Drug-Drug Interactions Leading to Adverse Drug Reactions with Rivaroxaban: A Systematic Review of the Literature and Analysis of VigiBase

Abstract

Rivaroxaban has become an alternative to vitamin K antagonists, which are considered to be at higher risk of drug-drug interactions (DDI) and more difficult to use. However, DDI do occur. We systematically reviewed studies that evaluated them and analysed DDI and subsequent adverse drug reactions (ADR) reported in spontaneous reports and VigiBase. We systematically searched articles that explored DDI with rivaroxaban up to 20 August 2018 via Medline, Embase and Google Scholar. Data from VigiBase came from spontaneous reports recovered up to 2 January 2018, where Omega was used to detect signals and identify potential interactions in terms of triplets with two drugs and one ADR. We identified 31 studies and 28 case reports. Studies showed significant variation in the pharmacokinetic for rivaroxaban, and an increased risk of haemorrhage or thromboembolic events due to DDI was highlighted in case reports. From VigiBase, a total of 21,261 triplets were analysed and the most reported was rivaroxaban–aspirin–gastrointestinal haemorrhage. In VigiBase, only 34.8% of the DDI reported were described or understood, and most were pharmacodynamic DDI. These data suggest that rivaroxaban should be considered to have significant potential for DDI, especially with CYP3A/P-gp modulators or with drugs that impair haemostasis.

Association between road traffic accidents and drugs belonging to the antiseizure medications class: A pharmacovigilance analysis in VigiBase

“…The primary outcome was the reporting association between each individual ASMs and RTAs. The secondary outcomes were: (i) the description of the ASMs‐associated RTAs cases; and (ii) an investigation of potential DDI occurring between coprescribed ASMs and RTAs 14,15 . Classes of ASMs were not analysed as such against the reporting of RTAs, but individual ASM results were sorted according to ASM classes, for clarity (Tables 1 and 2).…”

A systematic review on hepatoprotective potential of grape and polyphenolic compounds: molecular mechanism and future prospective

“…However, the occurrence of clinically severe liver injury or impaired liver function (with prolonged PT or hypoalbuminemia) that leads to deficient protein synthesis is rare (Figure 2). Jaundice, gastrointestinal discomfort, itching, and other symptoms are among them (Fernandez et al, 2021).…”

Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban

“…Because the anticoagulant activity of direct factor Xa inhibitors is closely related to plasma concentrations, concurrent use of diltiazem with apixaban or rivaroxaban could increase bleeding complications. Although there are case reports of hemorrhage in patients treated with diltiazem while receiving these anticoagulants, the clinical impact of this potential drug-drug interaction is uncertain. Although both the US Food and Drug Administration labels for apixaban and rivaroxaban and the American College of Cardiology, American Heart Association, American College of Clinical Pharmacy, and Heart Rhythm Society guidelines for management of atrial fibrillation acknowledge that anticoagulant management should consider drug-drug interactions, neither specifically mentions increased risk of bleeding as a potential consequence of diltiazem coadministration.…”