Fedratinib and Colchicine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fedratinib
Colchicine
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.
Here's what's going on. Fedratinib (Inrebic) slows down a liver enzyme called CYP3A4. Your body uses that same enzyme to break down colchicine. So when you take both, colchicine can build up higher than usual in your blood.
That matters because too much colchicine can cause nausea, diarrhea, stomach pain, and, at higher levels, more serious problems affecting the muscles or blood cells. The good news is your care team knows how to handle this. They may lower your colchicine dose or watch you more closely for side effects. Please don't change anything on your own, but do tell your pharmacist or doctor you're taking both so they can keep you safe.
Mechanism: Fedratinib is a moderate CYP3A4 inhibitor; colchicine is a CYP3A4 (and P-gp) substrate. Inhibition reduces colchicine metabolism, increasing systemic exposure.
Direction/magnitude: Increased colchicine AUC/Cmax expected. Fedratinib raised midazolam AUC ~4-fold in single-dose PK studies, indicating meaningful inhibitory potential. Evidence: probable. Onset: unspecified.
Risk: Colchicine has a narrow therapeutic index; excess exposure risks GI toxicity, myelosuppression, neuromyopathy, and rare life-threatening toxicity, especially in renal or hepatic impairment.
- Monitor for colchicine toxicity (GI symptoms, myopathy, cytopenias).
- Reduce colchicine dose per care team judgment; individualize.
- Exercise added caution with renal/hepatic impairment.
What happens
Increased CYP3A4 substrate exposure
Interaction Deep Dive
Taking fedratinib (which inhibits CYP3A4) together with substrates of CYP3A4 can raise the levels of those substrates and elevate the likelihood of adverse reactions associated with them. Single-dose pharmacokinetic research showed that fedratinib produced a 4-fold rise in the AUC of midazolam, a CYP3A4 substrate. When the two must be given together, watch for adverse reactions and modify the dosage of CYP3A4 substrate medications1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated substrate metabolism by fedratinib
How to manage this interaction
Keep taking both as prescribed unless your care team tells you otherwise. This interaction can be managed.
Because fedratinib can raise colchicine levels, your team may:
- Adjust and individualize your colchicine dose.
- Monitor you more closely for side effects.
Watch for and report: ongoing diarrhea, vomiting, stomach pain, muscle weakness or pain, tingling, unusual tiredness, fever, or easy bruising. Let your team know if you have kidney or liver problems, since that raises the risk. Always check with your pharmacist or prescriber before starting, stopping, or changing either medicine.
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 produced a 4-fold rise in the AUC of midazolam 1.
Common questions
Can I take Fedratinib and Colchicine together?
Fedratinib can raise colchicine levels by slowing its breakdown, increasing the chance of side effects; keep taking both as prescribed and let your care team adjust the colchicine dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fedratinib and Colchicine 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 Colchicine interaction managed?
Keep taking both as prescribed unless your care team tells you otherwise. This interaction can be managed. Because fedratinib can raise colchicine levels, your team may: Adjust and individualize your colchicine dose. Monitor you more closely for side effects. Watch for and report: ongoing diarrhea, vomiting, stomach pain, muscle weakness or pain, tingling, unusual tiredness, fever, or easy bruisin… 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.
Questions for your pharmacist
- Does my dose of Fedratinib or Colchicine 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 Colchicine
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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