Simvastatin

How it works

It competitively inhibits HMG-CoA reductase, the rate-limiting enzyme of hepatic cholesterol synthesis, upregulating LDL receptors and lowering circulating LDL cholesterol.

Prescribing in practice

• In older people the higher dose is generally avoided because the risk of myopathy and rhabdomyolysis rises with dose, age and interacting drugs, and simvastatin has several important dose-limiting and contraindicated interactions (for example certain CYP3A4 inhibitors, some macrolides and azole antifungals, and grapefruit juice).
• It is contraindicated in active liver disease and in pregnancy and breast-feeding.
• The risk of muscle toxicity is increased by concomitant fibrates, amiodarone, calcium-channel blockers and other interacting agents, so review combinations carefully.

Monitoring

Check liver function before treatment and review, and check creatine kinase if there is muscle pain, particularly in older patients on interacting drugs.

Counselling the patient

• Take in the evening and avoid grapefruit juice.
• Report unexplained muscle pain, tenderness or weakness promptly.

Evidence & guidelines

Statin trials such as the Heart Protection Study showed cardiovascular benefit including in older adults, and MHRA advice details simvastatin's dose-related myopathy risk and interactions.