Colchicine and Nefazodone: 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
Nefazodone
No brand names on recordColchicine
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.
Nefazodone can make colchicine build up in your body to dangerous levels. Nefazodone is a strong blocker of a liver enzyme (called CYP3A4) that normally breaks colchicine down. When that breakdown is slowed, colchicine can climb too high, and that has caused serious, even fatal, poisoning. Warning signs of too much colchicine include bad diarrhea, vomiting, stomach pain, muscle weakness, and feeling unusually run down.
Please do not stop or change either medicine on your own. This combination is usually avoided, but your doctor or pharmacist can sort out the safest plan for you, whether that means a different antidepressant, a lower colchicine dose, or close monitoring. Give them a call before your next dose.
Mechanism: Nefazodone is a strong CYP3A4 inhibitor; colchicine is a CYP3A4 (and P-gp) substrate. Inhibition reduces colchicine clearance, raising exposure (AUC/Cmax) and the risk of life-threatening toxicity. Colchicine is active drug, not a prodrug, so the effect is increased colchicine effect.
Severity/evidence: Contraindicated; evidence probable.
- Renal/hepatic impairment: combination contraindicated.
- Normal organ function: reduce colchicine dose. Gout flare: 0.6 mg then 0.3 mg 1 h later, repeat no sooner than 3 days. Prophylaxis: halve dose/frequency. FMF: max 0.6 mg/day.
- Monitor closely for GI, myelosuppression, neuromuscular toxicity.
What happens
Increased colchicine exposure and an increased risk of fatal toxicity
Interaction Deep Dive
Because therapeutic doses of colchicine have been linked to life-threatening and fatal colchicine toxicity when combined with strong CYP3A4 inhibitors, the two must not be given together1. In patients with renal or hepatic impairment, colchicine is contraindicated alongside strong CYP3A4 inhibitors, a category that encompasses every protease inhibitor other than fosamprenavir. When renal and hepatic function are normal, the colchicine dose must be modified in patients receiving a strong CYP3A4 inhibitor concurrently or within the previous 14 days. To manage a gout flare, lower the colchicine dose to a single 0.6 mg tablet followed by 0.3 mg one hour afterward, and do not repeat this dose sooner than 3 days. For gout flare prophylaxis, decrease colchicine from an original regimen of 0.6 mg twice daily to 0.3 mg once daily, or from an original regimen of 0.6 mg once daily to 0.3 mg every other day. In familial Mediterranean fever, keep the maximum daily colchicine dose at or below 0.6 mg (which can be administered as 0.3 mg twice daily)2. When colchicine must be coadministered with CYP3A4 inhibitors that are additionally P-gp inhibitors4, 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
This pairing is generally avoided, but your care team can manage it safely. Keep taking both exactly as prescribed until you speak with them.
- If you have kidney or liver problems, this combination is not recommended, so raise it promptly.
- If your kidneys and liver are healthy, your colchicine dose may be reduced and individualized by your team (for example, smaller doses or less frequent dosing).
- Your team may monitor you more closely for colchicine toxicity.
- Call your pharmacist or prescriber before any dose changes, and report diarrhea, vomiting, muscle weakness, or unusual fatigue right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) While the interaction between colchicine and boceprevir has not been investigated, an interaction between colchicine and clarithromycin, a potent CYP3A4 inhibitor, led to fatal colchicine toxicity. 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, colchicine Cmax and AUC rose by 227.2% and 281.5%, respectively 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) produced a 184.4% and 296% increase in colchicine Cmax and AUC compared with baseline values, respectively 51.
Common questions
Can I take Colchicine and Nefazodone together?
Nefazodone blocks the enzyme that clears colchicine, letting it build up to potentially fatal levels, so this combination is usually avoided; if either drug is needed, contact your prescriber or pharmacist before your next dose so they can adjust the plan and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Nefazodone 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 Nefazodone interaction managed?
This pairing is generally avoided, but your care team can manage it safely. Keep taking both exactly as prescribed until you speak with them. If you have kidney or liver problems, this combination is not recommended, so raise it promptly. If your kidneys and liver are healthy, your colchicine dose may be reduced and individualized by your team (for example, smaller doses or less frequent dosing).… 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 Nefazodone 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 Nefazodone
Keep reading about Colchicine
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