Berotralstat and Colchicine: 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
Berotralstat
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.
Berotralstat (Orladeyo) can slow down how your body clears colchicine. It blocks a transporter (called P-gp) and an enzyme (CYP3A4) that normally help remove colchicine. When those are blocked, colchicine can build up to dangerously high levels.
This matters because too much colchicine can cause serious, even life-threatening harm. This is why combining them is generally not recommended. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. They may lower your colchicine dose, space it out differently, or choose another option. This is very manageable with the right plan.
Effect: Berotralstat inhibits both P-gp-mediated efflux and CYP3A4-mediated metabolism of colchicine, increasing colchicine exposure and the risk of serious or fatal toxicity. Colchicine is a narrow-therapeutic-index substrate; neither drug here is a prodrug, so this is a straightforward exposure increase.
- Direction: increased colchicine AUC/Cmax
- Severity: contraindicated (dual P-gp + CYP3A4 inhibition)
- Evidence: probable
- Management: If coadministration is necessary, reduce colchicine daily dose by 50 to 75% or reduce frequency. Contraindicated in renal or hepatic impairment (fatal toxicity reported). Monitor for colchicine toxicity (GI symptoms, myopathy, myelosuppression).
What happens
Increased colchicine exposure and an increased risk of fatal toxicity
Interaction Deep Dive
Taking colchicine together with P-gp inhibitors is contraindicated1. When colchicine is combined with agents that inhibit both CYP3A4 and P-gp, there is a risk of severe, potentially fatal toxicity. Should colchicine and a P-gp inhibitor need to be given together, the colchicine dose must be modified, either by lowering the daily amount by 50% to 75% 3 or by decreasing how often it is taken. Furthermore, in patients who have renal or hepatic impairment, the simultaneous use of colchicine with P-gp and CYP3A4 inhibitors is contraindicated 3. In such patients with renal and hepatic impairment, pairing these inhibitors with colchicine has produced colchicine toxicity that was life-threatening or fatal 2.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of colchicine; inhibition of CYP3A4-mediated metabolism of colchicine
How to manage this interaction
Keep taking both medicines exactly as prescribed until your care team advises otherwise, and raise this combination with your pharmacist or prescriber promptly.
- Because berotralstat can raise colchicine levels, your team may reduce your colchicine dose by 50% to 75% or space out how often you take it.
- This combination is not used in people with kidney or liver problems, so make sure your team knows your full health history.
- Report warning signs like severe diarrhea, vomiting, muscle pain or weakness, numbness, or unusual bruising right away.
Your dose can be individualized and monitored, so this is manageable with the right plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Berotralstat and Colchicine together?
Berotralstat can push colchicine to dangerous levels, so combining them is generally contraindicated. Do not change either medicine yourself; contact your pharmacist or doctor, who can adjust the colchicine dose or choose a safer option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Berotralstat and Colchicine 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 Berotralstat and Colchicine interaction managed?
Keep taking both medicines exactly as prescribed until your care team advises otherwise, and raise this combination with your pharmacist or prescriber promptly. Because berotralstat can raise colchicine levels, your team may reduce your colchicine dose by 50% to 75% or space out how often you take it. This combination is not used in people with kidney or liver problems, so make sure your team know… 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 Berotralstat or Colchicine 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: MITIGARE(R) oral capsules, colchicine oral capsules. Hikma Specialty USA Inc (per FDA), Columbus, OH, 2024. DailyMed
- Hansten PD, Tan MS, Horn JR, et al: Colchicine drug interaction errors and misunderstandings: recommendations for improved evidence-based management. Drug Saf 2023; 46(3):223-242. PubMed
Keep reading about Berotralstat
Keep reading about Colchicine
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