Introduction
Colchicine is an ancient medication derived from the autumn crocus (Colchicum autumnale) that remains a cornerstone therapy for acute gout flares and familial Mediterranean fever (FMF). This microtubule inhibitor possesses unique anti-inflammatory properties distinct from NSAIDs or corticosteroids, making it particularly valuable in specific inflammatory conditions.
Mechanism of Action
Colchicine binds to tubulin, a protein subunit of microtubules, inhibiting microtubule polymerization. This action:
- Disrupts mitosis by arresting cell division in metaphase
- Inhibits neutrophil motility and adhesion
- Reduces phagocytosis in inflammatory cells
- Decreases production of chemotactic factors and inflammatory cytokines
- Inhibits NLRP3 inflammasome-mediated release of interleukin-1β
Indications
FDA-approved:- Treatment of acute gout flares
- Prophylaxis of gout flares
- Familial Mediterranean fever (FMF)
- Pericarditis (acute and recurrent)
- Behçet's disease
- Calcium pyrophosphate deposition disease (pseudogout)
- Hepatic cirrhosis
- Dermatologic conditions (such as psoriasis and Sweet's syndrome)
Dosage and Administration
Acute gout flare:- Initial dose: 1.2 mg at symptom onset, followed by 0.6 mg 1 hour later
- Maximum total dose: 1.8 mg over 1 hour
- Course should not be repeated within 3 days
- 0.6 mg once or twice daily
- Maximum: 1.2 mg/day
- Adults: 1.2-2.4 mg daily, may increase by 0.3 mg/day to maximum 3 mg/day
- Children: 0.3-2.4 mg/day based on age and response
- CrCl 30-80 mL/min: Reduce dose; monitor closely
- CrCl <30 mL/min: Avoid or use extreme caution with reduced dosing
- ESRD: Contraindicated
- Reduce dose in mild to moderate impairment
- Contraindicated in severe hepatic impairment
Pharmacokinetics
Absorption: Oral bioavailability approximately 45%; high first-pass metabolism Distribution: Wide distribution; concentrates in leukocytes, kidney, liver, and spleen Metabolism: Extensive hepatic metabolism via CYP3A4 Elimination: Primarily fecal excretion (40-65%); renal excretion 10-20% Half-life: 27-31 hours (prolonged in hepatic/renal impairment)Contraindications
- Severe renal impairment (CrCl <30 mL/min)
- Severe hepatic impairment
- Concomitant use of strong CYP3A4 inhibitors or P-glycoprotein inhibitors in patients with renal or hepatic impairment
- Blood dyscrasias
- Hypersensitivity to colchicine
Warnings and Precautions
Black Box Warning: Fatal overdoses have been reported. May cause bone marrow suppression, renal failure, death, and neuromuscular toxicity.- Monitor for signs of toxicity: nausea, vomiting, diarrhea, abdominal pain
- Blood dyscrasias: agranulocytosis, aplastic anemia, thrombocytopenia
- Rhabdomyolysis, especially with concomitant statin use
- Neuromuscular toxicity: myopathy, neuropathy
- Teratogenic potential (pregnancy category C)
- Elderly patients at increased risk for adverse effects
Drug Interactions
Major interactions:- Strong CYP3A4 inhibitors (clarithromycin, ketoconazole, ritonavir): ↑ colchicine levels → toxicity
- P-glycoprotein inhibitors (cyclosporine, ranolazine): ↑ colchicine levels
- Statins, fibrates: ↑ risk of myopathy/rhabdomyolysis
- Macrolide antibiotics: ↑ colchicine toxicity
- Digoxin: possible ↑ digoxin levels
- CNS depressants: additive effects
Adverse Effects
Common (≥10%):- Gastrointestinal: nausea, vomiting, diarrhea, abdominal pain
- Neurological: peripheral neuropathy
- Bone marrow suppression
- Rhabdomyolysis
- Severe diarrhea leading to electrolyte imbalance
- Hepatotoxicity
- Renal failure
- Alopecia
- Stevens-Johnson syndrome
Monitoring Parameters
- CBC with differential (baseline and periodic)
- Renal function (Cr, BUN)
- Hepatic function (AST, ALT, bilirubin)
- CPK levels if muscle symptoms develop
- Signs of gastrointestinal toxicity
- Neuromuscular function assessment
- Therapeutic response and flare frequency
Patient Education
- Take as directed; do not exceed prescribed dosage
- Recognize early signs of toxicity: nausea, vomiting, diarrhea, abdominal pain, muscle pain/weakness
- Report unusual bleeding, bruising, or infections immediately
- Maintain adequate hydration
- Avoid grapefruit juice and St. John's wort
- Inform all healthcare providers about colchicine use
- Use effective contraception during treatment
- Store at room temperature, away from moisture
References
1. Terkeltaub RA. Colchicine update: 2008. Semin Arthritis Rheum. 2009;38(6):411-419. 2. Leung YY, Yao Hui LL, Kraus VB. Colchicine--update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. 2015;45(3):341-350. 3. FDA prescribing information: Colcrys (colchicine). Revised 2022. 4. Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila). 2010;48(5):407-414. 5. Imazio M, Brucato A, Cemin R, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013;369(16):1522-1528. 6. Schlesinger N, Detry MA, Holland BK, et al. Local ice therapy during bouts of acute gouty arthritis. J Rheumatol. 2002;29(2):331-334.