Colchicine Toxicity

Aka: Colchicine Toxicity, Colchicine Poisoning, Colchicine Overdose

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II. Mechanism

  1. See Colchicine

III. Pharmacokinetics

  1. See Colchicine
  2. Toxicity occurs with single or multiple excessive oral doses (narrow Therapeutic Index)
    1. Risk of progression to multisystem organ failure and death within days of Overdose
    2. Toxic Dose: 0.5 mg/kg
    3. Lethal Dose: 0.8 mg/kg
  3. Toxicity occurs in 3 phases
    1. Phase 1: Onset 10 to 24 hours after ingestion
      1. Gastroenteritis-like symptoms (if oral ingestion, may be absent with IV dosing)
    2. Phase 2: Onset 1 to 7 days after ingestion
      1. Multisystem organ dysfunction with risk of Sepsis and death
    3. Phase 3: Recovery within a few weeks of ingestion
      1. Recovery is typically complete except for complications from acute illness

IV. Findings

  1. Gastrointestinal
    1. Nausea or Vomiting (early effects)
    2. Diarrhea (early effects)
    3. Hepatic Centrilobular necrosis
  2. Cardiac
    1. Bradycardia
    2. Cardiogenic Shock
    3. Heart Block
  3. Respiratory
    1. Acute Respiratory Distress Syndrome (ARDS)
  4. Renal
    1. Prerenal Azotemia
    2. Acute Kidney Injury
  5. Hematologic
    1. Pancytopenia
  6. Neurologic
    1. Altered Level of Consciousness or confusion
    2. Neuropathy (late effect)

V. Labs

  1. See Unknown Ingestion for complete toxicologic workup (e.g. Serum Glucose, Acetaminophen level)
  2. Complete Blood Count
  3. Comprehensive metabolic panel
  4. Lactic Acid

VI. Diagnostics: Symptomatic Patients

  1. Electrocardiogram
  2. Chest XRay

VII. Management

  1. Consult poison control
    1. Various experimental protocols have been explored to aid Colchicine clearance and supportive care
    2. Examples: Exchange transfusion, Anticolchicine antibodies, Colony Stimulating Factors
  2. Activated Charcoal
    1. Indicated for ingestion within prior 1 to 2 hours and no contraindications (e.g. aspiration risk)
    2. Multi-dose acivated charcoal may be indicated (consult poison control)
  3. Hypotension
    1. Intravenous Fluids
    2. Vasopressors (e.g. Norepinephrine)
    3. Venoarterial ECMO
  4. Anuric Acute Renal Failure
    1. Hemodialysis
  5. Disposition
    1. Admit all symptomatic cases
    2. Asymptomatic cases of significant Overdose should be observed for at least 6 to 8 hours

VIII. Prognosis

  1. Poor prognostic factors include delayed presentation, pre-existing renal or liver dysfunction

IX. References

  1. Tomaszewski (2023) Crit Dec Emerg Med 37(11): 32
  2. Finkelstein (2010) Clin Toxicol 48(5):407-14 +PMID: 20586571 [PubMed]

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