Drug Interaction Report

Tolvaptan and Ketoconazole Topical: Interaction Details

A pharmacist-reviewed analysis of the Tolvaptan and Ketoconazole Topical 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 Topical

Extina® Foam Ketozole® Cream Kuric Nizoral AD® Shampoo Nizoral® Cream Nizoral® Shampoo Xolegel®
+

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
Contraindicated
These should generally not be used together.
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, 2 are rated contraindicated — 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
Contraindicated

What happens

Increased tolvaptan exposure

Interaction Deep Dive

Tolvaptan AUC and Cmax were increased by 5.4- and 3.5-fold, respectively, when coadministered with ketoconazole 200 mg given one day prior and concomitantly with tolvaptan 30 mg. Larger doses of the strong CYP3A inhibitor would be expected to produce larger increases in tolvaptan exposure. Concomitant use of tolvaptan and strong CYP3A inhibitors is contraindicated as it may increase tolvaptan exposure12.

Why it happens (mechanism)

Inhibition of CYP3A-mediated metabolism of tolvaptan

Literature reports

1 report — tap to read

a) In a drug interaction study, tolvaptan AUC and Cmax were increased by 5.4- and 3.5-fold, respectively, when coadministered with ketoconazole 200 mg given one day prior and concomitantly with tolvaptan 30 mg 12.

Common questions

Can I take Tolvaptan and Ketoconazole Topical together?

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

How serious is the Tolvaptan and Ketoconazole Topical interaction?

It is rated contraindicated. These should generally not be used together.

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 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)

  1. Product Information: SAMSCA(R) oral tablets, tolvaptan oral tablets. Otsuka America Pharmaceutical Inc (per FDA), Rockville, MD, 2021. DailyMed
  2. Product Information: JYNARQUE(R) oral tablets, tolvaptan oral tablets. Otsuka America Pharmaceutical Inc (per manufacturer), Rockville, MD, 2019. DailyMed
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Ketoconazole Topical

Keep reading about Ketoconazole Topical

All Ketoconazole Topical interactions (546) Ketoconazole Topical drug information
Also serious with: Colchicine Conivaptan Crizotinib Dabrafenib
Tolvaptan

Keep reading about Tolvaptan

All Tolvaptan interactions (44) Tolvaptan drug information
Also serious with: Colchicine Mitapivat Lenacapavir Injection Olutasidenib
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:

Tolvaptan + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Astaxanthin + 137 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.