Safety of tiotropium in renally impaired patients

Abstract

Background: Tiotropium is primarily renally excreted. Adverse events (AEs) including fatal AEs (FAEs), were analyzed by renal impairment in placebo-controlled trials of once-daily tiotropium HandiHaler 18 µg (HH) or Respimat 5 µg (R5). Methods: Fifteen HH and 7 R5 studies* estimating baseline creatinine clearance (Cockroft-Gault) included 10,805 evaluable patients in total. AE incidence rate ratios (IRR; tiotropium/placebo) were determined for renal impairment subgroups (normal ≥90, mild ≥60, moderate ≥30, severe <30 mL/min creatinine). Results: 95% confidence intervals (CI) of the IRRs for AEs and serious AEs (SAEs) included or were close to 1, and IRR did not correlate with worsening renal function for both HH and R5 (Table). IRR of FAEs did not increase with decreasing renal function. Selected system organ classes (fatal cardiac disorders, general disorders) did not show consistent IRR trends. Results for severe renal impairment were limited due to low patient numbers (n=52). Table: IRR (95% CI) for AEs, SAEs or FAEs categorized by renal function at baseline HH R5 Renal impairment N, tiotropium/ placebo Normal 860/700 Mild 1099/815 Moderate 448/347 Normal 1104/1040 Mild 1479/1539 Moderate 662/660 AE 0.94 (0.83, 1.06) 0.86 (0.77, 0.96) 0.79 (0.67, 0.94) 0.88 (0.80, 0.98) 0.98 (0.90, 1.07) 0.92 (0.81, 1.04) SAE 0.99 (0.72, 1.37) 0.96 (0.74, 1.26) 0.73 (0.51, 1.04) 1.08 (0.85, 1.38) 0.84 (0.70, 1.02) 0.95 (0.75, 1.20) FAE 0.82 (0.21, 3.14) 1.23 (0.43, 3.50) 0.61 (0.22, 1.72) 2.54 (0.80, 8.13) 1.09 (0.61, 1.94) 1.28 (0.70, 2.36) Conclusions: Incidence of AEs, SAEs or FAEs with tiotropium (HH or R5) showed no association with mild-to-moderately impaired renal function. *Reference list on request. Funded by Boehringer Ingelheim.