Colchicine is a time-tested, potent alkaloid medication derived from the autumn crocus (Colchicum autumnale). It is a cornerstone therapy for the acute treatment of gout flares and for the prophylaxis of flares during the initial phase of urate-lowering therapy. Furthermore, it is the standard of care for managing Familial Mediterranean Fever (FMF) and is indicated for the treatment of pericarditis. Its primary mechanism involves binding to tubulin, thereby inhibiting microtubule polymerization, which disrupts cellular functions—most critically, the migration and inflammatory activity of neutrophils. This targeted action makes it highly effective for specific inflammatory conditions without being a general analgesic or broad-spectrum anti-inflammatory.

Features

• Derived from the plant Colchicum autumnale.
• Potent anti-inflammatory agent with a unique mechanism of action.
• Specifically inhibits microtubule assembly by binding to tubulin.
• Disrupts neutrophil motility, adhesion, and degranulation.
• Available in oral tablet form (typically 0.6 mg).
• Also available in intravenous form for specific hospital-based uses (use with extreme caution).
• Not a pain reliever (analgesic) or a traditional nonsteroidal anti-inflammatory drug (NSAID).

Benefits

• Provides rapid and effective relief from the intense pain, swelling, and redness of acute gout attacks.
• Reduces the frequency and severity of gout flares when used prophylactically.
• Prevents debilitating febrile attacks and associated amyloidosis in patients with Familial Mediterranean Fever (FMF).
• Decreases the recurrence of pericarditis.
• Offers a targeted therapeutic option for specific inflammatory pathologies with a well-understood safety profile when dosed correctly.
• Allows for management of conditions without the gastrointestinal or cardiovascular risks associated with long-term NSAID use.

Common use

Colchicine is primarily prescribed for:

• Treatment of Acute Gout Flares: It is most effective when administered within the first 36 hours of the onset of symptoms.
• Prophylaxis of Gout Flares: Used at a lower dose to prevent flares when initiating urate-lowering drugs like allopurinol or febuxostat.
• Familial Mediterranean Fever (FMF): Used daily to prevent febrile episodes and the development of systemic amyloidosis.
• Recurrent Pericarditis: Used to reduce the incidence of recurrence.

Dosage and direction

Crucial Note: Dosing is highly specific and must be strictly adhered to due to a narrow therapeutic index. Always follow the precise instructions provided by the prescribing physician.

• Acute Gout Flare (Adults): A common regimen is 1.2 mg (two 0.6 mg tablets) at the first sign of a flare, followed by 0.6 mg one hour later. The total dose for an acute episode should not exceed 1.8 mg over a 1-hour period. A course of treatment for an acute flare should not be repeated within 3 days.
• Gout Prophylaxis (Adults): Typically 0.6 mg once or twice daily. The maximum dose for prophylaxis is usually 1.2 mg per day. Therapy often continues for at least 6 months while urate-lowering therapy takes effect.
• Familial Mediterranean Fever (Adults): 1.2 to 2.4 mg daily. The dose may be adjusted based on severity and tolerability, often divided into two doses.
• Pediatric Dosing for FMF: Dosing is based on age or body weight and must be determined by a specialist.
• Administration: Tablets are taken orally, with or without food. If gastrointestinal upset occurs, taking with food may help.

Precautions

• Narrow Therapeutic Index: There is a small difference between an effective dose and a toxic dose. Do not exceed prescribed doses.
• Renal Impairment: Patients with impaired kidney function are at significantly increased risk of severe and potentially fatal toxicity. Dose adjustment or avoidance is necessary in patients with severe renal impairment. It is contraindicated in patients with both renal and hepatic impairment.
• Hepatic Impairment: Patients with severe liver disease require careful monitoring and likely dose reduction due to altered metabolism.
• Elderly Patients: Older patients are more susceptible to adverse effects, particularly myotoxicity and neuropathy, often due to age-related decline in renal function. Lower doses are frequently required.
• Blood Dyscrasias: May cause myelosuppression (e.g., leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, aplastic anemia). Monitoring of complete blood counts is advised with chronic use.
• Neuromuscular Toxicity: Can cause myotoxicity (rhabdomyolysis) and peripheral neuropathy, especially in patients with renal dysfunction or on interacting drugs.
• Pregnancy and Lactation: Use during pregnancy may be considered for treating FMF but requires a rigorous risk-benefit assessment. It is present in breast milk; caution is advised during breastfeeding.

Contraindications

Colchicine is contraindicated in patients with:

• Hypersensitivity to colchicine or any ingredient in the formulation.
• Severe renal impairment (e.g., end-stage renal disease) and concomitant use of a strong P-glycoprotein (P-gp) or CYP3A4 inhibitor (see Drug Interactions).
• Severe hepatic impairment.
• Pre-existing blood dyscrasias.

Possible side effect

Common side effects are often gastrointestinal and dose-related:

• Nausea, vomiting, diarrhea, and abdominal pain.
• Less common but more serious side effects require immediate medical attention:
  • Symptoms of myotoxicity: unusual muscle pain, tenderness, or weakness, especially if accompanied by fever or dark urine (signs of rhabdomyolysis).
  • Symptoms of neuropathy: tingling, numbness, burning pain in the hands or feet.
  • Signs of infection (fever, chills, sore throat) which may indicate neutropenia.
  • Unusual bleeding or bruising (may indicate thrombocytopenia).
  • Severe diarrhea or vomiting leading to dehydration.
  • Hair loss (usually reversible).

Drug interaction

Colchicine is subject to numerous critical drug interactions that can lead to life-threatening toxicity. It is primarily metabolized by CYP3A4 and is a substrate for P-glycoprotein (P-gp).

• Strong CYP3A4 Inhibitors & P-gp Inhibitors: CONTRANDICATED in patients with renal or hepatic impairment. In others, co-administration with drugs like clarithromycin, ketoconazole, itraconazole, ritonavir, cyclosporine, and verapamil drastically increases colchicine plasma levels, requiring dose prohibition or significant reduction.
• Moderate CYP3A4 or P-gp Inhibitors: (e.g., aprepitant, diltiazem, erythromycin, fluconazole, quinidine, ranolazine) require caution and likely dose reduction.
• Statins (HMG-CoA Reductase Inhibitors) and Fibrates: Concomitant use (e.g., atorvastatin, simvastatin, gemfibrozil) significantly increases the risk of developing severe muscle toxicity (rhabdomyolysis).
• Other Macrolide Antibiotics: (e.g., azithromycin) may interact; caution is advised.
• Digoxin: Colchicine may increase digoxin concentrations.
• CNS Depressants: May enhance the adverse effects of other drugs that cause CNS depression.

Missed dose

• For chronic daily use (e.g., FMF prophylaxis): If a dose is missed, take it as soon as you remember. If it is almost time for the next dose, skip the missed dose and resume the normal dosing schedule. Do not double the dose to make up for a missed one.
• For acute gout treatment: The dosing regimen is a single course. A missed dose in this context is not applicable in the same way. Do not take extra tablets to make up for a missed dose within the course.

Overdose

Colchicine overdose is a MEDICAL EMERGENCY and can be FATAL. Symptoms can be delayed 2-24 hours and mimic sepsis. Seek immediate emergency medical attention or contact a Poison Control Center.

Overdose typically occurs in three phases:

1. 10-24 hours: Gastrointestinal phase - severe nausea, vomiting, diarrhea, abdominal pain, and fluid loss leading to dehydration and electrolyte imbalances.
2. 24-72 hours: Multi-organ failure phase - leukocytosis followed by pancytopenia, metabolic acidosis, arrhythmias, hypovolemic shock, rhabdomyolysis, acute renal failure, hepatic failure, respiratory distress, and progressive multi-organ failure. This phase has high mortality.
3. Recovery phase (after 7 days): If the patient survives, a rebound leukocytosis and alopecia may occur. Recovery can be prolonged.

There is no specific antidote. Treatment is supportive and includes gastric lavage (if early), aggressive fluid and electrolyte replacement, hemodynamic support, and management of bone marrow suppression (e.g., granulocyte colony-stimulating factor for neutropenia).

Storage

• Store at room temperature (20°C to 25°C or 68°F to 77°F).
• Keep the container tightly closed.
• Protect from light and moisture.
• Keep out of reach of children and pets.
• Do not flush medications down the toilet or pour them into a drain. Dispose of unused medication through a medicine take-back program.

Disclaimer

This information is for educational purposes only and is not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The author does not endorse any specific product or treatment. The information provided should not be used for diagnosing or treating a health problem or disease. It is not a substitute for professional medical care. Always consult your physician or other qualified health provider regarding any medical condition or treatment plan. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

• “As a rheumatologist with over 20 years of experience, colchicine remains an indispensable tool for managing acute gout. Its efficacy is remarkable when used correctly and promptly at the first sign of a flare. The key is patient education on the precise dosing regimen to avoid GI upset and the serious risks of overdose.” — Dr. E. Lawson, MD, Rheumatology
• “For my patients with Familial Mediterranean Fever, daily colchicine is life-changing. It prevents the painful and debilitating attacks and, most importantly, protects them from the development of amyloidosis, which is a serious complication. Monitoring is essential, but the benefits overwhelmingly outweigh the risks.” — Dr. A. Petrova, MD, Internal Medicine
• “The narrow therapeutic index of colchicine demands immense respect. In the hospital, we see the devastating consequences of overdose and drug interactions, particularly with common antibiotics. It is a powerful drug that underscores the absolute necessity of a complete medication review by a pharmacist or physician before prescription.” — Clinical Pharmacist Specialist