Products
Medicines containing colchicine are no longer on the market in many countries. Drugs are available abroad that can be imported. It may also be possible to prepare an extemporaneous formulation in a pharmacy (difficulties: toxicity, substance).
Stem plant
Colchicine is the main alkaloid of the autumn crocus (Colchicaceae), which contains it particularly abundantly in the seeds. It is also present in the tuber of African gloryweed, as well as in some -species.
Structure and properties
Colchicine (C22H25NO6, Mr = 399.4 g/mol) is a very weak, natural base from the tropolone alkaloid group. It builds up from the tricyclic ring system of benzoheptalene. Colchicine exists as a yellowish-white, crystalline or amorphous, bitter-tasting powder that is soluble in water. The powder turns dark when exposed to light.
Effects
Colchicine (ATC M04AC01) has anti-inflammatory and analgesic effects. It eliminates joint inflammation during the course of an acute gout attack, thereby relieving pain. Unlike uricostats and uricosurics, colchicine does not affect uric acid concentrations in the blood.
Indications
For prevention or treatment of acute gout attacks. Other indications are given in the literature, such as familial Mediterranean fever (indication in the United States), Behçet’s disease, and recurrent pericarditis. In many countries, there is no regulatory approval. For acute treatment of gout, the less toxic NSAIDs and glucocorticoids are also used. However, according to EULAR guidelines, colchicine remains among the 1st-line agents for acute treatment.
Dosage
According to the Drug Guide. The tablets can be taken independently of meals. According to the traditional regimen, to treat an acute attack in adults, 1 mg is taken initially, followed by 0.5 mg every 1-2 hours until symptoms subside or adverse effects occur. The maximum daily dose of 4-6 mg (previously 10 mg) should not be exceeded. Alternative therapeutic regimens are also mentioned in the literature. According to the Colcrys technical information, a maximum dose of 1.8 mg per day (3 tablets) should not be exceeded because this would not provide any additional benefit. The dose must be adjusted individually. The EULAR guidelines also recommend the low dose (0.5 mg 3 times daily).
Contraindications
Colchicine is contraindicated in hypersensitivity, during pregnancy, and in patients with impaired renal and hepatic function, gastrointestinal disease, blood count abnormalities, and cardiovascular disorders. Full details of precautions and interactions can be found in the Drug Information Leaflet.
Interactions
Colchicine is metabolized by CYP3A4 and transported by P-glycoprotein. CYP3A4 catalyzes the demethylation of methoxy groups and results in the formation of inactive metabolites. With concomitant use of CYP3A4 or P-gp inhibitors, plasma concentrations increase and severe poisoning may result. Strong CYP inhibitors include ciclosporin and macrolides such as clarithromycin, azole antifungals, and HIV protease inhibitors; ranolazine is a strong P-gp inhibitor. Other interactions are possible with statins, fibrates, and renal toxic agents. Colchicine is subject to enterohepatic circulation.
Adverse effects
Adverse effects may be signs of dose-related intoxication. The most common adverse effects include diarrhea, nausea, vomiting, and abdominal pain. The diarrhea is due to inhibition of cell renewal in the small intestinal epithelia. Patients frequently experience muscle disorders, muscle weakness, kidney damage, and skin disorders such as itching and burning. At high doses, blood count changes, anemia, nail growth disorders, hair loss, and hypersensitivity reactions have occasionally been observed. Hair loss and blood count changes are also a result of mitosis inhibition. Poisoning with fatal outcome has been reported.