Conivaptan and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Conivaptan
Simvastatin
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.
Conivaptan (Vaprisol) can raise the level of simvastatin (Zocor) in your body. Conivaptan blocks a liver enzyme called CYP3A that normally breaks simvastatin down. When that enzyme is slowed, simvastatin builds up, and higher levels can lead to more side effects like muscle aches, muscle weakness, or (rarely) serious muscle damage.
The good news is your care team can manage this. Conivaptan is usually given in the hospital for a short time, so these two are typically kept apart. Please don't stop or change either medicine on your own. Just talk with your doctor or pharmacist so they can plan the timing and keep an eye on you.
Effect: Increased simvastatin exposure via conivaptan inhibition of CYP3A-mediated metabolism. Simvastatin is an active drug (with active metabolites), so reduced clearance raises systemic exposure and myopathy/rhabdomyolysis risk.
- Direction: Increased simvastatin AUC (documented in interaction studies).
- Mechanism: Conivaptan is a strong CYP3A inhibitor; simvastatin is a CYP3A substrate.
- Onset: Unspecified; Evidence: theoretical/labeled.
- Management: Avoid concomitant use. Do not initiate the CYP3A substrate until at least 1 week after completing conivaptan. Monitor for muscle symptoms (pain, weakness, dark urine) and consider CK if symptomatic.
What happens
Increased CYP3A substrate exposure
Interaction Deep Dive
The combination of conivaptan, a potent CYP3A inhibitor, with agents that depend chiefly on CYP3A-mediated metabolism for their elimination should be avoided, because such pairing can raise the exposure of the CYP3A substrate. Increases in the AUC of the CYP3A substrates midazolam, simvastatin, and amLODIPine have been observed with conivaptan. A CYP3A substrate should not be started until at least 1 week has passed following the end of conivaptan therapy1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated substrate metabolism by conivaptan
How to manage this interaction
What your care team typically does:
- Avoids using conivaptan and simvastatin at the same time.
- Waits at least 1 week after conivaptan is finished before starting simvastatin again.
- Watches you more closely for muscle-related side effects, since raised statin levels increase that risk.
What you should do: Keep taking both exactly as prescribed and don't stop either one on your own. Tell your pharmacist or doctor right away if you notice unexplained muscle pain, tenderness, weakness, or dark-colored urine, and confirm the timing plan with them.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) Conivaptan, a potent CYP3A inhibitor, given at 40 mg/day IV raised the AUC of midazolam, a CYP3A substrate, by roughly 100% when midazolam was dosed at 1 mg IV and by 200% when dosed at 2 mg orally 1.
b) Conivaptan 30 mg/day IV increased the AUC of simvastatin, a CYP3A substrate, threefold 1.
c) Conivaptan 40 mg administered orally twice daily produced a twofold increase in the AUC and half-life of amLODIPine, a CYP3A substrate 1.
Common questions
Can I take Conivaptan and Simvastatin together?
Conivaptan blocks the enzyme that clears simvastatin, so simvastatin can build up and raise the risk of muscle problems; these two are generally kept apart, with simvastatin started no sooner than a week after conivaptan ends. Check the timing with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Conivaptan and Simvastatin 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 is the Conivaptan and Simvastatin interaction managed?
What your care team typically does: Avoids using conivaptan and simvastatin at the same time. Waits at least 1 week after conivaptan is finished before starting simvastatin again. Watches you more closely for muscle-related side effects, since raised statin levels increase that risk. What you should do: Keep taking both exactly as prescribed and don't stop either one on your own. Tell your pharmac… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Conivaptan or Simvastatin 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 Simvastatin
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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