Ezetimibe 💊
Related Subjects:
|Statins
|Atorvastatin
|Simvastatin
|Hyperlipidaemia
|Essential Hypertension
💊 Ezetimibe is a cholesterol-absorption inhibitor. It is mainly used added to a statin when lipid targets are not met, or alone when statins are not tolerated or are contraindicated.
📖 About
- Acts at the brush border of the small intestine to block uptake of dietary and biliary cholesterol.
- Lowers LDL cholesterol by roughly 15–20% on its own and by a further ~20% when added to a statin.
- Always check the BNF for up-to-date prescribing information.
⚙️ Mode of Action
- Inhibits the NPC1L1 sterol transporter on enterocytes → less cholesterol delivered to the liver.
- The liver responds by up-regulating LDL receptors → ↓ plasma LDL-C.
- Complements statins, which reduce hepatic cholesterol synthesis.
🎯 Indications (NICE NG238 / TA385)
- Primary hypercholesterolaemia or mixed dyslipidaemia, added to a maximum tolerated statin when non-HDL/LDL targets are not achieved.
- Statin intolerance or contraindication: ezetimibe monotherapy, or with bempedoic acid.
- Heterozygous familial hypercholesterolaemia (with statin) and homozygous FH (specialist).
- Homozygous sitosterolaemia (rare).
💊 Dose
| Indication | Dose | Notes |
|---|
| Hypercholesterolaemia (adult) | 10 mg once daily | Any time of day, with or without food |
| With a bile acid sequestrant | 10 mg once daily | Take ≥2 h before or ≥4 h after the sequestrant |
🧪 Monitoring
- Lipid profile 2–3 months after starting, then annually.
- LFTs if combined with a statin (as for the statin).
- Ask about muscle symptoms; check CK if myalgia is significant.
🔄 Interactions
- Ciclosporin: raises levels of both drugs - monitor ciclosporin.
- Bile acid sequestrants (colestyramine): reduce ezetimibe absorption.
- Fibrates: possible ↑ risk of gallstones; avoid with fibrates other than fenofibrate.
- Warfarin: monitor INR when starting.
⚠️ Cautions
- Moderate–severe hepatic impairment: avoid (raised exposure).
- With a statin: watch for myopathy; stop if CK >5× ULN or symptoms are severe.
🚫 Contraindications
- Combination with a statin in active liver disease or unexplained persistently raised transaminases.
- Pregnancy and breastfeeding when combined with a statin (avoid ezetimibe alone in pregnancy unless clearly needed).
💥 Side Effects
- Common: GI upset (abdominal pain, diarrhoea, flatulence), fatigue, headache.
- With a statin: raised transaminases, myalgia.
- Rare: hypersensitivity (rash, angio-oedema), hepatitis, pancreatitis, cholelithiasis, myopathy/rhabdomyolysis.
🎓 Exam Pearls
- Ezetimibe lowers LDL but has modest outcome data - IMPROVE-IT showed a small reduction in CV events when added to simvastatin after ACS.
- Statin first; ezetimibe is the usual next step before PCSK9 inhibitors or inclisiran.
📚 References
