Adverse Drug Events in Patients with Chronic Kidney Disease Associated with Multiple Drug Interactions and Polypharmacy
Background and Purpose
Chronic kidney disease (CKD) is associated with adverse drug events due to medication errors and the risks of polypharmacy. The aim of this study was to investigate whether multiple pharmacodynamic interactions are a significant problem in CKD patients to improve medication safety.
The discharge medication of 200 elderly patients with stage 3, 4 and 5/5D CKD was analysed in a retrospective observational study with respect to kidney-related medication errors and multiple pharmacodynamic interactions. The clinical relevance of the most common and hazardous multiple interactions was assessed by evaluating adverse events at the primary or the subsequent hospital stay.
Findings showed that 29.5% of the study cohort were at risk of QTc-interval prolongation in association with their medication combinations and half of them exhibited QTc-interval prolongation. The QTc interval was extended among all patients receiving a combination of two or more drugs with ‘known’ risk of Torsades de pointes. Amiodarone, citalopram and ciprofloxacin turned out to be the most hazardous drugs in this context. Eight percent of the patient population received a regimen of 4–6 potassium-enhancing drugs during their hospital stay, which was not de-escalated in 75.0% in the ambulatory setting. Despite close monitoring in the clinical setting, 37.5% of these patients developed hyperkalaemic episodes during their primary stay and 66.7% during rehospitalization. Of the study cohort, 8.5% received a combination of three drugs with antithrombotic or antiplatelet effects. Of these, 64.7% developed haemorrhagic events with two of them proving fatal.
Multiple pharmacodynamic interactions related to QTc prolongation, hyperkalaemia and haemorrhage are frequently associated with a negative outcome in older adults with CKD and often require recurrent medical treatment or rehospitalization.
JS conceived and designed the investigation and the database for data analysis, collected and interpreted the data, performed the literature research and wrote the paper. HR contributed to the study design, data interpretation and writing of the paper. AS contributed to data interpretation. Each author contributed important intellectual content during manuscript drafting.
Compliance with Ethical Standards
This study was funded by a grant from the Klinikum Bayreuth GmbH and by a grant from the Förderinitiative Pharmazeutische Betreuung e.V. There was no commercial funding for this study.
Conflict of interest
The results presented in this paper have not been published previously in whole or in part. All authors have reported that they have no relationships relevant to the contents of this article to disclose.
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