When can Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) be restarted after discontinuing Eliquis (Apixaban)?

When to Restart NSAIDs After Discontinuing Eliquis (Apixaban)

NSAIDs can typically be restarted 24-48 hours after discontinuing apixaban for low bleeding risk situations, and 48-72 hours for high bleeding risk situations, once adequate hemostasis is confirmed. 1

Timing Based on Bleeding Risk Stratification

The timing of NSAID resumption depends primarily on the bleeding risk of the clinical scenario and whether adequate hemostasis has been achieved:

Low Bleeding Risk Scenarios

• Restart NSAIDs at 24 hours after the last dose of apixaban if hemostasis is adequate 1
• This applies to routine procedures or situations without significant bleeding complications 1

High Bleeding Risk Scenarios

• Restart NSAIDs at 48-72 hours after the last dose of apixaban 1
• High bleeding risk includes procedures with high vascular tissue involvement, anticipated difficulty achieving hemostasis, or where bleeding complications could be catastrophic 1
• If bleeding risk remains elevated or hemostasis is incomplete, consider delaying NSAID resumption further 2

Critical Considerations Before Restarting NSAIDs

Assess Hemostasis Status

• Confirm adequate hemostasis before restarting any NSAID therapy 2
• If bleeding risk remains high or hemostasis is incomplete, delay full resumption and consider whether NSAIDs are truly necessary 2

Evaluate the Indication for NSAIDs

• For primary prevention or non-critical indications: Consider permanent discontinuation of NSAIDs, as the bleeding risk may outweigh benefits 3
• For essential indications: Proceed with resumption at the appropriate timeframe based on bleeding risk 3

Consider Alternative Analgesics

• Acetaminophen can be used as an alternative for pain management without the antiplatelet effects of NSAIDs 4
• Topical anti-inflammatory preparations may be suitable alternatives for musculoskeletal pain 4

Special Clinical Scenarios

Post-Gastrointestinal Bleeding

• If apixaban was discontinued due to gastrointestinal bleeding, NSAIDs should be stopped for at least mild (>5 mL) hemoptysis or bleeding 3
• Consider permanent discontinuation of NSAIDs in patients with history of gastrointestinal bleeding, as the combination of apixaban and NSAIDs significantly increases bleeding risk 5
• If NSAIDs must be restarted, use a COX-2 inhibitor plus proton pump inhibitor for maximum risk reduction 3

Cardiovascular Disease Context

• In patients with acute coronary syndrome or recent MI who were taking NSAIDs, these should be discontinued immediately and not restarted 3
• The cardiovascular risks of NSAIDs (particularly COX-2 inhibitors) must be weighed against any benefits 3

Diverticular Bleeding

• For patients with colonic diverticular bleeding, discontinuing NSAIDs reduces recurrence risk by 94% (hazard ratio 0.06) 4
• Strong consideration should be given to permanent NSAID discontinuation in this population 4

Monitoring After NSAID Resumption

Watch for Bleeding Complications

• Monitor for signs of bleeding in the first week after restarting NSAIDs, as incident NSAID use increases major bleeding risk by 61% and clinically relevant non-major bleeding by 70% in anticoagulated patients 5
• The combination of NSAIDs with apixaban increases bleeding risk even when apixaban is therapeutic 5

Renal Function Monitoring

• Monitor renal function after procedures, as surgical interventions may affect kidney function and alter drug clearance 1
• This is particularly important as both apixaban and NSAIDs can affect renal function 1

Common Pitfalls to Avoid

• Resuming NSAIDs too early after high bleeding risk procedures can lead to significant bleeding complications 1
• Failing to account for the specific bleeding risk of the clinical scenario when determining timing 1
• Not considering permanent discontinuation when NSAIDs are for non-essential indications, particularly in patients with prior bleeding 3, 4
• Inadequate communication between the proceduralist and prescriber regarding timing of both apixaban interruption and NSAID resumption 1
• Assuming all NSAIDs carry equal risk: COX-2 inhibitors with proton pump inhibitors offer better gastrointestinal safety profiles than traditional NSAIDs 3