Colchicine is FDA approved for the treatment and prophylaxis of gout and familial Mediterranean fever. It is also used for acute and recurrent pericarditis and a variety of inflammatory conditions such as Behçet disease. It is available in tablet form, and it is also found in certain plants, such as Colchicum autumnale (autumn crocus or meadow saffron) and Gloriosa superba (glory lily). The injectable form of colchicine was banned in 2009 by the FDA due to serious toxicity. Its antimitotic mechanism of action is similar to that of some chemotherapeutic agents, and colchicine overdoses are extremely serious, with considerable mortality.
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–66).
The maximum FDA-approved therapeutic dose of oral colchicine for acute gout 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. The dose used for familial Mediterranean fever in adults is slightly higher at 1.2–2.4 mg per day. Dosing should be reduced for renal dysfunction for all uses of colchicine.
Prior to the ban on injectable colchicine, healthy individuals receiving a cumulative dose of greater than 4 mg of IV colchicine per treatment course were at risk for significant toxicity and death.
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.