Cabozantinib and Conivaptan: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Conivaptan
Cabozantinib
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 cabozantinib exposure
Interaction Deep Dive
Avoid concomitant use of cabozantinib (CYP3A substrate) with conivaptan (strong CYP3A inhibitor), as this may result in increased exposure of cabozantinib. Cabozantinib may be initiated no sooner than 1 week after completion of conivaptan therapy4. If coadministration is required in patients with thyroid cancer, reduce the daily cabozantinib dosage by 40 mg (eg, from 140 mg to 100 mg daily) 2. If coadministration is required in patients with renal or hepatocellular cancer, reduce the daily cabozantinib dosage by 20 mg (eg, from 60 mg to 40 mg daily). Resume the cabozantinib dose that was used prior to initiating conivaptan 2 to 3 days after discontinuation of conivaptan 1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated cabozantinib metabolism
Literature reports
4 reports — tap to read
a) In a pharmacokinetic study in 27 healthy subjects, the administration of a single dose of cabozantinib 140 mg (CYP3A substrate) after 7 continuous daily doses of ketoconazole 400 mg (strong CYP3A inhibitor) increased the cabozantinib AUC by 38% and the elimination half-life increased from 122 to 144 hours 3.
b) 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 4.
c) Conivaptan 30 mg/day IV tripled the AUC of simvastatin, a CYP3A substrate 4.
d) Conivaptan 40 mg orally twice daily doubled the AUC and half-life of amlodipine, a CYP3A substrate 4.
Common questions
Can I take Cabozantinib and Conivaptan together?
Increased cabozantinib exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cabozantinib and Conivaptan 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 Cabozantinib 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 (4)
- Product Information: CABOMETYX(R) oral tablets, cabozantinib oral tablets. Exelixis Inc (per manufacturer), Alameda, CA, 2019. DailyMed
- Product Information: COMETRIQ(TM) oral capsules, cabozantinib oral capsules. Exelixis, Inc. (per manufacturer), South San Francisco, CA, 2012. DailyMed
- Nguyen L, Holland J, Miles D, et al: Pharmacokinetic (PK) drug interaction studies of cabozantinib: effect of CYP3A inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK. J Clin Pharmacol 2015; 55(9):1012-1023. PubMed
- Product Information: VAPRISOL(R) intravenous injection, conivaptan HCl intravenous injection. Cumberland Pharmaceuticals Inc (per FDA), Nashville, TN, 2016.
Keep reading about Conivaptan
Keep reading about Cabozantinib
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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