3-hydroxy-3-methylglutaryl-CoA reductase
Also known as: HMG-CoA, HMGCR
Rate-limiting enzyme of cholesterol synthesis (converts HMG-CoA to mevalonate). It is the therapeutic target of statins.
Statins (simvastatin, atorvastatin) are metabolised by CYP3A4 and transported by OATP1B1; inhibition by ketoconazole, clarithromycin, ciclosporin or amiodarone increases the risk of myopathy and rhabdomyolysis.
Substrates: HMG-CoA (yields mevalonate and cholesterol).
Inhibitors (of statins via CYP3A4/OATP1B1): clarithromycin, ketoconazole, itraconazole, ciclosporin, gemfibrozil, amiodarone, grapefruit juice.
Inducers: rifampicin, carbamazepine, phenytoin.
Avoid simvastatin + clarithromycin/gemfibrozil/ciclosporin (rhabdomyolysis risk); limit atorvastatin dose with clarithromycin.
DailyMed/FDA (NIH/NLM) — approved labels (simvastatin, atorvastatin); EMC-UK (MHRA) — SmPC
