Simvastatin

How it works

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

Prescribing in practice

• It can cause myopathy and rarely rhabdomyolysis, a risk increased by interacting drugs (including certain strong CYP3A4 inhibitors and other lipid-lowering agents) and by higher doses, so unexplained muscle pain should prompt creatine kinase measurement.
• It is contraindicated in pregnancy, breastfeeding and active liver disease, and dose limits apply with several interacting medicines such as amiodarone, verapamil, diltiazem and amlodipine.
• Advise patients to avoid grapefruit juice, which raises simvastatin exposure and the risk of toxicity.

Monitoring

Check liver function before and as indicated after starting, and assess lipids and any muscle symptoms with creatine kinase if myopathy is suspected.

Counselling the patient

• Report promptly any unexplained muscle pain, tenderness or weakness.
• Avoid grapefruit juice while taking this medicine.
• Tell your clinician if you could be pregnant or are planning pregnancy, as the statin should be stopped.

Evidence & guidelines

Large randomised trials have shown simvastatin reduces major cardiovascular events, and statins are recommended by NICE for cardiovascular risk reduction.