Azithromycin × Simvastatin

Simvastatin is broken down by the CYP3A4 enzyme. Strong inhibitors of this enzyme, including erythromycin and clarithromycin, raise the risk of myopathy and rhabdomyolysis and are contraindicated with simvastatin (simvastatin SmPC). Azithromycin is not on this list: it is a weak inhibitor of cytochrome P450 enzymes, although inhibition of CYP3A4 cannot be fully ruled out (azithromycin SmPC). There are no data on higher simvastatin levels with azithromycin, but post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC).

Muscle pain, weakness, cramps or tenderness, sometimes with malaise and fever. In rhabdomyolysis, urine turns dark from myoglobin and there is a risk of acute kidney injury (statin SmPCs).

Use the combination with caution: post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC). Azithromycin is not among the strong CYP3A4 inhibitors that are contraindicated with simvastatin (simvastatin SmPC). Warn patients who start simvastatin or raise its dose about the risk of myopathy and ask them to report unexplained muscle pain, tenderness or weakness at once. If these occur, measure creatine kinase (CK): stop simvastatin if CK is above 5 times the upper limit of normal (simvastatin SmPC).