Antigout alkaloid (anti-inflammatory via microtubules)
Colchicine is a medicine used to treat and prevent gout flares and to treat familial Mediterranean fever. It is effective, but has a narrow therapeutic window: excessive doses are toxic. It must be used very cautiously in people with kidney or liver disease.
Also known as: colchicine, Yuzu
Colchicine + statin: increased risk of myopathy/rhabdomyolysis.
Both colchicine and statins can cause myopathy, and the combination increases the risk of rhabdomyolysis, especially in patients with renal impairment, the elderly or with high colchicine doses (e.g., acute gout flare in a patient on a statin). Colchicine is also a CYP3A4/P-gp substrate, sharing pathways with atorvastatin. In practice, use the lowest effective colchicine dose for the shortest time, monitor muscle symptoms and CK, and consider temporarily stopping the statin during a colchicine course in at-risk patients.
Atorvastatin + colchicine: additive risk of myopathy/rhabdomyolysis. Use with caution, especially with renal impairment.
Additive effect on skeletal muscle, especially in patients with reduced renal function.
CPK and renal function in symptomatic patients.
Myalgia, muscle weakness, dark urine.
Watch for muscle symptoms; consider reducing colchicine or stopping the statin.
DailyMed (FDA) — approved Colchicine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ae87893-a065-468e-b8da-f1db86afcaef ; approved Atorvastatin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fbd1c5da-67fb-4412-acb5-4d4c74a43654 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Colchicine + potent CYP3A4/P-gp inhibitor: risk of severe colchicine toxicity.
Colchicine is a substrate of CYP3A4 and P-glycoprotein; clarithromycin inhibits both pathways and can multiply colchicine exposure, causing severe toxicity: intense gastrointestinal symptoms, pancytopenia, neuropathy and rhabdomyolysis, sometimes fatal. The approved colchicine label contraindicates the combination with potent CYP3A4/P-gp inhibitors in patients with renal or hepatic impairment and, in the others, requires dose reduction — in practice, the combination should be avoided whenever possible, choosing an alternative antibiotic (e.g. azithromycin).
Clarithromycin (CYP3A4 and P-gp inhibitor) greatly increases colchicine levels, with risk of severe and potentially fatal toxicity (diarrhoea, myelosuppression, rhabdomyolysis). Do not combine; use an alternative.
Clarithromycin inhibits CYP3A4 and P-glycoprotein, markedly raising colchicine concentrations.
Watch for colchicine toxicity symptoms (GI, neuromuscular).
Severe diarrhoea, vomiting, rhabdomyolysis, pancytopenia, arrhythmias.
Contraindicated; prefer an alternative antibiotic. If unavoidable, strongly reduce the colchicine dose.
DailyMed (FDA) — approved Colchicine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ae87893-a065-468e-b8da-f1db86afcaef ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Colchicine + anticoagulant: possible increased anticoagulant effect.
Colchicine is a substrate and inhibitor of CYP3A4, an enzyme involved in warfarin metabolism; the inhibition can reduce warfarin clearance and raise the INR. The interaction is especially relevant in prolonged treatment (e.g. gout prophylaxis, familial Mediterranean fever), in which the effect accumulates. Monitor the INR when starting colchicine and after dose changes, and watch for bleeding signs; in renal or hepatic impairment, the toxicity risk of both drugs increases.
Colchicine inhibits CYP3A4 and can raise warfarin levels and the INR. Monitor the INR when starting and adjust the dose.
Colchicine may interfere with warfarin metabolism/effect, raising INR.
Periodic INR during the combination.
Bleeding, spontaneous ecchymosis.
Monitor INR after starting or changing colchicine dose.
DailyMed (FDA) — approved Colchicine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ae87893-a065-468e-b8da-f1db86afcaef ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Alcohol may increase the GI effects of colchicine.
Limit alcohol intake.
EMC-UK (MHRA) — approved Colchicine SmPC: https://www.medicines.org.uk/emc/product/14362/smpc
Grapefruit inhibits CYP3A4 and P-glycoprotein, raising colchicine concentrations.
Avoid grapefruit juice during treatment.
EMC-UK (MHRA) — approved Colchicine SmPC: https://www.medicines.org.uk/emc/product/14362/smpc
Colchicine causes diarrhoea and may worsen inflammatory GI disease.
Use with caution; watch for severe diarrhoea (sign of toxicity).
EMC-UK (MHRA) — approved Colchicine SmPC: https://www.medicines.org.uk/emc/product/14362/smpc
Reduced hepatic metabolism raises colchicine concentrations.
Contraindicated in severe hepatic impairment.
EMC-UK (MHRA) — approved Colchicine SmPC: https://www.medicines.org.uk/emc/product/14362/smpc
Colchicine accumulates in renal impairment, with risk of severe toxicity.
Contraindicated in severe renal impairment; adjust dose in moderate impairment.
EMC-UK (MHRA) — approved Colchicine SmPC: https://www.medicines.org.uk/emc/product/14362/smpc
Limited data; low doses appear to carry low risk, but exposure should be minimised.
Use only if clearly necessary and at the lowest dose, especially in the 1st trimester.
Limited data; prefer to avoid during breastfeeding.
No formal contraception requirement, but minimise exposure.
EMC-UK (MHRA) — approved Colchicine SmPC: https://www.medicines.org.uk/emc/product/14362/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Anti-inflammatory that interrupts the inflammatory cascade of the gout flare: binds to tubulin and inhibits mitosis, neutrophil chemotaxis and neutrophil adhesion to the endothelium, blocking the release of inflammatory mediators. It has no direct analgesic effect nor does it lower uric acid.
Colchicine binds to beta-tubulin forming colchicine-tubulin complexes that prevent microtubule polymerisation. In neutrophils, it inhibits chemotaxis, adhesion and the production of inflammatory mediators (including the NLRP3 inflammasome), explaining efficacy in gout flares and familial Mediterranean fever.
Colchicine is absorbed orally with a mean Cmax of 2.5 ng/mL in 1–2 hours (fasting); absolute bioavailability is approximately 45%. Food does not change the rate but decreases the extent of absorption by ~15%. The volume of distribution is ~5–8 L/kg and serum protein binding is low (39 ± 5%).
Colchicine is demethylated to two primary metabolites (2-O-demethyl and 3-O-demethylcolchicine) and one minor (10-O-demethyl), via CYP3A4 (in vitro in human liver microsomes). Plasma levels of the metabolites are minimal (<5% of parent drug). It is also a P-glycoprotein substrate.
After multiple doses (0.6 mg twice daily), the mean elimination half-life is 26.6–31.2 hours in healthy young adults. 40–65% of the oral dose is recovered unchanged in urine; there is enterohepatic recirculation and biliary excretion. It is not removed by haemodialysis.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
