Colchicine × Verapamil

Verapamil inhibits the CYP3A4 enzyme and the P-glycoprotein transporter (verapamil SmPC), the two colchicine clearance pathways. With verapamil, colchicine exposure (area under the curve, AUC) doubles and peak concentration rises 1.3-fold (verapamil SmPC). The risk of myopathy, neuropathy and bone marrow suppression grows; one case of tetraparesis has been reported with this combination (verapamil SmPC).

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, and names verapamil in its interactions section (colchicine SmPC). The verapamil SmPC requires a lower colchicine dose (verapamil SmPC). US labels allow the combination only if there is no alternative and only with a reduced colchicine dose: for gout flare prophylaxis 0.3 mg twice daily or 0.6 mg once daily instead of 0.6 mg twice daily, for a flare 1.2 mg as a single dose, repeated no earlier than 3 days later (colchicine label, US Food and Drug Administration, FDA). In renal or hepatic impairment the combination is avoided (colchicine SmPC). At the first sign of nausea, vomiting, abdominal pain or diarrhoea, colchicine is stopped and the patient needs urgent care (colchicine SmPC).