Flutiform: novel asthma combination inhaler

PHARMACOLOGY

Flutiform contains a new combination of agents: the selective LABA, formoterol, and the synthetic corticosteroid, fluticasone. The LABA acts as a bronchodilator whilst the corticosteroid exerts a potent anti-inflammatory effect.¹

Flutiform is available in three strengths, with a dose schedule of two puffs twice daily. Flutiform 5 microgram/50 microgram and 5 microgram/125 microgram are licensed for use in adults and adolescents aged 12 years and above. Flutiform 10 microgram/250 microgram is licensed for use only in adults.¹

CLINICAL STUDIES

A randomised, double-blind, international trial compared the efficacy of the formoterol/fluticasone combination inhaler with its individual components in separate inhalers, over an eight-week period. The study included patients 18 years and older with a history of severe, persistent reversible asthma for six months or more. The primary endpoint was the mean change from baseline to end of treatment in pre-morning dose forced expiratory volume in one second (FEV₁).²

Combination formoterol/fluticasone treatment (two puffs of 10 microgram/250 microgram twice daily) was at least as effective as administration via separate inhalers (two puffs of formoterol 12 microgram and fluticasone 250 microgram, twice daily), with increases in mean pre-morning dose FEV₁ of 345ml and 284ml, respectively (n=273; p<0.001). The combination was also non-inferior to separate inhalers in terms of change in FEV₁ from baseline pre-morning dose to two hours post-morning dose after eight weeks (p<0.001).²

Safety and tolerability of the combination inhaler were similar to that of the separate inhalers. The most commonly observed adverse events overall were headache, nasopharyngitis, pharyngitis, asthma and viral infection.²

A 12-week, open-label, non-inferiority study (n=202) compared the formoterol/fluticasone combination inhaler with a commercially available salmeterol/fluticasone combination inhaler (Seretide). The study included patients aged 18 years or older with a history of mild to severe persistent reversible asthma for six months or more. Patients were randomised to receive formoterol/ fluticasone as two puffs of 5 microgram/50 microgram or 5 microgram/125 microgram twice daily, or salmeterol/fluticasone as two puffs of 25 microgram/50 microgram or 25 microgram/125 microgram twice daily.³

The primary endpoint, mean pre-dose FEV₁ at week 12, was comparable in the two arms and met the predefined non-inferiority margin in the per-protocol analysis (p=0.007). Formoterol/fluticasone had a faster onset of action than fluticasone/salmeterol throughout the study (p<0.001). Other secondary efficacy measures and rates of adverse events were similar in the two groups.³

An international open-label study of patients with mild to severe asthma investigated the long-term safety of the formoterol/fluticasone combination inhaler. A total of 472 patients were enrolled and received treatment for either six or 12 months at doses of 10 microgram/250 microgram or 10 microgram/100 microgram twice daily; 413 patients (87.5%) completed the study. Seven patients withdrew because of adverse events. There were 18 treatment-related adverse events, of which one was severe. Overall, the safety profile of the combination was similar to that observed in previous studies.⁴

BTS/SIGN guidelines on the management of asthma recommend the use of combination LABA/steroid inhalers to improve adherence and to ensure LABAs are not taken without an inhaled steroid.⁵

References: 

1. Flutiform Summary of Product Characteristics, August 2012.
2. Bodzenta-Lukaszyk A et al. Respir Med 2011; 105: 674-82.
3. Bodzenta-Lukaszyk A et al. BMC Pulm Med 2011; 11: 28.
4. Mansur A. Poster presented at European Respiratory Society Annual Congress, Berlin, October 2008; P3625.
5. BTS/SIGN. British Guideline on the Management of Asthma (May 2008 — revised January 2012).

View Flutiform drug record

Further information: Napp