What is the reason for not using Eliquis (apixaban) or Xarelto (rivaroxaban) in a patient with a history of bleeding or impaired renal function who is currently taking cumin?

Contraindications and Cautions for Eliquis (Apixaban) and Xarelto (Rivaroxaban)

The primary reasons for not using Eliquis or Xarelto are severe renal impairment (CrCl <15 mL/min for both agents), active pathological bleeding, and concomitant use with combined P-glycoprotein and strong CYP3A4 inhibitors. 1, 2

Absolute Contraindications

Severe Renal Impairment

• Both Eliquis and Xarelto are contraindicated when creatinine clearance is <15 mL/min 1, 2
• Rivaroxaban has approximately 33% renal elimination, while apixaban has approximately 25% renal elimination, but both accumulate dangerously at severe renal dysfunction 1
• Dabigatran is contraindicated at CrCl 15-30 mL/min (more restrictive than the factor Xa inhibitors due to 80% renal elimination) 1

Active Bleeding

• Active pathological bleeding is an absolute contraindication to initiating either agent 2
• History of DOAC-associated bleeding requires careful risk-benefit assessment before restarting 1

Drug Interactions

• Avoid concomitant use with combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir) as these dramatically increase drug exposure and bleeding risk 2
• In patients with CrCl 15-80 mL/min, avoid combined P-gp and moderate CYP3A inhibitors (erythromycin) unless benefit clearly outweighs risk 2

Relative Contraindications and High-Risk Scenarios

Moderate Renal Impairment (CrCl 15-50 mL/min)

• Use with extreme caution in CrCl 15-30 mL/min - this range is "not recommended" for apixaban/rivaroxaban/edoxaban per guidelines 1
• Drug elimination is significantly prolonged, requiring dose reduction and close monitoring 1, 3
• The combination of moderate renal impairment with P-gp/CYP3A inhibitors creates dangerous drug accumulation 2, 3

Hepatic Impairment

• Avoid rivaroxaban in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment or any hepatic disease with coagulopathy 2
• Rivaroxaban AUC increases 127% in Child-Pugh B patients 2

Bleeding History

• Prior gastrointestinal bleeding while on DOACs warrants consideration of alternative anticoagulation strategies 1
• Apixaban may have lower GI bleeding risk compared to rivaroxaban and dabigatran, making it potentially preferable if a DOAC must be used 4, 5, 6

Concomitant Antiplatelet or NSAID Use

• Chronic NSAID use, aspirin, or clopidogrel significantly increases bleeding risk when combined with DOACs 2
• Promptly evaluate any signs of blood loss in patients on combination therapy 2

Perioperative Considerations

High-Risk Procedures

• For neuraxial anesthesia or intracranial surgery, DOACs must be discontinued for 5 days (apixaban/rivaroxaban) or longer for dabigatran with renal impairment 1
• Performing spinal/epidural procedures with residual DOAC concentration risks catastrophic bleeding 1

Timing Based on Renal Function

For high-risk procedures 1:

• CrCl >80 mL/min: Hold apixaban/rivaroxaban for 2 days
• CrCl 50-80 mL/min: Hold apixaban/rivaroxaban for 2 days; dabigatran for 3 days
• CrCl 30-50 mL/min: Hold apixaban/rivaroxaban for 2 days; dabigatran for 4 days
• CrCl 15-30 mL/min: Dabigatran contraindicated; apixaban/rivaroxaban hold for 2 days but "not recommended" 1

Clinical Pitfalls to Avoid

Underestimating Drug Accumulation

• Multiple renally cleared medications can compound renal impairment and cause unexpected DOAC accumulation 3
• Always calculate CrCl using Cockcroft-Gault formula before prescribing, not just serum creatinine 1

Lack of Reversal Agents

• Unlike warfarin, vitamin K does not reverse DOACs 1
• Andexanet alfa is available for life-threatening bleeding with apixaban/rivaroxaban, but may not be immediately accessible 7
• Only dabigatran is dialyzable; rivaroxaban and apixaban have high protein binding and cannot be removed by dialysis 1, 2

Inadequate Monitoring in Acute Bleeding

• Standard PT/INR and aPTT do not reliably indicate DOAC anticoagulation levels 1
• For mild bleeding with hemodynamic stability, temporary cessation is usually sufficient due to short half-lives (unless renal impairment prolongs clearance) 1
• Activated charcoal may help if DOAC was taken <3 hours prior to presentation 1