Colchicine × Diltiazem

Diltiazem is a moderate CYP3A4 inhibitor and a weak P-glycoprotein inhibitor (diltiazem SmPC). Colchicine is cleared through both pathways and has a narrow therapeutic margin (colchicine SmPC). Diltiazem 240 mg/day raised colchicine exposure (area under the curve, AUC) by 93%, almost twofold (colchicine label, US Food and Drug Administration, FDA). Higher levels bring a higher risk of bone marrow suppression and nerve and muscle toxicity.

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 diltiazem in its interactions section (colchicine SmPC). The diltiazem SmPC does not recommend combining it with colchicine (diltiazem SmPC). US labels allow it 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, and neuromuscular toxicity has been reported with diltiazem (colchicine label, FDA). At the first sign of nausea, vomiting, abdominal pain or diarrhoea, colchicine is stopped and the patient needs urgent care (colchicine SmPC).