Rivaroxaban and selective serotonin reuptake inhibitors: Bleeding risk resulting from their concomitant use

Abstract

ObjectiveThe combination of selective serotonin reuptake inhibitors with rivaroxaban may result in a dual interaction (pharmacokinetic and pharmacodynamic) depending on the type of selective serotonin reuptake inhibitor employed (CYP3A4-inhibiting vs. non-CYP3A4 inhibiting). The purpose of this study was to use real world data to determine if the type of selective serotonin reuptake inhibitor used plays a role in the risk and severity of bleeding in patients receiving rivaroxaban. MethodThis was a single-center retrospective longitudinal observational study carried out between January 2016 and February 2020 in patients aged 18 years or older treated concurrently with rivaroxaban (prescribed for treatments) and a selective serotonin reuptake inhibitor. Patients were divided into two groups according to the selective serotonin reuptake inhibitor they received, i.e., a CYP3A4 inhibitor (group 1): sertraline, fluoxetine and paroxetine, or a non-CYP3A4 inhibitor (group 2): citalopram and escitalopram. We analyzed the bleeding events and severity, the daily dose of rivaroxaban used and the medication administered concomitantly. ResultsA total of 146 patients were included (89 in group 1 and 57 in group 2) and 35 bleeding events (24% of patients) were identified, of which 12 were major and 23 were minor. The bleeding rate was higher in group 1 (25.8% vs 21.0%) but there were no differences in major bleeding (10.1% vs 5.3%; p = 0.235) or minor bleeding (13.5% vs 15.8%; p = 0.496). The bleeding rate with a daily rivaroxaban dose of 20 mg was 9% (8/89) in group 1 and 14% (8/57) in group 2 (p = 0.2137), as compared with 16.9% (15/89) in group 1 versus 7% (4/57) in group 2 (p = 0.042) for a daily 15 mg dose. ConclusionsAlthough the type of selective serotonin reuptake inhibitor used concurrently with rivaroxaban was not found to influence the patients’ bleeding risk, a significant increase in the risk of bleeding was observed based on the dose of rivaroxaban used.