Apalutamide and Apixaban: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Aug 8, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Apalutamide
Apixaban
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Let's talk about taking Erleada (apalutamide) together with Eliquis (apixaban). Apixaban is a blood thinner that helps prevent dangerous clots and strokes. The problem is that apalutamide speeds up how fast your body breaks down and clears apixaban. That means there may be too little apixaban in your blood to do its job.
If apixaban gets too weak, you could be at higher risk for a clot or stroke, which is exactly what the medicine is meant to prevent. This is a well-documented interaction, so please don't stop either drug on your own. Your care team can manage this by adjusting your plan or watching you more closely.
Effect: Apalutamide, a combined strong CYP3A4 inducer and P-gp inducer, increases metabolism and efflux of apixaban, reducing apixaban exposure (AUC) and Cmax. This lowers anticoagulant efficacy and raises the risk of stroke and thromboembolic events.
- Direction: reduced apixaban effect (induction; apixaban is not a prodrug)
- Magnitude: with rifampin, levels fell below the 5th percentile in ~half of patients in a retrospective study
- Evidence: established; severity: major; onset unspecified
Management: Avoid the combination if possible. If coadministration is necessary, consider DOAC concentration monitoring and reassess anticoagulant strategy with the care team.
What happens
Reduced apixaban exposure, reduced efficacy of apixaban and an increased risk of stroke and other thromboembolic events
Interaction Deep Dive
Do not use apixaban together with agents that act as both P-glycoprotein and strong CYP3A4 inducers, including rifAMPin, carBAMazepine, phenytoin, and St. John's Wort. Pharmacokinetic investigations showed reductions in both apixaban exposure and Cmax during coadministration with rifAMPin1, and a retrospective study found that apixaban concentrations fell below the fifth percentile of anticipated values in half of the patients who received apixaban alongside an enzyme-inducing agent. When it is necessary to combine a direct oral anticoagulant (DOAC) with an enzyme-inducing drug, measuring the DOAC concentration may be helpful 5.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of apixaban; induction of P-gp-mediated efflux transport of apixaban
How to manage this interaction
Keep taking both medicines exactly as prescribed until your care team advises otherwise. This is a known interaction that your team can manage.
- This combination is generally avoided when possible, so your prescriber may consider a different treatment approach.
- If both drugs must be used together, your team may monitor your apixaban level and watch you more closely for clotting problems.
- Tell your pharmacist or doctor about all your medicines, including St. John's Wort and any new prescriptions.
Seek urgent care for signs of a clot or stroke, such as sudden weakness, trouble speaking, chest pain, or leg swelling.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
6 reports — tap to read
a) A retrospective cohort study using propensity score matching in adults (n=14,078 eligible episodes) found no difference in the risk of thromboembolic events between those receiving direct-acting oral anticoagulant (DOAC) therapy (apixaban, dabigatran, or rivaroxaban) together with enzyme-inducing antiseizure medications (EI-ASMs), namely carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, or topiramate, and those receiving non-EI-ASMs (adjusted HR, 1.1 [95% CI, 0.82 to 1.46]). A secondary analysis (n=14,158 eligible episodes) showed a significant decrease in major bleeding events when DOACs were used along with EI-ASMs versus non-EI-ASMs (adjusted HR, 0.63 [95% CI, 0.44 to 0.89]) 2.
b) A significantly higher risk of stroke/systemic embolism was observed when direct-acting oral anticoagulant (DOAC) drugs were given together with carBAMazepine (adjusted OR, 2.15; 95% CI, 1.07 to 4.3) or phenytoin (OR, 4.46; 95% CI, 2.46 to 8.08) in a propensity-score adjusted nested case-control study of patients with atrial fibrillation or recent DVT/PE (N=89,284). The patients were new users of DOAC therapy, with 54.8% on apixaban, 31.3% on rivaroxaban, and 14% on dabigatran. The results were adjusted for demographic and lifestyle variables 3.
c) In a prospective cohort study of patients with nonvalvular atrial fibrillation taking direct-acting oral anticoagulant therapy (DOAC) along with antiepileptic drugs (N=91), the composite endpoint of ischemic stroke, transient ischemic attack, and systemic embolism was seen in 9 patients (5.7% patient-year; 3 fatalities) over a median follow up of 17.5 +/- 14.5 months; however, the patients who had a thromboembolic event were older (75 years or greater), had a prior stroke, and had a higher risk score (CHA(2)DS(2)-VASc greater than 3). Although no direct comparisons were performed, this rate of thromboembolic events was reported to be higher than the rates seen in cohort studies of patients with atrial fibrillation treated with DOAC therapy alone. Major bleeding was seen in 3 patients (1.9% patient-year; 1 fatality). Within the study, 46.2%, 27.5%, 16.5%, and 9.9% of patients received apixaban, rivaroxaban, dabigatran, and edoxaban, respectively. Concomitant antiepileptic therapy consisted of 45% receiving levETIRAcetam, 22% valproic acid, 12% PHENobarbital, 11% carBAMazepine, and 10% other antiepileptic therapy 4.
d) In a retrospective study of hospitalized patients who received concomitant direct oral anticoagulants (DOACs; apixaban, 77%; rivaroxaban, 15%; dabigatran, 8%) with an enzyme-inducing drug (total study population, 1596; 22 [1.4%] received the concomitant prescriptions), a DOAC concentration below the fifth percentile of the expected concentration was found in 6 of 11 patients who had measured DOAC levels. Peak apixaban concentrations ranged from 35.8 to 205.4 mcg/L in 10 patients, compared with a fifth percentile of 91 mcg/mL and a ninety-fifth percentile of 321 mcg/mL based on standard apixaban dosing from the ARISTOTLE study; 5 of the patients in the ARISTOTLE study had levels below the fifth percentile. The DOACs were prescribed for atrial fibrillation (86%) or VTE (14%), and the enzyme inducer was indicated primarily for seizure (55%), but also for neuropathy, essential tremor, or depression 5.
e) Mean apixaban Cmax fell by 42% and AUC(0 to infinity) fell by 54% when oral apixaban was coadministered with oral rifAMPin in healthy subjects (N=20). The oral bioavailability of apixaban decreased by 25% and the mean apparent clearance rose by 2.1-fold. Subjects were given a single IV dose of apixaban 5 mg on Day 1, followed by a 10-mg oral dose on Day 3. Then, rifAMPin 600 mg orally once daily was given on Days 5 to 15. Finally, a single dose of apixaban 5 mg IV and 10 mg orally were given separately on Days 12 and 14 in randomized sequence 6.
f) In a drug interaction study, coadministering rifAMPin 600 mg with apixaban led to reductions in apixaban Cmax and AUC of about 0.6-fold and 0.5-fold, respectively 1.
Common questions
Can I take Apalutamide and Apixaban together?
Apalutamide can make apixaban work too weakly, raising the risk of clots or stroke, so this combination is usually avoided. Do not stop either drug on your own; ask your care team about a safer plan or closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apalutamide and Apixaban interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Apalutamide and Apixaban interaction managed?
Keep taking both medicines exactly as prescribed until your care team advises otherwise. This is a known interaction that your team can manage. This combination is generally avoided when possible, so your prescriber may consider a different treatment approach. If both drugs must be used together, your team may monitor your apixaban level and watch you more closely for clotting problems. Tell your… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Apalutamide or Apixaban need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: ELIQUIS(R) oral film coated tablets, apixaban oral film coated tablets. Bristol-Myers Squibb Company (per Dailymed), Princeton, NJ, 2024. DailyMed
- Acton EK, Hennessy S, Gelfand MA, et al: Direct-acting oral anticoagulants and antiseizure medications for atrial fibrillation and epilepsy and risk of thromboembolic events. JAMA Neurol 2024; Epub:Epub. DOI
- Gronich N, Stein N, & Muszkat M: Association between use of pharmacokinetic-interacting drugs and effectiveness and safety of direct acting oral anticoagulants: nested case-control study. Clin Pharmacol Ther 2021; 110(6):1526-1536. PubMed
- Giustozzi M, Mazzetti M, Paciaroni M, et al: Concomitant use of direct oral anticoagulants and antiepileptic drugs: a prospective cohort study in patients with atrial fibrillation. Clin Drug Investig 2021; 41(1):43-51. DOI
- Perlman A, Hochberg-Klein S, Choshen Cohen L, et al: Management strategies of the interaction between direct oral anticoagulant and drug-metabolizing enzyme inducers. J Thromb Thrombolysis 2019; 47(4):590-595. PubMed
- Vakkalagadda B, Frost C, Byon W, et al: Effect of rifampin on the pharmacokinetics of apixaban, an oral direct inhibitor of Factor Xa. Am J Cardiovasc Drugs 2016; 16(2):119-127. PubMed
Keep reading about Apalutamide
Keep reading about Apixaban
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist