Colchicine and Levoketoconazole: 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
Levoketoconazole
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. Colchicine (Colcrys, Gloperba, Mitigare) is normally broken down and cleared from your body by an enzyme called CYP3A4 and a transporter called P-gp. Levoketoconazole (Recorlev) blocks both of these. That means colchicine can build up to much higher levels than intended.
Because colchicine is a drug where even small increases can cause serious problems (like severe stomach upset, muscle weakness, or effects on blood cells), this combination is considered off-limits. The good news: your care team has other options and can choose a safer plan. Please talk with your doctor or pharmacist before taking both.
Contraindicated combination. Levoketoconazole is a potent inhibitor of CYP3A4 and P-gp, the primary pathways for colchicine metabolism and efflux. Inhibition markedly increases colchicine exposure (AUC/Cmax), raising the risk of dose-dependent toxicity (GI toxicity, myelosuppression, neuromyopathy, and at extremes life-threatening multiorgan effects).
- Direction: increased colchicine exposure (colchicine is not a prodrug; more drug = more effect/toxicity).
- Magnitude: labeled index substrate felodipine showed ~10-fold AUC increase.
- Evidence: probable; onset: unspecified.
- Management: avoid concomitant use; select a non-interacting alternative or defer colchicine per specialist guidance.
What happens
Increased exposure of CYP3A4/P-gp substrate
Interaction Deep Dive
The combination of levoketoconazole with sensitive CYP3A4 substrates or with combined CYP3A4/P-gp substrates is contraindicated. Because levoketoconazole inhibits CYP3A4, giving it alongside a sensitive CYP3A4 substrate or a combined CYP3A4/P-gp substrate can raise substrate exposure and heighten the potential for adverse reactions. When levoketoconazole 400 mg once daily was given together with felodipine (a sensitive CYP3A4 substrate), felodipine AUC rose by 1007% and its Cmax by 937%1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism and/or P-gp efflux transport by levoketoconazole
How to manage this interaction
This pairing is labeled contraindicated, so the usual approach is to avoid using them together. Do not stop or change either medicine on your own, but do flag this combination promptly.
- Tell your prescriber and pharmacist that you have been prescribed both colchicine and levoketoconazole (Recorlev).
- Your care team may choose an alternative, adjust timing, or hold one medicine so the two are not used at the same time.
- Watch for and report warning signs such as severe diarrhea, vomiting, unusual muscle pain or weakness, numbness, or signs of infection.
Your team can manage this safely by tailoring your treatment plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When levoketoconazole 400 mg once daily was given together with felodipine (a sensitive CYP3A4 substrate), the AUC and Cmax of felodipine rose by 1007% and 937%, respectively, relative to giving felodipine on its own (N=14) 1.
Common questions
Can I take Colchicine and Levoketoconazole together?
Combining colchicine with levoketoconazole is contraindicated because colchicine can build up to toxic levels; do not take them together and contact your prescriber or pharmacist right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Levoketoconazole 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 Levoketoconazole interaction managed?
This pairing is labeled contraindicated, so the usual approach is to avoid using them together. Do not stop or change either medicine on your own, but do flag this combination promptly. Tell your prescriber and pharmacist that you have been prescribed both colchicine and levoketoconazole (Recorlev). Your care team may choose an alternative, adjust timing, or hold one medicine so the two are not us… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Colchicine or Levoketoconazole 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: RECORLEV(R) oral tablets, levoketoconazole oral tablets. Xeris Pharmaceuticals Inc (per FDA), Chicago, IL, 2023. DailyMed
Keep reading about Colchicine
Keep reading about Levoketoconazole
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