colchicine
anti-gout· Brands: Colcrys, Mitigare, GloperbaPO
Mechanism of action
Colchicine binds to tubulin, inhibiting microtubule polymerisation. This disrupts cell migration, particularly of neutrophils, and reduces their chemotactic response to urate crystals. It also inhibits leukotriene B4 synthesis, thereby lessening the inflammatory cascade in acute gout attacks.
Pharmacokinetics
Colchicine is well absorbed after oral administration, reaching peak plasma concentrations within 1 to 2 hours. It is metabolised in the liver, primarily by CYP3A4, and to a lesser extent by other enzymes. Excretion occurs mainly via the biliary and renal routes. The elimination half-life is approximately 9 hours but is prolonged in patients with renal or hepatic impairment. It crosses the placental barrier.
Indications & dosing
Acute gout flare
Given as 1 mg followed by 0.5 mg after 1 hour. Do not repeat within 12 hours.
- adult · PO: 1.5 mg Single course · Given as 1 mg followed by 0.5 mg after 1 hour. Do not repeat within 12 hours.
Prophylaxis of gout flares
0.5 mg once or twice daily depending on indication and tolerability.
- adult · PO: 0.5–1 mg Daily · 0.5 mg once or twice daily depending on indication and tolerability.
Familial Mediterranean fever
Dose adjusted based on renal function and response.
- adult · PO: 0.5–1 mg Once daily · Dose adjusted based on renal function and response.
Pericarditisoff-label
Off-label use for acute or recurrent pericarditis. Monitor for toxicity.
- adult · PO: 0.5–1 mg Once daily · Off-label use for acute or recurrent pericarditis. Monitor for toxicity.
Contraindications & precautions
- Hypersensitivity to colchicine · Includes patients with a history of allergic reaction to colchicine.
- Severe renal impairment · e.g. creatinine clearance <30 mL/min; risk of accumulation and toxicity.
- Severe hepatic impairment · Colchicine is extensively metabolised in the liver; impairment increases toxicity risk.
- Concurrent use of strong CYP3A4 or P-glycoprotein inhibitors · e.g. clarithromycin, ketoconazole, ciclosporin; increases colchicine levels and toxicity risk.
- Pregnancy · Use only if clearly needed; may affect fetal development. Seek specialist advice.
- Breastfeeding · Colchicine passes into breast milk; seek specialist advice before use.
- Use with caution in mild to moderate renal impairment; adjust dose and monitor for toxicity.
- Use with caution in hepatic impairment; reduce dose if necessary.
- Caution in elderly or debilitated patients; consider dose reduction.
- Advise patients to report muscle weakness, numbness, or signs of infection; monitor blood counts periodically.
- Avoid concurrent use with strong CYP3A4 or P-glycoprotein inhibitors; if unavoidable, reduce colchicine dose.
- Monitor for gastrointestinal symptoms, as diarrhoea may indicate toxicity and necessitate dose reduction.
Adverse effects
- Diarrhoea
- Nausea and vomiting
- Myopathyserious
- Neuropathyserious
- Bone marrow suppressionserious
- Rhabdomyolysisserious
Interactions
- clarithromycinmajorAvoid co-prescription whenever possible, especially in patients with renal or hepatic impairment. If a macrolide is needed, consider azithromycin, which does not significantly inhibit CYP3A4. If co-administration is unavoidable in a patient with normal renal and hepatic function, reduce the colchicine dose (e.g., to 0.6 mg once daily) and monitor closely for signs of toxicity, including blood counts and renal function.
- simvastatinmajorAvoid concomitant use where possible. If the combination is necessary, use the lowest effective doses and monitor for muscle symptoms and serum creatine kinase. Consider alternative statins that are not metabolised by CYP3A4, such as pravastatin or rosuvastatin. In patients with renal impairment, dose adjustment of colchicine is essential.
Renal & hepatic adjustment
- eGFR 60+: No dose adjustment required for normal renal function.
- eGFR 30–60: Reduce dose by 50% and monitor closely. Consider alternative therapy for acute gout if possible.
- eGFR 0–30: Avoid or use extreme caution with substantial dose reduction. Use alternative if possible. (avoid)
- Hepatic impairment (mild): No specific adjustment needed, but monitor for toxicity.
- Hepatic impairment (moderate): Use with caution; consider dose reduction and monitor closely.
- Hepatic impairment (severe): Avoid or reduce dose significantly; monitor for toxicity. (avoid)
Monitoring, pregnancy & toxicity
- Renal function (eGFR/creatinine) · Before and during therapy, especially in renal impairment
- Full blood count · Periodically, as bone marrow suppression may occur
- Liver function tests · Periodically
- Signs of toxicity (diarrhoea, vomiting, abdominal pain) · At each assessment
- Drug interactions (e.g. CYP3A4/P-gp inhibitors) · Before and during therapy
- Pregnancy: Not routinely recommended in pregnancy, particularly for acute gout; consider alternative therapies (e.g. NSAIDs, corticosteroids). Specialist advice is needed for women requiring colchicine (e.g. familial Mediterranean fever).
- Toxicity: Gastrointestinal effects (e.g. diarrhoea, nausea, vomiting, abdominal pain) · Discontinue colchicine; these are early signs of toxicity. Provide supportive care.
- Toxicity: Bone marrow suppression (e.g. pancytopenia) · Monitor full blood count; discontinue drug; supportive care.
- Toxicity: Cardiac arrhythmias, multi-organ failure in severe overdose · Discontinue drug; supportive care; seek specialist advice. Consider activated charcoal if recent ingestion.
- Toxicity: Acute overdose · Emergency hospital management; treat symptomatically; consider activated charcoal; no specific antidote.
Clinical notes
Colchicine is used for the treatment of acute gout flares, for prophylaxis during initiation of urate-lowering therapy, and in familial Mediterranean fever. Doses vary by indication and must be adjusted in patients with chronic kidney disease or liver disease. Common adverse effects include gastrointestinal upset, particularly diarrhoea and nausea. More serious but rare effects include neuromuscular toxicity, bone marrow suppression, and rhabdomyolysis. Concomitant use with strong CYP3A4 inhibitors such as macrolides or with P-glycoprotein inhibitors like cyclosporine increases the risk of toxicity. Blood counts and renal function should be monitored. Colchicine is contraindicated in patients with severe renal or hepatic impairment.
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BNF; local formulary