Rivaroxaban with Levetiracetam Interaction Details

Brand Names Associated with Rivaroxaban

Brand Names Associated with Levetiracetam

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 15, 2023

Interaction Effect

Decreased rivaroxaban exposure and possible subtherapeutic anticoagulation which could lead to a thrombotic event

Interaction Summary

Reduced rivaroxaban levels have been reported with concomitant use of levetiracetam. This effect may be enhanced in the presence of other drugs that may cause reduced rivaroxaban levels, and should be undertaken with caution  due to possible increased risk of thromboembolic events . Avoid coadministration if possible . If coadministration is necessary, consider measuring rivaroxaban levels when used concomitantly with a P-gp inducer (such as levetiracetam) .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of rivaroxaban with levetiracetam may lead to reduced rivaroxaban levels, especially in the presence of other drugs that may cause reduced rivaroxaban levels, and should be undertaken with caution  due to possible increased risk of thromboembolic events . Avoid coadministration if possible . If coadministration is necessary, consider measuring rivaroxaban levels when used concomitantly with a P-gp inducer (such as levetiracetam) .

Mechanism Of Interaction

Possible induction of P-glycoprotein-mediated efflux transport by levetiracetam; possible P-gp competition

Literature Reports

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 .

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 .

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 .

Rivaroxaban Overview

• Rivaroxaban is used to treat deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in adults. Rivaroxaban is also used to prevent DVT and PE from happening again after initial treatment is completed in adults. It is also used to help prevent strokes or serious blood clots in adults who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body, and possibly causing strokes) that is not caused by heart valve disease. Rivaroxaban is also used to prevent DVT and PE in adults who are having hip replacement or knee replacement surgery or in people who are hospitalized for serious illnesses and are at risk of developing a clot due to decreased ability to move around or other risk factors. It is also used along with aspirin to lower the risk of a heart attack, stroke, or death in adults with coronary artery disease (narrowing of the blood vessels that supply blood to the heart) or peripheral arterial disease (poor circulation in the blood vessels that supply blood to the arms and legs). Rivaroxaban is also used to treat and prevent DVT and PE from happening again in children and certain infants who have received at least 5 days of initial anticoagulation (blood thinner) treatment. It is also used to prevent DVT and PE after heart surgery in children 2 years of age or older who have congenital heart disease (abnormality in the heart that develops before birth). Rivaroxaban is in a class of medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that helps blood clots to form.

Levetiracetam Overview

• Levetiracetam is used alone and along with other medications to control partial-onset seizures (seizures that involve only one part of the brain) in adults, children, and infants 1 month of age or older. Levetiracetam is also used in combination with other medications to treat seizure in adults and children 12 years of age or older with juvenile myoclonic epilepsy. Levetiracetam is also used in combination with other medications to treat primary generalized tonic-clonic seizures (formerly known as a grand mal seizure; seizure that involves the entire body) in adults and children 6 years of age or older with epilepsy. Levetiracetam is in a class of medications called anticonvulsants. It works by decreasing abnormal excitement in the brain.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

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Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.