What are the side effects of colchicine?

Side Effects of Colchicine

The most common side effects of colchicine include gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain, which can be dose-dependent and may limit the ability to achieve therapeutic doses. 1, 2

Common Side Effects

Gastrointestinal Effects

• Diarrhea (occurs in approximately 17.9% of patients vs. 13.1% in control groups) 3
• Nausea and vomiting
• Abdominal pain and cramping
• Hyperperistalsis

These gastrointestinal side effects may be:

• Transient or persistent
• More common with higher doses
• Potentially reduced by splitting the daily dose
• Associated with lactose intolerance in some patients 1

Musculoskeletal Effects

• Myalgia (muscle pain) - reported in 4.2% of colchicine users 3
• Weakness
• Risk of myopathy, especially when combined with statins 4, 5

Severe Side Effects

Hematological Effects

• Blood dyscrasias (rare)
• Bone marrow depression (primarily in acute colchicine intoxication) 6

Hepatic Effects

• Elevated liver enzymes (reported in 1.9% of users) 3
• Liver dysfunction, especially with pre-existing liver disease 1

Neuromuscular Effects

• Peripheral neuropathy with long-term use 6
• Numbness or tingling in fingers or toes 2

Renal Effects

• Increased risk of toxicity in patients with renal impairment 4

Drug Interactions

Critical Interactions

• CYP3A4 inhibitors (clarithromycin, erythromycin, ketoconazole, protease inhibitors) can increase colchicine levels by 200-300% 4, 7
• P-glycoprotein inhibitors (cyclosporine, verapamil) increase colchicine toxicity 4, 7
• Statins (particularly simvastatin and atorvastatin) increase risk of myopathy 4
• Grapefruit juice can increase colchicine levels 2

Toxicity and Overdose

Signs of Toxicity

• Severe diarrhea and vomiting
• Muscle weakness or pain
• Unusual bleeding or bruising
• Increased infections
• Weakness or fatigue
• Pale or gray color to lips, tongue, or palms 2

Overdose Concerns

• Colchicine has a narrow therapeutic index with no clear distinction between therapeutic, toxic, and lethal doses 7
• Overdose can be fatal - the lowest reported lethal doses are 7-26 mg 7
• Acute toxicity presents in three phases:
  1. Gastrointestinal phase (10-24 hours)
  2. Multi-organ dysfunction (24 hours to 7 days)
  3. Recovery phase (within weeks) 7

Risk Reduction Strategies

Dosing Considerations

• Start with lower doses and increase gradually
• For FMF: 1.0-1.5 mg/day for adults is recommended 1
• For gout: Lower doses (0.5-0.6 mg three times daily) may be sufficient 1
• Consider single daily dosing to improve compliance, but divided doses may reduce side effects 1

Special Populations

• Reduce dose in patients with renal impairment 4
• Use with extreme caution in patients with severe renal or hepatic impairment 4
• Avoid in patients taking strong CYP3A4 inhibitors 4, 2

Monitoring

• Regular monitoring of complete blood counts and liver function tests 1, 4
• Monitor serum creatine kinase if muscle symptoms develop 4
• Follow up more frequently at initial diagnosis and when disease is unstable 1

Management of Side Effects

For Gastrointestinal Effects

• Temporary reduction of dairy products if lactose intolerance is suspected
• Split doses to reduce peak concentrations
• Dose reduction
• Use of antidiarrheal and spasmolytic agents
• Gradual reintroduction of the regular dose once symptoms resolve 1

For Severe Reactions

• Discontinue colchicine and seek immediate medical attention
• Consider alternative treatments such as IL-1 blockers for FMF or corticosteroids for gout 1

Colchicine remains an effective treatment for conditions like gout and FMF, but careful dosing, monitoring, and awareness of potential side effects and drug interactions are essential for safe use.