Colchicine (kol-chih-seen) is an alkaloid that is extracted from plants of the genus Colchicum (autumn crocus) and used mostly for gout and occasionally for familial Mediterranean fever. It has been used for Behcet’s disease and pericarditis and was briefly advocated for COVID-19. Colchicine has been used used as early as 1500BC to treat joint pain and inflammation, being described in an Egyptian medical text from that time. It was approved by the FDA in 1961.
Used for gout prophylaxis and for relief from acute attacks, so may help in establishing the diagnosis. NSAIDs are more widely used now for this.
Mechanism of action:
In gout, colchicine interferes with the inflammation by inhibiting microtubule polymerization by binding with the protein, tubulin with is needed for mitosis which will inhibits the activation and migration of neutrophils.This will reduce the inflammatory response.
It may also interrupt the deposition of monosodium urate crystal into the joint tissues.
Colchicine has no effect on plasma concentrations or urinary excretion of uric acid, so generally used with other agents (eg allopurinol and uricosuric drugs)
Pharmacokinetics:
Absorption: Rapidly and well absorbed after taken orally; bioavailability of about 45% (but can be very variable)
Maximum plasma concentrations are usually after 30 to 120 minutes
40% binding primarily to albumin
Metabolism: Metabolized in the liver where it is demethylated to its major metabolites
Excretion: ~85% via feces of both metabolites and the active product. 10-20% is excreted in the urine.
Elimination half-life: around 30 hours
Contraindications:
Hypersensitivity; serious GI disorders, severe renal/hepatic or cardiac disorders.
Not used in those on haemodialysis as it cannot be removed by dialysis.
Precautions: breast feeding, blood dyscrasias, hepatic disease
Safety in pregnancy unclear (Category C in USA and D in Australia); it does cross the placenta.
Avoid alcohol.
Dose:
1-1.2 mg initially with 0.5-0.6 mg after one hour; no more for >12 hrs; after 12 hrs, 0.5-0.6 mg every 8 hours.
Adverse effects:
Gastrointestinal: Nausea, vomiting, anorexia, metallic taste in the mouth, diarrhea (in up to 25%), cramps, peptic ulcer
Genitourinary: Hematuria, oliguria, rhabdomyolysis
Hematologic: Agranulocytosis, thrombocytopenia, pancytopenia
Skin: alopecia, dermatitis, pruritus, purpura, erythema
Other: myopathy, malaise
Overdose:
Colchicine has a very narrow therapeutic index, so overdoses are a significant risk. Fatal dose may be as low as 7-10mg. Initially there are gastrointestinal symptoms up to 8 hours after ingestion. This is followed by multiple organ dysfunction that occur anywhere from 24 hours to 7 days after the overdose. This then develops into multiple organ failure or recovers over a period of several weeks.
Treatment:
No specific antidote.
Treatment is supportive to relieve abdominal pain and manage shock and control of the airways.
Interactions:
If taking other CYP3A4 inhibitors (eg clarithromycin, itraconazole, ketoconazole, cyclosporine) reduce dose; otherwise increased colchicine levels (may be toxic level).
Use with inhibitors of P-glycoprotein (eg clarithromycin, ketoconazole, cyclosporine, etc) shpould be avoided.
Use with NSAIDs may increase the GI effects.
Grapefruit juice increases serum colchicine levels.
Brand names: Colcrys (0.6mg), Colgout (0.5mg), Mitigare (0.6 mg), Gloperba (0.6 mg), and others.
Chemical formula: C22H25NO6
Chemical classification: Colchicum autumnale alkaloid
Patient Education:
Importance of lifestyle and other medications for gout.
Awareness of potentially serious side effects, especially gastrointestinal (and toxicity).
Avoid grapefruit.
Not necessary to take with food.
In Australia, colchicine is on the National Podiatry Scheduled Medicines List for use by authorised Podiatrists, only for 24 hours.
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