fostair is a combination ofbeclometasone, the oldest (andmost used world-wide) inhaledsteroid, and formoterol , the rapid-onset LABA, in a CFC-free is unlikely to be a major con-cern because of the well-establishedtrack record of its clinical trial evidence(reviewed above) suggests thatFostair 100/6 g is equivalent toSeretide 125/25 g and Symbicort200/6 g, all two puffs twice daily,in terms of morning ,2A number of interesting pointsare raised, however:1.

10 How should equivalence of com-bination inhalers be measured?2. Should noninferiority studiesinclude a placebo arm?3. What about noninferiority ofother important end-points, egexacerbations? Two good studieswere powered for change in morn-ing PEF but information aboutother measures is How do these findings, in a selectpopulation (patients with moder-ate-severe persistent asthma with amarked bronchodilator responsedespite inhaled steroid 800 g perday, as recruited in most LABA tri-als), apply in the real world?