Adverse drug reactions with oral anticoagulants: data from sicilian spontaneous reporting system database

Abstract

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.

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database

“…This study is the first overview of ADRs related to the drugs approved for the treatment of MS based on a SRS database. SRS is the most used method to carry out post-marketing surveillance and to research ADRs not occurring during the preclinical and clinical studies ( Barbieri et al, 2021a ). Indeed, the post-marketing phase allows to analyze the onset of ADRs related to the use of DMTs in a real-world context, considering all risk factors probably associated with each individual event, such as comorbidities and polytherapy.…”

Risk of Bleeding Associated with Antidepressant Drugs: The Competitive Impact of Antithrombotics in Quantitative Signal Detection

“…As we removed all reports associated with antithrombotics from the database, the number of reports of haemorrhages related to ADs was strongly reduced because many reports were associated with an antithrombotic comedication, thus affecting the results of our disproportionality analysis. This might especially affect the analysis of gastrointestinal bleeding events, as not only warfarin but also direct oral anticoagulants are strongly associated with an increased risk of gastrointestinal bleeding as recent analyses of drug safety databases demonstrated [ 40 , 41 ]. Therefore, we hypothesise a major impact of the well-known aspect of a drug–drug interaction regarding the bleeding risk related to SSRIs (in terms of two substance groups are associated with an increased risk for the ADR of interest), which cannot be adequately considered by using the present methodology.…”

Safety profile of tyrosine kinase inhibitors used in non-small-cell lung cancer: An analysis from the Italian pharmacovigilance database

“…This is the first European study focusing on ADRs related to the use of TKIs approved for the treatment of NSCLC based on a spontaneous reporting database. Spontaneous reporting System (SRS) is one of the most commonly used pharmacovigilance methods, particularly useful for identifying newly approved drug-related ADRs undetected during pre-marketing studies when the drug is administered to a relatively small number of selected patients and under controlled conditions ( 60 – 62 ). Information coming from multiple ICSRs are a fundamental tool to identify potential safety signals.…”