Simvastatin

Simvastatin is a lipid-lowering medication in the statin class. It is an HMG-CoA reductase inhibitor that reduces hepatic cholesterol synthesis. Simvastatin is a lipophilic lactone prodrug that is hydrolyzed to the active beta-hydroxy acid form and is mainly metabolized by the liver enzyme CYP3A4.

By inhibiting HMG-CoA reductase, simvastatin decreases intrahepatic cholesterol production and upregulates LDL receptors, lowering low-density lipoprotein cholesterol (LDL-C). It can modestly raise high-density lipoprotein cholesterol (HDL-C) and lower triglycerides. These effects contribute to reduced risk of atherosclerotic cardiovascular events when combined with lifestyle changes.

Indications include hyperlipidemia management and reduction of cardiovascular risk in primary or secondary prevention, including familial hypercholesterolemia. It is typically used alongside diet and other risk-reduction measures in adults; pediatric use is limited to specific indications and ages.

Administration is oral, usually taken in the evening to align with higher nocturnal cholesterol synthesis. Dosing commonly starts at 10–20 mg once daily, with a typical maximum of 40 mg daily in many settings; an 80 mg dose is reserved for select patients who have previously tolerated it and have no interacting medications or factors that raise myopathy risk.

Common adverse effects include muscle pain and weakness, elevated liver enzymes, and, rarely, myopathy or rhabdomyolysis, especially with drug interactions or when misuse occurs. Serious liver injury is uncommon but monitored through liver enzyme tests. Other adverse effects may include digestive symptoms and, rarely, cognitive effects or memory concerns.

Important interactions exist with CYP3A4 inhibitors and inducers, certain antifungals and antibiotics, grapefruits, and other lipid-lowering agents like fibrates. Contraindications include active liver disease, pregnancy, and breastfeeding. Patients should discuss all medications and supplements with a clinician due to interaction risks.