Amiodarone × Colchicine

Amiodarone blocks CYP3A4 and the P-glycoprotein transporter – two colchicine clearance routes. Colchicine plasma levels rise; myopathy and neuropathy risk grows.

The first signs of colchicine toxicity are nausea, vomiting, abdominal pain and diarrhoea (colchicine SmPC). Muscle weakness and pain, peripheral neuropathy with numbness and tingling in the feet and hands, and rhabdomyolysis may follow; with prolonged use, bone marrow suppression with falling white cells and platelets, up to aplastic anaemia (colchicine SmPC).

The combination is contraindicated: the Spanish colchicine SmPC forbids colchicine during use of CYP3A4 or P-glycoprotein inhibitors and for 14 days afterwards (colchicine SmPC), and amiodarone inhibits both pathways (amiodarone SmPC). The US label of colchicine 0.5 mg for cardiovascular prevention, approved by the US Food and Drug Administration (FDA), also contraindicates it with P-glycoprotein inhibitors (colchicine label, FDA). Amiodarone interactions can persist for several months after it is stopped (amiodarone SmPC). Other colchicine manufacturers require a lower maximum colchicine dose and close monitoring with a P-glycoprotein inhibitor, and avoid the combination whenever possible in renal or hepatic impairment (colchicine SmPC). At the first sign of nausea, vomiting, abdominal pain or diarrhoea, colchicine is stopped and the patient needs urgent care (colchicine SmPC).