How do you manage drug-drug interactions between oral anticoagulants and the ARSI agents such as apalutamide and enzalutamide?

Commonly used oral anticoagulants, such as apixaban, rivaroxaban, and warfarin are substrates of hepatic cytochrome P450 enzymes (CYP). Co-administration of an AR signaling inhibitor (ARSI) variably affects the concentration of those drugs depending on the effect on the type of CYP enzymes. For example, apalutamide and enzalutamide are strong inhibitors of CYP34A, and a combination with apixaban or rivaroxaban is not recommended. Apalutamide and enzalutamide are weak/moderate inhibitors of CYP2C9 and warfarin can be used with close monitoring. On the other hand, darolutamide and abiraterone do not have clinically significant interactions with any of these anticoagulants and can be used concurrently.

As a general rule, if someone needs apixaban or rivaroxaban as an anticoagulant, I avoid enzalutamide or apalutamide and choose darolutamide or abi/pred depending on the indication. Most ARSIs can be used with concurrent use of warfarin, with monitoring of INR and dose adjustments as appropriate.