Colchicine and Ranolazine: 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
Ranolazine
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 don't mix well. Ranolazine (Ranexa) slows down two of the pathways your body uses to clear colchicine out of your system. When colchicine can't leave your body the way it should, it builds up, and even normal doses can reach dangerous levels. Colchicine toxicity is serious and can be life-threatening, so this combination is generally not recommended.
The good news is that your care team knows how to handle this. Please don't stop or change either medicine on your own. Instead, talk with your doctor or pharmacist. They can decide whether the combination is safe for you, adjust your colchicine dose, and watch you closely for any warning signs.
Contraindicated. Ranolazine inhibits both P-gp and CYP3A4, the main pathways clearing colchicine (a P-gp/CYP3A4 substrate with a narrow therapeutic index). Result: increased colchicine exposure and risk of life-threatening/fatal toxicity. Onset delayed; evidence established.
- Renal or hepatic impairment: combination contraindicated.
- Normal renal/hepatic function, if co-use unavoidable (including ranolazine within prior 14 days): gout flare, 0.6 mg x1, repeat no sooner than 3 days; prophylaxis, reduce 0.6 mg BID to 0.3 mg daily, or 0.6 mg daily to 0.3 mg every other day; FMF, max 0.6 mg/day.
- Monitor for colchicine toxicity (GI symptoms, myopathy, cytopenias); discontinue colchicine immediately if suspected.
What happens
Increased colchicine exposure and an increased risk of potential life-threatening toxicity
Interaction Deep Dive
Taking colchicine together with ranolazine (a P-gp inhibitor) is contraindicated, because life-threatening and fatal colchicine toxicity has been documented in such patients even when colchicine was administered at therapeutic doses13. This combination is likewise contraindicated in patients who have renal or hepatic impairment, since life-threatening and fatal drug interactions have been observed. For patients whose renal and hepatic function is normal, when colchicine must be combined with ranolazine, or when ranolazine has been used within the previous 14 days, the colchicine dose used to treat a gout flare should be lowered to a single 0.6 mg dose, with the repeat dose delayed until at least 3 days later. When colchicine is used to prevent gout flares, the dose should be decreased from an original 0.6 mg twice daily to 0.3 mg once daily, or from an original 0.6 mg once daily to 0.3 mg every other day. For patients with familial Mediterranean fever, the colchicine dose should not exceed 0.6 mg per day (this may be administered as 0.3 mg twice daily). Watch for signs of colchicine toxicity and stop colchicine at once if toxicity is suspected2. Furthermore, giving ranolazine and colchicine together (both CYP3A4 substrates with a narrow therapeutic index) may raise colchicine exposure, and a colchicine dose adjustment may be needed4.
Why it happens (mechanism)
Inhibition of P-gp-mediated metabolism of colchicine; inhibition of CYP3A4-mediated metabolism of colchicine
How to manage this interaction
Keep taking both exactly as prescribed until you speak with your care team. This combination is flagged as one to avoid, especially if you have kidney or liver problems, so it needs a direct conversation.
- Tell your prescriber and pharmacist that you are on (or recently stopped) ranolazine before starting colchicine, and vice versa.
- Your team may lower your colchicine dose and space out doses, tailoring it to your kidney and liver function.
- They will monitor you more closely for toxicity, such as diarrhea, nausea, vomiting, muscle pain or weakness, or unusual bruising.
- If any of those symptoms appear, contact your care team right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a study involving 23 patients, giving a single 100 mg dose of cycloSPORINE together with a 0.6 mg dose of colchicine produced increases from baseline of 270% (range, 62% to 606.9%) in colchicine Cmax and 259% (range, 75.8% to 511.9%) in colchicine AUC 2.
Common questions
Can I take Colchicine and Ranolazine together?
Ranolazine can cause colchicine to build up to dangerous levels, so this combination is generally avoided; do not change either drug yourself, and check with your doctor or pharmacist, who may reduce the colchicine dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Colchicine and Ranolazine interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Colchicine and Ranolazine interaction managed?
Keep taking both exactly as prescribed until you speak with your care team. This combination is flagged as one to avoid, especially if you have kidney or liver problems, so it needs a direct conversation. Tell your prescriber and pharmacist that you are on (or recently stopped) ranolazine before starting colchicine, and vice versa. Your team may lower your colchicine dose and space out doses, tail… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Colchicine or Ranolazine 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 (4)
- 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: RANOLAZINE oral extended-release tablets, ranolazine oral extended-release tablets. Viona Pharmaceuticals Inc. (per Dailymed), Cranford, NJ, 2023. DailyMed
Keep reading about Ranolazine
Keep reading about Colchicine
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