Major
Colchicine × diltiazem
Antigout agents×Calcium channel blocker, non-DHP (benzothiazepine derivative)
Mechanism
Diltiazem is a moderate CYP3A4 and P-glycoprotein inhibitor. Colchicine is a substrate of both with a narrow therapeutic window. Colchicine plasma levels rise 2- to 3-fold; myelosuppression and neuromyopathy risk.
Symptoms
Profuse diarrhoea, vomiting, abdominal pain. With prolonged combination: muscle weakness, peripheral neuropathy, falling leukocytes and platelets.
Management
In chronic kidney disease or hepatic impairment, the combination is not prescribed. With preserved function, colchicine 0.3 mg every other day for no more than 5 days. Alternative for gout: intra-articular glucocorticoid.