Ezetimibe

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Cat Number

API163222331

CAS Number

163222-33-1

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Product Detail Description Scientific Support Customer Q&A

CAS Number

163222-33-1

EINECS

682-606-0

Storage

Store at room temperature

Synonyms

Zetia; Ezetrol; Ezedoc; (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one; SCH 58235

Molecular Formula

C24H21F2NO3

Molecular Weight

409.4

Smiles

C1=CC(=CC=C1[C@@H]2[C@H](C(=O)N2C3=CC=C(C=C3)F)CC[C@@H](C4=CC=C(C=C4)F)O)O

Appearance

White to off-white crystalline powder

Melting Point

164-166℃

Boiling Point

654.9℃ at 760 mmHg

Relative Density

1.334±0.06 (Predicted)

General Description

Ezetimibe is a lipid-lowering agent that reduces intestinal cholesterol absorption through a mechanism distinct from statins. It is available either alone or in fixed-dose combinations with simvastatin or atorvastatin. The drug is well-tolerated and acts locally in the gastrointestinal tract with minimal systemic exposure.

Mechanism of Action

Ezetimibe targets the Niemann-Pick C1-Like 1 (NPC1L1) protein localized on the brush border of enterocytes, inhibiting the transport of dietary and biliary cholesterol into the intestinal epithelium. This blockade reduces the delivery of cholesterol to the liver, leading to upregulation of LDL receptors and increased clearance of circulating LDL cholesterol. The drug does not affect the absorption of fat-soluble vitamins or triglycerides.

Application

Ezetimibe is indicated as adjunctive therapy to diet and statins for the treatment of primary hyperlipidemia and homozygous sitosterolemia. When added to statin therapy, it provides an additional 15-20% reduction in LDL cholesterol without significant systemic toxicity. The IMPROVE-IT trial demonstrated that adding ezetimibe to simvastatin reduces cardiovascular events compared to statin alone in high-risk patients.

In this phase 3 double‑blind trial, 301 high‑risk hypercholesterolemic patients on maximally tolerated statins received bempedoic acid 180 mg, ezetimibe 10 mg, their fixed‑dose combination (FDC), or placebo for 12 weeks. At week 12, the FDC reduced LDL‑C by 36.2%, significantly outperforming placebo (1.8% increase; corrected difference –38.0%), ezetimibe alone (–23.2%), and bempedoic acid alone (–17.2%). Benefits were consistent across subgroups, including high‑intensity statin users. The FDC also improved high‑sensitivity C‑reactive protein and was well tolerated. The authors conclude that adding this FDC to maximally tolerated statins provides substantial LDL‑C lowering with a favorable safety profile.

Fig. 1 Change from baseline to week 12 in low-density lipoprotein (LDL) cholesterol and high-sensitivity C-reactive protein (hsCRP), post hoc population. (Ballantyne CM, et al., 2020)

References

Ballantyne CM, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prev Cardiol. 2020;27(6):593-603.

Does Ezetimibe require protection from light during long-term storage?

Yes, it is photosensitive. UV light can cause photodegradation of the β-lactam ring and the fluorophenyl groups. Store in light-resistant containers.

What is the recommended storage temperature for Ezetimibe?

Store at controlled room temperature (15-25°C). Avoid temperatures above 30°C, which can accelerate oxidative degradation and formation of the ring-opened impurity.

Is Ezetimibe susceptible to moisture-induced degradation?

It is slightly hygroscopic. Under high humidity (>70% RH), it may absorb moisture and convert to a hydrate form, which can affect dissolution. Store with desiccant.

How is the impurity (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one monitored?

This process-related impurity is quantified using a stability-indicating HPLC method, ensuring it remains below ICH qualification thresholds.