Itraconazole is the strongest CYP3A4 inhibitor in clinical use. Simvastatin is a sensitive substrate; its concentration rises 10–20 fold. Risk of rhabdomyolysis with acute kidney injury is the highest among statin–azole combinations.
Symptoms
Rhabdomyolysis within 3–7 days: myalgia, weakness, dark urine. CK above 50× ULN, oliguria.
Management
Combination contraindicated. Stop simvastatin one week before starting itraconazole and resume 2 weeks after the last dose. Alternative: pravastatin or rosuvastatin.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.