Colchicine: Effects, Uses & Risks

Colchicine represents the longest known active ingredient for the therapy of acute gout attacks. The potent spindle poison is extracted from the tubers and seeds of the autumn crocus.

What is colchicine?

Colchicine represents the longest-known active ingredient for the treatment of acute gout attacks. Colchicine is the name given to a toxic active ingredient belonging to the group of tropolone alkaloids (naturally occurring compounds), which is extracted primarily from the seeds and tubers of the autumn crocus (Colchicum autumnale). Colchicine is used primarily for the prevention and treatment of acute attacks of gout. The active ingredient has analgesic and anti-inflammatory properties by interfering with mitosis (cell nuclear division) as a spindle poison. Colchicine itself exists as a bitter-tasting, yellow-white, amorphous or crystalline and water-soluble powder that turns dark when exposed to light. Colchicine is eliminated via the enterohepatic circulation (kidneys and bile).

Pharmacological action

Colchicine possesses analgesic and anti-inflammatory activity by stopping the inflammatory processes in the joints during an acute attack of gout, thus minimizing pain. Here, the active ingredient reduces pain symptoms by an indirect route. In an acute gout attack, there is an increased concentration of urate (uric acid crystals), which are phagocytized (taken up) by the macrophages (scavenger cells) of the immune system. In the process, these scavenger cells release inflammatory mediators (substances that promote inflammation), which causes the pain during the course of the attacks. Colchicine intervenes in this chain of action by preventing the macrophages from taking up the uric acid crystals so that inflammatory mediators are no longer released. Unlike uricosurics (which promote uric acid excretion) or uricostats (which inhibit uric acid formation), the active ingredient does not affect the concentration of uric acid in the blood. In addition, as a cell and spindle poison, colchicine impairs mitosis (cell nucleus division) and inhibits the formation of microtubules, an important component of the cytoskeleton of eukaryotes, in cells by binding to the protein tubulin (the main component of microtubules), thus preventing the formation of the spindle fiber apparatus. Because of this toxic effect, the use of colchicine is associated with a number of side effects and is increasingly being reduced. For example, as a result of mitosis inhibition by colchicine, cell renewal of the epithelia of the small intestine may be impaired, which is why gastrointestinal symptoms (diarrhea) may manifest. Accordingly, the lowest possible dosage should be used in any case during colchicine therapy.

Medical application and use

Colchicine is used primarily for the therapy and prevention of acute gout attacks. In addition, other uses can be found in the literature such as familial Mediterranean fever (recurrent polyserositis), Behçet’s disease (chronic vasculitis), or recurrent pericarditis (pericarditis). Homeopathic preparations of the active ingredient can also be used for external therapy in acute joint complaints in the context of inflammatory rheumatic diseases, joint effusions, gastrointestinal inflammation or tendovaginitis. As a rule, colchicine is administered in tablet form or orally as a solution. For the treatment of an acute attack of gout in an adult, 1 mg is used initially and then 0.5 mg every 1 to 2 hours until the symptoms subside or until undesirable side effects manifest themselves. Here, the daily dose should not exceed 4 to 6 mg. For the prevention of acute gout attacks, colchicine can be applied in low doses (maximum 1.5 mg per day), and the total duration of this prophylactic therapy should not exceed three months. In addition, a daily dose of 0.5 to 1.5 mg of colchicine per day may prevent attacks of familial Mediterranean fever. For an adult, the lethal dose is about 20 mg, although isolated deaths have been observed even with lower amounts of colchicine.

Risks and side effects

The most common adverse side effects of colchicine therapy are diarrhea (diarrhea), vomiting (vomiting), nausea, and abdominal pain.Impairments of muscle function (including muscle weakness), kidney damage and skin complaints (pruritus, burning skin) can also frequently be observed. High dosages in some cases lead to changes in blood count, anemia, hair loss, and/or impaired nail growth. Therapy with colchicine is contraindicated in the presence of hypersensitivity to the active substance, pregnancy, impaired hepatic and renal function, diseases of the gastrointestinal tract, changes in the blood count, and impaired cardiovascular function. Because colchicine is metabolized (degraded) by the isoenzyme CYP3A4 and transported by multidrug resistance protein 1 (MDR1 or P-gp), numerous relevant interactions with other drugs must be considered when treating the drug. For example, parallel therapy with CYP3A4 (including ciclosporin, macrolides) or P-gp inhibitors (including ranolazine) may cause an increase in plasma concentrations as well as pronounced poisoning.