Ezetimibe
Ezetrol · Atozet · Inegy
Inhibits intestinal cholesterol uptake via NPC1L1 and reduces LDL by an additional 20–25 % on top of a statin, independently of the statin dose. The first step when the statin is maximised and the LDL target is still not reached — a fixed dose of 10 mg, no titration, essentially no interactions, and an adverse effect profile barely distinguishable from placebo. IMPROVE-IT showed that the additional LDL lowering also translates into fewer cardiovascular events, making ezetimibe the first non-statin drug with outcome data.
Ezetimibe is safe in itself but invites undertreatment: it is an adjunct to a statin, not a replacement. As monotherapy it lowers LDL by only around 18 % and lacks documented benefit on myocardial infarction and death.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Insufficient LDL lowering on statin | 10 mg orally daily as add-on | lowers LDL by an additional 20–25 % |
| After acute coronary syndrome | 10 mg orally daily added to high-intensity statin | IMPROVE-IT: LDL 1,4 vs 1,8 mmol/l and fewer events |
| Statin intolerance | 10 mg orally daily as monotherapy | lowers LDL approximately 18 % — no outcome data |
| Familial hypercholesterolaemia | 10 mg orally daily with high-intensity statin | often insufficient; a PCSK9 inhibitor may be needed |
| Simplified regimen | Fixed combination with atorvastatin or simvastatin | one tablet improves adherence |
No dose adjustment at any degree of renal impairment; may be given on dialysis. Combination products containing a statin are governed by the statin's renal restrictions.
No adjustment in mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe hepatic impairment (Child-Pugh B–C) where exposure increases three to fourfold.
From age 6 years in familial hypercholesterolaemia, 10 mg daily, initiated by a paediatrician.
Do not initiate ezetimibe as sole treatment in a patient who reports statin-related myalgia without first conducting a structured review of the statin. Most patients tolerate a lower dose or a different agent, and that combination lowers LDL far more than ezetimibe alone.
Pharmacokinetics
- BIOAVAIL.
- Cannot be determined (practically insoluble)
- Tmax
- 1–2 h (ezetimibe glucuronide)
- t½
- 22 h
- PROTEIN BINDING
- > 90 %
- METABOLISM
- Glucuronidation in intestinal wall and liver (UGT)
- EXCRETION
- Faecal approximately 78 %, renal approximately 11 %
- ENTEROHEPATIC RECIRCULATION
- Yes — explains the long half-life
- ONSET
- Full LDL effect after 2 weeks