Incidence of and Risk Factors for Repeat Adverse Drug Events: A Systematic Review

Adverse drug events (ADEs) are unintended harm resulting from appropriate or inappropriate medication use. Many ADE-related emergency department visits are repeat events that occur after re-exposure to a medication that previously caused harm. Identifying risks and risk factors for repeat ADEs could inform clinical decision-making. We conducted a systematic review of literature on repeat ADEs published over a 20-year period. We applied a predefined search strategy in MEDLINE, Embase, and Scopus and extracted data on risk factors (e.g., age, sex, drug type, re-exposure type) and ADE outcomes. We conducted a meta-analysis if 2 or more studies reported on the same drug class, re-exposure type, ADE outcome, and follow-up period. We screened 13,452 articles and included 55. Most studies reported on re-exposures to the same drug (n=44), with few reporting on exposures to new drugs (n=5). The most studied drug classes were antineoplastics (n=20), anticoagulants (n=10), and antibiotics (n=5). The proportion of Repeat ADEs varied widely across studies from <1 to 88%. We were only able to pool data from studies on re-exposure to anticoagulants and found that 10% (95% confidence interval: 4%-19%) rebled within 90 days. Repeat ADE risks varied by drug class, reflecting different patient populations, medications and indicating conditions. Inconsistent reporting prevented quantification of risk factors. Pooled repeat ADE incidence, where available, can inform shared decision-making by providing estimates of ADE risk in the context of re-exposures to treat underlying conditions. Repeat ADEs remain an understudied area, highlighting the need for further research given their clinical significance.