Simvastatin and Fosnetupitant: 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
Fosnetupitant
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.
Let's talk about taking these two together. Fosnetupitant is a medicine used to prevent nausea from chemotherapy. Inside your body it turns into netupitant, which slows down a liver enzyme (called CYP3A4) that normally breaks down simvastatin (a cholesterol drug, also sold as Zocor).
Because that enzyme is slowed, more simvastatin can build up in your blood. That can raise the chance of statin side effects like muscle aches, weakness, or (rarely) more serious muscle problems. This buildup can last up to a week. The good news is this is expected and manageable. Your care team can lower the statin dose or adjust timing, so please check with your doctor or pharmacist before taking both.
Effect: Increased simvastatin exposure (a CYP3A4 substrate) when given with fosnetupitant.
Mechanism: Fosnetupitant is a prodrug of netupitant, a moderate CYP3A4 inhibitor, reducing simvastatin's first-pass and systemic metabolism. Increased AUC/Cmax raises myopathy and rhabdomyolysis risk.
- Onset: Rapid; inhibition can persist up to ~1 week (dexamethasone AUC effects seen up to 8 days).
- Evidence: Theoretical (extrapolated from erythromycin and dexamethasone PK data).
- Severity: Major.
- Management: Avoid concomitant use for 1 week after netupitant/fosnetupitant. If unavoidable, consider a reduced simvastatin dose and monitor for muscle symptoms/CK.
What happens
Increased exposure of CYP3A4 substrate
Interaction Deep Dive
For a period of 1 week, do not combine CYP3A4 substrates with netupitant or fosnetupitant (the prodrug form of netupitant), which acts as a moderate CYP3A4 inhibitor. Taking netupitant or fosnetupitant together with CYP3A4 substrates can raise the exposure of those substrates. In a pharmacokinetic study, coadministration of netupitant led to increases in the mean AUC and Cmax of erythromycin, a CYP3A4 substrate. For the CYP3A4 probe substrate dexAMETHasone, elevated AUC values persisted for as long as 8 days after a single netupitant dose. CYP3A4 substrates should therefore not be given alongside netupitant for 1 week. Should a CYP3A4 substrate need to be given within that 1 week window following netupitant, consider lowering the dose of the CYP3A4 substrate1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism by netupitant
How to manage this interaction
Your care team can manage this safely. Keep taking your medications as prescribed and do not stop or change anything on your own.
- Your prescriber may avoid combining simvastatin with fosnetupitant for about a week, since the enzyme effect can linger.
- If both are needed within that week, your simvastatin dose may be reduced and individualized by your team.
- Your team may monitor you more closely for muscle pain, tenderness, weakness, or dark urine.
Please tell your pharmacist or doctor that you are on both, and report any new muscle symptoms right away.
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 lasted 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 netupitant 300 mg/palonosetron 0.5 mg combination 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 raised the mean AUC of erythromycin by 56% and increased the Cmax by 92% 1.
Common questions
Can I take Simvastatin and Fosnetupitant together?
Fosnetupitant can raise simvastatin levels and increase muscle-related side effects for up to a week; your care team may hold or lower the statin dose, so check with them before combining. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Fosnetupitant 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 Simvastatin and Fosnetupitant interaction managed?
Your care team can manage this safely. Keep taking your medications as prescribed and do not stop or change anything on your own. Your prescriber may avoid combining simvastatin with fosnetupitant for about a week, since the enzyme effect can linger. If both are needed within that week, your simvastatin dose may be reduced and individualized by your team. Your team may monitor you more closely for… 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 Simvastatin or Fosnetupitant 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 Fosnetupitant
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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