Colchicine and Ketoconazole: 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
Ketoconazole
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.
Ketoconazole can cause colchicine to build up in your body to dangerous levels. Your body normally breaks down and clears colchicine using an enzyme (called CYP3A4) and a pump (called P-gp). Ketoconazole blocks both of these, so colchicine can climb far higher than it should. That raises the risk of serious, even life-threatening colchicine poisoning, which can start with severe diarrhea, vomiting, muscle weakness, and worse.
The good news is your care team can manage this. In some situations this combination is avoided entirely, and in others the colchicine dose is lowered. Please don't stop or change either medicine on your own, just talk with your pharmacist or doctor so they can guide you safely.
Direction: Ketoconazole (strong dual CYP3A4 + P-gp inhibitor) reduces colchicine metabolism and efflux, markedly increasing colchicine exposure and toxicity risk. Neither is a prodrug; this is straightforward inhibition raising the active drug.
- Severity/evidence: Contraindicated; established, with fatal cases reported at therapeutic colchicine doses.
- Contraindicated absolutely in renal or hepatic impairment.
- Normal renal/hepatic function (concurrent or ketoconazole within 14 days): dose-reduce colchicine.
- Gout flare: 0.6 mg once, then 0.3 mg 1 hour later; do not repeat before 3 days.
- Gout prophylaxis: 0.6 mg BID to 0.3 mg daily; or 0.6 mg daily to 0.3 mg every other day.
- FMF: max 0.6 mg/day (may split as 0.3 mg BID).
Monitor for GI toxicity, myopathy, and cytopenias.
What happens
Increased colchicine exposure and an increased risk of colchicine toxicity
Interaction Deep Dive
Both CYP3A4 and P-gp metabolize colchicine, which is a substrate of each. Because therapeutic doses of colchicine have produced reports of fatal and life-threatening toxicity when combined with agents that strongly inhibit both CYP3A4 and P-gp, such dual inhibitor combinations are contraindicated1. Likewise, colchicine paired with a dual CYP3A4 and P-gp inhibitor like ketoconazole is contraindicated for anyone with hepatic or renal impairment3. When renal and hepatic function are normal, however, patients taking ketoconazole at the same time, or who have taken it within the previous 14 days, need their colchicine dose adjusted. To treat a gout flare, cut the colchicine dose to a single 0.6 mg tablet, then 0.3 mg (half a tablet) one hour afterward, and do not repeat the dose sooner than 3 days. For gout flare prophylaxis, lower the colchicine dose to 0.3 mg once daily from a starting dose of 0.6 mg twice daily, or to 0.3 mg every other day from a starting dose of 0.6 mg once daily. In the treatment of familial Mediterranean fever, the colchicine daily total should not exceed 0.6 mg (which may be administered as 0.3 mg twice daily)2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of colchicine; and P-gp-mediated efflux transport of colchicine
How to manage this interaction
This combination is taken seriously, but your care team has clear ways to manage it.
- In some cases (especially if you have kidney or liver problems), the two drugs are not used together at all, and an alternative is chosen.
- If your kidneys and liver are healthy, your prescriber will lower your colchicine dose based on why you take it (gout treatment, gout prevention, or familial Mediterranean fever).
- This reduced dosing also applies if you have taken ketoconazole in the past 14 days.
Keep taking both exactly as prescribed and do not adjust doses yourself. Tell your pharmacist or doctor you are on both, and get medical help right away for severe diarrhea, vomiting, muscle weakness, or unusual bruising.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) In a study involving 24 patients, taking a 0.6 mg dose of colchicine together with ketoconazole 200 mg twice daily for 5 days produced increases of 101.7% in colchicine Cmax and 212.2% in colchicine AUC compared with baseline 2.
b) In a study involving 23 patients, taking a 0.6 mg dose of colchicine together with clarithromycin 250 mg twice daily for 7 days produced increases of 227.2% in colchicine Cmax and 281.5% in colchicine AUC compared with baseline 2.
Common questions
Can I take Colchicine and Ketoconazole together?
Ketoconazole can push colchicine to toxic, potentially fatal levels, so this pairing is contraindicated when kidney or liver function is impaired and otherwise requires a lowered colchicine dose. Do not combine them without your prescriber's guidance. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Ketoconazole 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 Ketoconazole interaction managed?
This combination is taken seriously, but your care team has clear ways to manage it. In some cases (especially if you have kidney or liver problems), the two drugs are not used together at all, and an alternative is chosen. If your kidneys and liver are healthy, your prescriber will lower your colchicine dose based on why you take it (gout treatment, gout prevention, or familial Mediterranean feve… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Colchicine or Ketoconazole 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. SCILEX Pharmaceuticals Inc. (per FDA), Palo Alto, CA, 2024. DailyMed
Keep reading about Ketoconazole
Keep reading about Colchicine
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