Fedratinib 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
Fedratinib
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.
These two medicines can interact. Fedratinib (Inrebic) slows down a liver enzyme called CYP3A4. Your body uses that same enzyme to clear simvastatin (Zocor) out of your system. When fedratinib blocks it, simvastatin can build up to higher levels than intended.
Higher statin levels raise the risk of statin side effects, especially muscle aches, weakness, or tenderness, and in rare cases a more serious muscle problem. The good news is this is very manageable. Keep taking both exactly as prescribed, and let your pharmacist or doctor know you take them together so they can watch you closely and adjust your simvastatin dose if needed.
Interaction: Fedratinib is a moderate CYP3A4 inhibitor; simvastatin is a CYP3A4 substrate. Inhibition reduces simvastatin metabolism, increasing systemic exposure (AUC/Cmax) and the risk of dose-dependent toxicity (myopathy, rhabdomyolysis).
- Direction: increased simvastatin exposure and effect.
- Magnitude: not quantified for simvastatin; fedratinib raised midazolam AUC ~4-fold.
- Onset: unspecified. Evidence: probable. Severity: major.
- Management: if coadministration is necessary, monitor for muscle symptoms and consider dose reduction of simvastatin, individualized by the care team; consider an alternative statin less dependent on CYP3A4.
What happens
Increased CYP3A4 substrate exposure
Interaction Deep Dive
When fedratinib, which inhibits CYP3A4, is taken together with drugs that serve as CYP3A4 substrates, the levels of those substrates can rise, thereby heightening the likelihood of adverse reactions associated with them. Studies of single-dose pharmacokinetics demonstrated a 4-fold rise in the AUC of midazolam (a CYP3A4 substrate) when given with fedratinib. Should combined use be required, watch for adverse reactions and modify the dosing of CYP3A4 substrate medications1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated substrate metabolism by fedratinib
How to manage this interaction
This is manageable with your care team. Keep taking both medicines as prescribed unless told otherwise.
- Your team may monitor you more closely for statin side effects while you are on both.
- Your simvastatin dose may need to be adjusted and individualized by your care team, or they may consider a different statin.
- Report right away any new or unexplained muscle pain, tenderness, weakness, or dark-colored urine.
- Tell your pharmacist and prescriber that you take both so they can plan the safest approach.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Giving a single 2 mg dose of midazolam (a CYP3A4 substrate) together with fedratinib raised the AUC of midazolam by 4-fold 1.
Common questions
Can I take Fedratinib and Simvastatin together?
Fedratinib can raise simvastatin levels and increase the risk of muscle side effects, so watch for muscle pain or weakness and let your care team adjust the dose or monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fedratinib 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 Fedratinib and Simvastatin interaction managed?
This is manageable with your care team. Keep taking both medicines as prescribed unless told otherwise. Your team may monitor you more closely for statin side effects while you are on both. Your simvastatin dose may need to be adjusted and individualized by your care team, or they may consider a different statin. Report right away any new or unexplained muscle pain, tenderness, weakness, or dark-c… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Fedratinib 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: INREBIC(R) oral capsules, fedratinib oral capsules. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2023. DailyMed
Keep reading about Fedratinib
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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