Is it safe to take Celebrex (celecoxib) while on Eliquis (apixaban)?

Safety of Taking Celebrex While on Eliquis

Concurrent use of Celebrex (celecoxib) and Eliquis (apixaban) significantly increases bleeding risk and should be avoided whenever possible due to their synergistic effects on hemostasis.1, 2

Mechanism of Increased Risk

• Celecoxib has antiplatelet effects while apixaban directly inhibits factor Xa, creating a dangerous combination that can significantly impair normal blood clotting 2
• The FDA label for celecoxib specifically warns that "celecoxib and anticoagulants such as warfarin have a synergistic effect on bleeding" and that "concomitant use of Celebrex and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone" 1
• Studies show that combining NSAIDs with anticoagulants increases bleeding risk 3-6 times compared to anticoagulants alone 2

Risk Stratification

High-Risk Patients (Contraindicated Combination)

• Patients with history of gastrointestinal bleeding 2, 3
• Elderly patients over 75 years of age 2, 3
• Patients with severe renal impairment (CrCl <30 mL/min) 3, 2
• Patients with hepatic impairment 3, 2
• Patients with uncontrolled hypertension 3, 2

Moderate Risk Patients (Use with Extreme Caution)

• Patients aged 65-75 years 2
• Patients with stable cardiovascular disease 3, 2
• Patients with mild-moderate renal impairment (CrCl 30-50 mL/min) 3, 2

Alternative Approaches

• Consider non-pharmacological pain management approaches first (physical therapy, heat/cold therapy) 2
• Acetaminophen is the preferred alternative for pain management in patients on apixaban 2
• If an NSAID is absolutely necessary, use the lowest effective dose of celecoxib (100mg daily) for the shortest duration possible 2, 4
• Consider adding a proton pump inhibitor for gastrointestinal protection if the combination cannot be avoided 2, 5

Monitoring Requirements if Combination is Necessary

• Regular complete blood count monitoring 2, 3
• Monitoring for occult blood in stool 2
• Regular blood pressure measurements 3, 2
• Renal function tests 2, 3
• Patient education on signs of bleeding to report immediately (unusual bruising, black tarry stools, blood in urine) 2

Drug Interaction Mechanism

• Apixaban is metabolized via CYP3A4 and is a substrate of P-glycoprotein (P-gp) 3
• While celecoxib itself is not a strong inhibitor of these pathways, the combination creates additive bleeding risks through different mechanisms 1, 6
• A retrospective analysis found a mild but non-significant increase in bleeding complications in patients taking celecoxib with warfarin compared to warfarin alone, suggesting similar concerns may apply to apixaban 7

Important Caveats

• The American Heart Association warns that NSAIDs, including COX-2 inhibitors like celecoxib, can increase cardiovascular risk 3
• Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk when taking celecoxib 3
• Gastrointestinal risk is particularly high in elderly patients 3, 1
• The CONCERN trial showed that even with proton pump inhibitor protection, recurrent upper gastrointestinal bleeding can occur with celecoxib in high-risk patients 5