Products
Ezetimibe is commercially available in tablet form, as a monopreparation (Ezetrol, generic), and as a fixed combination with simvastatin (Inegy, generic) and with atorvastatin (Atozet). Also released is a combination with rosuvastatin. Ezetimibe was approved in many countries and in the United States in 2002. Generic and auto-generics entered the market in November 2017. The active ingredient is also known as ezetimibe. However, this is the English name of the active ingredient. In German, ezetimibe is correct.
Structure and properties
Ezetimibe (C24H21F2NO3, Mr = 409.43 g/mol) exists as a white crystalline powder that is practically insoluble in water. It is a 2-azetidinone that is fluorinated at critical sites to prevent oxidation. It is therefore not biotransformed by CYP450 isoenzymes, but only glucuronidated. The glucuronide is also active.
Effects
Ezetimibe (ATC C10AX09) has lipid-lowering properties by inhibiting the uptake of endo- and exogenous cholesterol (bile, food) and phytosterols such as sitosterol and campesterol from the small intestine into the bloodstream. The effects are based on inhibition of the transport of lipids from the intestine into the blood by binding to the transport protein NPC1L1 (Niemann-Pick C1-Like 1). NPC1L1 is located on the apical membrane of enterocytes in the intestine. The effect is specific, i.e., absorption of fat-soluble vitamins or triglycerides is not inhibited. Ezetimibe lowers total cholesterol, LDL, ApoB, and triglycerides and increases HDL. The half-life is 22 hours for ezetimibe and the glucuronide.
Indications
- Primary hypercholesterolemia
- Homozygous familial hypercholesterolemia
- Homozygous sitosterolemia (phytosterolemia).
Dosage
According to the professional information. Tablets are taken once daily, independent of meals. Ezetimibe may be combined with fenofibrate OR with a statin (eg, simvastatin or atorvastatin).
Contraindications
- Hypersensitivity
- During pregnancy and lactation in combination with a statin.
- Patients with active liver disease or unexplained persistent elevation of serum transaminases in combination with a statin
For complete precautions, see the drug label.
Interactions
Ezetimibe does not interact with CYP450 enzymes and is mainly glucuronidated. Drug-drug interactions have been described with the following agents, among others: Antacids, colestyramine, fibrates, and warfarin.
Adverse effects
The most common potential adverse effects of monotherapy include abdominal pain, diarrhea, flatulence, and fatigue.
