Kolchin

• Gout:
• Treatment of acute gout flares to reduce pain and inflammation.
• Prophylaxis of recurrent gout attacks in chronic gout patients.
• Familial Mediterranean Fever (FMF): Prevention and treatment of acute inflammatory attacks.
• Pericarditis: Adjunctive treatment for acute and recurrent pericarditis.
• Off-label uses:
• Behçet’s disease.
• Certain dermatological conditions like leukocytoclastic vasculitis.
• Other inflammatory conditions, as determined by specialist clinicians.

• Acute Gout Flare (Adults):
• Initial dose: 1.2 mg orally at first sign of flare, followed by 0.6 mg one hour later.
• Maintenance dosing: 0.6 mg once or twice daily after flare subsides.
• Gout Prophylaxis (Adults):
• 0.6 mg once or twice daily, adjusted based on tolerance and renal function.
• Familial Mediterranean Fever (Adults and Pediatrics ≥4 years):
• Adults: 1.2 mg to 2.4 mg daily in divided doses.
• Pediatrics: 0.5 mg to 1 mg daily, adjusted per weight and clinical response.
• Pericarditis (Adults):
• 0.5 mg to 0.6 mg twice daily for 3 months, sometimes with tapering.
• Special Populations:
• Dose reduction recommended in renal or hepatic impairment.
• Use caution in elderly; start at lower doses and monitor.
• Administration: Oral route with or without food; maintain hydration.

Colchicine binds to tubulin, inhibiting its polymerization into microtubules. This disrupts cytoskeletal functions essential for neutrophil motility and activity, thereby reducing neutrophil-mediated inflammation. It also impairs inflammasome activation and the release of pro-inflammatory cytokines like IL-1β. The cumulative effect is a decrease in leukocyte infiltration and inflammatory response, providing relief in gout and other autoinflammatory diseases.

• Absorption: Rapid oral absorption with bioavailability of approximately 45%.
• Distribution: Widely distributed with large volume of distribution (~5–8 L/kg); concentrates in leukocytes, kidneys, liver, spleen, and intestine.
• Metabolism: Undergoes extensive hepatic first-pass metabolism via CYP3A4.
• Active Metabolites: Minimal; primarily parent drug active.
• Elimination: Primarily excreted unchanged in feces (major route) and urine (~10-20%).
• Half-life: Approximately 26–31 hours; prolonged in renal or hepatic impairment.
• Onset of action: Symptomatic relief often begins within 12–24 hours of dosing.

• Pregnancy: FDA Category C; animal studies show fetal risk at high doses, but no well-controlled human studies. Use only if clearly needed and benefits outweigh risks.
• Lactation: Colchicine is excreted in breast milk in low amounts; caution advised. Monitor infants for adverse effects.

• Primary class: Anti-inflammatory Agent
• Subclass: Anti-gout Agent; Microtubule Inhibitor

·         Known hypersensitivity to colchicine or formulation excipients.

·         Severe renal or hepatic impairment (unless closely monitored).

·         Concomitant use with strong CYP3A4 or P-glycoprotein inhibitors in patients with renal/hepatic impairment (due to toxicity risk).

·         Blood dyscrasias or bone marrow suppression.

• High risk of toxicity with overdose; narrow therapeutic index.
• Monitor for gastrointestinal toxicity (diarrhea, nausea), myelosuppression, neuromyopathy, and rhabdomyolysis.
• Avoid concomitant use with CYP3A4 inhibitors (e.g., clarithromycin) or P-gp inhibitors without dose adjustment.
• Use cautiously in elderly, renal, and hepatic impairment.
• Discontinue if severe adverse reactions occur.
• Educate patients on signs of toxicity (muscle pain, weakness, unusual bleeding).
• Not recommended during breastfeeding unless benefits outweigh risks.

Common:

• Gastrointestinal: Diarrhea, nausea, vomiting, abdominal pain.
• Mild myalgia or fatigue.

Serious/Rare:

• Bone marrow suppression (leukopenia, thrombocytopenia, aplastic anemia).
• Myopathy and neuropathy, especially with renal impairment or concomitant statins.
• Rhabdomyolysis.
• Allergic reactions including rash and angioedema.

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): Increase colchicine plasma levels, risk of toxicity.
• P-glycoprotein inhibitors (e.g., cyclosporine, verapamil): Increase colchicine exposure.
• Statins and fibrates: Increased risk of myopathy and rhabdomyolysis.
• Digoxin: May increase digoxin toxicity.
• Rifampin: May decrease colchicine levels by enzyme induction.
• Avoid concomitant use with drugs causing bone marrow suppression.

• Updated gout management guidelines emphasize colchicine dose reduction for prophylaxis to minimize toxicity.
• Strong recommendations to avoid high-dose colchicine for acute flares due to increased adverse effects.
• Increased awareness and warnings about drug interactions and toxicity risks.
• Emphasis on individualized dosing in renal/hepatic impairment and elderly patients.

• Store at 20°C to 25°C (68°F to 77°F) in a dry place protected from light.
• Keep container tightly closed.
• Keep out of reach of children.
• No special refrigeration required.