Tiotropium bromide, a new, once-daily inhaled anticholinergic bronchodilator for chronic-obstructive pulmonary disease

Jul 22, 2004Expert opinion on pharmacotherapy

Tiotropium bromide: a new once-daily inhaler that opens airways in chronic obstructive lung disease

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Abstract

Tiotropium bromide is a once-daily inhaled medication approved for the long-term treatment of bronchospasm in COPD, delivering 18 micrograms per dose.

Long-term use of tiotropium is associated with a trough increase in forced expiratory volume in 1 second of approximately 0.12 liters and a peak increase of approximately 0.25 liters.
Significant reductions in static lung volumes have been observed in hyperinflated patients with COPD, which may help alleviate dyspnoea.
Regular use of tiotropium has led to clinically meaningful increases in the Transitional Dyspnoea Index, indicating reduced difficulty in breathing during daily activities.
Improvements have been documented in respiratory-specific health status, as evidenced by enhanced scores on the St George's Respiratory Questionnaire.
Pooled data from multiple studies show a 20% to 28% reduction in the number of exacerbations per patient per year with tiotropium.
The most common side effect, dry mouth, was reported in 6% to 16% of patients, rarely leading to discontinuation.

AI simplified

Tiotropium bromide is a quaternary ammonium compound structurally related to ipratropium and has recently been approved in the US for the long-term, once-daily, maintenance treatment of bronchospasm associated with chronic-obstructive pulmonary disease (COPD). It is available in a dry powder form, where 18 microg [corrected] of the drug is inhaled once-daily through a device, the HandiHaler). The potency and long duration of effect of this anticholinergic bronchodilator result primarily from a prolonged blockade of the M1 and M3 muscarinic receptors in the airways and a relatively more rapid dissociation from the M2 receptor (which provides inhibitory feedback). Multiple studies of up to a duration of 1 year have demonstrated its effectiveness as a bronchodilator for COPD, with a trough increase (measured approximately 24 h after administration of the drug) in forced expiratory volume in 1 s of approximately 0.12 l and a peak increase of approximately 0.25 l. Tiotropium inhalation also leads to a significant reduction in static lung volumes in hyperinflated patients with COPD; this probably contributes to the reduction in dyspnoea that is associated with long-term use of this maintenance bronchodilator. Regular use of the drug was associated with clinically meaningful increases in the Transitional Dyspnoea Index, which indicate reductions in dyspnoea associated with daily activities. Improvement in the respiratory-specific health status questionnaire, the St George's Respiratory Questionnaire component and total scores was also documented. Finally, pooled data from two 1-year studies and two 6-month studies documented 20 and 28% reductions in the number of exacerbations per patient per year. Side effects have been relatively minimal, with dry mouth the most common symptom, ranging 6 - 16% of patients and rarely leading to discontinuation of the study drug. Limited comparisons of efficacy with other bronchodilators are available. Once-daily tiotropium has been demonstrated to be clearly superior to ipratropium four times daily as a bronchodilator for COPD. Combined results from two studies comparing once-daily tiotropium to twice-daily inhalation of standard doses of salmeterol, indicate a magnitude of the bronchodilator response similar in the two drugs early in the study. However, by 6 months, the bronchodilator effect of tiotropium was somewhat greater than that of the long-acting beta-agonist. Preliminary data suggest that combining tiotropium with long-acting beta-agonists may produce additional bronchodilator action in COPD.

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Tiotropium bromide, a new, once-daily inhaled anticholinergic bronchodilator for chronic-obstructive pulmonary disease

Abstract

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