Carbamazepine with Rivaroxaban Interaction Details

Brand Names Associated with Carbamazepine

Brand Names Associated with Rivaroxaban

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 25, 2023

Interaction Effect

Reduced rivaroxaban plasma concentrations

Interaction Summary

Concomitant use of carbamazepine, a combined P-glycoprotein and strong CYP3A4 inducer, and rivaroxaban may decrease rivaroxaban exposure and is not recommended. In a case report, a 55-year-old man taking rivaroxaban and carbamazepine developed a thrombosis in his right leg 4 months after starting rivaroxaban to treat an unprovoked venous thrombosis in his right leg .

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of carbamazepine, a combined P-glycoprotein and strong CYP3A4 inducer, and rivaroxaban may decrease rivaroxaban exposure and is not recommended.

Mechanism Of Interaction

Induction of CYP3A4-mediated metabolism by carbamazepine; induction of P-glycoprotein-mediated efflux transport by carbamazepine

Literature Reports

A) In a retrospective study (N=131) of patients receiving carbamazepine (n=10) or other enzyme-inducing antiseizure medications (EI-ASM; n=22) concomitantly with direct oral anticoagulant (DOAC) therapy, 37.5% experienced DOAC concentrations below the therapeutic range compared with 9.3% who were not receiving carbamazepine or other enzyme-inducing antiseizure medications (OR, 5.82; 95% CI, 2.03 to 16.66). Apixaban was used by 85% (111 patients) of patients within the study, however, some patients received rivaroxaban (14 patients) or dabigatran (6 patients) .

B) A significantly increased risk of stroke/systemic embolism was noted with administration of direct-acting oral anticoagulant (DOAC) drugs concomitantly with carbamazepine (adjusted OR, 2.15; 95% CI, 1.07 to 4.3) 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 .

C) 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 .

D) Although formal drug-interaction studies have not been performed with carbamazepine, concomitant use of rifampicin (also a combined P-glycoprotein and strong CYP3A4 inducer) titrated up to 600 mg once daily and a single dose of rivaroxaban 20 mg administered with food led to an approximate 50% decrease in the mean AUC and a 22% decrease in the mean Cmax of rivaroxaban. Similar decreases in pharmacodynamic effects were also noted .

E) A 55-year-old man (weight, 113 kg) receiving rivaroxaban and carbamazepine developed thrombosis in his right leg. He was started on rivaroxaban 20 mg daily 4 months prior for an unprovoked venous thrombosis in his right leg. Concomitant medications included carbamazepine 900 mg daily for epilepsy. He presented with pain and increasing swelling of his right leg and sonography revealed thrombosis in his right popliteal and femoral veins. He reported being compliant with his anticoagulation therapy. Anti-factor Xa activity was less than 20 nanograms/mL; carbamazepine level was within the therapeutic range. Rivaroxaban therapy was stopped and low molecular weight heparin therapy followed by phenprocoumon was started; the swelling and pain subsided and he was discharged 5 days later .

Carbamazepine Overview

• Carbamazepine is used alone or in combination with other medications to control certain types of seizures in people with epilepsy. It is also used to treat trigeminal neuralgia (a condition that causes facial nerve pain). Carbamazepine extended-release capsules (Equetro brand only) are also used to treat episodes of mania (frenzied, abnormally excited or irritated mood) or mixed episodes (symptoms of mania and depression that happen at the same time) in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Carbamazepine is in a class of medications called anticonvulsants. It works by reducing abnormal electrical activity in the brain.

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.

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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.

Where Does Our Information Come From?

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.