Eliquis and Xtandi - Drug Interaction

[Hawk56]

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.

[tango65]

You could suggest changing to dabigatran (Pradaxa), edoxaban (Savaysa), or betrixaban (Bevyxxa) which do not interact with enzalutamide.

[Hawk56 in reply to tango65]

thanx, will bring it up with the cardiologist.

[lcfcpolo]

I was diagnosed with my Advanced Prostate Cancer after having a 2nd DVT in my leg, 5 months after my first DVT. This set off all of the alarm bells and I was given my first ever PSA test, which was sadly 1311.

So in May 2020 I started on 2 x 5mg Eliquis (APIXABAN) tablets a day. I started on 4 x Enzalutamide (Xtandi) tablets a day in July 2020. I have remained on both ever since (2 years 9 months) along with ADT.

So far so good. They ran some tests to see if I should drop down to 1 x 5mg Eliquis tablets a day but the Dr's seemed happy that I stay on x 2 Eliquis tablets a day.

I am unsure if this helps you and I would welcome any comments. I'm so wrapped up in my advanced prostate cancer diagnosis that I wrongly ignore the DVTs and medication.

[Hawk56 in reply to lcfcpolo]

the study I posted and referenced did not have any solid trial data supporting the interactions but did say the manufacturer did not recommend combining the two....

Like many others, do we err on the side of precaution and find alternatives or accept risk and...

Time for my cardiologist to do his job, determine whether I need to say on Eliquis or is there an acceptable alternative

[leebeth]

Looking at the data for Eliquis in afib, compared to the other anticoagulants, Eliquis is the most effective with the lowest risk of side effects.

My recommendation would be to consider darolutamide rather than enzalutamide.

No such drug interaction exists

sciencedirect.com/science/a...

[Hawk56 in reply to leebeth]

Thanx,will discuss with my oncologist.

[marnieg46]

Not sure if this is helpful or relevant but no doubt you can check with your medical advisors if you think it might be of interest.

My husband was on Eliquis for AF. After he had his prostate removed he had severe bleeding and clotting for the best part of two years with numerous admissions to ER.

In 2018 it was decided that he had to go off blood thinners and a Watchman Device was recommended. It's a small device that goes into the left atrial appendage of the heart and reduces the risk of stroke in people with AF and eliminates the need for blood thinners. Also reducing the long term risk of bleeding caused by blood thinners.

It was a very simple operation - day surgery and Eliquis tapered off over a week. A fabulous outcome in his case.

[Hawk56 in reply to marnieg46]

Thanx, will ask my cardiologist about it.

[rogerwegner in reply to Hawk56]

Good luck , somtimes older and cheaper drugs are better

[MandMP13]

Here is another suggestion that may help you. My father was diagnosed IV in 2021 and was already taking Eliquis. So the specialty pharmacy suggested Zytiga instead of Xtandi as there are no interactions with Zytiga & Eliquis. He has been taking Zytiga along with 5 mg Prednisone daily since diagnosis. Best of luck to you!

[Hawk56 in reply to MandMP13]

Thaanx, will discuss with my oncologist. I was trying to avoid prednisone though, had it while doing taxotere, ugh.

[rogerwegner]

am going through the same problem with Erleada and Eliquis. The solution is to go back on warfarin. That way the level of protection from cIots is manegable through INR checks

[Hawk56 in reply to rogerwegner]

thanx, an option I will discuss with my cardiologist!