Pharmacology Update

Indacaterol Inhalation Powder (Arcapta™ Neohaler)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.

An ultra long-acting, orally-inhaled beta2-adrenergic agonist (LABA) has been approved for the treatment of chronic obstructive pulmonary disease (COPD). Indacaterol is formulated as a dry powder and is the first beta2-agonist to be dosed once-daily. It is marketed by Novartis as Arcapta™.

Indications

Indacaterol is approved for the treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.1

Dosage

The recommended dose is 75 mcg inhaled once daily using the Neohaler inhaler.1 Indacaterol is available as hard capsules each containing containing 75 mcg of inhalation powder.

Potential Advantages

Indacaterol has a long effective half-life (40 to 56 hours) and is dosed once-daily compared to salmeterol and formoterol which are dosed twice-daily.

Potential Disadvantages

Indacaterol shares the same warning for increased risk of asthma-related death as other LABAs, although it is not clear if this applies to COPD patients.

Comments

Indacaterol is an LABA. The efficacy of the FDA- approved dose of 75 mcg daily was shown in two 12-week, Phase 3, placebo-controlled studies involving 641 patients with COPD.1 Subjects were 40 years of age or older, had smoking histories of at least 10 pack years, post-bronchodilator FEV1 less than 80%, and at least 30% of the predicted normal value and post-bronchodilator ratio of FEV1/FVC of less than 70%. The primary efficacy endpoint, trough FEV1 values at 12 weeks, were 1.38 liters for indacaterol and 1.26 liters for placebo, treatment difference (95% confidence interval [CI]) of 0.12 L (0.08, 0.15) in one study and 1.49 L and 1.35 L (treatment difference 0.14 L [0.10, 0.18]) in the second study. The bronchodilatory effect was observed 5 minutes after dose administration with the peak effect occurring at 4 hours. Improvement of pulmonary function was maintained over 12 weeks.

In addition, there was reduced use of short-acting beta2-agonists and improvement in health-related quality of life as measured by the St. George Respiratory Questionnaire. Indacaterol was generally well tolerated. Common adverse events included cough (6.5%), nasopharyngitis (5.3%), and headache (5.1%).1 In a 12-week randomized, parallel-group study in patients with moderate-to-severe COPD (n = 1123), indacaterol 150 mcg once-daily was statistically more effective than salmeterol 50 mcg twice-daily in terms of lung function (FEV1 difference of 60 mL, 95% CI: 35, 79).2 In a study involving similar patients (n = 1598), indacaterol was at least as effective as tiotropium 18 mcg in terms of lung function, but more effective in clinical outcomes and was associated with lower use of albuterol rescue.3 The FDA only approved the 75 mcg dose, concluding that there was no statistically significant difference among the three doses and deciding not to approve the higher doses.4 In Europe, however, the 150 mcg and 300 mcg doses are available (e.g., Onbrez Breezhaler).

Clinical Implications

Indacaterol is the first once-daily beta2-agonist to be approved for COPD in the United States. Long-acting agents are indicated for patients with moderate to very severe COPD.5

References

1. Arcapta Neohaler Prescribing Information. Novartis Pharmaceuticals. July 2011.

2. Korn S, et al. Indacaterol once-daily provides superior efficacy to salmeterol twice-daily in COPD: A 12-week study. Respir Med 2011;105:719-726.

3. Buhl R, et al. Blinded 12-week comparison of once-daily indacaterol and tiotropium in COPD. Eur Respir J 2011;38:797-803.

4. Indacaterol Summary Review. Centers for Drug Evaluation and Research. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails. Accessed Sept. 20, 2011.

5. Gobal Initiative for Chronic Obstructive Lung disease: Management Reference for Chronic Obstructive Pulmonary Disease. www.goldcopd.org. Accessed Sept. 23, 2011.