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Colchicine
General information
Colchicine is an antimitotic agent, highly effective in the treatment of gout, but associated with considerable toxicity. Diarrhea is used as a criterion for adequate dosage. Accidental overdosage occurs relatively often and can be dangerous. For these reasons, NSAIDs (except aspirin) are often used in acute gout instead of colchicine.
There is controversy about the long-term toxicity of colchicine. In familial Mediterranean fever, low dosages of colchicine (1–2 mg/day) for 15–18 years have been well tolerated, even by young patients [ ].
Prescribers have been reminded by New Zealand’s Medsafe Pharmacovigilance Team of the revised dosage advice for colchicine, which is now second-line therapy for acute gout, because of the risk of serious adverse effects [ , ]. Colchicine is very toxic in overdose, and deaths have occurred. The use of high doses in acute gout is not appropriate, especially in patients who are elderly, have impaired renal or hepatic function, or weigh less than 50 kg. Medsafe advised that:
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Colchicine should be considered a second-line treatment for acute gout, when NSAIDs are contraindicated, inefficacious, or poorly tolerated;
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The dosage interval should be increased to 6 hours;
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The maximum daily dose in the first 24 hours should be 2.5 mg;
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The maximum cumulative dose over 4 days should not exceed 6 mg or 3 mg in elderly people;
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Colchicine is contraindicated in severe renal or hepatic impairment and the dose should be reduced in patients with less severe impairment.
In addition, continued dosing until adverse gastrointestinal events occur “is no longer considered safe or appropriate”. Medsafe has urged prescribers to write clear dosage advice on the prescription, to inform patients of the revised dosage advice, to stress how important it is not to exceed the maximum doses, to warn patients of the symptoms of colchicine toxicity, and to advise them to stop taking the drug immediately and see a doctor if symptoms such as nausea, vomiting, and diarrhea occur.
Organs and systems
Nervous system
Neuropathy, polyneuritis, toxic encephalitis, delirium, and coma have occurred only in severe colchicine intoxication. During prolonged treatment, neuritis, muscular weakness and myopathy occur more commonly than was previously thought in patients with impaired renal function. In some cases the neuromyopathy was part of multiorgan system failure, but in others the syndrome was not accompanied by other features of colchicine toxicity. Patients taking long-term colchicine should take low dosages (probably no more than 0.6 mg/day) and have their serum creatine kinase monitored [ ].
Psychological
Despite that fact that studies in animals have suggested that colchicine may adversely affect cognitive function, in 55 patients, mean age 74 years, with familial Mediterranean fever colchicine for an average of 25 years had no adverse effects on cognitive function [ ].
Metabolism
Transient diabetes and hyperlipidemia have been reported. Metabolic acidosis is probably a consequence of heavy, cholera-like diarrhea. Progressive reduction of libido was attributed to colchicine in patients with familial Mediterranean fever [ ].
Electrolyte balance
Water and electrolyte disturbances, including inappropriate antidiuresis, can occur in patients who have taken high doses of colchicine [ , ], including hypernatremia and polyuria [ ].
Hematologic
Bone marrow depression is common after colchicine overdose and intoxication and less common in therapeutic doses. Fatal cases of agranulocytosis are more often associated with bone marrow aplasia [ ]. Bone marrow depression usually occurs between the third and sixth days of acute intoxication. Cytoplasmic inclusions in neutrophils and megaloblastic anemia have been described. Administration of therapeutic doses intravenously and orally to two patients with reduced renal function caused profound prolonged neutropenia complicated by septicemia, which ended in death [ ].
Gastrointestinal
Gastrointestinal symptoms often develop after therapeutic doses and are even used for dose titration. Diarrhea is often followed by nausea, vomiting, and abdominal pain. Long-term therapy can provoke steatorrhea, malabsorption, and defects in intestinal enzyme activity [ ].
Urinary tract
Acute renal insufficiency has been associated with colchicine intoxication [ ].
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