Tiotropium: A Long-Acting Muscarinic Antagonist for COPD and Asthma
Tiotropium is a long-acting muscarinic antagonist (LAMA) bronchodilator that works by inhibiting M3 receptors in airway smooth muscle, providing once-daily treatment for chronic obstructive pulmonary disease (COPD) and as add-on therapy for moderate to severe asthma. 1, 2
Mechanism of Action
- Tiotropium is an anticholinergic medication that competitively and reversibly antagonizes muscarinic receptors (M1-M5), with particularly high affinity and slow dissociation from M1 and M3 receptors 2, 3
- It exhibits pharmacological effects through inhibition of M3-receptors on airway smooth muscle, leading to bronchodilation by blocking acetylcholine-mediated bronchoconstriction 2
- The bronchodilation following inhalation of tiotropium is predominantly a site-specific effect in the airways 2
- Vagal-mediated tone through released acetylcholine at motor nerve endings is responsible for both resting and bronchoconstrictive airway responses, which tiotropium effectively blocks 1
Clinical Applications
COPD
- Tiotropium is recommended as first-line maintenance therapy for COPD patients in GOLD groups B, C, and D 4
- It provides significant improvements in lung function with approximately 12% increase in trough FEV1 over baseline 5
- Clinical benefits include reduced dyspnea, improved health-related quality of life, increased exercise tolerance, and fewer COPD exacerbations and hospitalizations 4, 5
Asthma
- Approved in the United States in 2015 for asthmatic patients aged 12 years and older at a once-daily 5 μg dose 6
- Recommended as add-on therapy in children aged 6 years and older with moderate to severe asthma that remains uncontrolled despite inhaled corticosteroids with or without additional controller medications 6
- Addition of 5 μg tiotropium to inhaled corticosteroids provides significant improvement in lung function in adolescents with moderate symptomatic asthma 1
- Can be considered as an alternative to increasing inhaled corticosteroid dose to high-dose or adding a long-acting beta agonist in children with uncontrolled asthma 6
Administration and Formulations
- Initially available as an inhalation powder delivered via a dry-powder inhaler (DPI) 4
- Later became available as an inhalation spray delivered via a soft mist inhaler (SMI), which was designed to overcome limitations of DPIs (such as the need for strong inspiratory airflow) 4
- Tiotropium administered by pressurized metered-dose inhaler (pMDI) with spacer shows similar therapeutic efficacy to tiotropium administered by DPI 7
- Standard dose is 18 μg once daily for COPD and 5 μg once daily for asthma 6, 5
Safety Profile
- Generally well-tolerated with few side effects 3
- Most common adverse effect is dry mouth, occurring in approximately 10-16% of patients 5, 3
- Other potential side effects include urinary retention and glaucoma 1
- A large multicenter prospective randomized trial has alleviated concerns about cardiovascular side effects and increased stroke risk 3
Clinical Considerations
- Tiotropium has been shown to be non-inferior to salmeterol (a long-acting beta-agonist) and superior to placebo in patients with moderate-to-severe asthma whose symptoms were not adequately controlled by inhaled corticosteroids 1
- The response to inhaled corticosteroids and tiotropium in reducing asthma exacerbations is independent of the high or low type 2 eosinophilic phenotype 1
- For patients who cannot generate sufficient inspiratory flows required for dry powder inhaler devices, tiotropium administered through a pMDI and spacer is recommended 7
- In combination therapy, tiotropium is available with olodaterol (a long-acting β2-agonist) as a fixed-dose combination 2