Summary

• XARELTO increases the risk of bleeding and can cause serious or fatal bleeding. Concomitant use of drugs affecting hemostasis increases the risk of bleeding.¹
• Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding.^2-11
• Patients should be cautioned about the risk of bleeding associated with the concomitant use of SSRIs/SNRIs and drugs that affect coagulation.^2-11
• ROCKET-AF: SSRI use was associated with a 35% increased risk of combined major and non-major clinically relevant bleeding.¹²
• Additional citations identified during a literature search are included in the REFERENCES section for your review.^14,15

PRODUCT LABELING

WARNINGS AND PRECAUTIONS

Risk of Bleeding

XARELTO increases the risk of bleeding and can cause serious or fatal bleeding. In deciding whether to prescribe XARELTOto patients at increased risk of bleeding, the risk of thrombotic events should be weighed against the risk of bleeding.

Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin, P2Y₁₂ platelet inhibitors, other antithrombotic agents, fibrinolytic therapy, non-steroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors.

PRACTICAL CONSIDERATIONS

Certain SSRIs^2-7 (e.g., citalopram, paroxetine, sertraline) and SNRIs^8-11 (e.g., desvenlafaxine, duloxetine, venlafaxine) may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to the risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages. Patients should be cautioned about the risk of bleeding associated with the concomitant use of SSRIs/SNRIs and drugs that affect coagulation.^2-11

CLINICAL STUDIES

ROCKET-AF

A propensity matched analysis of 713 patients taking SSRIs during the ROCKET-AF study showed that SSRI use was associated with a 35% increased risk of combined major and non-major clinically relevant bleeding.¹² There were no significant differences in these safety measures between XARELTO and warfarin treated patients. The analysis also compared the rates of stroke in SSRI and non-SSRI taking patients using an intention-to-treat approach: See Figure: ROCKET- AF: Efficacy and Safety with and without concomitant SSRI use

RETROSPECTIVE REVIEW

A retrospective review of electronic medical record data identified 3 patients that received antidepressants and XARELTO.¹³ No cases of decreased platelets or reports of increased bleeding symptoms were identified for this cohort.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 24 December 2024.