Colchicine
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.
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