Colchicine and Lonafarnib: 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
Lonafarnib
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.
These two medicines can be a dangerous combination. Lonafarnib (Zokinvy) blocks a liver enzyme called CYP3A4, which is the same enzyme your body uses to break down colchicine. When that pathway is slowed, colchicine can build up to unsafe levels in your body.
That matters because too much colchicine can cause serious, even fatal, poisoning, with problems like severe diarrhea, muscle weakness, and damage to your blood cells and organs. The good news is that your care team can manage this safely by adjusting your colchicine dose, sometimes choosing another option, and watching you closely. Please talk with your doctor or pharmacist before taking both, and never change your doses on your own.
Mechanism: Lonafarnib is a strong CYP3A4 inhibitor; colchicine is a CYP3A4 (and P-gp) substrate. Inhibition reduces colchicine clearance, increasing systemic exposure (AUC/Cmax) and the risk of life-threatening or fatal toxicity. Neither drug is a prodrug here, so the effect is straightforward accumulation.
- Direction: increased colchicine effect/toxicity
- Evidence: probable; severity contraindicated
- Contraindicated in renal or hepatic impairment.
- Normal renal/hepatic function: reduce colchicine dose per indication (gout flare: 0.6 mg then 0.3 mg 1 h later, no repeat for 3 days; prophylaxis: halve to 0.3 mg; FMF: max 0.6 mg/day).
- Monitor for GI symptoms, myelosuppression, neuromyopathy.
What happens
Increased colchicine exposure and an increased risk of fatal toxicity
Interaction Deep Dive
Because therapeutic doses of colchicine have been associated with reports of fatal and life-threatening colchicine toxicity, giving colchicine together with strong CYP3A4 inhibitors is contraindicated1. In patients who have renal or hepatic impairment, coadministration of colchicine with strong CYP3A4 inhibitors (which includes every protease inhibitor other than fosamprenavir) is contraindicated. For patients whose renal and hepatic function is normal and who are concurrently taking, or have taken within the previous 14 days, a strong CYP3A4 inhibitor, the colchicine dose must be adjusted. To treat a gout flare, lower the colchicine dose to a single 0.6 mg tablet followed by 0.3 mg one hour afterward, with any repeat dose delayed until no sooner than 3 days. For gout flare prophylaxis, decrease the colchicine dose from an initial 0.6 mg twice daily to 0.3 mg once daily, or from an initial 0.6 mg once daily to 0.3 mg once every other day. When treating familial Mediterranean fever, the colchicine daily dose should not exceed 0.6 mg (which may be administered as 0.3 mg twice daily)2. When colchicine must be given alongside CYP3A4 inhibitors that also inhibit P-gp4, modify the colchicine dose by lowering either the daily amount or the frequency of dosing. Watch closely for signs of colchicine toxicity3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of colchicine
How to manage this interaction
Do not stop or change either medicine on your own. This pairing needs your prescriber's guidance because colchicine can build up to harmful levels.
- If you have kidney or liver problems, this combination is generally not used, so your team may choose an alternative.
- If your kidney and liver function are normal, your colchicine dose will likely be lowered and individualized by your care team, based on why you take it.
- Your team may monitor you more closely for signs of colchicine toxicity.
Call your doctor or pharmacist promptly if you notice severe diarrhea, vomiting, muscle weakness, numbness, or unusual weakness or fever.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) While the colchicine and boceprevir interaction has not been investigated, an interaction between colchicine and clarithromycin, a potent CYP3A4 inhibitor, produced fatal colchicine toxicity. Colchicine Cmax and AUC rose by 227.2% and 281.5%, respectively, when a single 0.6 mg dose of colchicine was given to patients (n=23) who were receiving clarithromycin 250 mg twice daily for 7 days 21.
b) In a pharmacokinetic study, giving a single dose of colchicine to patients who had received ritonavir 100 mg twice daily for 5 days (n=18) led to a 184.4% and 296% rise in colchicine Cmax and AUC, respectively, relative to baseline levels 51.
Common questions
Can I take Colchicine and Lonafarnib together?
Lonafarnib strongly blocks the enzyme that clears colchicine, so colchicine can build up to dangerous or fatal levels; this combination is contraindicated (especially with kidney or liver impairment), and any use requires a lowered colchicine dose and close monitoring set by your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Lonafarnib 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 Lonafarnib interaction managed?
Do not stop or change either medicine on your own. This pairing needs your prescriber's guidance because colchicine can build up to harmful levels. If you have kidney or liver problems, this combination is generally not used, so your team may choose an alternative. If your kidney and liver function are normal, your colchicine dose will likely be lowered and individualized by your care team, based… 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 Lonafarnib 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 (5)
- 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
- Product Information: MITIGARE(R) oral capsules, colchicine oral capsules. Hikma Specialty USA Inc (per FDA), Columbus, OH, 2024. DailyMed
- Product Information: COLCRYS(TM) oral tablets, colchicine oral tablets. AR Scientific, Inc. Philadelphia, PA, 2009. DailyMed
Keep reading about Lonafarnib
Keep reading about Colchicine
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