Drug Interaction Report

Digoxin and Fosphenytoin: Interaction Details

A pharmacist-reviewed analysis of the Digoxin and Fosphenytoin 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

Fosphenytoin

Cerebyx
+

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

Reduced digoxin exposure

Interaction Deep Dive

Coadministration of digoxin and phenytoin or fosphenytoin (prodrug of phenytoin) (P-gp inducer) may reduce digoxin exposure. Measure digoxin exposure prior to initiation of concurrent use. Increase the digoxin dose by approximately 20% to 40%, if necessary, and continue monitoring digoxin exposure12. Consider digoxin dose adjustments to achieve optimal clinical response when phenytoin or fosphenytoin is added to or withdrawn from a patient's regimen 345.

Why it happens (mechanism)

Induction of P-gp mediated efflux transport of digoxin

Common questions

Can I take Digoxin and Fosphenytoin together?

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

How serious is the Digoxin and Fosphenytoin 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 Fosphenytoin 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 (5)

  1. Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
  2. Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. DailyMed
  3. Product Information: FOSPHENYTOIN SODIUM intravenous and intramuscular injection, fosphenytoin sodium intravenous and intramuscular injection. SAGENT Pharmaceuticals (per Dailymed), Schaumburg, IL, 2024. DailyMed
  4. Product Information: PHENYTOIN SODIUM intravenous and intramuscular injection, phenytoin sodium intravenous and intramuscular injection. Acella Pharmaceuticals, LLC (per Dailymed), Alpharetta, GA, 2024. DailyMed
  5. Product Information: PHENYTOIN SODIUM oral extended-release capsules, phenytoin sodium oral extended-release capsules. Sun Pharmaceutical Industries, Inc. (per Dailymed), Cranbury, NJ, 2023. DailyMed
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Fosphenytoin

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Digoxin

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All Digoxin interactions (453) Digoxin drug information
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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:

Fosphenytoin + 1,4-butanediol American Hellebore Arsenic Beer Cesium Ephedra Gamma-hydroxybutyrate (ghb) Grapefruit + 197 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.