Drug Interaction Report

Digoxin and Ketoconazole: Interaction Details

A pharmacist-reviewed analysis of the Digoxin and Ketoconazole interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Ketoconazole

Extina Ketodan Kuric Nizoral Recorlev T8 Keto Flush Xolegel
+

Digoxin

Cardoxin® Digitek Digitek® Digox Lanoxicaps® Lanoxin Lanoxin®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 453 documented Digoxin interactions, 359 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased digoxin exposure

Interaction Deep Dive

Exert caution when digoxin (P-gp substrate) and ketoconazole (P-gp inhibitor) are coadministered. Rare cases of elevated digoxin exposure have been reported with concomitant use of digoxin and ketoconazole. It is unclear whether this increase in digoxin exposure was due to the combination use of these drugs. Therefore, if these agents are coadministered, monitor digoxin exposure1.

Why it happens (mechanism)

Inhibition of P-gp-mediated efflux transport of ketoconazole

Common questions

Can I take Digoxin and Ketoconazole together?

Increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Digoxin and Ketoconazole interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

Questions for your pharmacist

  • Does my dose of Digoxin or Ketoconazole 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 (1)

  1. Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
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Ketoconazole

Keep reading about Ketoconazole

All Ketoconazole interactions (186)
Also serious with: Dihydroergotamine Injection Finerenone Lefamulin Loperamide
Digoxin

Keep reading about Digoxin

All Digoxin interactions (453) Digoxin drug information
Also serious with: Levoketoconazole Meclofenamate Mavorixafor Parathyroid Hormone Injection
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Ketoconazole + Activated Charcoal Beer Grapefruit Siberian Cocklebur St. John's Wort Wine Acacia Rigidula Adrafinil + 174 more
Digoxin + Activated Charcoal Aloe Blue Flag Danshen European Buckthorn Foxglove Indian Snakeroot Lily-of-the-valley + 105 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.