From the FDA Drug Label
The mechanism by which Colchicine Tablets, USP exert their beneficial effect in patients with FMF has not been fully elucidated; however, evidence suggests that colchicine may interfere with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β Additionally, colchicine disrupts cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules, and consequently prevents the activation, degranulation and migration of neutrophils thought to mediate some gout symptoms.
The mechanism of action of colchicine is not fully understood, but it is thought to involve:
- Interference with the intracellular assembly of the inflammasome complex, which mediates activation of interleukin-1β
- Disruption of cytoskeletal functions through inhibition of β-tubulin polymerization into microtubules, which prevents the activation, degranulation, and migration of neutrophils 1
From the Research
Introduction to Colchicine
Colchicine is a medication that has been used for centuries to treat various inflammatory conditions, including gout and autoinflammatory diseases. Its mechanism of action is complex and involves the modulation of multiple pro- and anti-inflammatory pathways.
Mechanism of Action
Colchicine exerts its effects mainly through the inhibition of microtubule polymerization, which affects various cellular processes such as maintenance of shape, signaling, division, migration, and cellular transport 2, 3. This inhibition disrupts inflammasome activation, microtubule-based inflammatory cell chemotaxis, generation of leukotrienes and cytokines, and phagocytosis. Colchicine also interferes with several inflammatory pathways, including adhesion and recruitment of neutrophils, superoxide production, and the tumor necrosis factor alpha (TNF-α) -induced nuclear factor κΒ (NF-κΒ) pathway, thereby attenuating the inflammatory response 3.
Key Findings
- Colchicine prevents microtubule assembly, which is essential for the activation of inflammasomes and the recruitment of inflammatory cells to the site of inflammation 2.
- Colchicine induces the release of hepatokines, such as growth differentiation factor 15 (GDF15), which have anti-inflammatory effects and inhibit myeloid cell activation 4.
- The efficacy and safety of colchicine depend on its selective action on hepatocytes, which triggers the release of anti-inflammatory hepatokines 4.
Treatment and Dosage
Colchicine is commonly used to treat acute gout flares and prevent gout relapses. The typical dosage is 0.6 mg orally every hour until relief is obtained or until a maximum dose of 4.8 mg is reached. For prophylaxis, the dosage is 0.6 mg orally once or twice daily.
Differentials and Caveats
- Colchicine is not effective in treating all types of inflammatory conditions and should be used with caution in patients with certain medical conditions, such as kidney or liver disease.
- The use of colchicine in autoinflammatory diseases, such as familial Mediterranean fever and periodic fever with aphthous stomatitis, pharyngitis, and adenitis, is still being studied and its efficacy and safety in these conditions are not fully established 5.
- Colchicine can cause gastrointestinal side effects, such as nausea, vomiting, and diarrhea, which are dose-related and occur in 5-10% of patients 3.