Simvastatin with ezetimibe

How it works

Simvastatin inhibits hepatic HMG-CoA reductase to reduce cholesterol synthesis and upregulate LDL receptors, while ezetimibe blocks the intestinal NPC1L1 transporter to cut dietary and biliary cholesterol uptake, giving complementary LDL lowering.

Prescribing in practice

• Simvastatin has more clinically significant drug interactions than other statins via CYP3A4 — it is contraindicated with potent CYP3A4 inhibitors (including certain azole antifungals, macrolides and HIV protease inhibitors) and high doses carry an increased myopathy/rhabdomyolysis risk, so combination with fibrates, amiodarone, diltiazem, verapamil or amlodipine requires dose limits per the SPC.
• Avoid large quantities of grapefruit juice, which raises simvastatin exposure and myopathy risk.
• Both components are contraindicated in active liver disease and in pregnancy and breastfeeding.

Monitoring

Check a lipid profile and liver transaminases before starting and periodically thereafter, and measure creatine kinase if the patient reports unexplained muscle pain, tenderness or weakness.

Counselling the patient

• Report any unexplained muscle pain, tenderness or weakness promptly.
• Take the dose in the evening and avoid grapefruit juice.
• Continue lifestyle and dietary measures alongside the tablet.

Evidence & guidelines

The IMPROVE-IT trial showed adding ezetimibe to a statin further reduced cardiovascular events after acute coronary syndrome, supporting combined therapy when statin monotherapy is insufficient.