Comparison of adverse drug reactions of heparin and its derivates in the European Economic Area based on data from EudraVigilance between 2017 and 2021.

Abstract

Introduction: Hemodialysis patients need long-term frequent use of parenteral anticoagulants, and the side effects need to be taken seriously. This study aimed to assess the reporting of adverse drug reactions (ADRs) following administration of unfractionated heparin (UFH), low molecular weight heparins (LMWHs), fondaparinux, and danaparoid, in relation to their usage in European Economic Area (EEA).

Materials and methods: The total number of ADRs of each anticoagulant between 2017 to 2021 was collected using data from the EudraVigilance database. The number of hemorrhages, thrombocytopenia, injection-site reaction, liver injury, hypersensitivity and bone disorder were collected, respectively. Usage of these anticoagulants was estimated using sales data from the IQVIA MIDAS database. The reporting rates of ADRs were calculated and compared using χ²-test.

Results: Between 2017 and 2021 in the EEA, the overall ADRs reporting rates per 10,000,000 standard units (SU) of UFH, enoxaparin, nadroparin, dalteparin, fondaparinux, and danaparoid were 12.3, 40.8, 23.6, 36.5, 91.4, and 430.0, respectively. There were significant differences among these drugs (χ² = 7,239.26, p < 0.001). Specifically, hemorrhage and thrombocytopenia were reported at higher rates, ranging from 2.8 to 140.1, and 2.0 to 115.9 per 10,000,000 SU among different anticoagulants. Injection-site reactions and hypersensitivity came in second, between 0.2 - 29.0 and 0.1 - 53.1 per 10,000,000 SU, respectively. The reporting rates for liver injury and bone disorder were reported at low rates.

Conclusion: The reporting rates of ADRs for heparin and its derivates were all very low. In comparison, the reporting rate of ADRs for danaparoid and fondaparinux was relatively high. The most commonly reported ADRs were hemorrhage, thrombocytopenia, followed by injection-site reactions and hypersensitivity.