Rivaroxaban with Ketoconazole Interaction Details
Brand Names Associated with Rivaroxaban
- Rivaroxaban
- Xarelto®
Brand Names Associated with Ketoconazole
- Ketoconazole
- Nizoral®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Dec 02, 2023
Interaction Effect
Increased rivaroxaban exposure
Interaction Summary
The concomitant administration of ketoconazole, a strong inhibitor of CYP3A4 and P-glycoprotein, and rivaroxaban may result in increased rivaroxaban exposure. During drug interaction studies, coadministration of ketoconazole and rivaroxaban resulted in statistically significant increases in rivaroxaban AUC and Cmax and decreased rivaroxaban clearance . Therefore, avoid concurrent use of ketoconazole and rivaroxaban due to the potential increased risk for bleeding .
Severity
Major
Onset
Delayed
Evidence
Established
How To Manage Interaction
The concomitant use of ketoconazole, a CYP3A4 and P-glycoprotein inhibitor, and rivaroxaban may cause increased rivaroxaban exposure; therefore, avoid concurrent use.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated metabolism and P-glycoprotein-mediated efflux transport of rivaroxaban by ketoconazole
Literature Reports
A) During a randomized, open-label, 2-way crossover study, coadministration of ketoconazole and rivaroxaban resulted in statistically significant increases in rivaroxaban AUC and Cmax. Healthy subjects (n=12) received a single dose of rivaroxaban 10 mg alone or in combination with ketoconazole 200 mg daily. Coadministration of ketoconazole 200 mg daily increased rivaroxaban mean AUC by 82% (90% CI, 59% to 108%) and increased rivaroxaban mean Cmax by 53% (90% CI, 27% to 85%). In addition, coadministration of ketoconazole significantly decreased the plasma clearance of rivaroxaban by a mean of 45% (90% CI, -52% to -37%). In an additional nonrandomized, open-label study, healthy subjects (n=20) received rivaroxaban 10 mg daily for 5 days followed by concomitant rivaroxaban 10 mg and ketoconazole 400 mg daily for an additional 5 days. Concurrent administration of ketoconazole 400 mg resulted in statistically significant and potentially clinically significant increases in rivaroxaban mean AUC (158%; 90% CI, 136% to 182%) and increased rivaroxaban mean Cmax (72%; 90% CI, 61% to 83%). Similar to the crossover study, coadministration of ketoconazole also decreased rivaroxaban mean plasma clearance by 61% (90% CI, -65% to -58%) and decreased rivaroxaban clearance by active renal secretion by a mean of 44% (90% CI, -50% to -32%) .
B) In drug-interaction studies, the concomitant administration of ketoconazole and rivaroxaban resulted in increased rivaroxaban AUC and Cmax. Patients received rivaroxaban concurrently with ketoconazole 400 mg once daily. Comparing ketoconazole plus rivaroxaban versus rivaroxaban administration alone, the AUC and Cmax increased 2.6-fold and 1.7-fold, respectively. Significant increases in pharmacodynamic effects leading to an increased risk of bleeding were also observed .
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.
Ketoconazole Overview
-
Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningitis (infection of the membranes surrounding the brain and spinal cord caused by a fungus) or fungal nail infections. Ketoconazole is in a class of antifungals called imidazoles. It works by slowing the growth of fungi that cause infection.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
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.