Xtandi (Enzalutamide) and Eliquis (Apixaban) Interaction Management
Enzalutamide (Xtandi) is likely to decrease apixaban (Eliquis) levels by approximately 31%, potentially reducing its anticoagulant effectiveness, so alternative anticoagulation should be considered when possible. 1
Mechanism of Interaction
Enzalutamide affects apixaban through two opposing mechanisms:
- Strong induction of CYP3A4 (decreasing apixaban levels)
- Weak inhibition of P-glycoprotein (P-gp) (potentially increasing apixaban levels)
The net effect is a predicted 31% decrease in apixaban AUC with no significant change in maximum concentration (Cmax) 1. This reduction could compromise anticoagulant efficacy.
Clinical Recommendations
Preferred Alternatives
Consider edoxaban as the first-choice DOAC if a direct oral anticoagulant must be used with enzalutamide 2
- Edoxaban is less affected by CYP3A4 induction
- Expected to have the least interaction with enzalutamide
Consider LMWH (dalteparin) if the patient has:
- Active cancer
- High thrombotic risk
- Gastrointestinal or gastroesophageal tumors (higher bleeding risk with DOACs) 2
If Apixaban Must Be Used
If apixaban must be continued with enzalutamide due to patient-specific factors:
- Monitor closely for signs of reduced anticoagulant effect
- Watch for thrombotic events
- Consider more frequent clinical follow-up
- Be vigilant about medication adherence
Risk Assessment
Factors Increasing Risk
- Advanced age (≥80 years)
- Low body weight (≤60 kg)
- Renal impairment
- Concurrent use of antiplatelet medications
- History of bleeding 3
Monitoring Recommendations
- No specific laboratory monitoring is validated for apixaban efficacy
- Watch for clinical signs of thrombosis
- Monitor for bleeding complications despite the expected reduction in apixaban levels
Special Considerations
- Enzalutamide has a long half-life (5.8 days) 4, so interaction effects may persist even after discontinuation
- The interaction with apixaban is different from warfarin, where a case report showed no clinically significant interaction 5
- Patients with gastrointestinal malignancies have higher bleeding risk with DOACs and may benefit from LMWH instead 2
Conclusion
While co-administration of enzalutamide and apixaban is not absolutely contraindicated, the predicted 31% reduction in apixaban exposure raises concerns about reduced anticoagulant efficacy. When possible, consider alternative anticoagulants like edoxaban or LMWH that may have more favorable interaction profiles with enzalutamide.