Vepdegestrant 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
Colchicine
Vepdegestrant
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.
Colchicine (for gout) is cleared from your body partly by a pump called P-gp. Vepdegestrant can block that pump. When the pump is blocked, colchicine can build up to higher levels than usual, which raises the chance of side effects like nausea, vomiting, diarrhea, or muscle problems.
Colchicine has a narrow safety window, so even small increases can matter. The good news: your care team can manage this. Please don't stop or change either medicine on your own. Just let your pharmacist or doctor know you take both so they can decide the safest plan for you.
Mechanism: Vepdegestrant inhibits P-glycoprotein (P-gp), reducing efflux of colchicine (a P-gp substrate with a narrow therapeutic index). This raises colchicine systemic exposure and toxicity risk.
- Direction: Increased colchicine exposure (increases drug effect/toxicity). Neither agent is activated by P-gp, so no prodrug reversal applies.
- Magnitude: Not quantified for colchicine; a probe study with dabigatran showed AUC 2-fold and Cmax 1.9-fold increases.
- Evidence: Theoretical; onset unspecified.
- Management: Manufacturer advises avoiding concomitant use with NTI P-gp substrates. If unavoidable, individualize colchicine dosing and monitor for GI, myelosuppressive, and neuromuscular toxicity.
What happens
Increased P-gp substrate exposure and an increased risk of P-gp substrate-related adverse reactions
Interaction Deep Dive
Do not use vepdegestrant (a P-gp inhibitor) together with P-gp substrates that have a narrow therapeutic index (NTI), because doing so may raise the exposure of these NTI substrates and thereby heighten the adverse reactions associated with them. During drug interaction studies, giving a single 200 mg dose of vepdegestrant alongside dabigatran etexilate (a P-gp substrate) produced a 2-fold rise in AUC and a 1.9-fold rise in Cmax1.
Why it happens (mechanism)
Inhibition of P-gp-mediated metabolism of vepdegestrant
How to manage this interaction
Your care team knows how to handle this combination. Because vepdegestrant can raise colchicine levels, they may choose to avoid using them together, adjust your colchicine dose, or watch you more closely for side effects.
- Keep taking both medicines as prescribed unless your doctor tells you otherwise.
- Tell your pharmacist and prescriber you take both so the colchicine dose can be adjusted and individualized if needed.
- Report side effects like diarrhea, vomiting, muscle pain or weakness, or unusual tiredness.
The dose may need to be tailored to you, and your team may monitor you more closely to keep things safe.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In drug interaction studies, giving vepdegestrant (a single 200 mg dose) together with dabigatran etexilate (a P-gp substrate) raised the AUC by 2-fold and the Cmax by 1.9-fold 1.
Common questions
Can I take Vepdegestrant and Colchicine together?
Vepdegestrant can raise colchicine levels by blocking P-gp, which increases the risk of colchicine side effects. Don't change anything on your own; tell your pharmacist or doctor you take both so they can adjust the dose or monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Vepdegestrant 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 Vepdegestrant and Colchicine interaction managed?
Your care team knows how to handle this combination. Because vepdegestrant can raise colchicine levels, they may choose to avoid using them together, adjust your colchicine dose, or watch you more closely for side effects. Keep taking both medicines as prescribed unless your doctor tells you otherwise. Tell your pharmacist and prescriber you take both so the colchicine dose can be adjusted and ind… 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 Vepdegestrant 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: VEPPANU oral tablet, vepdegestrant oral tablet. Pfizer Inc. New York, NY, 2026. DailyMed
Keep reading about Colchicine
Keep reading about Vepdegestrant
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