Colchicine × Ketoconazole

Colchicine is cleared via CYP3A4 and P-glycoprotein. Ketoconazole strongly inhibits both. Colchicine plasma levels rise several-fold. FDA Colcrys carries a boxed warning for fatal toxicity.

Profuse diarrhoea, vomiting, abdominal pain – first signs of toxicity. Pancytopenia (drop in leukocytes, erythrocytes, platelets), muscle weakness, peripheral neuropathy, hepatic and renal injury follow. Fatal cases have been reported.

For patients with renal or hepatic impairment, the combination is not prescribed. With preserved function, use colchicine 0.3 mg every other day, no more than 5 days. Alternative antifungals: terbinafine or echinocandins.