Objective:

The 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.

Method:

This 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.

Results:

A 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.

Conclusions:

Although 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.