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Tiotropium

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Tiotropium

  • 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 dry mouth
    • dry mouth was the most common adverse effect of tiotropium (about 14% of patients) in one-year studies, but it was usually mild and often resolved as treatment continued (1,2)
      • more patients developed dry mouth with tiotropium than with ipratropium (1,2)
    • 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 (1)
      • there have also been isolated reports of atrial fibrillation and supraventricular tachycardia
    • care should be taken to avoid co-prescription of preparations containing anticholinergics (1)
    • 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 (1)
  • 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 dyspnea, lung hyperinflation, exacerbations, and use of rescue medication compared with placebo or active comparators. (2)
  • 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. (2)

The Drug and Therapeutics review concluded that "..To determine tiotropium's place in practice, trials using clinically relevant endpoints are needed to compare it with ipratropium (including 80µg four times daily) and with oxitropium twice daily". (3)

Reference:

  1. MeReC Briefing 2006;33:1-8.
  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
  3. Tiotropium for chronic obstructive pulmonary disease. Drug and Therapeutics Bulletin 2003;41:15-16.

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