Affiliation:
1. ICES Western London Ontario Canada
2. Department of Physiology and Pharmacology Western University London Ontario Canada
3. Department of Epidemiology and Biostatistics Western University London Ontario Canada
4. Division of Nephrology, Department of Medicine Western University London Ontario Canada
5. Lawson Health Research Institute London Health Sciences Centre London Ontario Canada
6. Department of Biology Western University London Ontario Canada
7. Division of Clinical Pharmacology, Department of Medicine Western University London Ontario Canada
Abstract
AbstractImportanceTrimethoprim‐sulfamethoxazole (TMP‐SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity.ObjectiveTo characterize the risk of digoxin toxicity in older adults taking digoxin following co‐prescription of TMP‐SMX compared with co‐prescription of amoxicillin.Design, Settings, and ParticipantsRetrospective population‐based cohort study in Ontario, Canada (2002–2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74–86]) who were newly treated with TMP‐SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688).ExposureCo‐prescription of TMP‐SMX versus amoxicillin in older adults concurrently taking digoxin.Main Outcome and MeasureThe primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD.ResultsA hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP‐SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]).Conclusion and RelevanceIn older adults taking digoxin, the 30‐day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co‐prescribed TMP‐SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP‐SMX must be co‐prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose‐reduced on an individual basis.