Colchicine

Colchicine is a medication used to prevent and treat gout,[2][3] to treat familial Mediterranean fever[4] and Behçet's disease,[5] and to reduce the risk of myocardial infarction.[6] The American College of Rheumatology recommends colchicine, nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids in the treatment of gout.[7][8] Other uses for colchicine include the management of pericarditis.[9]

Colchicine is taken by mouth.[10] 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.[11][12]

Colchicine has a narrow therapeutic index, so overdosing is a significant risk. Common side effects of colchicine include gastrointestinal upset, particularly at high doses.[13] Severe side effects may include pancytopenia (low blood cell counts) and rhabdomyolysis (damage to skeletal muscle), and the medication can be deadly in overdose.[10] Whether colchicine is safe for use during pregnancy is unclear, but its use during breastfeeding appears to be safe.[10] Colchicine works by decreasing inflammation via multiple mechanisms.[14]

Colchicine, in the form of autumn crocus (Colchicum autumnale) crude extract, was used as early as 1500 BC to treat joint swelling.[15] It was approved for medical use in the United States in 1961.[16] It is available as a generic medication.[17] In 2023, it was the 215th most commonly prescribed medication in the United States, with more than 2million prescriptions.[18][19]

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.

Medical uses

Contraindications

Long-term (prophylactic) regimens of oral colchicine are absolutely contraindicated in people with advanced kidney failure (including those on dialysis). About 10–20% of a colchicine dose is excreted unchanged by the kidneys; it is not removed by hemodialysis. Cumulative toxicity is a high probability in this clinical setting, and a severe neuromyopathy may result. The presentation includes a progressive onset of proximal weakness, elevated creatine kinase, and sensorimotor polyneuropathy. Colchicine toxicity can be potentiated by the concomitant use of cholesterol-lowering drugs.

Adverse effects

Deaths – both accidental and intentional – have resulted from overdose of colchicine. Typical side effects of moderate doses may include gastrointestinal upset, diarrhea, and neutropenia.[21] High doses can also damage bone marrow, lead to anemia, and cause hair loss. All of these side effects can result from inhibition of mitosis,[39] which may include neuromuscular toxicity and rhabdomyolysis.

Toxicity

According to one review, colchicine poisoning by overdose (range of acute doses of 7 to 26 mg) begins with a gastrointestinal phase occurring 10–24 hours after ingestion, followed by multiple organ dysfunction occurring 24 hours to 7 days after ingestion, after which the affected person either declines into multiple organ failure or recovers over several weeks.

Colchicine can be toxic when ingested, inhaled, or absorbed in the eyes.[21] It can cause a temporary clouding of the cornea and be absorbed into the body, causing systemic toxicity. Symptoms of colchicine overdose start 2 to 24 hours after the toxic dose has been ingested, and include burning in the mouth and throat, fever, vomiting, diarrhea, and abdominal pain. This can cause hypovolemic shock due to extreme vascular damage and fluid loss through the gastrointestinal tract, which can be fatal.[40]

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

Drug interactions

Colchicine interacts with the P-glycoprotein transporter, and the CYP3A4 enzyme involved in drug and toxin metabolism.[41] Fatal drug interactions have occurred when colchicine was taken with other drugs that inhibit P-glycoprotein and CYP3A4, such as erythromycin or clarithromycin.

People taking macrolide antibiotics, ketoconazole, or cyclosporine, or those who have liver or kidney disease, should not take colchicine, as these drugs and conditions may interfere with colchicine metabolism and raise its blood levels, potentially increasing its toxicity abruptly.[41] Symptoms of toxicity include gastrointestinal upset, fever, muscle pain, low blood cell counts, and organ failure.[21] People with HIV/AIDS taking atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, or saquinavir may experience colchicine toxicity.

Pharmacology

History

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.[46] It is a toxic alkaloid and secondary metabolite.[21][47][48] 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.[49]

Sources and uses

External links