Digoxin Dosing Errors, Drug Interactions and Off-Label Risks: Insights from an EudraVigilance Disproportionality Analysis.

Background/

Objectives

Digoxin, a positive inotropic agent with a narrow therapeutic window, is used in heart failure but carries toxicity risks. This study aims to characterize the profile of digoxin-associated adverse drug reactions reported in the EudraVigilance database, focusing on drug-drug interactions, dosing errors, and off-label use.

Methods

Descriptive and disproportionality analyses were performed on Individual Case Safety Reports (ICSRs) until 25 January 2026. Digoxin was compared with other inotropic agents by calculating the Reporting Odds Ratio and 95% confidence intervals.

Results

Digoxin recorded 11,426 ICSRs, with a predominance in patients aged 65-85 years (46.4%) and over 85 years (25.1%). Higher reporting probabilities were identified for the terms "Drug interaction" and "Overdose" compared to other inotropes. Fatal outcomes were reported in 19 cases related to drug interactions and 41 cases related to overdose. Consistent disproportionality signals were found for gastrointestinal, renal, and nervous system disorders. Off-label use was reported in 0.8% of cases and was associated with unfavorable clinical outcomes. Risks are exacerbated by polypharmacy and renal decline in elderly patients.

Conclusions

Digoxin toxicity and cardiac complications are the primary drivers of reported morbidity. This risk profile highlights the need for the rigorous clinical monitoring, precise dose adjustments and heightened vigilance regarding drug-drug interactions.