Colchicine and Mibefradil: 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
Mibefradil
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 don't mix well. Colchicine (Colcrys, Gloperba, Lodoco, Mitigare) is normally pushed out of your body by a kind of built-in pump. Mibefradil blocks that pump, so colchicine can build up in your body to dangerous levels.
When colchicine gets too high, it can cause serious problems like severe diarrhea, vomiting, muscle weakness, and effects on the blood and other organs. This can become life-threatening. Because of that risk, taking these two together is usually not allowed. The good news: your care team can prevent this by choosing a different medicine or, in certain cases, carefully adjusting your colchicine dose and watching you closely. Please talk with your pharmacist or doctor before taking both.
Interaction: Mibefradil is a potent P-gp (and CYP3A4) inhibitor; colchicine is a P-gp and CYP3A4 substrate. Inhibition of P-gp-mediated colchicine efflux increases colchicine exposure and risk of toxicity. Colchicine is not a prodrug, so this raises active drug levels.
- Direction: increased colchicine AUC/Cmax, higher toxicity risk (GI, myelosuppression, neuromyopathy, multi-organ failure).
- Severity: contraindicated; life-threatening and fatal toxicity reported at therapeutic colchicine doses.
- Evidence: theoretical for this pair, extrapolated from known P-gp/CYP3A4 inhibitor cases.
- Management: avoid combination, especially with renal or hepatic impairment. If unavoidable in patients with normal organ function, reduce colchicine daily dose or frequency and monitor closely.
What happens
Increased colchicine exposure and an increased risk of colchicine toxicity
Interaction Deep Dive
Colchicine acts as a substrate for both CYP3A4 and P-gp. Toxic effects have been documented when it was given together with clarithromycin, an agent that inhibits both CYP3A4 and P-gp. Such toxicities have likewise been seen when colchicine was combined with a CYP3A4 inhibitor and when it was combined with a P-gp inhibitor3. Using colchicine at the same time as P-gp inhibitors is contraindicated, since life-threatening and fatal colchicine toxicity has been reported in these patients even when colchicine was taken at therapeutic doses 1. This combination is likewise contraindicated for patients with renal or hepatic impairment, because life-threatening and fatal drug interactions have been observed. For patients whose renal and hepatic function is normal 2, when colchicine must be given together with a P-gp inhibitor, adjust the colchicine dose by lowering the daily amount or by decreasing how often it is taken. 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
The safest approach is usually to avoid this combination. Because mibefradil can raise colchicine to harmful levels, using them together is generally contraindicated, and especially so if you have kidney or liver problems.
- Keep taking your medicines as prescribed. Do not start, stop, or change anything on your own.
- Tell your pharmacist and prescriber that you may be taking both so they can review your regimen.
- Your team may choose an alternative medicine, or (in people with normal kidney and liver function) reduce your colchicine dose or dose frequency and monitor you more closely.
- Watch for warning signs like severe diarrhea, vomiting, muscle weakness, or unusual fatigue, and report them right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Colchicine and Mibefradil together?
Combining colchicine with mibefradil can push colchicine to toxic, potentially fatal levels, so this pairing is generally contraindicated. Talk to your pharmacist or doctor, who can pick a safer option or carefully adjust and monitor your colchicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Mibefradil 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 Mibefradil interaction managed?
The safest approach is usually to avoid this combination. Because mibefradil can raise colchicine to harmful levels, using them together is generally contraindicated, and especially so if you have kidney or liver problems. Keep taking your medicines as prescribed. Do not start, stop, or change anything on your own. Tell your pharmacist and prescriber that you may be taking both so they can review… 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 Mibefradil 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 Colchicine
Keep reading about Mibefradil
These medications also interact with supplements
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist