Colchicine and Propafenone: 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
Propafenone
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.
Taking colchicine (Colcrys, Mitigare, Gloperba, Lodoco) with propafenone (Rythmol) needs a close look from your care team. Propafenone can block a natural "pump" (called P-gp) that normally helps your body clear colchicine out. When that pump is slowed, more colchicine can build up in your body.
Too much colchicine can cause serious problems like severe stomach upset, muscle weakness, and other dangerous effects. Because of this risk, this combination is generally flagged as one to avoid. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor. They can review your kidney and liver health and either adjust your colchicine or choose a safer plan.
Effect: Propafenone (a P-gp inhibitor) can reduce P-gp-mediated efflux of colchicine, increasing colchicine exposure and risk of toxicity. Colchicine is a P-gp and CYP3A4 substrate; neither drug is a prodrug, so the interaction increases colchicine effect.
- Direction: Increased colchicine AUC/systemic exposure.
- Severity: Contraindicated per labeling.
- Evidence: Theoretical, extrapolated from documented P-gp/CYP3A4 inhibitor cases.
- Management: Contraindicated in renal or hepatic impairment. In normal organ function, if unavoidable, reduce colchicine daily dose or frequency and monitor closely for toxicity (GI symptoms, myopathy, myelosuppression).
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. Instances of toxicity have been documented when colchicine was given alongside clarithromycin, which inhibits both CYP3A4 and P-gp. Toxicity has similarly been seen when colchicine was combined with a CYP3A4 inhibitor and when it was combined with a P-gp inhibitor3. The simultaneous administration of colchicine with P-gp inhibitors is contraindicated, since life-threatening and fatal colchicine toxicity has been observed in such patients even when colchicine was taken at therapeutic doses 1. This combination is likewise contraindicated in individuals with renal or hepatic impairment, because life-threatening and fatal drug interactions have been reported. For patients whose renal and hepatic function is normal 2, when coadministration of colchicine with a P-gp inhibitor cannot be avoided, adjust the colchicine dose either 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
Keep taking both medicines exactly as prescribed until you speak with your care team. Because propafenone can raise colchicine levels, your team will decide the safest approach.
- This combination is usually avoided, especially if you have kidney or liver problems, where it can be dangerous.
- If both drugs are truly needed and your kidney and liver function are normal, your colchicine dose may be lowered or given less often. This can be adjusted and individualized by your care team.
- Your team may monitor you more closely for signs of colchicine toxicity, such as severe diarrhea, nausea, muscle pain or weakness, or unusual fatigue.
Ask your pharmacist or prescriber to review this combination and confirm what's right for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Colchicine and Propafenone together?
Propafenone can cause colchicine to build up to potentially dangerous levels, so this combination is generally avoided; do not stop or change either drug on your own, and have your pharmacist or doctor review it right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Propafenone 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 Propafenone interaction managed?
Keep taking both medicines exactly as prescribed until you speak with your care team. Because propafenone can raise colchicine levels, your team will decide the safest approach. This combination is usually avoided, especially if you have kidney or liver problems, where it can be dangerous. If both drugs are truly needed and your kidney and liver function are normal, your colchicine dose may be low… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Colchicine or Propafenone 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 Propafenone
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.
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