Clarithromycin × Simvastatin

Simvastatin clearance is 98% dependent on hepatic CYP3A4. Clarithromycin is a potent inhibitor of this enzyme; simvastatin plasma concentrations rise 10-fold or more. The FDA lists this combination as an absolute contraindication.

Pain and weakness in large muscle groups, dark urine, elevated creatine kinase on lab work. Severe cases progress to rhabdomyolysis with acute kidney injury. First signs appear within 3–7 days of concurrent dosing.

The combination is not prescribed. Hold simvastatin for the duration of clarithromycin therapy or switch the patient to pravastatin or rosuvastatin – these statins use a different metabolic pathway and do not interact. If simvastatin cannot be paused, replace the antibiotic: azithromycin or a non-macrolide class based on susceptibility.