Colchicine Past and Present

The anti-inflammatory drug colchicine has been used for many centuries to treat acute flares of gout. In more recent times, it has also been used for treatment of familial Mediterranean fever, various dermatologic conditions, pericarditis and now, reviewed on our website, coronary artery disease. Colchicine is found in the seeds, flowers and underground stems of Colchicum autumnale or autumn crocus, which is mentioned as a treatment for pain and swelling in the oldest known textbook of medicine, the Ebers Papyrus, which was produced in Egypt in about 1550 BCE. The drug is named for the Greek city of Colchis, where C. autumnale grows in abundance. In subsequent centuries, colchicine was better known as a poison, and indeed overdoses of the drug can be fatal. It was first described as a treatment for gout by the Greek physician Galen, who died in the year 200 CE. The 17th century English physician Thomas Sydenham is said to have concluded that deaths from gout were most likely the result of the treatment rather than the disease. Benjamin Franklin, who suffered from gout, was treated with colchicine when he was the American ambassador to France and on his return introduced the drug to his home country.1

Colchicine has been used since the 1970’s to treat familial Mediterranean fever, which like gout is characterized by recurrent painful attacks. It is the drug of choice not only for prevention of attacks, but also for prevention of secondary amyloidosis, proteinuria and renal failure. In addition, colchicine has been used to treat a number of dermatologic diseases, some of which, like Behcet’s syndrome and recurrent apthous stomatitis, also present as painful inflammatory recurrences.2 More recently, colchicine has been used to treat recurrent pericarditis and pericarditis associated with cardiac injury, particularly after ablation for atrial fibrillation.3

In 2009, this 3000-year old drug, which had been available in the US since the 19th century as a  generic prescription drug, received FDA approval for use as Colcrys with 3 years of market exclusivity for treatment of gout and 7 years for treatment of familial Mediterranean fever. URL Pharma conducted a clinical trial that confirmed the safety and efficacy of the drug and reported that a shorter duration of treatment was as efficacious as the longer regimen then used by some physicians and produced fewer adverse effects. URL sued the generic manufacturers to enforce its market exclusivity and raised the price of the drug 50-fold.4 The FDA responded to criticism of its actions by pointing out that they were required by law (Waxman-Hatch Act; Orphan Drug Act) and that the agency had no authority to control prices. The FDA representatives also stated that generic colchicine had been associated with 117 non-overdose deaths, of which 51% involved an interaction with clarithromycin.5 Needless to say, the new label would include a strong warning about that.

Now all the years of exclusivity have passed, and colchicine is available generically once more. Guidelines may be recommending its use for a condition that is much more common than gout. Would that be justified? Will Galen’s ancient remedy become as ubiquitous as a statin? Will the list of strong CYP3A4 inhibitors like clarithromycin be printed and reprinted in the health columns of newspapers and magazines? It’s hard to know, but reading our article would be a good way to start forming an opinion.

  1. N Nerlekar et al. Colchicine – a short history of an ancient drug. Med J Aust 2014; 201:687.
  2. B Dasgeb et al. Colchicine: an ancient drug with novel applications. Br J Dermatol 2018; 178:350.
  3. A Telmesani et al. The use of colchicine in pericardial diseases. JACC 2019 December 5 (epub).
  4. AS Kesselheim and DH Solomon. Incentives for drug development – the curious case of colchicine. N Engl J Med 2010; 362:2045.
  5. J Woodcock and S Okada. Incentives for drug development – the curious case of colchicine. Comment. N Engl J Med 2010; 363:1484.

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Comments

  1. The fact that colchicine is potent and can be problematic didn’t justify a 5000% price hike. Like all such drugs it needs to be used cautiously under the careful supervision of a physician and with suitable patient education. There’s nothing like it though. I suffered a gouty attack many years ago. NSAIDs including indomethacin did nothing much. Neither as I recall did steroids. A few doses of colchicine over less than 24 hours and my foot, which was so swollen and purple that my rheumatologist actually laughed and said he hadn’t seen one like that in ages, was half the size it had been the day before.

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