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

• Acute respiratory distress syndrome

Neurologic

• Myopathy
• Neuropathy
• Myoneuropathy
• Seizures

Musculoskeletal

• Rhabdomyolysis

Differential Diagnosis

Heavy metal toxicity

• Aluminum toxicity
• Antimony toxicity
• Arsenic toxicity
• Barium toxicity
• Bismuth toxicity
• Cadmium toxicity
• Chromium toxicity
• Cobalt toxicity
• Copper toxicity
• Gold toxicity
• Iron toxicity
• Lead toxicity
• Lithium toxicity
• Manganese toxicity
• Mercury toxicity
• Nickel toxicity
• Phosphorous toxicity
• Platinum toxicity
• Selenium toxicity
• Silver toxicity
• Thallium toxicity
• Tin toxicity
• Zinc 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
  • Troponin
  • ABG
  • Lactate
  • Fibrinogen

Management

• Supportive care
• GI Decontamination
  • Orogastric lavage in patients who present within 1-2 hours without vomiting
  • Activated charcoal and consider Multidose activated charcoal
• 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