Ezetrol (Merck Sharp & Dohme)
10 mg tablets
Approved indications: hypercholesterolaemia and sitosterolaemia
Australian Medicines Handbook section 6.6
Familial hypercholesterolaemia is caused by a mutation in the gene which codes for the receptors for low density lipoprotein (LDL) cholesterol. The homozygous form of the disorder results in very high concentrations of cholesterol in the blood. This greatly increases the patient's risk of cardiovascular disease.
Sitosterolaemia (phytosterolaemia) is another genetic disorder which can cause hypercholesterolaemia. There is increased absorption of cholesterol and plant sterols from the gut.
Ezetimibe may benefit homozygous patients with familial hypercholesterolaemia or sitosterolaemia because it selectively inhibits absorption of cholesterol and phytosterols from the small intestine. The drug is taken once a day and its absorption is not affected by food. It is metabolised in the small intestine and mostly excreted in the faeces. The half-life of ezetimibe and its main metabolite is approximately 22 hours.
Monotherapy with ezetimibe reduces concentrations of LDL cholesterol by approximately 17%. As patients with hypercholesterolaemia are often treated with an HMG CoA reductase inhibitor, ezetimibe has been studied in combination with these 'statins'.
In a study of 50 patients with homozygous familial hypercholesterolaemia 12 weeks of treatment with ezetimibe and either atorvastatin or simvastatin had greater efficacy than statin therapy alone. Combined treatment reduced LDL cholesterol by 20.7% while high-dose (80 mg/day) statin therapy reduced it by 6.7%.1Adding ezetimibe to the treatment regimen of 37 patients with homozygous sitosterolaemia reduced their sitosterol concentrations by 21% and their campesterol concentrations by 24%.
Caution is needed when prescribing ezetimibe to patients who are being treated with a bile acid binding resin such as cholestyramine. The drugs interact resulting in reduced concentrations of ezetimibe. Combined therapy with fibrates is not recommended. When ezetimibe is combined with a statin the patient's liver enzymes should be checked. The combination is contraindicated in patients with altered liver function.
Although 5% of patients treated with ezetimibe may complain of myalgia, there are currently no reports of rhabdomyolysis. Other symptoms reported in clinical trials include abdominal pain, diarrhoea, chest pain, headache and dizziness.
Ezetimibe does improve patients' lipid profiles, but it will be several years before any effect on morbidity and mortality emerges. Familial hypercholesterolaemia is a relatively uncommon form of primary hypercholesterolaemia. Although ezetimibe has also been approved for other forms of primary hypercholesterolaemia its use for this indication will probably be limited to patients who cannot tolerate statins.
- Ezetimibe Study Group. Efficacy and safety of ezetimibe co-administered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolaemia. Circulation 2002;105:2469-75.