colchicine

Colchicine is a plant-derived alkaloid used to treat and prevent gout flares and to manage certain autoinflammatory conditions. It is obtained from Colchicum autumnale (autumn crocus) and related species. Colchicine exerts its anti-inflammatory effect by binding to tubulin and inhibiting microtubule polymerization. This action disrupts leukocyte function, including neutrophil chemotaxis and degranulation, which dampens the inflammatory response seen in gout and other inflammatory disorders.

Clinical uses include treatment of acute gout attacks (most effective when started early), prophylaxis of gout in patients commencing urate-lowering therapy, and management of familial Mediterranean fever (FMF) to reduce febrile episodes and risk of amyloidosis. It is also used as adjunctive therapy in pericarditis to reduce recurrence. Other uses are off-label and determined by clinician discretion.

Administration and pharmacokinetics vary: colchicine is typically given orally, with variable bioavailability and extensive tissue distribution. It has a relatively long half-life and is subject to hepatic metabolism, mainly by CYP3A4, and transport by P-glycoprotein; excretion occurs via urine and bile. Renal impairment reduces clearance, increasing toxicity risk and often requiring dose adjustments. There is a narrow therapeutic index, making careful dosing essential.

Adverse effects commonly include gastrointestinal symptoms such as nausea, vomiting, and diarrhea. More serious toxicity can involve bone marrow suppression, neuromyopathy, hepatotoxicity, and, in overdose, multiorgan failure. Drug interactions with strong CYP3A4 or P-gp inhibitors (for example certain antibiotics and antifungals, and some immunosuppressants) can markedly raise colchicine levels and toxicity risk. The intravenous form is used in some settings but is less common due to safety concerns.