Colchicine and Sotorasib: 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
Sotorasib
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. Sotorasib (Lumakras) can slow down a natural "pump" in your body called P-gp that normally helps move colchicine out. When that pump is blocked, colchicine can build up to higher levels than intended. Because colchicine is a drug where even small increases can cause serious problems, this matters.
Too much colchicine can cause things like nausea, vomiting, diarrhea, muscle weakness, and, in serious cases, harm to the blood or other organs. The good news is your care team can manage this by adjusting your colchicine dose and keeping a closer eye on you. Please don't change either medicine on your own, just talk with your pharmacist or doctor.
Mechanism: Sotorasib inhibits P-glycoprotein (P-gp) efflux transport, increasing exposure (AUC/Cmax) of colchicine, a P-gp substrate. Direction is increased colchicine exposure and toxicity risk. Neither drug is a prodrug here.
- Severity: Major; evidence: probable (digoxin clinical study demonstrated significant P-gp interaction).
- Concern: Colchicine has a narrow therapeutic index; small exposure increases risk GI toxicity, myelosuppression, neuromuscular toxicity, and rhabdomyolysis, especially with renal/hepatic impairment.
- Management: Avoid concomitant use where feasible. If required, reduce colchicine dose and monitor for toxicity. Onset unspecified.
What happens
Increased exposure to P-gp substrate and risk of toxicity
Interaction Deep Dive
Do not combine sotorasib with a P-gp substrate in situations where even slight changes in concentration could produce serious or life-threatening toxicities. Clinical study data showed that giving sotorasib together with digoxin (a P-gp substrate) markedly raised sotorasib exposure. When concurrent use cannot be avoided, lower the dose of the P-gp substrate as appropriate1.
Why it happens (mechanism)
Inhibition of efflux transport of the P-gp substrate by sotorasib
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 as appropriate and individualize it to you.
- Monitor you more closely for signs colchicine is building up.
What you can do:
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise.
- Tell your pharmacist or doctor about all your medicines, and mention any nausea, vomiting, diarrhea, muscle pain or weakness, numbness, or unusual tiredness.
- Ask your care team before starting or stopping either drug.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a clinical study, giving sotorasib together with digoxin (a P-gp substrate) raised digoxin exposure, with Cmax increasing by 91% and AUC increasing by 21% 2.
Common questions
Can I take Colchicine and Sotorasib together?
Sotorasib can raise colchicine levels by blocking the P-gp pump, and because colchicine is easy to overshoot, this combination should be avoided when possible or the colchicine dose lowered with close monitoring. Talk with your pharmacist or doctor before changing anything. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Sotorasib 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 Colchicine and Sotorasib 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 as appropriate and individualize it to you. Monitor you more closely for signs colchicine is building up. What you can do: Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Tell your pharmacist or doctor about all your medicines, and… 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 Colchicine or Sotorasib 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 (2)
Keep reading about Sotorasib
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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