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Long-term safety of tiotropium delivered by Respimat ® SoftMist ™ Inhaler: patient selection and special considerations

View Article: PubMed Central - PubMed

ABSTRACT

Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in patients with chronic respiratory disease. It has been available since 2002 as a single-dose dry powder formulation via the HandiHaler® dry powder inhaler (DPI) device, and since 2007 as the Respimat® SoftMist™ Inhaler (SMI). The latter is a novel method of medication delivery that utilizes a multidose aqueous solution to deliver the drug as a fine mist. Potential benefits include more efficient drug deposition throughout the respiratory tract, reduced systemic exposure, and greater ease of use and patient satisfaction compared with the use of HandiHaler DPI. Although tiotropium bromide delivered via the HandiHaler DPI has been clearly shown to improve lung function, dyspnea, and quality of life and to reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), there is accumulating evidence regarding the use of tiotropium HandiHaler in other respiratory diseases characterized by airflow limitation, such as asthma and cystic fibrosis. Developed more recently, tiotropium delivered via the Respimat SMI appears to have a similar efficacy and safety profile to the HandiHaler DPI, and early data raising the possibility of safety concerns with its use in COPD have been refuted by more recent evidence. The benefits over the HandiHaler DPI, however, remain unclear. This paper will review the evidence for tiotropium delivered via the Respimat SMI inhaler, in particular as an alternative to the HandiHaler DPI, and will focus on the safety profile for each of the chronic lung diseases in which it has been trialed, as well as an approach to appropriate patient selection.

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(A) Mean tiotropium plasma concentration–time profile following inhalations as Respimat SMI solution or HandiHaler DPI. (B) Steady-state plasma concentrations (Cmax, ss) by dose and device.Note: Adapted from Hohlfeld J, Sharma A, Van Noord J, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54(4):405–414. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.21Abbreviations: DPI, dry powder inhaler; max, maximum; min, minimum; P10, 10th percentile; Q1, first quartile; Gmean, geometric mean; Q3, third quartile; P90, 90th percentile, of the tiotropium plasma steady state concentration in the group; SMI, SoftMist™ Inhaler.
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f1-tcrm-12-1433: (A) Mean tiotropium plasma concentration–time profile following inhalations as Respimat SMI solution or HandiHaler DPI. (B) Steady-state plasma concentrations (Cmax, ss) by dose and device.Note: Adapted from Hohlfeld J, Sharma A, Van Noord J, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54(4):405–414. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.21Abbreviations: DPI, dry powder inhaler; max, maximum; min, minimum; P10, 10th percentile; Q1, first quartile; Gmean, geometric mean; Q3, third quartile; P90, 90th percentile, of the tiotropium plasma steady state concentration in the group; SMI, SoftMist™ Inhaler.

Mentions: However, pharmacokinetic data from clinical trials have been conflicting. Some have shown generally similar profiles,18,19 others have suggested increased systemic exposure with the Respimat SMI,20 and still others have more recently demonstrated the opposite.21 In 2014, a crossover trial enrolled 154 COPD patients who were then randomized into five different treatment arms comprising placebo, tiotropium HandiHaler DPI 18 μg, and tiotropium Respimat SMI 1.25, 2.5, and 5 μg, respectively.19 This study found lower peak plasma concentrations (Cmax, ss) in the tiotropium Respimat SMI 5-μg solution group compared to the HandiHaler DPI group (Figure 1), although it was still greater than in the manufacturer’s report.1 On the other hand, plasma concentrations of tiotropium HandiHaler DPI were significantly less in pharmacological studies compared to the manufacturer’s reported value.10,20,21 Given the conflicting pharmacokinetic data, in vitro bioequivalence cannot be assumed between the HandiHaler and Respimat devices.21


Long-term safety of tiotropium delivered by Respimat ® SoftMist ™ Inhaler: patient selection and special considerations
(A) Mean tiotropium plasma concentration–time profile following inhalations as Respimat SMI solution or HandiHaler DPI. (B) Steady-state plasma concentrations (Cmax, ss) by dose and device.Note: Adapted from Hohlfeld J, Sharma A, Van Noord J, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54(4):405–414. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.21Abbreviations: DPI, dry powder inhaler; max, maximum; min, minimum; P10, 10th percentile; Q1, first quartile; Gmean, geometric mean; Q3, third quartile; P90, 90th percentile, of the tiotropium plasma steady state concentration in the group; SMI, SoftMist™ Inhaler.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5036544&req=5

f1-tcrm-12-1433: (A) Mean tiotropium plasma concentration–time profile following inhalations as Respimat SMI solution or HandiHaler DPI. (B) Steady-state plasma concentrations (Cmax, ss) by dose and device.Note: Adapted from Hohlfeld J, Sharma A, Van Noord J, et al. Pharmacokinetics and pharmacodynamics of tiotropium solution and tiotropium powder in chronic obstructive pulmonary disease. J Clin Pharmacol. 2014;54(4):405–414. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.21Abbreviations: DPI, dry powder inhaler; max, maximum; min, minimum; P10, 10th percentile; Q1, first quartile; Gmean, geometric mean; Q3, third quartile; P90, 90th percentile, of the tiotropium plasma steady state concentration in the group; SMI, SoftMist™ Inhaler.
Mentions: However, pharmacokinetic data from clinical trials have been conflicting. Some have shown generally similar profiles,18,19 others have suggested increased systemic exposure with the Respimat SMI,20 and still others have more recently demonstrated the opposite.21 In 2014, a crossover trial enrolled 154 COPD patients who were then randomized into five different treatment arms comprising placebo, tiotropium HandiHaler DPI 18 μg, and tiotropium Respimat SMI 1.25, 2.5, and 5 μg, respectively.19 This study found lower peak plasma concentrations (Cmax, ss) in the tiotropium Respimat SMI 5-μg solution group compared to the HandiHaler DPI group (Figure 1), although it was still greater than in the manufacturer’s report.1 On the other hand, plasma concentrations of tiotropium HandiHaler DPI were significantly less in pharmacological studies compared to the manufacturer’s reported value.10,20,21 Given the conflicting pharmacokinetic data, in vitro bioequivalence cannot be assumed between the HandiHaler and Respimat devices.21

View Article: PubMed Central - PubMed

ABSTRACT

Tiotropium bromide is a long-acting inhaled muscarinic antagonist used in patients with chronic respiratory disease. It has been available since 2002 as a single-dose dry powder formulation via the HandiHaler® dry powder inhaler (DPI) device, and since 2007 as the Respimat® SoftMist™ Inhaler (SMI). The latter is a novel method of medication delivery that utilizes a multidose aqueous solution to deliver the drug as a fine mist. Potential benefits include more efficient drug deposition throughout the respiratory tract, reduced systemic exposure, and greater ease of use and patient satisfaction compared with the use of HandiHaler DPI. Although tiotropium bromide delivered via the HandiHaler DPI has been clearly shown to improve lung function, dyspnea, and quality of life and to reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), there is accumulating evidence regarding the use of tiotropium HandiHaler in other respiratory diseases characterized by airflow limitation, such as asthma and cystic fibrosis. Developed more recently, tiotropium delivered via the Respimat SMI appears to have a similar efficacy and safety profile to the HandiHaler DPI, and early data raising the possibility of safety concerns with its use in COPD have been refuted by more recent evidence. The benefits over the HandiHaler DPI, however, remain unclear. This paper will review the evidence for tiotropium delivered via the Respimat SMI inhaler, in particular as an alternative to the HandiHaler DPI, and will focus on the safety profile for each of the chronic lung diseases in which it has been trialed, as well as an approach to appropriate patient selection.

No MeSH data available.


Related in: MedlinePlus