Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Onbrez Breezhaler (Novartis)
capsules containing 150 microgram and 300 microgram as dry powder for inhalation
Approved indication: chronic obstructive pulmonary disease
Australian Medicines Handbook section 19.1.1
Patients with chronic obstructive pulmonary disease (COPD) who have symptoms despite using short-acting bronchodilators may obtain relief by adding a long-acting bronchodilator. The choice of drug includes beta2 agonists such as eformoterol, salmeterol and now indacaterol.
A specific device is used to inhale indacaterol. Bronchodilation begins within five minutes of inhalation, with a peak effect after 2–4 hours. This action is prolonged so indacaterol is suitable for once-daily dosing. Some of the dose is absorbed into the circulation and then metabolised with very little being excreted in the urine.
Indacaterol was compared with placebo in a 28-day study of 163 patients with moderately severe COPD. From the first day the mean improvement in the forced expiratory volume in one second (FEV1) with indacaterol was significantly greater than with placebo. On day 28, FEV1 was 220 mL greater than placebo with 400 microgram indacaterol and 210 mL greater with 800 microgram once-daily.1
A lower dose (150 microgram) was used in a 12-week placebo-controlled trial involving 416 patients. FEV1 increased with indacaterol from day 1 and at the end of the study was 160 mL greater than with placebo. The trough FEV1, measured 24 hours after the final dose, was 130 mL higher than with placebo. The patients given indacaterol needed to use sulbutamol less often as a 'rescue' medication for their symptoms.2
In the placebo-controlled studies adverse events occurred with a similar frequency in all groups, although inhaling indacaterol was more likely to cause the patients to cough.12 From all the studies of indacaterol, the adverse events which have occurred more frequently than with placebo include upper respiratory tract infections, cough, muscle spasms and headache. At therapeutic doses, indacaterol does not appear to significantly affect the heart rate. There may be small changes in blood glucose and potassium.
Once-daily indacaterol has been studied with twice-daily (e)formoterol in a year-long trial. There were 437 patients randomised to inhale 300 microgram indacaterol, 428 to inhale 600 microgram, 435 to inhale 12 microgram formoterol (twice daily) and 432 to inhale placebo. Both doses of indacaterol had increased the trough FEV1 by 170 mL more than placebo and 100 mL more than formoterol, when assessed after 12 weeks. The differences between the active treatments and placebo remained significant after 12 months. Both drugs improved the control of symptoms and reduced the requirement for rescue doses of salbutamol. However, the study was not primarily powered to detect significant differences between indacaterol and formoterol.3
Another option for maintenance treatment of COPD is the long-acting anticholinergic drug tiotropium. This drug is also taken as a once-daily inhalation of dry powder. Tiotropium 18 microgram and indacaterol 150 microgram or 300 microgram were compared with placebo in a study of 1683 patients with moderate to severe COPD. After 12 weeks trough FEV1 had increased by 140 mL with tiotropium and by 180 mL with both strengths of indacaterol compared to placebo. The difference between treatments was still present after 26 weeks. Indacaterol had a greater effect on some symptoms than tiotropium did, but, as tiotropium was given open-label, any differences in efficacy will need confirmation.4
Although indacaterol has been studied in asthma, it has not been approved for this indication and it is also not recommended for mixed airways disease. While indacaterol is an efficacious bronchodilator in patients with moderate–severe COPD, the extent of long-term clinical benefit is unknown.
The Transparency Score () is explained in New drugs: transparency, Vol 37 No 1, Aust Prescr 2014;37:27.
- Feldman G, Siler T, Prasad N, Jack D, Piggott S, Owen R, et al. Efficacy and safety of indacaterol 150 microg once-daily in COPD: a double-blind, randomised, 12-week study. BMC Pulm Med 2010;10:11.
- Dahl R, Chung KF, Buhl R, Magnussen H, Nonikov V, Jack D, et al. Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax 2010;65:473-9.
- Donohue JF, Fogarty C, Lotvall J, Mahler DA, Worth H, Yorgancioglu A, et al; INHANCE Study Investigators. Once-daily bronchodilators for chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;182:155-62.