J Korean Med Sci.  2024 Jul;39(28):e205. 10.3346/jkms.2024.39.e205.

Polypharmacy and Elevated Risk of Severe Adverse Events in Older Adults Based on the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database

• Kim GJ
• Lee JS
• Jang S
• Lee S
• Jeon S
• Lee S
• Kim JH
• Lee KH

• KMID: 2558243
• DOI: http://doi.org/10.3346/jkms.2024.39.e205

Abstract

Background
Older adults are at a higher risk of severe adverse drug events (ADEs) because of multimorbidity, polypharmacy, and lower physiological function. This study aimed to determine whether polypharmacy, defined as the use of ≥ 5 active drug ingredients, was associated with severe ADEs in this population.
Methods
We used ADE reports from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database, a national spontaneous ADE report system, from 2012 to 2021 to examine and compare the strength of association between polypharmacy and severe ADEs in older adults (≥ 65 years) and younger adults (20–64 years) using disproportionality analysis.
Results
We found a significant association between severe ADEs of cardiac and renal/ urinary Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC) with polypharmacy in older adults. Regarding individual-level ADEs included in these MedDRA SOCs, acute cardiac arrest and renal failure were more significantly associated with polypharmacy in older adults compared with younger adults.
Conclusion
The addition of new drugs to the regimens of older adults warrants close monitoring of renal and cardiac symptoms.

Keyword

Drug-Related Side Effects and Adverse Reactions; Spontaneous Reports; Polypharmacy; Elderly

Figure

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  Fig. 1 KIDS-KD ADE report filtering process.ADE = adverse drug event, KIDS-KD = Korea Institute of Drug Safety and Risk Management-Korean Adverse Event Reporting System database.aDataset ID: 2206A0046.

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  Fig. 2 Age distribution of ADE reports.ADE = adverse drug event.

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  Fig. 3 Association between polypharmacy and severe ADEs. Effect of age and polypharmacy interaction on severe ADE risk was statistically significant at P < 0.001. A proportional reporting ratio > 1 indicates that polypharmacy is associated with an increased risk of severe ADEs.ADE = adverse drug event, PRR = proportional reporting ratio, CI = confidence interval.

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  Fig. 4 MedDRA SOC-grouped severe ADEs significantly associated with polypharmacy. Shown are those where the strength of the association differed significantly between subjects aged ≥ 65 and < 65 years. The interaction P between age and polypharmacy obtained with Poisson regression are shown in parenthesis. A proportional reporting ratio > 1 indicates the association of polypharmacy with an increased risk of severe ADEs in the MedDRA SOC.MedDRA SOC = Medical Dictionary Regulatory Activity System Organ Class, ADE = adverse drug event, PRR = proportional reporting ratio, CI = confidence interval.

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  Fig. 5 Severe ADEs in the MedDRA SOCs where the degree of association with polypharmacy was significant. Shown are those where the strength of association differed significantly between subjects aged ≥ 65 and < 65 years. The interaction P between age and polypharmacy obtained with Poisson regression are shown in parenthesis. A proportional reporting ratio > 1 indicates the association of polypharmacy with an increased risk of severe ADEs.ADE = adverse drug event, PRR = proportional reporting ratio, CI = confidence interval, MedDRA SOC = Medical Dictionary Regulatory Activity System Organ Class.

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