Colchicine - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Fatal overdoses have been reported with colchicine in adults and children.

Keep colchicine tablets out of the reach of children ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Blood dyscrasias: myelosuppression, leukopenia, granulocytopenia, thrombocytopenia and aplastic anemia have been reported ( Error! Hyperlink reference not valid. ). • Monitor for toxicity and if present consider temporary interruption or discontinuation of colchicine ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • Drug interaction P-gp and/or CYP3A4 inhibitors: Coadministration of colchicine with P-gp and/or strong CYP3A4 inhibitors has resulted in life-threatening interactions and death ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ). • 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 tablets ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ).

5.1 Fatal Overdose Fatal overdoses, both accidental and intentional, have been reported in adults and children who have ingested colchicine [see Error! Hyperlink reference not valid. ] .

Colchicine tablets should be kept out of the reach of children.

5.2 Blood Dyscrasias Myelosuppression, leukopenia, granulocytopenia, thrombocytopenia, pancytopenia and aplastic anemia have been reported with colchicine used in therapeutic doses.

5.3 Drug Interactions Colchicine is a P-gp and CYP3A4 substrate.

Life-threatening and fatal drug interactions have been reported in patients treated with colchicine given with P-gp and strong CYP3A4 inhibitors.

If treatment with a P-gp or strong CYP3A4 inhibitor is required in patients with normal renal and hepatic function, the patient’s dose of colchicine may need to be reduced or interrupted [see Error! Hyperlink reference not valid. ] .

Use of colchicine tablets in conjunction with P-gp or strong CYP3A4 inhibitors (this includes all protease inhibitors except fosamprenavir) is contraindicated in patients with renal or hepatic impairment [see Error! Hyperlink reference not valid. ].

5.4 Neuromuscular Toxicity Colchicine-induced neuromuscular toxicity and rhabdomyolysis have been reported with chronic treatment in therapeutic doses.

Patients with renal dysfunction and elderly patients, even those with normal renal and hepatic function, are at increased risk.

Concomitant use of atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, gemfibrozil, fenofibrate, fenofibric acid or benzafibrate (themselves associated with myotoxicity) or cyclosporine with colchicine tablets may potentiate the development of myopathy [see Error! Hyperlink reference not valid. ] .

Once colchicine is stopped, the symptoms generally resolve within one week to several months.