Ketoconazole Topical and Conivaptan: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Conivaptan
Ketoconazole Topical
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 conivaptan exposure and an increased CYP3A substrate exposure
Interaction Deep Dive
Concomitant use of conivaptan (strong CYP3A inhibitor and CYP3A substrate) and a strong CYP3A inhibitor that is also a CYP3A substrate is contraindicated, as this may result in increased exposure of one or both agents. The Cmax and AUC of conivaptan increased 4- and 11-fold, respectively, with the concomitant administration of oral conivaptan hydrochloride 10 mg and ketoconazole 200 mg. Conivaptan increased the AUC of CYP3A substrates midazolam, simvastatin, and amLODIPine. Do not initiate the CYP3A substrate sooner than 1 week after completion of conivaptan therapy1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of conivaptan; inhibition of the CYP3A substrate metabolism by conivaptan
Literature reports
4 reports — tap to read
a) The strong CYP3A inhibitor conivaptan 40 mg/day IV increased the AUC of midazolam, a CYP3A substrate, by approximately 100% with a 1-mg IV dose and by 200% with a 2-mg oral dose 1.
b) Conivaptan 30 mg/day IV tripled the AUC of simvastatin, a CYP3A substrate 1.
c) Conivaptan 40 mg orally twice daily doubled the AUC and half-life of amLODIPine, a CYP3A substrate 1.
d) In a drug interaction study, coadministration of oral conivaptan hydrochloride 10 mg with ketoconazole (strong CYP3A inhibitor) 200 mg resulted in 4- and 11-fold increases in Cmax and AUC of conivaptan, respectively 1.
Common questions
Can I take Ketoconazole Topical and Conivaptan together?
Increased conivaptan exposure and an increased CYP3A substrate exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Conivaptan 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 Ketoconazole Topical or Conivaptan 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)
- Product Information: VAPRISOL(R) intravenous injection, conivaptan HCl intravenous injection. Cumberland Pharmaceuticals Inc. (per manufacturer), Nashville, TN, 2014.
Keep reading about Conivaptan
Keep reading about Ketoconazole Topical
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