Dr. Corum called yesterday evening, said the pharmacist called, there was a drug interaction between Xtandi and Eliquis, making Eliquis less effective. Given my cardiovascular history with AFIB, the PE and DVT in 2010, wants the cardiologist to determine whether or not I could come off Eliquis or an alternative. Geez…so, I did what I do, went to inform myself. There may be…read am article - ascopubs.org/doi/full/10.12... from the JCO Oncology, Management of Anticoagulation in Patients With Prostate Cancer Receiving Enzalutamide.
Enzalutamide, a novel, oral androgen receptor antagonist used for the treatment of metastatic, castration-resistant prostate cancer, has been shown to improve overall and progression-free survival, prolong time to initiation of chemotherapy, reduce skeletal-related events, and carry a favorable adverse effect profile.
Enzalutamide interacts with several anticoagulants through various mechanisms, making their concurrent use clinically challenging. As such, complex decisions about anticoagulation in these patients are frequently encountered by treating physicians.
Enzalutamide interacts with multiple enzymatic pathways that directly impact the plasma levels of various anticoagulants. Specifically, enzalutamide is a moderate inducer of CYP2C9 and CYP2C19, and a strong inducer of CYP3A4.4 In vitro data suggest it may also inhibit P-glycoprotein (P-gp).5 These metabolic effects can potentially lead to sub- or supratherapeutic anticoagulant drug levels, breakthrough thromboembolism, or clinically significant bleeding.
Apixaban (Eliquis) has several potential interactions with enzalutamide that makes simultaneous use of these agents potentially challenging. Because apixaban is metabolized by CYP3A4, the presence of strong CYP3A4 inducers such as enzalutamide will increase apixaban metabolism, reducing the AUC and maximum concentration (Cmax).21 Similar strong CYP34A inducers, such as rifampin, decrease the AUC of apixaban by nearly 50%.22 In vitro data also suggest enzalutamide may inhibit P-gp, though in vivo studies have yet to corroborate this finding.
In vitro data also suggest enzalutamide may inhibit P-gp, though in vivo studies have yet to corroborate this finding.5 P-gp is an ATP-binding cassette transporter that functions to extrude toxins and xenobiotics out of cells.23 P-gp inhibitors can increase the absorption of apixaban, increasing both the AUC and Cmax.21 The degree to which enzalutamide creates this effect is unclear because, to our knowledge, no studies have evaluated the pharmacokinetics of the two drugs administered simultaneously. In summary, the opposing effects of enzalutamide on apixaban metabolism via the CYP3A4 and P-gp pathways is difficult to predict. The manufacturer of apixaban currently recommends against the use of apixaban with strong CYP3A4 inducers such as enzalutamide.
…as overall survival in patients with metastatic prostate cancer continues to improve, management of long-term anticoagulation concurrently with cancer treatment is becoming increasingly relevant. The thrombotic complications of malignancy and cancer therapies can potentially cause significant patient morbidity and mortality, and need to be considered in the context of each individual’s treatment.47 Enzalutamide offers many potential therapeutic benefits to those with metastatic, castration-resistant prostate cancer, but, as detailed in this review, it has drug interactions with most anticoagulants.2 Although this incurs significant challenges to practicing physicians, with careful forethought and knowledge of these interactions, most complications can be averted.
It is important to note that given the lack of clinical trial data specific to the use of anticoagulation in patients taking enzalutamide, recommendations based on the highest grade of evidence cannot be made.
…recommended algorithms for anticoagulation in patients receiving enzalutamide, based on the indication for anticoagulation, are summarized in Figure 4. More data are required to define the safest and most effective management of concurrent anticoagulation. Until then, the guidelines we have presented here are based on the best available evidence and represent reasonable management strategies for these patients.
So, sent a note to my cardiologist, included my radiologist, oncologist and GP, see if there is a solution allowing me to safely go on Xtandi.
enzalutamide (XTANDI®, Astellas Pharma Inc.) for patients with metastatic castration-sensitive prostate cancer (mCSPC). 
Enzalutamide and PSMA
