Adagrasib 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
Adagrasib
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.
Your cancer medicine adagrasib (Krazati) 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 expected.
Higher colchicine levels raise the chance of side effects like stomach upset, diarrhea, nausea, muscle aches or weakness. Colchicine has a narrow safe range, so even small increases matter. The good news is your care team knows how to handle this. Please don't stop or change either medicine on your own. Talk with your doctor or pharmacist, who can decide the safest plan for you.
Mechanism: Adagrasib inhibits P-glycoprotein (P-gp)-mediated efflux. Colchicine is a P-gp substrate, so co-administration is predicted to increase colchicine exposure (AUC/Cmax) and the risk of colchicine toxicity.
- Direction: Increased colchicine effect/exposure.
- Magnitude: Not quantified for colchicine; for reference, adagrasib 600 mg BID raised digoxin AUC ~1.5-fold and Cmax ~1.9-fold.
- Evidence: Theoretical; severity major; onset unspecified.
- Management: Manufacturer advises avoiding concomitant use given colchicine's narrow index. If unavoidable, dose reduction and close monitoring for GI, myelosuppressive, and neuromuscular toxicity are warranted, especially with hepatic/renal impairment.
What happens
Increased exposure to P-gp substrates and an increased risk of P-gp substrates-related adverse effects
Interaction Deep Dive
Do not combine adagrasib with substrates of P-gp when even small shifts in concentration could trigger serious adverse reactions. When P-gp substrates are given alongside adagrasib, the exposure to those substrates rises, potentially heightening the likelihood of adverse reactions tied to them. For instance, when adagrasib at 600 mg twice daily is used together with digoxin (a P-gp substrate), digoxin's AUC and Cmax are projected to rise by 1.5-fold and 1.9-fold, respectively1.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport by adagrasib
How to manage this interaction
Because adagrasib can raise colchicine levels, your care team may take steps to keep you safe:
- They may avoid using the two together when possible, or choose an alternative.
- If both are needed, your colchicine dose may be adjusted and individualized by your team, and they may monitor you more closely for side effects.
Keep taking both medicines exactly as prescribed unless your doctor tells you otherwise. Let your pharmacist or prescriber know right away if you notice diarrhea, vomiting, muscle pain or weakness, numbness, or unusual tiredness, and always share your full medication list.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When adagrasib 600 mg administered twice daily is used together with digoxin (a P-gp substrate), the anticipated rise in digoxin AUC is 1.5-fold and the anticipated rise in Cmax is 1.9-fold 1.
Common questions
Can I take Adagrasib and Colchicine together?
Adagrasib can push colchicine levels up by blocking a transporter, and colchicine is risky when it accumulates, so the combination is generally avoided; check with your doctor or pharmacist before taking both. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Adagrasib 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 Adagrasib and Colchicine interaction managed?
Because adagrasib can raise colchicine levels, your care team may take steps to keep you safe: They may avoid using the two together when possible, or choose an alternative. If both are needed, your colchicine dose may be adjusted and individualized by your team, and they may monitor you more closely for side effects. Keep taking both medicines exactly as prescribed unless your doctor tells you ot… 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.
Questions for your pharmacist
- Does my dose of Adagrasib 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: KRAZATI(TM) oral tablets, adagrasib oral tablets. Mirati Therapeutics Inc (per FDA), San Diego, CA, 2024. DailyMed
Keep reading about Adagrasib
Keep reading about Colchicine
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