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Colchicine, sold under the brand name Colbenemid among others, is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids in the treatment of gout. Other uses for colchicine include the management of pericarditis.
Colchicine is taken by mouth. The injectable route of administration for colchicine can be toxic. In 2008, the US Food and Drug Administration removed all injectable colchicine from the US market.
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Colchicine has a narrow therapeutic index, so overdosing is a significant risk. Common side effects of colchicine include gastrointestinal upset, particularly at high doses. Severe side effects may include pancytopenia (low blood cell counts) and rhabdomyolysis (damage to skeletal muscle), and the medication can be deadly in overdose.
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Colchicine, in the form of autumn crocus (Colchicum autumnale) crude extract, was used as early as 1500 BC to treat joint swelling. It was approved for medical use in the United States in 1961. It is available as a generic medication. In 2023, it was the 215th most commonly prescribed medication in the United States, with more than 2million prescriptions.
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Colchicine is used in plant breeding to induce polyploidy, in which the number of chromosomes in plant cells are doubled. This helps produce larger, hardier, faster-growing, and in general, more desirable plants than the normally diploid parents. Low doses (1.2 mg in one hour, followed by 0.6 mg an hour later) appear to be well tolerated and may reduce gout symptoms and pain, perhaps as effectively as NSAIDs. At higher doses, side effects (primarily diarrhea, nausea, or vomiting) limit its use. adverse gastrointestinal effects may occur, though overall the risk of serious side effects is low.
Risk of cardiovascular disorders
In June 2023, the US FDA approved a low-dose regimen of colchicine (brand name Lodoco) to reduce the risk of further disorders in adults with existing cardiovascular diseases. As an anti-inflammatory drug, Lodoco in a dose of 0.5 mg per day reduced the rate of cardiovascular events by 31% in people with established atherosclerosis and by 23% in people with recent myocardial infarction. It appears to have limited effect in relapsing polychondritis, as it may only be useful for the treatment of chondritis and mild skin symptoms. It is a component of therapy for several other conditions, including pericarditis, pulmonary fibrosis, biliary cirrhosis, various vasculitides, pseudogout, spondyloarthropathy, calcinosis, scleroderma, and amyloidosis.
Research regarding the efficacy of colchicine in many of these diseases has not been performed.
Colchicine is effective for prevention of atrial fibrillation after cardiac surgery. In people with recent myocardial infarction (recent heart attack), it has been found to reduce risk of future cardiovascular events. Its clinical use may grow to include this indication.
Contraindications
Long-term (prophylactic) regimens of oral colchicine are absolutely contraindicated in people with advanced kidney failure (including those on dialysis). which may include neuromuscular toxicity and rhabdomyolysis.
If the affected persons survive the gastrointestinal phase of toxicity, they may experience multiple organ failure and critical illness. This includes kidney damage, which causes low urine output and bloody urine; low white blood cell counts that can last for several days; anemia; muscular weakness; liver failure; hepatomegaly; bone marrow suppression; thrombocytopenia; and ascending paralysis leading to potentially fatal respiratory failure. Neurologic symptoms are also evident, including seizures, confusion, and delirium; children may experience hallucinations. Recovery may begin within six to eight days and begins with rebound leukocytosis and alopecia as organ functions return to normal. Fatal drug interactions have occurred when colchicine was taken with other drugs that inhibit P-glycoprotein and CYP3A4, such as erythromycin or clarithromycin.
Pharmacology
Mechanism of action
In gout, inflammation in joints results from the precipitation of uric acid as needle-like crystals of monosodium urate in and around synovial fluid and soft tissues of joints.
History
thumb|right|200x150px|Group of autumn crocus (Colchicum autumnale) on an alpine meadow
The plant source of colchicine, the autumn crocus (Colchicum autumnale), was described for treatment of rheumatism and swelling in the Ebers Papyrus (circa 1500 BC), an Egyptian medical text. It is a toxic alkaloid and secondary metabolite. Colchicum extract was first described as a treatment for gout in De Materia Medica by Pedanius Dioscorides, in the first century AD. Use of the bulb-like corms of Colchicum to treat gout probably dates to around 550 AD, as the "hermodactyl" recommended by Alexander of Tralles. Colchicum corms were used by the Persian physician Avicenna, and were recommended by Ambroise Paré in the 16th century, and appeared in the London Pharmacopoeia of 1618.
Colchicine was first isolated in 1820 by French chemists P. S. Pelletier and J. B. Caventou. In 1833, P. L. Geiger purified an active ingredient, which he named colchicine. It quickly became a popular remedy for gout.
The full synthesis of colchicine was achieved by the Swiss organic chemist Albert Eschenmoser in 1959.
Sources and uses
Physical properties
Colchicine has a melting point of . It has a molecular weight of 399.4 grams per mole.
Structure
Colchicine has one stereocenter located at carbon 7. The natural configuration of this stereocenter is S. The molecule also contains one chiral axis - the single bond between rings A and C. The natural configuration of this axis is aS. Although colchicine has four stereoisomers, the only one found in nature is the aS,7s configuration.
Light sensitivity
Colchicine is a light-sensitive compound, so needs to be stored in a dark bottle. Upon exposure to light, colchicine undergoes photoisomerization and transforms into structural isomers, called lumicolchicine. After this transformation, colchicine is no longer effective in its mechanistic binding to tubulin, so is not effective as a drug.
Regulation
It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the US Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002) and is subject to strict reporting requirements by facilities that produce, store, or use it in significant quantities.
Formulations and dosing
Bramd names for colchicine include Colcrys and Mitigare. Colchicine is also prepared as a white, yellow, or purple pill (tablet) having a dose of 0.6 mg. However, the tropolone ring of colchicine resulted from the expansion of the tyrosine ring. Radioactive feeding experiments of C. autumnale revealed that colchicine can be synthesized biosynthetically from (S)-autumnaline. That biosynthetic pathway occurs primarily through a phenolic coupling reaction involving the intermediate isoandrocymbine. The resulting molecule undergoes O-methylation directed by S-adenosylmethionine. Two oxidation steps followed by the cleavage of the cyclopropane ring lead to the formation of the tropolone ring contained by N-formyldemecolcine. N-formyldemecolcine hydrolyzes then to generate the molecule demecolcine, which also goes through an oxidative demethylation that generates deacetylcolchicine. The molecule of colchicine appears finally after the addition of acetyl-coenzyme A to deacetylcolchicine.
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Purification
Colchicine may be purified from Colchicum autumnale (autumn crocus) or Gloriosa superba (glory lily). Concentrations of colchicine in C. autumnale peak in the summer, and range from 0.1% in the flower to 0.8% in the bulb and seeds. When used to induce polyploidy in plants, colchicine cream is usually applied to a growth point of the plant, such as an apical tip, shoot, or sucker. Seeds can be presoaked in a colchicine solution before planting. Since chromosome segregation is driven by microtubules, colchicine alters cellular division by inhibiting chromosome segregation during mitosis; half the resulting daughter cells, therefore, contain no chromosomes, while the other half contains double the usual number of chromosomes (i.e., tetraploid instead of diploid), and lead to cell nuclei with double the usual number of chromosomes (i.e., tetraploid instead of diploid).
Society and culture
Legal status
In May 2026, the Committee for Medicinal Products for Human Use of the EMA adopted a positive opinion recommending the granting of a marketing authorization for the medicinal product Colchicine Agepha Pharma, intended for the secondary prevention of atherothrombotic events in adults with coronary disease who have been stable for at least six months. Colchicine Agepha Pharma is a hybrid medicine of Colchicine Tiofarma, which has been authorized in the European Union since 1998.