Indacaterol

Indacaterol is a beta2 sympathomimetic of the long-acting sympathomimetic type. The pharmacon has the molecular formula C24H28N2O3 and has a molar mass of 392.49 g-mol-1. The average half-life is about 40.0 h.

Indacaterol leads to a long-lasting activation of ß2-adrenergic receptors, which catalyses the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAmP). The increased concentration of cAmP leads to relaxation of the bronchial muscles. Inhaled indacaterol thus acts locally in the lungs as a bronchodilator. On a median it takes about 15 minutes after application of a single inhalation dose or repeated inhalation doses until peak concentrations of indacaterol in serum are reached. Indacaterol is characterized by a very long duration of action (indacaterol belongs to the so-called uLABA = ultra-long acting beta agonist). Therefore, in contrast to other long-acting β2 sympathomimetics (LABA, e.g. Salmeterol and Formoterol), it is only applied 1x /day. The absolute bioavailability of indacaterol after one inhalation dose is 43 % on average. Indacaterol is excreted >50% via the feces mostly unchanged.

COPD. In contrast to salmeterol and formoterol, which are also approved for bronchial asthma, the indication for indacaterol is limited to bronchodilatory maintenance therapy in patients with chronic obstructive pulmonary disease (COPD).

The approval of the preparation is based on several studies involving 3,809 patients (average age 64 years) with moderate (51% to 56%) to severe (39% to 43%) COPD. The forced expiratory volume in one second (FEV1) increased significantly after 12 weeks by 150 ml to 190 ml compared to baseline (baseline FEV1 1,300-1,500 ml), while it remained nearly unchanged under placebo.

Common (≥ 1/100, < 1/10): skeletal muscle spasm, tremor, rhinorrhea, nasopharyngitis, upper respiratory tract infections, sinusitis, hyperglycemia, headache, symptoms of ischaemic heart disease, cough, pharyngolaryngeal pain, airway obstruction, peripheral oedema

Indacaterol causes a post-inhalation coughing irritation in a proportion of patients, which is not associated with the severity or exacerbations of COPD. (Period 6 months: indacaterol: 17% to 20%, placebo: 2%, formoterol 0.9%, tiotropium 0.8%).

Inhalation of high doses of indacaterol may possibly lead to an increase in blood sugar levels. In patients with diabetes, blood glucose levels should be closely monitored after starting treatment with indacaterol. Indacaterol may cause significant hypokalemia in some patients, which may cause adverse cardiovascular effects.

Occasional (≥ 1/1000, < 1/100) paraesthesia, atrial fibrillation, non-cardiac chest pain

The simultaneous use of other sympathomimetic drugs (alone or as part of a combination therapy) may increase the adverse effects of indacaterol. Indacaterol must not be used together with other long-acting beta-2-adrenergic agonists or drugs containing long-acting beta-2-adrenergic agonists. Simultaneous potassium-lowering treatment with methylxanthine derivatives, glucocorticoids or nonpotassium-sparing diuretics may increase hypokalemia possibly caused by beta-2-adrenergic agonists.

Beta-blockers may attenuate or antagonize the action of beta-2 adrenergic agonists. Indacaterol should therefore not be used together with beta-blockers (including eye drops). In patients with CHD or heart failure and COPD, beta-blocker therapy may be indicated to reduce cardiovascular events. Inhibition of the main components of indacaterol clearance, CYP3A4 and P-glycoprotein (P-gp), increases the systemic concentration of indacaterol up to two times.

Onbrez Breezhaler©; each capsule contains 150 micrograms or 300 micrograms of indacaterol as indacaterol maleate

From severity level II of COPD, airway obstruction with simultaneous moderate FEV1 reduction (FEV1 values between 50 % and less than 80 % of the target value), the administration of one or more long-acting inhaled bronchodilators (long-acting beta-2 agonists (LABA) and/or anticholinergics) is part of the standard therapy for COPD. Inhaled corticosteroids (ICS) should only be prescribed to patients whose FEV1 is < 50% of the target value and who have more than two exacerbations per year requiring antibiotic and/or oral corticosteroid therapy. The indication should be checked regularly during the course of the treatment. Treatment objectives are to reduce the rate of exacerbation and to slow the rate of deterioration, which is not necessarily reflected in lung function data (1-3).

1. Donohue JF et al( 2010) Once-daily bronchodilators for chronic obstructive pulmonary disease: indacaterol versus tiotropium. At J Respir Crit Care Med 182: 155-162.
2. EMEA: European Evaluation Report (EPAR) ONBREZ BREEZHALER, status Dec. 2009;
3. Global Initiative for Chronic Obstructive Lung Disease: Global Strategy for Diagnosis, Management, and Prevention of COPD, December 2009;
4. Korn S et al (2011) Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: a 12-week study. Respir Med 105: 719- 726
5. Metaxas EI et al (2018) The safety of indacaterol for the treatment of COPD. Expert Opinion Drug Saf 17:637-642.