Mô tả
Azithromycin inhibits P-glycoprotein and CYP3A4-mediated metabolism of colchicine, increasing colchicine plasma concentrations and the risk of colchicine toxicity, including neuromuscular and gastrointestinal toxicity.
Cơ chế
Colchicine is a P-gp and CYP3A4 substrate; azithromycin's weak CYP3A4 and moderate P-gp inhibition reduce colchicine clearance; narrow therapeutic index of colchicine makes even modest exposure increases clinically relevant.
Ý nghĩa lâm sàng
Case reports describe colchicine toxicity (nausea, myopathy, peripheral neuropathy) during azithromycin co-administration; serious toxicity is uncommon at standard doses but warrants vigilance.
Xử trí
Reduce colchicine dose by approximately 50% during azithromycin therapy; avoid combination in patients with renal or hepatic impairment; monitor for GI and neuromuscular symptoms.