Netupitant 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
Netupitant
No brand names on recordSimvastatin
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.
Netupitant is a medicine used to help prevent nausea and vomiting from chemotherapy. Simvastatin (Zocor) is a cholesterol-lowering statin. Netupitant can slow down the liver enzyme (called CYP3A4) that normally breaks down simvastatin. When that happens, simvastatin can build up in your body and reach higher levels than usual.
Higher statin levels can raise the chance of side effects like muscle aches or muscle soreness. This effect can last for about a week after netupitant is given. The good news is your care team knows about this and can manage it, often by adjusting your statin dose or watching you a little more closely. Please talk with your pharmacist or doctor before changing anything.
Mechanism: Netupitant (and its prodrug fosnetupitant) is a moderate CYP3A4 inhibitor. Simvastatin is a sensitive CYP3A4 substrate, so inhibition reduces its metabolism and increases exposure (AUC/Cmax).
- Direction: Increased simvastatin exposure, raising myopathy/rhabdomyolysis risk.
- Onset: Rapid; inhibition can persist up to ~1 week (dexamethasone AUC elevated up to 8 days after a single netupitant dose).
- Evidence: Theoretical for this pair; supported by PK data with erythromycin and dexamethasone.
- Management: Avoid coadministration for 1 week after netupitant. If unavoidable, consider reducing the simvastatin dose and monitor for muscle symptoms.
What happens
Increased exposure of CYP3A4 substrate
Interaction Deep Dive
For a period of one week, the joint administration of CYP3A4 substrates alongside netupitant or fosnetupitant (the prodrug form of netupitant), which acts as a moderate CYP3A4 inhibitor, should be avoided. Taking netupitant or fosnetupitant together with CYP3A4 substrates can raise the exposure to those substrates. In a pharmacokinetic study, coadministering netupitant led to a rise in the mean AUC and Cmax of erythromycin, a CYP3A4 substrate. Following a single netupitant dose, elevations in the AUC of the CYP3A4 probe substrate dexAMETHasone persisted for as long as 8 days. Concurrent administration of CYP3A4 substrates with netupitant should therefore be avoided over a one-week interval. Should a CYP3A4 substrate need to be given within one week of netupitant, a reduction in the CYP3A4 substrate dose should be considered1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism by netupitant
How to manage this interaction
Keep taking both medicines exactly as prescribed, and do not stop or change either one on your own.
- Your care team may avoid using them together for about a week around your netupitant dose, since the effect can linger.
- If simvastatin is needed during that window, your statin dose may be adjusted and individualized by your team, and they may watch you more closely.
- Report any muscle pain, tenderness, weakness, or dark urine to your pharmacist or doctor right away.
Ask your pharmacist to review the timing of these two medicines so it can be handled safely.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a study that evaluated how long CYP3A4 inhibition persisted using dexAMETHasone as a CYP3A4 probe substrate, the mean AUC of dexAMETHasone rose by 1.6-fold on day 1, 2.4-fold on day 4, 1.5-fold on day 6, and 1.2-fold on day 8 following a single dose of the combination netupitant 300 mg/palonosetron 0.5 mg given to participants on day 1. These participants had received a dexAMETHasone regimen consisting of 12 mg on day 1 and then 8 mg on days 2, 3, 4, 6, 8, and 10 1.
b) A pharmacokinetic study showed that coadministration of erythromycin 500 mg with netupitant 300 mg produced a 56% increase in the mean AUC of erythromycin and a 92% increase in the Cmax 1.
Common questions
Can I take Netupitant and Simvastatin together?
Netupitant can raise simvastatin levels by slowing its breakdown, which increases muscle-related side effect risk; your care team can manage this by adjusting the timing or dose and monitoring you. Report any muscle pain and check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Netupitant 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 "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Netupitant and Simvastatin interaction managed?
Keep taking both medicines exactly as prescribed, and do not stop or change either one on your own. Your care team may avoid using them together for about a week around your netupitant dose, since the effect can linger. If simvastatin is needed during that window, your statin dose may be adjusted and individualized by your team, and they may watch you more closely. Report any muscle pain, tenderne… 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 Netupitant 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: AKYNZEO(R) oral capsules, netupitant palonosetron oral capsules. Helsinn Therapeutics (US), Inc (per FDA), Iselin, NJ, 2018. DailyMed
Keep reading about Netupitant
Keep reading about Simvastatin
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