Colchicine is FDA-approved for the treatment of gout and familial Mediterranean fever. It is available in tablet form as well as an injectable solution, and it is also found in certain plants, such as Colchicum autumnale (autumn crocus or meadow saffron) and Gloriosa superba (glory lily). Its antimitotic mechanism of action is similar to that of some chemotherapeutic agents, and colchicine overdoses are extremely serious, with considerable mortality.
Mechanism of toxicity. Colchicine inhibits microtubular formation and function, arresting dividing cells during mitosis. Pharmacokinetics: Colchicine is rapidly absorbed after oral administration and extensively distributed to body tissues. It is eliminated in the liver by CYP3A4 with a half-life of 4.4–31 hours (see also Table II–61)
Toxic dose. The maximum FDA-approved therapeutic dose of oral colchicine is 1.2 mg followed by 0.6 mg after 1 hour, for a total dose of 1.8 mg. This is a significant reduction from the previously recommended maximum dose of 8 mg. In a series of 150 cases, doses of 0.5 mg/kg or less were associated with diarrhea and vomiting but not death, doses of 0.5–0.8 mg/kg were associated with bone marrow aplasia and 10% mortality, and ingestions greater than 0.8 mg/kg uniformly resulted in death. Fatalities, however, have been reported with single ingestions of as little as 7 mg, although other case reports describe survival after ingestions of more than 60 mg. Ingestions of parts of colchicine-containing plants have resulted in severe toxicity and death.
Healthy individuals receiving a cumulative dose of greater than 4 mg of IV colchicine per treatment course are also at risk for significant toxicity and death.
Clinical presentation. Colchicine poisoning affects many organ systems, with toxic effects occurring from hours to several days after exposure.
After an acute overdose, symptoms typically are delayed for 2–12 hours and include nausea, vomiting, abdominal pain, and severe bloody diarrhea. Shock results from depressed cardiac contractility and fluid loss into the GI tract and other tissues. Delirium, seizures, or coma may occur. Lactic acidosis related to shock and inhibition of cellular metabolism is common. Other manifestations of colchicine poisoning include acute myocardial injury, rhabdomyolysis with myoglobinuria, disseminated intravascular coagulation, and acute renal failure.
Chronic colchicine poisoning presents with a more insidious onset. Factors precipitating toxicity from chronic use include renal insufficiency, liver disease, and drug interactions (erythromycin, cimetidine, cyclosporine) that can inhibit colchicine clearance.
Death usually occurs after 8–36 hours and is caused by respiratory failure, intractable shock, and cardiac arrhythmias or sudden cardiac arrest.
Late complications include bone marrow suppression, particularly leukopenia and thrombocytopenia (4–5 days) and alopecia (2–3 weeks). Chronic colchicine therapy may produce myopathy (proximal muscle weakness and elevated creatine kinase [CK] levels) and polyneuropathy. This also has occurred after acute poisoning.
Diagnosis. A syndrome beginning with severe gastroenteritis, leukocytosis, shock, rhabdomyolysis, and acute renal failure, followed by leukopenia and thrombocytopenia, should suggest colchicine poisoning. A history of gout or familial Mediterranean fever in the patient or a family member is also suggestive.