Antigout agents
ATC code: M04AC01 (Colchicine)
Brand names
Colcrys, Mitigare
Alkaloid from autumn crocus (Colchicum autumnale). Binds tubulin and disrupts microtubule polymerization in neutrophils — suppresses chemotaxis, phagocytosis, and inflammatory mediator release. Suppresses inflammation triggered by monosodium urate crystals in joints. Narrow therapeutic index — overdose can be fatal without a specific antidote. Metabolized via CYP3A4 and P-gp, creating dangerous interactions with clarithromycin, HIV protease inhibitors, and cyclosporine.
First line
Per 2020 and 2017, colchicine is a first-line option for acute gout attacks alongside NSAIDs and corticosteroids. Dose 1.0–1.2 mg at the first symptoms, then 0.5–0.6 mg one hour later. Max 1.8 mg on day 1. The old 'one tablet hourly until diarrhea' regimen caused frequent severe adverse effects and was abandoned per AGREE 2010. Long-term prophylaxis at urate-lowering therapy initiation: 0.5–1 mg daily for 3–6 months.
Individual decision
COLCOT (NEJM 2019, over 4,700 patients) and LoDoCo2 (NEJM 2020, 5,522 patients) showed low-dose colchicine 0.5 mg daily in chronic CAD or post-ACS reduced MACE by 23–30 %. 2024 includes colchicine in secondary prevention recommendations for patients with residual inflammatory risk. The effect is attributed to anti-inflammatory action. Off-label in Russia.
Low-dose (0.5 mg daily) in post-ACS or chronic CAD patients.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Colchicine is an anti-inflammatory drug that inhibits microtubule polymerization. It is prescribed for acute gout, familial Mediterranean fever, pericarditis, and Behçet's disease ( 2023, AEMPS Ficha Técnica). Colchicine is positioned as a drug to suppress cytokine storm in colds and flu. The COLCORONA trial (Tardif 2021) in outpatient COVID-19 did not meet the primary endpoint; international clinical guidelines ( Living Guideline 2023, NIH COVID-19 Guidelines 2024) do not include colchicine for COVID-19 or common colds. The drug has a narrow therapeutic index: overdose causes severe diarrhea, vomiting, myelosuppression, neuropathy, myopathy, and multi-organ failure; fatalities have been described at doses from 7 mg. If colchicine was recommended for an ordinary cold or respiratory infection, consider seeking a second opinion.
17 pairs found. Sorted from critical to minor.
Mechanism
Cyclosporine inhibits both CYP3A4 and P-glycoprotein – the clearance routes of colchicine. Fatal myopathy, neuropathy, and pancytopenia have been reported in transplant patients on both drugs.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain – first signs of toxicity. Pancytopenia (drop in leukocytes, erythrocytes, platelets), muscle weakness, peripheral neuropathy, hepatic and renal injury follow. Fatal cases have been reported.
Management
For patients with renal or hepatic impairment, the combination is not prescribed. With preserved function, colchicine 0.3 mg every other day. For acute gout in a transplant patient, an alternative is intra-articular or short-course systemic glucocorticoid.
Mechanism
Colchicine is cleared via hepatic CYP3A4 and the P-glycoprotein transporter. Clarithromycin inhibits both. Colchicine plasma levels rise several-fold. The narrow therapeutic window makes any increase clinically dangerous. Colcrys carries a boxed warning for fatal toxicity.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain – first signs of toxicity. Pancytopenia (drop in leukocytes, erythrocytes, platelets), muscle weakness, peripheral neuropathy, hepatic and renal injury follow. Fatal cases have been reported.
Management
For patients with renal impairment (creatinine clearance below 60 mL/min) or hepatic impairment, the combination is not prescribed. With preserved renal and hepatic function, use colchicine 0.3 mg every other day, no more than 5 days. Alternative antibiotic: azithromycin (minimal interaction).
Sources
Mechanism
Colchicine is cleared via CYP3A4 and P-glycoprotein. Ketoconazole strongly inhibits both. Colchicine plasma levels rise several-fold. Colcrys carries a boxed warning for fatal toxicity.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain – first signs of toxicity. Pancytopenia (drop in leukocytes, erythrocytes, platelets), muscle weakness, peripheral neuropathy, hepatic and renal injury follow. Fatal cases have been reported.
Management
For patients with renal or hepatic impairment, the combination is not prescribed. With preserved function, use colchicine 0.3 mg every other day, no more than 5 days. Alternative antifungals: terbinafine or echinocandins.
Mechanism
Colchicine is a CYP3A4 and P-glycoprotein substrate with narrow therapeutic window. Ritonavir is the strongest CYP3A4 inhibitor and a notable P-glycoprotein inhibitor. Colchicine levels rise 4-fold or more. carries a boxed warning.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain – first signs of toxicity. Pancytopenia (drop in leukocytes, erythrocytes, platelets), muscle weakness, peripheral neuropathy, hepatic and renal injury follow. Fatal cases have been reported.
Management
The combination is not prescribed. For acute gout in a patient on ritonavir, use glucocorticoids (intra-articular or short systemic) or NSAIDs. For long-term prophylaxis, allopurinol.
Mechanism
Amiodarone blocks CYP3A4 and the P-glycoprotein transporter – two colchicine clearance routes. Colchicine plasma levels rise; myopathy and neuropathy risk grows.
Symptoms
Muscle weakness and pain, peripheral neuropathy (numbness, tingling in feet and hands), nausea, diarrhoea. Severe cases include pancytopenia and rhabdomyolysis. Symptoms appear within 1–4 weeks of co-administration.
Management
Do not prescribe in chronic kidney disease or impaired hepatic function. With preserved function, reduce colchicine to 0.3 mg every other day. Alternative for gout on amiodarone: intra-articular or short systemic glucocorticoid.
Mechanism
Additive myopathy and rhabdomyolysis risk. Atorvastatin injures muscle fibre by suppressing ubiquinone synthesis; colchicine disrupts microtubule function in myocytes. Particularly dangerous in older patients and chronic kidney disease.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Avoid prolonged combination. For acute gout, a short colchicine course (3–5 days) at 0.3 mg every other day is acceptable with muscle symptom and creatine kinase monitoring. Alternative for gout: intra-articular or short systemic glucocorticoid.
Mechanism
Azithromycin inhibits the P-glycoprotein transporter less than clarithromycin but still blocks a colchicine clearance route. Colchicine plasma levels rise moderately; toxicity has been reported with prolonged combination, especially in older patients and chronic kidney disease.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain as first signs. With prolonged combination, muscle weakness, peripheral neuropathy, and pancytopenia follow.
Management
For short azithromycin courses (3–5 days), no special measures are needed. In chronic kidney disease or hepatic impairment, temporarily halve the colchicine dose. For prolonged azithromycin therapy, switch antibiotic (doxycycline) or replace colchicine with allopurinol.
Mechanism
Carvedilol is a moderate P-glycoprotein inhibitor; colchicine is a P-glycoprotein substrate with a narrow therapeutic window. Colchicine plasma levels rise; myelosuppression and neuromyopathy risk.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.
Management
In chronic kidney disease or hepatic impairment, the combination is not prescribed. With preserved function, colchicine 0.3 mg every other day for no more than 5 days. Alternative for gout: intra-articular glucocorticoid.
Mechanism
Diltiazem is a moderate CYP3A4 and P-glycoprotein inhibitor. Colchicine is a substrate of both with a narrow therapeutic window. Colchicine plasma levels rise 2- to 3-fold; myelosuppression and neuromyopathy risk.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.
Management
In chronic kidney disease or hepatic impairment, the combination is not prescribed. With preserved function, colchicine 0.3 mg every other day for no more than 5 days. Alternative for gout: intra-articular glucocorticoid.
Mechanism
Dronedarone strongly blocks both P-glycoprotein and CYP3A4 – two colchicine clearance routes. Colchicine plasma levels rise; myopathy, neuropathy, and pancytopenia risks grow.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.
Management
In chronic kidney disease or hepatic impairment, do not prescribe the combination. With preserved function: colchicine 0.3 mg every other day for no more than 5 days. Alternative for gout on dronedarone: intra-articular or short systemic glucocorticoid.
Mechanism
Fluconazole at 200 mg/day or above blocks CYP3A4 – the main colchicine clearance route. Colchicine plasma levels rise; myopathy risk grows with prolonged therapy.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.
Management
For short fluconazole courses (up to 7 days), no special measures are needed. For prolonged systemic therapy with preserved renal function, colchicine 0.3 mg every other day. In chronic kidney disease, do not prescribe; alternative for gout: intra-articular glucocorticoid.
Mechanism
Additive myopathy and rhabdomyolysis risk. Rosuvastatin suppresses muscle ubiquinone synthesis; colchicine disrupts microtubule function in myocytes. Severe muscle toxicity has been reported, especially in older patients and chronic kidney disease.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Avoid prolonged combination. For acute gout, a short colchicine course (3–5 days) at 0.3 mg every other day is acceptable with muscle symptom and creatine kinase monitoring. Alternative: intra-articular or short systemic glucocorticoid.
Mechanism
Simvastatin is metabolised by CYP3A4; colchicine uses the same route and inhibits it. Simvastatin plasma levels rise, amplifying additive myotoxicity.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
Avoid prolonged combination. For acute gout, a short colchicine course (3–5 days) at 0.3 mg every other day is acceptable with muscle symptom and creatine kinase monitoring. For long-term gout prophylaxis, switch to pravastatin (no CYP3A4 dependence) or replace colchicine with allopurinol.
Mechanism
Tacrolimus and colchicine are both P-glycoprotein substrates. Competition at this transporter raises colchicine levels, especially in transplant patients with borderline renal function.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets. In transplant patients: accelerated graft decline.
Management
For acute gout in transplant patients, a short colchicine course (3–5 days) at 0.3 mg every other day with muscle symptom and blood count monitoring. For chronic gout, allopurinol. For acute attacks, intra-articular glucocorticoid.
Mechanism
Verapamil blocks CYP3A4 and the P-glycoprotein transporter – two colchicine clearance routes. Colchicine plasma levels rise; myopathy, neuropathy, and pancytopenia risks grow.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.
Management
In chronic kidney disease or hepatic impairment, do not prescribe. With preserved function: colchicine 0.3 mg every other day for no more than 5 days. Alternative for gout on verapamil: intra-articular or short systemic glucocorticoid.
Mechanism
Ciprofloxacin is a weak P-glycoprotein inhibitor and may slightly raise colchicine levels. Clinically significant colchicine toxicity is rare, mainly in chronic kidney disease.
Symptoms
Nausea, vomiting, diarrhoea, muscle weakness, paraesthesias. With severe toxicity: myopathy, neuropathy, bone marrow suppression.
Management
For short ciprofloxacin courses (5–7 days) with normal renal function, no colchicine adjustment needed. With creatinine clearance below 50 mL/min, halve the colchicine dose or pause it. In gout patients needing an antibiotic, alternative: a cephalosporin (no P-glycoprotein effect).
Mechanism
Spironolactone is a weak P-glycoprotein inhibitor and may slightly raise colchicine levels. Clinically significant toxicity is described in chronic kidney disease and on long-term combination.
Symptoms
Nausea, vomiting, diarrhoea, muscle weakness, paraesthesias. With severe toxicity: myopathy, neuropathy, bone marrow suppression.
Management
With normal renal function, no dose adjustment needed. With creatinine clearance below 50 mL/min, halve the colchicine dose. Check creatinine, CK, and CBC every 3 months. In gout flares, a short colchicine course (0.5 mg 2–3 times daily for 1–3 days) is better tolerated than long-term use.
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FDA categories were retired in 2015. In familial Mediterranean fever, colchicine is continued throughout pregnancy — fetal safety is established. In pregnant gout patients, colchicine for severe attacks is individualized.
Transfers into milk. In FMF patients, compatible with breastfeeding under observation. For occasional use, with caution.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Colchicine is evaluated for the following indications with varying evidence strength: Gout (evidence tier A), Established ASCVD, secondary prevention (evidence tier B), Immune support and respiratory infection care (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Colchicine (≥ 1 in 100): Diarrhea (main dose-related symptom, marker of overdose), Nausea, vomiting, Abdominal pain, Headache. See the Safety section for uncommon and serious reactions.
FDA category C. FDA categories were retired in 2015. In familial Mediterranean fever, colchicine is continued throughout pregnancy — fetal safety is established. In pregnant gout patients, colchicine for severe attacks is individualized.
Transfers into milk. In FMF patients, compatible with breastfeeding under observation. For occasional use, with caution.
Colchicine is contraindicated in: Severe renal impairment combined with severe hepatic impairment; Concomitant strong CYP3A4 or P-gp inhibitors (especially in renal/hepatic impairment); Hypersensitivity. Full list in the Safety section.