Selpercatinib 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
Selpercatinib
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. Selpercatinib (Retevmo) is a cancer medicine that slows down two of your body's clean-up systems, an enzyme called CYP3A and a transporter called P-gp. Colchicine (used for gout and pericarditis) relies on both of those systems to leave your body. So when you take them together, colchicine can build up higher than intended.
Colchicine has a narrow safety window, meaning even small increases can cause more side effects like nausea, diarrhea, muscle weakness, or more serious problems. The good news is your care team knows how to handle this. Please don't stop or change either medicine on your own. Just talk with your pharmacist or doctor so they can adjust your dose or watch you more closely.
Mechanism: Selpercatinib inhibits both CYP3A-mediated metabolism and P-gp-mediated efflux. Colchicine is a substrate of both and is a narrow-therapeutic-index drug, so combined inhibition raises colchicine exposure and toxicity risk.
Direction/magnitude: Increased colchicine AUC/Cmax expected. Benchmarks: selpercatinib raised midazolam AUC ~54%/Cmax ~39% (CYP3A) and dabigatran AUC ~38%/Cmax ~43% (P-gp).
- Severity: Major; evidence probable; onset unspecified.
- Management: Avoid coadministration if possible. If necessary, follow P-gp substrate dosing recommendations (colchicine dose reduction) and monitor for colchicine toxicity (GI, myotoxicity, cytopenias), particularly in renal/hepatic impairment.
What happens
Increased CYP3A and P-gp substrate with NTI exposure and an increased risk of CYP3A and P-gp with NTI-related adverse events
Interaction Deep Dive
Selpercatinib acts as an inhibitor of both CYP3A and P-gp, so it should not be given together with a CYP3A4 and P-gp substrate that has a narrow therapeutic index (NTI), because doing so may raise the exposure of the NTI substrate and heighten the likelihood of adverse reactions linked to those substrates. A pharmacokinetic study showed that when selpercatinib was given alongside midazolam (a sensitive CYP3A substrate), the midazolam AUC(0 to inf) rose by 54% and its Cmax by 39%. Likewise, giving selpercatinib together with dabigatran (a P-gp substrate) produced a 38% increase in dabigatran AUC(0 to inf) and a 43% increase in Cmax. When their combined use cannot be avoided, follow the applicable recommendations for the P-gp substrate1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport by selpercatinib; inhibition of CYP3A-mediated metabolism by selpercatinib
How to manage this interaction
What your care team may do:
- Try to avoid using these two together when possible.
- If both are truly needed, reduce the colchicine dose following P-gp substrate guidance. The dose may need to be adjusted and individualized by your care team.
- Watch you more closely for signs of too much colchicine, such as diarrhea, nausea, or muscle weakness.
What you should do: Keep taking both exactly as prescribed unless told otherwise. Tell your pharmacist or doctor you take both, and report any new stomach upset, muscle aches, or unusual weakness right away, especially if you have kidney or liver problems.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
Common questions
Can I take Selpercatinib and Colchicine together?
Selpercatinib can raise colchicine levels and side-effect risk because it blocks both CYP3A and P-gp; your team will likely avoid the combination or lower the colchicine dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Selpercatinib 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 Selpercatinib and Colchicine interaction managed?
What your care team may do: Try to avoid using these two together when possible. If both are truly needed, reduce the colchicine dose following P-gp substrate guidance. The dose may need to be adjusted and individualized by your care team. Watch you more closely for signs of too much colchicine, such as diarrhea, nausea, or muscle weakness. What you should do: Keep taking both exactly as prescribe… 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 Selpercatinib 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: RETEVMO(R) oral capsules, tablets, selpercatinib oral capsules, tablets. Lilly USA LLC (per FDA), Indianapolis, IN, 2024. DailyMed
Keep reading about Selpercatinib
Keep reading about Colchicine
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