Tiotropium Bromide

Rationale: The slope of decline in forced expiratory volume in 1 second (FEV₁) is commonly used to reflect the rate of disease progression for descriptive studies and therapeutic trials in chronic obstructive pulmonary disease (COPD). The frequency and duration of spirometric testing needed to report the true slope are unknown. Objectives: We sought to define the minimum frequency and follow-up duration needed to accurately describe the annualized rate of FEV₁ change among patients with moderate to very severe COPD. Methods: We performed a post hoc analysis of the annualized rate of FEV₁ change among 4,412 subjects previously enrolled in the 4-year Understanding Potential Long-Term Impacts on Function with Tiotropium-or, UPLIFT-trial of tiotropium versus placebo. Slope estimates were modeled for different iterations of semiannual or annual testing over a variable duration up to 42 months. All models were compared with a reference of semiannual spirometry for 42 months. Results: The overall annual rate of postbronchodilator FEV₁ decline measured semiannually for 42 months (44.6 ml; 95% confidence interval [CI] = 42.5-46.6) did not differ significantly from annual spirometry over the same period (43.7 ml; 95% CI = 41.3-46.1) or semiannual spirometry over the first 2 years (44.3 ml; 95% CI = 41.1-47.5). Agreement was consistent for two follow-up values as far as 24 months apart (43.3 ml; 95% CI = 39.9-46.8). Models that are based on less than two follow-up values or a duration less than 18 months were characterized by relative underestimation of the slope. Conclusions: In a large cohort of patients with moderate to very severe COPD, the annualized rate of change in FEV₁ was accurately represented by a minimum of two annual follow-up measurements over 18 months compared with semiannual testing over 42 months.

Drug-induced dry mouth is an adverse reaction that can significantly affect the quality of life and mental state of patients. In this study, we aimed to identify the most common drugs associated with dry mouth using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

We accessed data from the FAERS database between the first quarter of 2004 and the first quarter of 2024. The Medical Dictionary for Regulatory Activities was used to identify reports of dry mouth, and disproportionality analyses (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker) were performed to examine the risk signals for dry mouth and its causative drugs.

A total of 75,899 adverse event reports were related to dry mouth. Tiotropium bromide monohydrate (2080 cases) was associated with the majority of dry mouth cases. Disproportionality analysis revealed that the top five drugs with the highest reporting odds ratio (ROR) were darifenacin, solifenacin succinate, fesoterodine fumarate, tolterodine tartrate, and niraparib. Moreover, eight of the top 19 drugs that caused dry mouth were not identified as having major side effects in the package inserts.

Tiotropium bromide monohydrate was the most frequently reported drug for dry mouth, whereas darifenacin had the highest ROR. Collectively, our findings emphasize the necessity for improved recognition and management of drug-induced dry mouth, particularly for medications not adequately flagged for this side effect in their labels.