Carbamazepine 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
Carbamazepine
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.
Carbamazepine can make apixaban (Eliquis) work less well. Apixaban is a blood thinner that helps prevent dangerous clots and strokes. Carbamazepine speeds up how fast your body breaks down and clears apixaban, so less of the blood thinner stays in your blood. That means it may not protect you as well, raising the risk of a clot or stroke.
This is a well-established interaction, so please don't ignore it, but also don't stop either medicine on your own. Talk with your pharmacist or doctor. Your care team can decide the safest plan for you, whether that means adjusting your medicines or watching you more closely.
Effect: Carbamazepine (strong CYP3A4 inducer and P-gp inducer) increases apixaban clearance, lowering apixaban AUC and Cmax. This reduces anticoagulant efficacy and raises the risk of stroke and thromboembolism.
- Mechanism: Induction of CYP3A4-mediated metabolism and P-gp-mediated efflux of apixaban (apixaban is the affected substrate, not a prodrug).
- Evidence: Established. PK data with rifampin show markedly reduced exposure; retrospective data show subtherapeutic levels in many patients on enzyme inducers.
- Management: Avoid the combination. If unavoidable, consider DOAC level monitoring and individualized therapy; consider an alternative anticoagulant strategy per specialist.
What happens
Reduced apixaban exposure, reduced efficacy of apixaban and an increased risk of stroke and other thromboembolic events
Interaction Deep Dive
Concurrent administration of apixaban together with agents that act as both P-glycoprotein and strong CYP3A4 inducers, including rifAMPin, carBAMazepine, phenytoin, and St. John's Wort, should be avoided. In pharmacokinetic investigations, coadministration with rifAMPin reduced both apixaban exposure and Cmax1. Furthermore, a retrospective study found that half of the patients taking apixaban alongside an enzyme-inducing agent had apixaban concentrations that fell below the fifth percentile of anticipated values. When a direct oral anticoagulant (DOAC) must be used in combination 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 you otherwise. This combination is generally avoided because carbamazepine can lower apixaban levels and reduce its clot-prevention protection.
- Bring this up with your pharmacist or prescriber so they can review your full medication list.
- Your team may choose an alternative anticoagulant or a different seizure/mood medication, or may monitor you more closely, including checking apixaban blood levels if needed.
- Watch for signs of a clot or stroke (sudden weakness, trouble speaking, chest pain, leg swelling or pain) and seek urgent care if they occur.
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-matched adults (n=14,078 eligible episodes) found no difference in thromboembolic event risk among those receiving direct-acting oral anticoagulant (DOAC) therapy (apixaban, dabigatran, or rivaroxaban) together with enzyme-inducing antiseizure medications (EI-ASMs), such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, or topiramate, versus 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 with EI-ASMs rather than non-EI-ASMs (adjusted HR, 0.63 [95% CI, 0.44 to 0.89]) 2.
b) A propensity-score adjusted nested case-control study of patients with atrial fibrillation or recent DVT/PE (N=89,284) found a significantly higher risk of stroke/systemic embolism 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). Patients were new users of DOAC therapy, comprising 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 receiving direct-acting oral anticoagulant therapy (DOAC) alongside 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 deaths) across a median follow up of 17.5 +/- 14.5 months; however, those with 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). While no direct comparisons were made, this rate of thromboembolic events was described as higher than the rates found in cohort studies of atrial fibrillation patients treated with DOAC therapy alone. Major bleeding was observed in 3 patients (1.9% patient-year; 1 death). Within the study, 46.2%, 27.5%, 16.5%, and 9.9% of patients received apixaban, rivaroxaban, dabigatran, and edoxaban, respectively. Concomitant antiepileptic therapy included 45% on levETIRAcetam, 22% on valproic acid, 12% on PHENobarbital, 11% on carBAMazepine, and 10% on other antiepileptic therapy 4.
d) In a retrospective study assessing hospitalized patients who received concomitant direct oral anticoagulants (DOACs; apixaban, 77%; rivaroxaban, 15%; dabigatran, 8%) along with an enzyme-inducing drug (total study population, 1596; 22 [1.4%] received the combined prescriptions), a DOAC concentration below the fifth percentile of the expected concentration was seen 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, versus a fifth percentile of 91 mcg/mL and a ninety-fifth percentile of 321 mcg/mL derived from standard apixaban dosing in the ARISTOTLE study; 5 of the patients from 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%), as well as for neuropathy, essential tremor, or depression 5.
e) In healthy subjects (N=20), coadministration of oral apixaban with oral rifAMPin reduced mean apixaban Cmax by 42% and AUC(0 to infinity) by 54%. Apixaban oral bioavailability fell by 25% and mean apparent clearance rose by 2.1-fold. Subjects were given a single IV dose of apixaban 5 mg on Day 1, then a 10-mg oral dose on Day 3. RifAMPin 600 mg orally once daily was then 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, giving rifAMPin 600 mg together with apixaban lowered apixaban Cmax and AUC by roughly 0.6-fold and 0.5-fold, respectively 1.
Common questions
Can I take Carbamazepine and Apixaban together?
Carbamazepine can make apixaban less effective and raise the risk of clots or stroke, so this pairing is usually avoided. Don't change anything on your own, contact your pharmacist or doctor to plan a safer option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Carbamazepine 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 Carbamazepine and Apixaban interaction managed?
Keep taking both medicines exactly as prescribed until your care team advises you otherwise. This combination is generally avoided because carbamazepine can lower apixaban levels and reduce its clot-prevention protection. Bring this up with your pharmacist or prescriber so they can review your full medication list. Your team may choose an alternative anticoagulant or a different seizure/mood medic… 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 Carbamazepine 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 Carbamazepine
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