Article
Potential life-threatening adverse drug reactions of fluoroquinolones – a pharmacoepidemiological analysis in German health claims data
Potentiell lebensbedrohliche unerwünschte Arzneimittelwirkungen von Fluorchinolonen - eine pharmakoepidemiologische Analyse deutscher Routinedaten
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Authors
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Julia Wicherski
- Federal Institute for Drugs and Medical Devices (BfArM), Pharmacoepidemiology, Bonn, Germany
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Jonas Peltner
- German Center for Neurodegenerative Diseases (DZNE), Pharmacoepidemiology, Bonn, Germany
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Anatoli Astvatsatourov
- Federal Institute for Drugs and Medical Devices (BfArM), Pharmacoepidemiology, Bonn, Germany
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Cornelia Becker
- Federal Institute for Drugs and Medical Devices (BfArM), Pharmacoepidemiology, Bonn, Germany
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Katrin Schüssel
- Scientific Institute of the AOK (WIdO), Berlin, Germany
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Gabriela Brückner
- Scientific Institute of the AOK (WIdO), Berlin, Germany
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Andrea Schlotmann
- Scientific Institute of the AOK (WIdO), Berlin, Germany
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Helmut Schröder
- Scientific Institute of the AOK (WIdO), Berlin, Germany
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Winfried Kern
- Division of Infectious Diseases, Department of Medicine II, Medical Center-University of Freiburg, Freiburg, Germany
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Birgitta Weltermann
- Institute of General Practice and Family Medicine, University of Bonn, Bonn, Germany
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Britta Haenisch
- Federal Institute for Drugs and Medical Devices (BfArM), Pharmacoepidemiology, Bonn, Germany
| Published: | November 7, 2023 |
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Outline
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Background: Evidence for fluoroquinolone (FQ)-associated aortic aneurysm/dissection (AAD), cardiac arrhythmia/sudden cardiac death (CASCD), and acute toxic liver injury/acute liver failure (ATLI/ALF) is increasing, but information about risk profiles and overall mortality of FQ users in large European countries is still needed to further improve drug therapy safety. This study aims to contribute to real-world evidence of FQ-associated incident AAD, CASCD, ATLI/ALF and all-cause mortality in routine care in Germany.
Materials and methods: We conducted a cohort study in an active comparator new user design, including adults with a filled prescription of systemic antibiotics 2014–2018 in German statutory health insurance data of the AOK. For each specific outcome, a separate data set was generated excluding patients with prevalent diagnoses. Follow-up for incident outcomes was up to 365 days after antibiotic exposure. Covariate-adjusted hazard ratios (aHRs) were estimated by piece-wise exponential additive mixed models. Various sensitivity analyses were applied to statistical methods, follow-up periods, censoring decisions and selection criteria as well as subgroup analyses on specific patient characteristics such as sex and age.
Results: Between 13 and 15 million antibiotic index episodes were included in the outcome-specific analyses. Among those, 18–19.2% were FQ index episodes. FQ-associated aHRs [95% CI] for AAD, CASCD, ATLI/ALF and all-cause mortality are 1.036 [1.014; 1.059], 1.029 [1.022; 1.036], 1.247 [1.207; 1.289] and 1.119 [1.116; 1.123] during the 365-day follow-up. In sensitivity analyses, including only hospital diagnoses in a 92-day follow-up, the aHRs [95% CI] all increase to 1.113 [1.054; 1.175], 1.152 [1.132; 1.173], 1.416 [1.311; 1.530] for AAD, CASCD, and ATLI/ALF. For all-cause mortality, aHR [95% CI] is 1.268 [1.255; 1.281] after 92 days. Moreover, aHRs increase significantly for male sex and younger age.
Conclusion: There is an association between AAD, CASCD, and ATLI/ALF or all-cause mortality within one year after a FQ index prescription. Sensitivity and subgroup analyses provide valuable insights for patient groups with higher vulnerability for potentially life-threatening adverse events after a FQ prescription.
