What are the recommended doses and frequencies of tiotropium (Tiotropium) and Incruse Ellipta (Umeclidinium) for severe Chronic Obstructive Pulmonary Disease (COPD)?

Recommended Dosing for Tiotropium and Umeclidinium in Severe COPD

For patients with severe COPD, tiotropium should be administered at a dose of 18 mcg once daily via HandiHaler or 5 mcg once daily via Respimat, while umeclidinium (Incruse Ellipta) should be administered at a dose of 62.5 mcg once daily. 1, 2

Tiotropium Dosing

• Tiotropium is recommended at a dose of 18 mcg once daily when delivered via HandiHaler 1, 3
• When using the Respimat Soft Mist Inhaler, the recommended dose is 5 mcg once daily 4
• The once-daily dosing of tiotropium provides bronchodilation for at least 24 hours, improving compliance compared to multiple daily dosing regimens 1
• Clinical studies have shown that tiotropium reaches steady-state bronchodilation within 48 hours of initiating therapy 3
• No dose adjustment is required based on age or for patients with renal impairment, though caution is advised in moderate-to-severe renal impairment 3

Umeclidinium (Incruse Ellipta) Dosing

• The FDA-approved dose for umeclidinium (Incruse Ellipta) is 62.5 mcg administered once daily by oral inhalation 2
• Umeclidinium should be used at the same time every day and should not be used more than once every 24 hours 2
• No dosage adjustment is required for elderly patients, patients with renal impairment, or patients with moderate hepatic impairment 2

Clinical Evidence Supporting These Recommendations

• Long-acting muscarinic antagonists (LAMAs) like tiotropium and umeclidinium are recommended over short-acting muscarinic antagonists for preventing COPD exacerbations (Grade 1A recommendation) 1
• Tiotropium has been shown to be superior to ipratropium (a short-acting muscarinic antagonist) in exacerbation prevention (OR, 0.71; 95% CI, 0.52-0.95) 1
• LAMAs are also recommended over long-acting β-agonists for preventing moderate to severe acute exacerbations of COPD (Grade 1C recommendation) 1
• Tiotropium was associated with a lower rate of exacerbations compared to long-acting β-agonists (OR, 0.86; 95% CI, 0.79-0.93) 1

Delivery Devices and Considerations

• For tiotropium, both the HandiHaler (dry powder) and Respimat (soft mist) delivery systems are effective 1, 4
• The 5 mcg dose of tiotropium via Respimat is comparable to the 18 mcg dose via HandiHaler in terms of efficacy, pharmacokinetics, and safety 4
• There have been some safety concerns with the Respimat delivery system, though a recent multicenter international RCT demonstrated its safety compared to HandiHaler 1
• Caution may still be warranted in specific patient populations who may be at higher risk for adverse events or mortality with Respimat 1

Common Pitfalls and Caveats

• Dry mouth is the most common side effect of tiotropium (16% vs 2.7% with placebo) but is generally well-tolerated 5
• Avoid exceeding the recommended once-daily dosing frequency, as this does not provide additional benefit and may increase the risk of adverse effects 2, 6
• Dose-finding studies for tiotropium have shown comparable bronchodilator responses at doses from 9 to 36 mcg, with 18 mcg selected as the optimal dose based on efficacy and safety profile 6
• Consistency in the timing of daily administration is important for maintaining steady-state drug levels and optimal bronchodilation 3, 5

Comparative Efficacy

• Both tiotropium and umeclidinium are effective once-daily LAMAs that provide significant bronchodilation and reduce the risk of COPD exacerbations 1, 7
• Tiotropium has been extensively studied and has demonstrated improvements in lung function, quality of life, and reduction in exacerbations compared to placebo 1, 5
• Umeclidinium delivered via the Ellipta inhaler is a newer LAMA that has shown effective bronchodilation lasting at least 24 hours 7
• The choice between these agents may depend on patient preference for delivery device, formulary considerations, and individual response 7