Colchicine and Ensitrelvir: 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
Ensitrelvir
No brand names on record
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.
These two medicines should not be taken together. Ensitrelvir slows down the body's ability to clear colchicine, so the colchicine can build up to dangerously high levels. Colchicine is already a drug where the safe amount and the harmful amount are close together.
When too much colchicine stays in your body, it can seriously harm your kidneys and liver and cause severe, even life-threatening problems. The good news is your care team knows about this and can plan around it. Please don't stop or start either drug on your own talk with your pharmacist or doctor, who can choose a safer option or the right timing for you.
Contraindicated combination. Ensitrelvir inhibits both CYP3A-mediated metabolism and P-gp-mediated efflux of colchicine (a CYP3A and P-gp substrate), raising colchicine exposure.
- Direction: increased colchicine AUC/Cmax; elevated risk of renal and/or hepatic impairment and severe, potentially fatal colchicine toxicity.
- NTI concern: colchicine has a narrow therapeutic index, so even modest exposure increases matter.
- Evidence: theoretical/mechanistic.
- Management: avoid co-administration. Initiate ensitrelvir only after evaluating the concomitant regimen; reintroduce colchicine based on the duration of CYP3A inhibition and patient-specific factors.
What happens
Increased colchicine exposure and an increased risk of renal and/or hepatic impairment
Interaction Deep Dive
Giving ensitrelvir together with colchicine (which is both a CYP3A substrate and a P-gp substrate) is contraindicated, because doing so may raise colchicine exposure, and that elevated exposure of colchicine could result in severe, life-threatening, or fatal events. Ensitrelvir should be started only after a careful review of the relevant clinical and pharmacokinetic factors associated with the coadministered drug. Furthermore, decisions to restart contraindicated CYP3A substrates should be guided by an evaluation of how long CYP3A inhibition persists as well as considerations specific to the individual patient1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of colchicine; inhibition of P-gp-mediated efflux transport of colchicine
How to manage this interaction
Because this combination is contraindicated, your care team will generally avoid using ensitrelvir and colchicine at the same time.
- Keep taking your medicines as prescribed, and do not start or stop either one on your own.
- Tell your prescriber and pharmacist you take colchicine before any ensitrelvir is started, so they can plan safely.
- Your team may pause one drug, choose an alternative, or time therapy around how long ensitrelvir affects your system before restarting colchicine.
- Report muscle pain or weakness, unusual tiredness, or signs of kidney or liver trouble right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) When midazolam (a CYP3A substrate) was given as a single 2 mg oral dose together with ensitrelvir at the clinical dose (375 mg on day 1 and 125 mg on days 2 to 5) on Day 5, the Cmax of midazolam rose approximately 2.80-fold and the AUC(0 to inf) rose 6.77-fold relative to midazolam given by itself. In addition, giving dexAMETHasone (single 1 mg dose) together with ensitrelvir (750 mg on day 1 and 250 mg on days 2 to 5, which is twice the recommended dose) on day 5, and giving it alone on day 9 (5 days after the final ensitrelvir dose) and day 14 (10 days after the final ensitrelvir dose), produced an approximately 1.47-fold increase in Cmax and a 3.47-fold increase in AUC(0 to inf) of dexAMETHasone on day 5, a 1.24-fold increase in Cmax and 2.38-fold increase in AUC(0 to inf) on day 9, and a 1.17-fold increase in Cmax and a 1.58-fold increase in AUC(0 to inf) on day 14, compared with dexAMETHasone given alone 1.
b) When ensitrelvir (single 500 mg dose, which is not a recommended dosage of ensitrelvir) was given together with a single oral dose of a transporter cocktail containing 0.25 mg digoxin, the Cmax of digoxin increased 2.17-fold and the AUC(0 to inf) increased 1.31-fold 1.
Common questions
Can I take Colchicine and Ensitrelvir together?
Ensitrelvir can push colchicine to toxic levels, so this pairing is contraindicated; do not take them together and let your pharmacist or doctor coordinate a safe plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Ensitrelvir 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 Ensitrelvir interaction managed?
Because this combination is contraindicated, your care team will generally avoid using ensitrelvir and colchicine at the same time. Keep taking your medicines as prescribed, and do not start or stop either one on your own. Tell your prescriber and pharmacist you take colchicine before any ensitrelvir is started, so they can plan safely. Your team may pause one drug, choose an alternative, or time… 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 Ensitrelvir 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: XOCOVA® oral tablets, ensitrelvir oral tablets. Shionogi Inc. Florham Park, NJ, 2026.
Keep reading about Colchicine
Keep reading about Ensitrelvir
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