What are the clinical findings of colchicine toxicity?

Clinical Findings of Colchicine Toxicity

Colchicine toxicity is a serious and potentially fatal complication that manifests in three sequential phases, beginning with gastrointestinal symptoms, progressing to multiorgan failure, and potentially ending with recovery or death. 1

Causes of Colchicine Toxicity

Colchicine toxicity can occur due to several factors:

• Exceeding recommended doses (maximum recommended doses are 3 mg daily in adults and 2 mg daily in children) 1
• Liver or renal failure (elimination half-life can increase up to sevenfold in liver cirrhosis) 1
• Drug interactions with medications metabolized by cytochrome 3A4 (macrolides, ketoconazole, ritonavir, verapamil, ciclosporin, statins) which can increase colchicine blood levels by 200-300% 1
• Intentional or accidental overdose 2

Clinical Manifestations by Phase

Phase 1 (0-24 hours after ingestion)

• Gastrointestinal symptoms predominate:
  • Severe abdominal pain 1
  • Nausea and vomiting 2
  • Diarrhea (often profuse, cholera-like) 1
  • Significant fluid loss leading to dehydration 2
  • Peripheral leukocytosis may be observed 2

Phase 2 (24-72 hours after ingestion)

• Multiorgan failure develops:
  • Bone marrow failure with severe myelosuppression 1
  • Renal insufficiency/acute renal failure 1, 2
  • Adult respiratory distress syndrome 1
  • Cardiac complications (arrhythmias, cardiovascular collapse) 1, 2
  • Disseminated intravascular coagulation 1
  • Neurological disturbances 1
  • Metabolic acidosis (particularly lactic acidosis) 3
  • Shock 1
  • Seizures 1
  • Death most commonly occurs during this phase 2, 3

Phase 3 (if patient survives)

• Recovery phase (can last several weeks):
  • Resolution of organ failure 1
  • Rebound leukocytosis 1, 2
  • Alopecia (hair loss) 1, 2

Dose-Related Toxicity

• Fatalities have occurred after ingestion of as little as 7 mg over four days 2
• Patients who ingested less than 0.5 mg/kg typically survived with milder toxicities 2
• Those who took 0.5-0.8 mg/kg experienced more severe reactions including myelosuppression 2
• 100% mortality has been reported in patients who ingested more than 0.8 mg/kg 2

Laboratory Findings

• Elevated liver enzymes (monitoring recommended; reduction of colchicine dose if >2× upper limit of normal) 1
• Elevated creatine phosphokinase (CPK), especially in patients with decreased renal function 1
• Leukopenia progressing to pancytopenia 3
• Elevated lactate levels 3
• Coagulation abnormalities 1

High-Risk Populations

• Patients with pre-existing renal impairment 1
• Patients with liver disease 1
• Patients taking medications that interact with colchicine 1
• Delayed presentation is associated with poor prognosis 3

Management Considerations

• No specific antidote is commercially available 3
• Treatment is primarily supportive 2, 3
• Gastric lavage and measures to prevent shock should be initiated promptly 2
• Colchicine is not effectively removed by dialysis 2
• Granulocyte colony-stimulating factor may be used for severe myelosuppression 3

Monitoring Recommendations

• Regular monitoring of liver enzymes in all patients on colchicine 1
• Careful monitoring of signs of toxicity and CPK in patients with decreased renal function 1
• Awareness of potential drug interactions that may increase colchicine levels 1

Prevention

• Adherence to recommended dosing guidelines 1
• Dose reduction in patients with renal or hepatic impairment 1
• Avoidance of interacting medications when possible 1
• Patient education about signs and symptoms of toxicity 1