Rivaroxaban and Levetiracetam: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rivaroxaban
Levetiracetam
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.
What happens
Decreased rivaroxaban exposure and possible subtherapeutic anticoagulation which could lead to a thrombotic event
Interaction Deep Dive
Reduced rivaroxaban levels have been reported with concomitant use of levetiracetam5. This effect may be enhanced in the presence of other drugs that may cause reduced rivaroxaban levels, and should be undertaken with caution 1 due to possible increased risk of thromboembolic events 23. Avoid coadministration if possible 4. If coadministration is necessary, consider measuring rivaroxaban levels when used concomitantly with a P-gp inducer (such as levetiracetam) 5.
Why it happens (mechanism)
Possible induction of P-glycoprotein-mediated efflux transport by levetiracetam; possible P-gp competition
Literature reports
3 reports — tap to read
a) A significantly increased risk of stroke/systemic embolism was noted with administration of direct-acting oral anticoagulant (DOAC) drugs concomitantly with levetiracetam (adjusted OR, 2.26; 95% CI, 1.13 to 4.54) in a propensity-score adjusted nested case-control study of patients with atrial fibrillation or recent DVT/PE (N=89,284). Patients were new users of DOAC therapy and included 54.8% on apixaban, 31.3% on rivaroxaban, and 14% on dabigatran. Results were adjusted for demographic and lifestyle variables 2.
b) In a prospective cohort study of patients with nonvalvular atrial fibrillation receiving direct-acting oral anticoagulant therapy (DOAC) concomitantly with antiepileptic drugs (N=91), the composite outcome of ischemic stroke, transient ischemic attack, and systemic embolism occurred in 9 patients (5.7% patient-year; 3 fatalities) over a median follow up of 17.5 +/- 14.5 months; however, patients who experienced a thromboembolic event were older (75 years or greater), had a history of stroke, and a higher risk score (CHA(2)DS(2)-VASc greater than 3). Although no direct comparisons were made, this incidence of thromboembolic events was noted to be higher than rates in cohort studies of patients with atrial fibrillation treated with DOAC therapy alone. Major bleeding occurred in 3 patients (1.9% patient-year; 1 fatality). In 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% receiving levetiracetam, 22% valproic acid, 12% phenobarbital, 11% carbamazepine, and 10% other antiepileptic therapy 3.
c) A 69-year-old man receiving rivaroxaban for nonvalvular atrial fibrillation developed recurrent transient ischemic attacks (TIA) several months after starting levetiracetam. The TIA attacks caused dysarthria with paralysis of the right lower face. His estimated GFR was 58 mL/min/1.73 m(2) and platelet count was 276 x 10(9) cells/L. Rivaroxaban levels during this time showed a peak of 87 mcg/L 2 hours after rivaroxaban administration (expected, 22 to 535 mcg/L) and a trough of 0 mcg/L immediately before the next scheduled rivaroxaban dose (expected, 6 to 239 mcg/L). Previously (2 years earlier) his rivaroxaban peak was 162.5 mcg/L and trough was 19.3 mcg/L. Levetiracetam (P-gp inducer) was suspected to be decreasing rivaroxaban (P-gp substrate) levels, therefore levetiracetam therapy was discontinued and lacosamide (no P-gp activity) was initiated. Rivaroxaban levels measured 2 months later were increased, demonstrating a peak of 174.6 mcg/L and trough of 40.2 mcg/L. No more TIAs occurred during the 9 months of follow up 5.
Common questions
Can I take Rivaroxaban and Levetiracetam together?
Decreased rivaroxaban exposure and possible subtherapeutic anticoagulation which could lead to a thrombotic event Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rivaroxaban and Levetiracetam 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 strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Rivaroxaban or Levetiracetam 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 (5)
- Steffel J, Collins R, Antz M, et al: 2021 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Europace 2021; 23(10):1612-1676.
- 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
- Stollberger C & Finsterer J: Interactions between non-vitamin K oral anticoagulants and antiepileptic drugs. Epilepsy Res 2016; 126:98-101. PubMed
- Paciullo F, Costa C, & Gresele P: Rivaroxaban plasma levels and levetiracetam: a case report. Ann Intern Med 2020; 173(1):71-72. PubMed
Keep reading about Rivaroxaban
Keep reading about Levetiracetam
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