Colchicine toxicity

Background
  • Derived from C. autumnale (wild saffron, meadow saffron, autum crocus, naked lady) and G. superba (glory lily)
    • C. autumnale resembles wild garlic
      C. autumnale
    • G. superba may be confused for sweet potatoes
      G. superba
  • First published in the first century in Pedanius Dioscorides De Materia Medica

Uses
  • Gout
  • Familial Mediterranean fever
  • Pericarditis

Toxicokinetics
  • Inhibitor of microtubule formation and function
  • Rapidly absorbed in the jenjunum and ileum
  • Bioavaiability of 25-50%
  • Lipid soluble
  • Volume of distribution from 2.2-12L/kg, may increase to 21L/kg in overdose
  • 50% bound to plasma proteins
  • Peak serum concentration in 1-3 hours
  • Metabolized by liver via CYP3A4
    • Undergoes enterohepatic recirculation
  • Serum half-life 9-108 minutes
  • Toxicity usually occurs at levels >3ng/ml

Clinical Features

Triphasic
  • Phase I
    • Onset 12-24 hours post ingestion
    • GI manifestations
  • Phase II
    • 24 hours- several days
    • Wide spread organ dysfunction
  • Phase III
    • Recovery or death
    • Lasts approximately 1 week

GI
  • Vomiting and diarrhea
  • Abdominal pain

Hematopoietic
  • Peripheral leukocytosis followed by profound leukopenia
  • Pancytopenia within 48-72 hours
  • Recovery of all cell lines occurs if patient survives

Cardiovascular
  • Dysrhythmias
  • Cardiac arrest
    • Occurs within 24-36 hours

Pulmonology

Neurologic
  • Myopathy
  • Neuropathy
  • Myoneuropathy
  • Seizures

Musculoskeletal
  • Rhabdomyolysis

Differential Diagnosis

Heavy metal toxicity

Evaluation
  • Colchicine levels do not return in a timely manner
    • No correlation with severity of illness
    • >3.0ng/ml generally associated with toxicity
  • BMP
    • Including calcium, magnesium, and phosphorus
  • LFTs
  • CBC
  • Coagulation factors
  • CPK
  • Urinalysis
  • EKG
  • CXR
  • Depending on clinical situation

Management
  • Supportive care
  • GI Decontamination
  • Antidotal therapy
    • Colchine-specific Fab fragments
      • Not commercially available
    • Granulocyte-colony stimulating factor (G-CSF)
      • useful in treating patients who develop leukopenia and thrombocytopenia
  • Extracorporeal elimination
    • No benefit

Disposition
  • All symptomatic patients require admission to ICU
  • Patients who do not develop GI symptoms within 8-12 hours after ingestion likely have not developed significant poisoning
  • Consult Toxicology or poison control

References

    Schier, J. Colchicine, Podophyllin and the Vinca Alkaloids. In: Goldfrank's Toxicologic Emergencies. 9th Ed. New York: McGraw-Hill; 2011: 537-547

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