Tiotropium

Tiotropium (1,2)

• is structurally related to ipratropium bromide
• is an antagonist of M1, M2 and M3 muscarinic receptors - however it dissociates more slowly from the M1 and M3 subtypes than from the M2 subtype
• has a long duration of action (terminal elimination half-life is 5-6 days), which allows it to be taken once daily
• with regular once-daily dosing, the maximum effect of tiotropium on forced vital capacity (FVC) may take more than a week to develop fully
• seems to be more effective than ipratropium bromide (40µg four times daily) in terms of reduction in exacerbations, but whether it is more effective in improving trough FEV1 is unclear
• the most common side effect is a dry mouth
  • other common adverse effects of tiotropium (affecting 1-10% of patients) include constipation, candidiasis, sinusitis and pharyngitis
  • uncommon adverse effects (0.1-1.0% of patients) include allergic reactions, urinary difficulty, urinary retention and tachycardia
    • there have also been isolated reports of atrial fibrillation and supraventricular tachycardia
  • care should be taken to avoid co-prescription of preparations containing anticholinergics
  • no consistent difference in health outcomes has been found between long-acting b2-agonists and tiotropium. Therefore, drug choice depends on individual factors and cost
• Results of short- and long-term randomized, controlled clinical trials of tiotropium in patients with COPD indicated tiotropium was safe and significantly improved lung function, health-related quality of life, and exercise endurance, and reduced dyspnoea, lung hyperinflation, exacerbations, and use of rescue medication compared with placebo or active comparators.
• Tiotropium is safe and efficacious as a long-term, once-daily LAMA for the maintenance treatment of COPD and for reducing COPD exacerbations. The soft mist inhaler (SMI) generates a low-velocity, long-duration aerosol spray with a high fine-particle fraction, which results in marked lung drug deposition.

Reference:

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2025 report. 2025 [internet publication].
2. Anzueto, A., Miravitlles, M. Tiotropium in chronic obstructive pulmonary disease – a review of clinical development. Respir Res 21, 199 (2020). https://doi.org/10.1186/s12931-020-01407-y