ezetimibe
Brand: Zetia
Prototype Drug
Drug Class: cholesterol absorption inhibitor
Drug Family: antilipemic
Subclass: NPC1L1 transporter inhibitor
Organ Systems: cardiovascular
Mechanism of Action
Inhibits intestinal NPC1L1 transporter preventing absorption of biliary and dietary cholesterol; reduces delivery of cholesterol to liver; compensatory LDL receptor upregulation.
NPC1L1 (Niemann-Pick C1-Like 1) transporter
Indications
- hyperlipidemia (adjunct to statin)
- homozygous familial hypercholesterolemia
- sitosterolemia
Contraindications
- active liver disease (with statin combination)
Adverse Effects
Common
- GI upset
- diarrhea
- arthralgia
Serious
- hepatotoxicity (when combined with statin)
Pharmacokinetics (ADME)
| Absorption | 35-65% oral absorption |
| Distribution | moderate |
| Metabolism | glucuronidation (enterohepatic recirculation) |
| Excretion | fecal 78%, renal 11% |
| Half-life | 22 hours |
| Onset | variable |
| Peak | 4-12 hours |
| Duration | 24 hours |
| Protein Binding | 99.7% |
| Vd | low |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| cyclosporine | increases ezetimibe levels (OATP inhibition) | moderate |
| bile acid sequestrants | cholestyramine reduces ezetimibe absorption (separate by 2h) | moderate |
Nursing Considerations
- IMPROVE-IT: ezetimibe + simvastatin reduced CV events vs simvastatin alone in post-ACS
- Additive to statin: 15-25% additional LDL reduction
- Enterohepatic recirculation: drug undergoes glucuronidation → excreted in bile → reabsorbed
- Useful when statin intolerance limits doses
Clinical Pearls
- IMPROVE-IT trial: first non-statin to show CV benefit — ezetimibe + simvastatin reduced major CV events post-ACS
- Monotherapy: modest LDL reduction (~20%); most effective as statin add-on
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
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