Is severe bleeding common with the combination of Lexapro (escitalopram) and Eliquis (apixaban)?

Is Severe Bleeding Common with Lexapro and Eliquis?

Severe bleeding is not common with the combination of escitalopram (Lexapro) and apixaban (Eliquis), but the risk is measurably increased compared to apixaban alone, and this combination requires careful monitoring.

Understanding the Bleeding Risk

The FDA-approved labeling for apixaban explicitly warns that SSRIs like escitalopram increase bleeding risk when combined with anticoagulants 1. The escitalopram label similarly states that SSRIs "may increase the risk of bleeding events" and that "concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to the risk" 2.

Quantifying the Risk

• In the ARISTOTLE trial of apixaban for atrial fibrillation, major bleeding occurred in 2.13% of patients per year on apixaban alone 3
• When apixaban was used in cancer patients (ADAM VTE trial), major bleeding occurred in 0% of apixaban patients versus 1.4% with dalteparin 3
• A published case report documented a limb-threatening hematoma in an 85-year-old patient taking citalopram (closely related to escitalopram) and apixaban concurrently, demonstrating the potential severity of this interaction 4

What You Should Expect

Common manifestations (not severe):

• Increased bruising is expected and does not necessarily indicate major bleeding risk 1
• Longer bleeding time from minor cuts 1
• More frequent nosebleeds 1

Severe bleeding warning signs requiring immediate medical attention:

• Red, pink, or brown urine 1
• Red or black stools (tar-like appearance) 1
• Coughing up blood or blood clots 1
• Vomiting blood or coffee-ground appearing vomit 1
• Severe headaches, dizziness, or weakness 1
• Unusual bleeding from gums that doesn't stop 1

Critical Risk Factors That Increase Bleeding

Your risk is substantially higher if you have:

• Renal impairment (creatinine clearance <60 mL/min) - present in 61% of patients with severe bleeding on DOACs 5
• Age ≥80 years 3
• Body weight ≤60 kg 3
• Concurrent use of NSAIDs or aspirin - taken by significant numbers of patients, often unknowingly 6
• Gastrointestinal lesions - particularly high risk with this combination 3

Management Approach

Before starting this combination:

• Verify renal function (creatinine clearance) 3, 7
• Review all medications including over-the-counter products - 33% of apixaban patients take potentially interacting OTC products daily 6
• Assess for history of bleeding disorders 1

During treatment:

• Monitor for any unusual bleeding symptoms 1
• Avoid NSAIDs (ibuprofen, naproxen) and aspirin unless specifically prescribed 1
• Regular renal function monitoring is advisable as changes affect apixaban clearance 7

Important Caveats

• No routine monitoring test exists for apixaban levels in standard clinical practice 8
• No specific antidote was available until recently; andexanet alfa is now FDA-approved for life-threatening bleeding but has limited availability 9
• In a registry of 732 patients with severe bleeding on DOACs, 14% mortality by day 30 was observed, though this varied significantly by bleeding site 5
• Approximately 66% of patients are uncertain or incorrect about the bleeding risk when combining anticoagulants with other medications 6

Bottom Line

While severe bleeding is not "common" in absolute terms (occurring in roughly 2-7% of patients annually depending on the clinical context), the combination of escitalopram and apixaban does create a synergistic bleeding risk 1, 2, 4. The key is recognizing warning signs early and avoiding additional risk factors, particularly NSAIDs and aspirin 1, 6.