ORIGINAL ARTICLE
Adverse drug reactions with oral anticoagulants: data from sicilian spontaneous reporting system database
Maria Antonietta Barbieri PharmD,
Paola Maria Cutroneo PharmD, PhD,
Chiara Baratelli MD,
Giuseppe Cicala PharmD,
Alessandro Battaglia MD,
Vincenza Santoro BSc, PhD,
Giuseppe Andò MD, PhD,
Edoardo Spina MD, PhD,
Maria Antonietta Barbieri PharmD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorPaola Maria Cutroneo PharmD, PhD
Sicilian Regional Pharmacovigilance Centre, University Hospital of Messina, Messina, Italy
Search for more papers by this authorChiara Baratelli MD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorGiuseppe Cicala PharmD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorAlessandro Battaglia MD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorVincenza Santoro BSc, PhD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorGiuseppe Andò MD, PhD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorCorresponding Author
Edoardo Spina MD, PhD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Correspondence
Edoardo Spina MD, PhD, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
Email: [email protected]
Search for more papers by this authorMaria Antonietta Barbieri PharmD,
Paola Maria Cutroneo PharmD, PhD,
Chiara Baratelli MD,
Giuseppe Cicala PharmD,
Alessandro Battaglia MD,
Vincenza Santoro BSc, PhD,
Giuseppe Andò MD, PhD,
Edoardo Spina MD, PhD,
Maria Antonietta Barbieri PharmD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorPaola Maria Cutroneo PharmD, PhD
Sicilian Regional Pharmacovigilance Centre, University Hospital of Messina, Messina, Italy
Search for more papers by this authorChiara Baratelli MD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorGiuseppe Cicala PharmD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorAlessandro Battaglia MD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorVincenza Santoro BSc, PhD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorGiuseppe Andò MD, PhD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Search for more papers by this authorCorresponding Author
Edoardo Spina MD, PhD
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Correspondence
Edoardo Spina MD, PhD, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
Email: [email protected]
Search for more papers by this authorAbstract
Objective
Direct oral anticoagulants (DOACs) were developed to avoid the limitations of vitamin K antagonists (VKAs). DOACs are associated with a greater incidence of gastrointestinal bleeding and a smaller number of intracranial haemorrhages than VKAs. Therefore, it is important to deepen our knowledge of their safety profiles. The aim of this study was thus to analyse adverse drug reaction (ADR) reports on DOACs and VKAs using the Sicilian Spontaneous Reporting System (SRS) database.
Methods
All ADR reports with DOACs and VKAs as suspected drugs that were entered into the Sicilian SRS database during the period 2001–2019 were selected. In detail, all reports with the following single active substances were included: dabigatran etexilate, rivaroxaban, apixaban and edoxaban; acenocoumarol and warfarin were included as a comparator group. Descriptive statistical methodology was used to evaluate characteristics of the reported cases with a case-by-case assessment.
Results and Discussion
Out of 521 reports related to anticoagulants, 444 (85.2%) and 77 (14.8%) involved DOACs and VKAs, respectively. DOAC-related reports were mainly of gastrointestinal disorders. In contrast, VKAs were mostly associated with blood and lymphatic system disorders, injury, investigations and vascular disorders. Many more cases of ADRs in the form of gastrointestinal disorders concerned dabigatran etexilate (n = 179, 73.7%) than the other DOACs, while ADRs in the form of blood disorders were mainly associated with acenocoumarol (n = 27, 57.4%). The most commonly reported Preferred Terms for DOACs were dyspepsia (n = 89, 17.1%), upper abdominal pain (n = 41, 9.2%) and pruritus (n = 26, 5.8%), whereas for VKAs, they were anaemia (n = 21, 27.3%) and hypocoagulable state (n = 18, 3.5%). Potentially interacting concomitant medications particularly included antithrombotic agents (n = 19, 4.3%) for DOACs and proton-pump inhibitors (PPIs) (n = 37, 48.1%) and antithrombotic agents (n = 13, 16.9%) for VKAs.
Conclusion
The ADRs most commonly associated with DOACs, especially dabigatran, were gastrointestinal disorders, particularly gastrointestinal bleeding. Our study also highlights the potential role of drug-drug interactions in the ADRs. The cases of gastrointestinal bleeding highlight the need for careful prescribing of DOACs and use of potentially interacting concomitant drugs.
CONFLICT OF INTEREST
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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