Colchicine and Tepotinib: 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
Tepotinib
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.
Taking these two together needs a close look from your care team. Tepotinib (Tepmetko) can block a 'pump' in your body called P-gp that normally helps push colchicine out. When that pump is slowed, colchicine can build up to higher levels than intended.
Colchicine at high levels can cause serious problems, including severe stomach upset, muscle weakness, and in extreme cases dangerous effects on the blood and other organs. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor before taking them together, especially if you have any kidney or liver problems. Your care team can decide the safest plan for you.
Effect: Increased colchicine exposure and risk of colchicine toxicity. Colchicine is a P-gp (and CYP3A4) substrate; tepotinib inhibits P-gp, reducing colchicine efflux and raising systemic exposure.
- Direction: Increased colchicine effect/toxicity (colchicine is the affected substrate, not a prodrug).
- Severity: Contraindicated per labeling; fatal toxicity reported with P-gp inhibitors at therapeutic colchicine doses.
- Evidence: Theoretical for this pair, extrapolated from documented P-gp/CYP3A4 inhibitor interactions.
- Management: Avoid in renal or hepatic impairment. If coadministration is required in normal organ function, reduce colchicine daily dose or dosing frequency and monitor closely for toxicity (GI, myopathy, myelosuppression).
What happens
Increased colchicine exposure and an increased risk of colchicine toxicity
Interaction Deep Dive
Colchicine serves as a substrate for both CYP3A4 and P-gp. When it was given together with clarithromycin, an agent that inhibits both CYP3A4 and P-gp, toxic effects have been documented. Such toxicities have similarly been seen when colchicine was combined with a CYP3A4 inhibitor and when it was combined with a P-gp inhibitor3. Because life-threatening and fatal colchicine toxicity has been reported in patients taking colchicine at therapeutic doses, concurrent administration of colchicine with P-gp inhibitors is contraindicated 1. This combination is likewise contraindicated in individuals with renal or hepatic impairment, since life-threatening and fatal drug interactions have occurred. For patients whose renal and hepatic function is normal 2, should coadministration of colchicine with a P-gp inhibitor be necessary, modify the colchicine dose by lowering either the daily amount or the frequency of dosing. Watch closely for signs of colchicine toxicity 3.
Why it happens (mechanism)
Inhibition of P-gp-mediated colchicine efflux transport
How to manage this interaction
What your care team may do:
- Because this combination is labeled as contraindicated, they may avoid using them together, especially if you have any kidney or liver impairment.
- If both are truly needed and your kidney and liver function are normal, your colchicine dose may need to be adjusted and individualized (lower daily dose or less frequent dosing).
- They may monitor you more closely for signs of colchicine toxicity.
What you should do: Keep taking both exactly as prescribed and don't change anything on your own. Tell your pharmacist or prescriber you're on both, and report muscle weakness, severe diarrhea, numbness, or unusual fatigue right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Colchicine and Tepotinib together?
Tepotinib can raise colchicine levels by blocking its P-gp pump, and this combination is considered contraindicated because colchicine toxicity can be life-threatening. Do not combine them without your doctor or pharmacist reviewing your kidney/liver function and adjusting or avoiding the colchicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Tepotinib interaction?
It is rated contraindicated. These should generally not be used together.
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 Tepotinib interaction managed?
What your care team may do: Because this combination is labeled as contraindicated, they may avoid using them together, especially if you have any kidney or liver impairment. If both are truly needed and your kidney and liver function are normal, your colchicine dose may need to be adjusted and individualized (lower daily dose or less frequent dosing). They may monitor you more closely for signs o… 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 Colchicine or Tepotinib 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 (3)
- Product Information: LODOCO(R) oral tablets, colchicine oral tablets. AGEPHA Pharma USA, LLC (per FDA), Parsippany, NJ, 2023. DailyMed
- Product Information: COLCRYS oral tablets, colchicine oral tablets. Takeda Pharmaceuticals America Inc (per FDA), Deerfield, IL, 2020. DailyMed
- Product Information: GLOPERBA(R) oral solution, colchicine oral solution. Romeg Therapeutics LLC (per FDA), Woburn, MA, 2019. DailyMed
Keep reading about Tepotinib
Keep reading about Colchicine
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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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