Colchicine × Fluconazole

Fluconazole is a moderate CYP3A4 inhibitor (fluconazole SmPC), and colchicine is cleared through CYP3A4 and the P-glycoprotein transporter and has a narrow therapeutic margin (colchicine SmPC). In a study, fluconazole 200 mg/day raised colchicine exposure (area under the curve, AUC) by 40% (colchicine label, US Food and Drug Administration, FDA). With long-term colchicine use the risk of nerve and muscle toxicity grows, up to rhabdomyolysis (colchicine 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 (colchicine SmPC), and fluconazole is a moderate CYP3A4 inhibitor (fluconazole SmPC). US labels are less strict: if there is no alternative, the colchicine dose is reduced with a moderate CYP3A4 inhibitor – 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 label, FDA). The fluconazole SmPC requires monitoring of patients who also take narrow therapeutic margin drugs metabolised by CYP3A4 (fluconazole SmPC). At the first sign of nausea, vomiting, abdominal pain or diarrhoea, colchicine is stopped and the patient needs urgent care (colchicine SmPC).