Colchicine × Dronedarone

Dronedarone is a moderate CYP3A4 inhibitor and a potent P-glycoprotein inhibitor (dronedarone SmPC). Colchicine is cleared through both pathways and has a narrow therapeutic margin (colchicine SmPC), so its blood levels rise, and with them the risk of myopathy, neuropathy and bone marrow suppression.

Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.

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 dronedarone inhibits both pathways (dronedarone 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). 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).