Indacaterol

Long-acting beta2-agonists (LABAs) increase the risk of asthma-related deaths. Indacaterol is not indicated for the treatment of asthma; the safety and efficacy of indacaterol in the treatment of asthma have not been established. In a large, randomized, placebo-controlled US clinical trial (SMART 2006), salmeterol was associated with an increase in asthma-related deaths (when added to usual asthma therapy); risk is considered a class effect among all LABAs. It is unknown if indacaterol increases asthma-related deaths. Data are not available to determine if the addition of an inhaled corticosteroid lessens this increased risk of death associated with LABA use; however, current guidelines recommend the use of an inhaled corticosteroid before adding a LABA (GINA 2015; NIH/NHLBI 2007). In a more recent multicenter, randomized, double-blinded trial, the use of salmeterol and an inhaled corticosteroid (ie, fluticasone) combined in a single inhaler in a large number of children, adolescent, and adult patients with persistent asthma (non-life threatening and stable) did not increase the risk of serious asthma-related events compared with fluticasone alone; in addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). No data exist associating LABA use with an increased risk of death in patients with COPD.

Paradoxical bronchospasm that may be life-threatening may occur with use of inhaled bronchodilating agents; this reaction should be distinguished from inadequate response. Discontinue immediately if paradoxical bronchospasm occurs and institute alternative therapy.

Immediate hypersensitivity reactions (difficulty in breathing or swallowing; swelling of tongue, lips, and face; urticaria; skin rash) have been reported; discontinue therapy immediately if patient develops an allergic reaction.

Do not exceed recommended dose or frequency or use with other medications containing LABAs; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics. Disease-related concerns:

Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension, or HF); beta-agonists may cause elevation in blood pressure and heart rate. Beta2-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.

Do not use for acute bronchospastic episodes of COPD. Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Data are not available to determine if LABA use increases the risk of death in patients with COPD.

Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose. The effect is usually transient.

Use with caution in patients with hyperthyroidism; may stimulate thyroid activity.

Use with caution in patients with hypokalemia; beta2-agonists may decrease serum potassium. The effect is usually transient.

Use with caution in patients with seizure disorders; beta2-agonists may result in CNS stimulation/excitation. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions for more detailed information. Dosage form specific issues:

Product contains lactose; allergic reactions possible in patients with severe milk protein allergy. Other warnings/precautions:

Patients using inhaled, short-acting beta2-agonists should be instructed to discontinue routine use of these medications prior to beginning treatment. Short-acting agents should still be provided to patients; however, use should be reserved for symptomatic relief of acute symptoms. Patients must be instructed to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of short-acting beta2-agonists may indicate deterioration of COPD, and medical evaluation must not be delayed.

Tolerance to the bronchodilator effect, measured by FEV1, has been observed in studies.