What are the potential side effects of colchicine?

Colchicine Side Effects

Colchicine can cause potentially life-threatening side effects due to its narrow therapeutic index, with common gastrointestinal effects occurring at therapeutic doses and severe multiorgan failure possible with overdose or drug interactions. 1

Common Side Effects

Gastrointestinal Effects

• Diarrhea (most common side effect) 1, 2
• Abdominal pain and cramping 1, 2
• Nausea and vomiting 2
• Hyperperistalsis 1

Hematologic Effects

• Neutropenia 1
• Thrombocytopenia 3
• Bone marrow suppression 2

Other Common Side Effects

• Mild abnormalities of liver enzymes 1
• Possible sperm reduction 1
• Myalgia (muscle pain) 2
• Fatigue and weakness 2

Severe Side Effects

Toxicity Progression

Colchicine toxicity typically progresses in three phases 3:

1. Initial phase (10-24 hours): Gastrointestinal symptoms resembling gastroenteritis
2. Second phase (24 hours to 7 days): Multi-organ dysfunction
3. Recovery phase: Typically occurs within weeks if the patient survives

Severe Adverse Effects

• Peripheral neuropathy 1
• Alopecia (hair loss) 1
• Myopathy and rhabdomyolysis 2, 4
• Acute renal failure 5
• Lactic acidosis 3
• Disseminated intravascular coagulation 1
• Adult respiratory distress syndrome 1
• Cardiac arrhythmias 1
• Seizures 1
• Coma and death 1, 3

Risk Factors for Toxicity

Dose-Related Factors

• Exceeding recommended doses (maximum 3 mg daily in adults, 2 mg daily in children for FMF) 1
• Narrow therapeutic index with no clear distinction between therapeutic and toxic doses 3
• Fatality reported with acute ingestions exceeding 0.5 mg/kg 3

Patient-Related Factors

• Renal impairment 1, 6
• Liver disease (cirrhosis can increase half-life up to sevenfold) 1, 6
• Multiple comorbidities 4
• Advanced age 3

Drug Interactions

• CYP3A4 inhibitors can increase colchicine levels by 200-300% 1, 3, 7:

  • Macrolide antibiotics (clarithromycin, erythromycin) 1, 6
  • Antifungals (ketoconazole) 1, 6
  • Protease inhibitors (ritonavir) 1, 6
  • Grapefruit juice 2

• P-glycoprotein inhibitors 1, 6, 7:

  • Cyclosporine
  • Verapamil

• Other interacting medications:

  • Statins (increased risk of myopathy) 1, 3, 4
  • Digoxin 2

Monitoring and Prevention

Monitoring Recommendations

• Regular assessment every 6 months for patients on long-term therapy 1
• More frequent monitoring during the first year of treatment 1
• Monitor for signs of toxicity (diarrhea, nausea, vomiting, abdominal pain) 6
• Check creatine phosphokinase (CPK) levels regularly in patients with renal impairment 6
• Assess renal function regularly in at-risk patients 6

Prevention Strategies

• Dose adjustment in renal impairment (start at 0.3 mg/day in severe renal impairment) 6
• Avoid colchicine completely in patients with renal impairment who are also taking P-gp or strong CYP3A4 inhibitors 6
• Do not repeat treatment courses more than once every two weeks in renal impairment 6
• Consider alternative treatments when colchicine is contraindicated:
  • Oral corticosteroids 6
  • Intra-articular corticosteroid injections 6
  • IL-1 inhibitors 6

Management of Toxicity

• No specific antidote is commercially available 3
• Supportive care is the mainstay of treatment 3
• Gastrointestinal decontamination with activated charcoal for recent ingestions 3
• Administration of granulocyte colony-stimulating factor may be beneficial 3
• Dose reduction may ameliorate adverse effects but must balance with disease control 1

Special Considerations

Pregnancy and Lactation

• Colchicine crosses the placenta but there is no evidence of fetal toxicity 3
• Excreted into breast milk but considered compatible with lactation 3

Important Precautions

• Store at room temperature (68°F-77°F) 2
• Keep out of light and in tightly closed container 2
• Keep out of reach of children 2
• Report unusual symptoms to healthcare provider immediately 2