Development in Prescriptions of Contraindicated and Potentially Harmful QT Interval–Prolonging Drugs in a Large Geriatric Inpatient Cohort From 2011 to 2021

Abstract

Regulatory authorities put major emphasis on QT (interval)-prolonging properties of new molecular entities. Product information/Summaries of Product Characteristics (SmPCs) of multiple drugs contain warnings or contraindications regarding QT prolongation, e.g., on coadministration of QT-prolonging drugs (QT drugs). To characterize the development of the QT drug burden, we performed a trend analysis of prescriptions and co-prescriptions of QT drugs in a large geriatric inpatient cohort. The German SmPCs (status of 2014 and of 2021) and the year-wise listings in the CredibleMeds® database from 2011 to 2021 were used as sources. There were 402,631 geriatric cases included. The group of QT drugs according to SmPCs in 2014, which must not be combined with other QT drugs, was less frequently involved in contraindicated co-prescriptions in 2021 compared with 2015 (3.0% (2.5-3.7%) of cases with at least one of those drugs in 2021 vs. 4.0% (3.5-4.5%) in 2015), with citalopram, escitalopram, and amiodarone involved in nearly 90% of the co-prescriptions. The number of CredibleMeds-QT-drugs per patient increased from 0.4 (SD=1.1) in 2011 to 1.8 (SD=3.9) in 2021. The percentage of contraindicated co-prescriptions of drugs with known risk for torsade de pointes according to CredibleMeds® listings at the beginning of the respective years increased from 1.7% in 2011 to 6.1% in 2021. Considering the regularly updated CredibleMeds® QT drugs list, the contraindicated co-prescriptions of QT drugs markedly increased in the last decade. If prescribers considered only the few most frequently (co-) prescribed QT drugs, then most of the medication errors regarding QT drugs could be prevented.The drug-induced long QT syndrome (diLQTS) poses an adverse event that can result in torsades de pointes arrhythmia (TdP) and sudden cardiac death. 1,2 Molecular mechanisms leading to diLQTS are complex. 3 Among others, genetic predispositions contributing to the phenotype of long QT syndrome (LQTS) make it difficult to stratify patients at increased risk for TdP. 3 The incidence of TdP

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“…Amiodarone is a commonly used antiarrhythmic drug recognized for its QT interval-prolonging potential ( Then et al, 2023 ). Due to the potential danger, administering amiodarone together with other medications that have QT-prolonging potential is contraindicated, even though multiple recent studies have been unable to show any significant risk ( Van Der Sijs et al, 2009 ; Meid et al, 2017 ; Then et al, 2023 ). According to the literature, voriconazole and domperidone can cause QT interval prolongation too ( Mourad et al, 2019 ).…”

“…The amiodarone + levofloxacin, voriconazole + amiodarone, and domperidone + voriconazole interactions observed in this study all have the potential to cause the aforementioned unwanted results. Amiodarone is a commonly used antiarrhythmic drug recognized for its QT interval-prolonging potential (Then et al, 2023). Due to the potential danger, administering amiodarone together with other medications that have QT-prolonging potential is contraindicated, even though multiple recent studies have been unable to show any significant risk (Van Der Sijs et al, 2009;Meid et al, 2017;Then 14.7 ± 9.3 (7-25) Reduce dose of Tac, monitor Tac concentrations, renal function and liver function DIPS, drug interaction probability scale; CNS, central nervous system; NA, not applicable (NA, is used when data cannot be collected), Tac, tacrolimus.…”