Rivaroxaban with Dronedarone Interaction Details
Brand Names Associated with Rivaroxaban
- Rivaroxaban
- Xarelto®
Brand Names Associated with Dronedarone
- Dronedarone
- Multaq®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 14, 2023
Interaction Effect
Increased rivaroxaban exposure and increased risk of bleeding
Interaction Summary
Concurrent use of rivaroxaban with dronedarone (a dual P-gp and moderate CYP3A4 inhibitor) may lead to increased rivaroxaban exposure and an increased risk of bleeding . If CrCl is less than 80 mL/min, avoid concomitant use of rivaroxaban and dual P-gp and moderate CYP3A4 inhibitors . In geriatric patients with atrial fibrillation receiving concomitant dronedarone, a reduced dosing regimen of rivaroxaban is recommended (15 mg every 24 for normal renal function or 10 mg every 24 hours for moderate or severe renal impairment) .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concurrent use of rivaroxaban with dronedarone (a dual P-gp and moderate CYP3A4 inhibitor) may lead to increased rivaroxaban exposure and an increased risk of bleeding . If CrCl is less than 80 mL/min, avoid concomitant use of rivaroxaban and dual P-gp and moderate CYP3A4 inhibitors . In geriatric patients with atrial fibrillation receiving concomitant dronedarone, a reduced dosing regimen of rivaroxaban is recommended (15 mg every 24 for normal renal function or 10 mg every 24 hours for moderate or severe renal impairment) .
Mechanism Of Interaction
Inhibition of CYP3A4-mediated apixaban metabolism; inhibition of P-gp-mediated efflux transport of rivaroxaban
Literature Reports
A) Coadministration of dronedarone 400 mg every 12 hours with rivaroxaban 20 mg every 24 hours for 14 days in geriatric patients (over 65 years) with atrial fibrillation led to a predicted 1.21-fold increase in rivaroxaban Cmax (90% CI, 1.1 to 1.36) and a 1.29-fold increase in rivaroxaban AUC (90% CI, 1.14 to 1.5) in a pharmacokinetic/pharmacodynamic modeling analysis. In geriatric patients with moderate renal impairment (estimated GFR 30 to 60 mL/min) receiving rivaroxaban 15 mg every 24 hours, Cmax was increased 1.21-fold (90% CI, 1.1 to 1.27) and AUC 1.29-fold (90% CI, 1.12 to 1.58); in those with severe renal impairment (eGFR less than 30), Cmax was increased 1.18-fold (90% CI, 1.05 to 1.25) and AUC 1.31-fold (90% CI, 1.12 to 1.46). Compared with patients receiving rivaroxaban alone, coadministration of rivaroxaban 20 mg every 24 hours (15 mg every 24 hours in those with renal impairment) with dronedarone increased bleeding risk by 1.17-fold (90% CI, 0.83 to 1.93) in those with normal renal function, 1.35-fold (90% CI, 0.94 to 3.21) in those with moderate renal impairment, and 1.36-fold (90% CI, 0.93 to 3.27) in those with severe impairment .
B) Treatment with a combined P-gp and moderate CYP3A4 inhibitor significantly increased risk of bleeding in patients taking apixaban or rivaroxaban for atrial fibrillation in a retrospective observational analysis (N=426). Bleeding, defined as the composite of major, clinically relevant non-major, and minor bleeding, occurred in 26.4% of the interacting agent group vs 18.4% in the propensity-matched control group (HR, 1.8; 95% CI, 1.19 to 2.73). Interacting agents consisted of diltiazem (68.1%), amiodarone (26.8%), verapamil (5.7%), dronedarone (2.3%), and multiple agents (2.8%); no patients received concomitant erythromycin. No significant differences in bleeding rates were identified when individual drug interactions were evaluated, and the impact of renal dysfunction, specific inhibitor, or specific anticoagulant were not evaluated .
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.
Dronedarone Overview
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Dronedarone is used to treat people who currently have normal heart rhythm, but have had atrial fibrillation in the past. Dronedarone decreases the risk that people who have this condition will need to be hospitalized to treat atrial fibrillation. Dronedarone is in a class of medications called antiarrhythmics. It works by helping the heart to beat normally.
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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:
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.