Drug Interaction Report

Tolvaptan and Digoxin: Interaction Details

A pharmacist-reviewed analysis of the Tolvaptan and Digoxin 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

Digoxin

Cardoxin® Digitek Digitek® Digox Lanoxicaps® Lanoxin Lanoxin®
+

Tolvaptan

Jynarque Samsca
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 44 documented Tolvaptan interactions, 38 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
probable
Severity
Major

What happens

Increased digoxin exposure

Interaction Deep Dive

Concomitant use of digoxin, a P-gp substrate, and tolvaptan, a P-gp inhibitor, increased digoxin Cmax by 30% and AUC by 20% in a pharmacokinetic study3. Therefore, measure digoxin concentrations prior to initiation of concurrent use. Reduce digoxin concentrations by reducing the digoxin dose by approximately 15% to 30% or by modifying the dosing frequency. Continue monitoring digoxin exposure. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing tolvaptan 12.

Why it happens (mechanism)

Inhibition of P-gp-mediated efflux transport of digoxin

Literature reports

2 reports — tap to read

a) During pharmacokinetic studies, coadministration of tolvaptan and oral digoxin resulted in a 30% increase in digoxin serum concentrations and a 20% increase in digoxin AUC 12.

b) Coadministration of digoxin 0.25 mg once daily for 12 days with tolvaptan 60 mg once daily on days 8 and 12 increased digoxin Cmax by 30% and AUC by 20%. Coadministration had no clinically relevant impact on the exposure of tolvaptan 3.

Common questions

Can I take Tolvaptan and Digoxin together?

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

How serious is the Tolvaptan and Digoxin 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 "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Tolvaptan or Digoxin 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 (3)

  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: SAMSCA(R) oral tablets, tolvaptan oral tablets. Otsuka America Pharmaceutical Inc (per FDA), Rockville, MD, 2021. DailyMed
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Digoxin

Keep reading about Digoxin

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

Keep reading about Tolvaptan

All Tolvaptan interactions (44) Tolvaptan drug information
Also serious with: Colchicine Ketoconazole Topical Methotrexate Injection Mitapivat
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:

Digoxin + Activated Charcoal Aloe Blue Flag Danshen European Buckthorn Foxglove Indian Snakeroot Lily-of-the-valley + 105 more
Tolvaptan + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Astaxanthin + 137 more

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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.