Rivaroxaban and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Rivaroxaban
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
Increased rivaroxaban exposure
Interaction Deep Dive
The concomitant administration of ketoconazole, (inhibitor of both P-gp and strong CYP3A4), and rivaroxaban (substrate of both P-gp and moderate CYP3A4) may result in increased rivaroxaban exposure1. During drug interaction studies, coadministration of ketoconazole and rivaroxaban resulted in statistically significant increases in rivaroxaban AUC and Cmax and decreased rivaroxaban clearance 2. Therefore, avoid concurrent use of ketoconazole and rivaroxaban due to the potential increased risk for bleeding 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism; inhibition of P-gp-mediated efflux transport of rivaroxaban
Literature reports
2 reports — tap to read
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%) 2.
b) In drug-interaction studies, the concomitant administration of ketoconazole (inhibitor of both P-gp and strong CYP3A4) and rivaroxaban (substrate of both P-gp and moderate CYP3A4) 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 1.
Common questions
Can I take Rivaroxaban and Ketoconazole Topical together?
Increased rivaroxaban exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rivaroxaban and Ketoconazole Topical interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
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 Ketoconazole Topical 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 (2)
- Product Information: XARELTO(R) oral tablets, oral suspension, rivaroxaban oral tablets, oral suspension. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2023. DailyMed
- Mueck W, Kubitza D, & Becka M: Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects. Br J Clin Pharmacol 2013; 76(3):455-466. PubMed
Keep reading about Ketoconazole Topical
Keep reading about Rivaroxaban
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