Colchicine

• It acts by inhibiting the production of tubulin, a protein essential for the development of microtubules.
• These form the spindles essential for cell division, intracellular transport of vesicles and proteins, flagella reassembly, and the ameboid motility of cells.
• In this way colchicine inhibits both the migration of macrophages/leukocytes and phagocytosis - reducing the inflammation and pain of gout.¹

• Acute gout
  • Common practice is to use NSAIDs rather than colchicine as first-line therapy for uncomplicated primary gout due to the latter's high toxicity.²
• Gout prophylaxis
  • As cover to prevent an acute attack when starting agents such as allopurinol.
  • Low doses can be effective as a prophylactic agent. This gets round the toxicity problem and can sometimes 'buy time' in patients undertaking lifestyle modification, before a lifelong commitment is made to uric acid lowering agents.
  • This approach is not suitable in patients who already have gouty arthritis or tophi.^3,4
• Familial mediterranean fever⁵

• Pregnancy - well-controlled trials have demonstrated potential to develop fetal abnormality. Weigh benefits against risks.⁶

• Lactation - colchicine passes into breast milk but no adverse effects reported. However, manufacturers recommend avoid using due to potential toxicity problems.¹
• The elderly - poorly tolerated, beware poor renal function.⁷
• Cardiac impairment - often cited, but most cases relate to the elderly with co-existing renal dysfunction. Indeed, colchicine has been used successfully in the treatment of cardiac conditions, e.g. myocarditis.⁸
• Hepatic impairment - caution recommended by manufacturers. However, adverse reports of liver damage mainly relate to high doses in people with previous normal liver function.⁹ Indeed, used with some success in the treatment of primary biliary cirrhosis.¹⁰
• Renal impairment - reduce dose if moderate impairment, avoid if possible if severe impairment.
• Co-existing gastro-intestinal disease - reduce dose or avoid depending on severity.¹¹

Cyclosporin

• This is said to increase potential for nephrotoxicity and myotoxicity by increasing cyclosporin plasma concentration.¹
• However, whilst a case can be made for myotoxicity,¹² several animal models suggest that colchicine may actually have a beneficial effect on cyclosporin-induced nephrotoxicity.¹³

• The high incidence of diarrhoea, vomiting and abdominal pain side-effects makes NSAIDs a more preferable first-line option.¹⁴
• To minimise side effects, it is recommended that a gap of three days is given between finishing one course of colchicine and starting another.

Less common

These occur mainly at higher doses:

• Gastro-intestinal bleeding
• Rash
• Renal damage¹⁴
• Liver damage¹⁵

Rare

Peripheral neuritis, myopathy, alopecia, inhibition of spermatogenesis, blood disorders (prolonged treatment).¹

Features of an acute overdose

• Symptoms of an acute overdose may set in only after an interval of three to six hours, even with large doses.
• Initially gastrointestinal symptoms predominate.
• Hypotension results from fluid loss into and from the gastro-intestinal tract, and from myocardial depression.
• Neurological features of delirium, seizures or coma can follow along with rhabdomyolysis, disseminated intravascular coagulation (DIC) and acute renal failure.
• Death from intractable shock, respiratory failure or cardiac arrest occurs in 7 to 36 hours.
• Treatment is generally limited to intensive supportive measures unless activated charcoal can be administered within approximately 1 hour of an acute overdose.
• Colchicine-specific antibodies have been used on occasion but are not widely available.
• Late complications with early survivors (and also seen in chronic toxicity) are bone marrow suppression, myopathy, and polyneuropathy.¹⁶

• Usually no time to wait for blood results, but be aware of contra-indications, age, etc., particularly when judging dosage
• Current UK practice is to start with lowest effective dose¹⁷ and titrate up to the licensed dose. This applies to management of acute attack and to prophylaxis.

Urea and electrolytes, liver function tests and full blood count in patients taking drug for long-term prophylaxis.