Colchicine

Colchicine capsules are indicated for prophylaxis of gout flares in adults. Limitations of Use: The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied. Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes. Colchicine capsules are an alkaloid indicated for prophylaxis of gout flares in adults. Limitations of Use: • The safety and effectiveness of colchicine capsules for acute treatment of gout flares during prophylaxis has not been studied. • Colchicine capsules are not an analgesic medication and should not be used to treat pain from other causes.

Colchicine’s effectiveness as a treatment for gout has been postulated to be due to its ability to block neutrophil-mediated inflammatory responses induced by monosodium urate crystals in synovial fluid. Colchicine disrupts the polymerization of β-tubulin into microtubules, thereby preventing the activation, degranulation, and migration of neutrophils to sites of inflammation. Colchicine also interferes with the inflammasome complex found in neutrophils and monocytes that mediates interleukin-1β (IL-1β) activation.

• The recommended dosage is 0.6 mg (one capsule) once or twice daily. Maximum dose 1.2 mg/day. • Colchicine capsules are administered orally, without regard to meals.

Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors. Combining these dual inhibitors with colchicine in patients with renal or hepatic impairment has resulted in life-threatening or fatal colchicine toxicity. Patients with both renal and hepatic impairment should not be given colchicine capsules. • Patients with renal or hepatic impairment should not be given colchicine capsules in conjunction with drugs that inhibit both P-gp and CYP3A4. • Patients with both renal and hepatic impairment should not be given colchicine capsules.

• Fatal overdoses have been reported with colchicine in adults and children. Keep colchicine capsules out of the reach of children. • Blood dyscrasias: Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, and aplastic anemia have been reported. • Monitor for toxicity and if present consider temporary interruption or discontinuation of colchicine. • Drug interaction with dual P-gp and CYP3A4 inhibitors: Co-administration of colchicine with dual P-gp and CYP3A4 inhibitors has resulted in life-threatening interactions and death. • Neuromuscular toxicity: Myotoxicity including rhabdomyolysis may occur, especially in combination with other drugs known to cause this effect. Consider temporary interruption or discontinuation of colchicine capsules.

Gastrointestinal disorders are the most common adverse reactions with colchicine. They are often the first signs of toxicity and may indicate that the colchicine dosage needs to be reduced or therapy stopped. These include diarrhea, nausea, vomiting, and abdominal pain. Colchicine has been reported to cause neuromuscular toxicity, which may present as muscle pain or weakness. Toxic manifestations associated with colchicine include myelosuppression, disseminated intravascular coagulation, and injury to cells in the renal, hepatic, circulatory, and central nervous system. These most often occur with excessive accumulation or overdosage. The following reactions have been reported with colchicine.

Colchicine is a substrate of the efflux transporter P-glycoprotein (P-gp), and the CYP3A4 metabolizing enzyme. Fatal drug interactions have been reported when colchicine is administered with clarithromycin, a dual inhibitor of CYP3A4 and P-glycoprotein. Toxicities have also been reported when colchicine is administered with inhibitors of CYP3A4 that may not be potent inhibitors of P-gp (e.g., grapefruit juice, erythromycin, verapamil), or inhibitors of P-gp that may not be potent inhibitors of CYP3A4 (e.g., cyclosporine). Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4. Combining these dual inhibitors with colchicine capsules in patients with renal and hepatic impairment has resulted in life-threatening or fatal colchicine toxicity.

Storage Store at 20°C to 25°C (68°F to 77°F). Protect from light and moisture.