Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study

被引：0

作者：

Muanda, Flory T. ^{[1
,2
,3
]}

Weir, Matthew A. ^{[1
,2
,4
]}

Ahmadi, Fatemeh ^{[1
,2
]}

McArthur, Eric ^{[1
,5
]}

Sontrop, Jessica M. ^{[3
]}

Abdullah, Sheikh S. ^{[1
,5
]}

Urquhart, Brad L. ^{[2
]}

Sadeghi, Hasti ^{[6
]}

Kim, Richard B. ^{[7
]}

Garg, Amit X. ^{[1
,2
,4
]}

机构：

[1] ICES Western, London, ON, Canada

[2] Western Univ, Dept Physiol & Pharmacol, Med Sci Bldg, 1151 Richmond St, Room 287, London, ON N6A 5C1, Canada

[3] Western Univ, Dept Epidemiol & Biostat, London, ON, Canada

[4] Western Univ, Dept Med, Div Nephrol, London, ON, Canada

[5] London Hlth Sci Ctr, Lawson Hlth Res Inst, London, ON, Canada

[6] Western Univ, Dept Biol, London, ON, Canada

[7] Western Univ, Dept Med, Div Clin Pharmacol, London, ON, Canada

来源：

PHARMACOTHERAPY | 2024年 / 44卷 / 07期

关键词：

amoxicillin; digoxin; drug drug interaction; TMP-SMX; toxicity; ASSOCIATION JOINT COMMITTEE; PROPENSITY SCORE METHODS; ATRIAL-FIBRILLATION; AMERICAN-COLLEGE; MANAGEMENT; GUIDELINE; MORTALITY; OUTCOMES; BLOCKER; MODELS;

D O I：

10.1002/phar.2948

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

ImportanceTrimethoprim-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. This graphical abstract illustrates the increased risk of digoxin toxicity in older adults who are co-prescribed digoxin and trimethoprim-sulfamethoxazole (TMP-SMX) compared to those co-prescribed digoxin and amoxicillin. The study highlights a significantly higher 30-day risk of hospitalization for digoxin toxicity in the TMP-SMX group, likely due to TMP-SMX's inhibition of renal clearance of digoxin. These findings underscore the clinical importance of cautious antibiotic selection to prevent adverse drug events in this vulnerable population.image

引用

页码：558 / 569

页数：12

共 44 条

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