Colchicine is FDA approved for the treatment and prophylaxis of gout and familial Mediterranean fever. It is used off-label for acute and recurrent pericarditis, a variety of inflammatory conditions such as Behçet disease, and post myocardial infarction to prevent major adverse cardiac events. 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.

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 reduction or cessation of colchicine is warranted in the setting of renal dysfunction or in patients initiating CYP3A4 or P-glycoprotein inhibitors.

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.

1. 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 from shock and inhibition of cellular metabolism is common. Other manifestations of colchicine poisoning include acute myocardial injury, rhabdomyolysis, 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.
2. Death usually occurs after 8-36 hours and is caused by respiratory failure, intractable shock, and cardiac arrhythmias or sudden cardiac arrest.
3. Late complications include bone marrow suppression, particularly leukopenia and thrombocytopenia (4-5 days) and alopecia (2-3 weeks). Myopathy (proximal muscle weakness and elevated creatine kinase [CK] levels) and polyneuropathy have been described after both acute and chronic poisoning.

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.

1. Specific levels. Colchicine levels in blood and urine are not readily available. However, levels may be useful for forensic purposes, especially in cases of unexplained pancytopenia and multiple-organ failure. Bone marrow biopsy may reveal metaphase arrest and “pseudo-Pelger-Huët” cells.
2. Other useful laboratory studies include CBC, electrolytes, hepatic enzymes, glucose, BUN, creatinine, uric acid, CK, cardiac troponin, urinalysis, and ECG monitoring. Elevated serum levels of troponin suggest greater severity of myocardial necrosis and higher mortality.

1. Emergency and supportive measures. Provide aggressive supportive care, with careful monitoring and treatment of fluid and electrolyte disturbances.
   1. Anticipate sudden respiratory or cardiac arrest and maintain an open airway and assist ventilation if necessary.
   2. Treatment of shock may require large amounts of crystalloid fluids and possibly blood (to replace losses from hemorrhagic gastroenteritis).
   3. Bone marrow depression requires specialized intensive care, including patient isolation for neutropenia and management of febrile episodes, as for other neutropenic conditions. Platelet transfusions may be required to control bleeding.
2. Specific drugs and antidotes. Previously, colchicine-specific antibodies (Fab fragments) were used experimentally to treat a single case of severe colchicine overdose. A recent study demonstrated efficacy of ovine derived colchicine-specific Fab fragments in an animal model. However, there are no human clinical studies and no commercially available or approved product. Granulocyte colony-stimulating factor (G-CSF) has been used for the treatment of severe leukopenia.
3. Decontamination. Administer activated charcoal orally if conditions are appropriate (see Table I-37). Consider gastric lavage if the ingestion has occurred within 60 minutes.
4. Enhanced elimination. Because colchicine is highly bound to tissues, with a large volume of distribution, hemodialysis and hemoperfusion are ineffective. Repeat-dose charcoal might accelerate elimination as colchicine undergoes enterohepatic recirculation, however efficacy has not been demonstrated. The use of rifampin to induce hepatic CYP3A4 elimination of colchicine has been suggested but not tested.