Rifampin 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
Rifampin
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.
Rifampin can make your blood thinner, apixaban (Eliquis), work less well. Rifampin speeds up how fast your body breaks down and removes apixaban, so less of it stays in your blood. Apixaban is what helps prevent dangerous blood clots, so if its levels drop too low, you could be at higher risk of a stroke or other clots.
The good news is your care team knows about this and can manage it. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor so they can look at your specific situation and decide the safest plan for you.
Effect: Rifampin (strong CYP3A4 and P-gp inducer) increases apixaban clearance, reducing apixaban AUC and Cmax, with loss of anticoagulant efficacy and increased thromboembolic/stroke risk. Apixaban is an active drug, not a prodrug, so induction lowers its effect.
- Mechanism: Induction of CYP3A4-mediated metabolism plus P-gp-mediated efflux of apixaban.
- Magnitude/evidence: Established; PK studies show reduced exposure, and a retrospective study found levels below the 5th percentile in ~half of patients on an enzyme inducer.
- Management: Avoid the combination. If unavoidable, DOAC concentration monitoring may be useful; consider an alternative anticoagulant.
What happens
Reduced apixaban exposure, reduced efficacy of apixaban and an increased risk of stroke and other thromboembolic events
Interaction Deep Dive
Do not administer 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 demonstrated reductions in both apixaban exposure and Cmax when the drug was given alongside rifAMPin1. Furthermore, in a retrospective analysis, half of the patients taking apixaban concurrently with an enzyme-inducing agent had apixaban concentrations that fell below the fifth percentile of anticipated values. When it becomes necessary to combine a direct oral anticoagulant (DOAC) with an enzyme-inducing medication, 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
This combination is generally avoided because rifampin can push apixaban levels too low to protect you from clots.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may choose a different anticoagulant, or if both drugs are truly needed, they may check your apixaban concentration to guide care.
- The right approach can be individualized and monitored by your team.
What to do: Let your pharmacist or doctor know you take both, and report any signs of a clot (such as sudden weakness, trouble speaking, chest pain, or leg swelling) right away.
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 among 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, 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 concurrently with EI-ASMs rather than 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) agents 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 involving patients with atrial fibrillation or recent DVT/PE (N=89,284). The patients were new users of DOAC therapy, comprising 54.8% on apixaban, 31.3% on rivaroxaban, and 14% on dabigatran. The findings were adjusted for demographic and lifestyle factors 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 deaths) across a median follow up of 17.5 +/- 14.5 months; nevertheless, patients who had a thromboembolic event were older (75 years or greater), had a prior history of 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 exceed the rates seen 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. Concurrent antiepileptic treatment 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 of hospitalized patients who received direct oral anticoagulants (DOACs; apixaban, 77%; rivaroxaban, 15%; dabigatran, 8%) together with an enzyme-inducing drug (total study population, 1596; 22 [1.4%] received the concurrent 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 were between 35.8 and 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 ARISTOTLE study patients had levels below the fifth percentile. The DOACs were prescribed for atrial fibrillation (86%) or VTE (14%), and the enzyme inducer was indicated mainly 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 order 6.
f) In a drug interaction study, giving rifAMPin 600 mg together 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 Rifampin and Apixaban together?
Rifampin can lower apixaban levels enough to leave you unprotected from clots, so this combination is usually avoided; talk to your doctor or pharmacist before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rifampin 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 Rifampin and Apixaban interaction managed?
This combination is generally avoided because rifampin can push apixaban levels too low to protect you from clots. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Your care team may choose a different anticoagulant, or if both drugs are truly needed, they may check your apixaban concentration to guide care. The right approach can be individualized and monitored b… 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 Rifampin 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 Rifampin
Keep reading about Apixaban
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