EZETROL

What it is

EZETROL contains 10 mg ezetimibe per tablet. EZETROL is a lipid-modifying compound that inhibits the intestinal absorption of cholesterol and related plant sterols, with a mechanism of action that differs from other classes of cholesterol reducing compounds such as statins, bile acid sequestrants, fibric acid derivatives, and plant sterols. The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-Like 1 (NPC1L1), which is responsible for the intestinal uptake of cholesterol and phytosterols. Ezetimibe inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver and a reduction of hepatic cholesterol stores with an increase in clearance of cholesterol from the blood.

Approved indications

— Primary hypercholesterolaemia (heterozygous familial and non-familial) in adults aged 18 years and over, administered alone or with a statin, as adjunctive therapy to diet. — Homozygous familial hypercholesterolaemia in adults, administered with a statin. — Homozygous sitosterolaemia (phytosterolaemia), for the reduction of elevated sitosterol and campesterol levels. — Prevention of cardiovascular disease in patients with coronary heart disease and a history of acute coronary syndrome, administered in combination with the maximum tolerated dose of a statin with proven cardiovascular benefit. — Heterozygous familial hypercholesterolaemia in adolescents aged 10 to 17 years (pubertal status: boys Tanner Stage II and above and girls at least one year post-menarche), co-administered with simvastatin as adjunctive therapy to diet. — Homozygous familial hypercholesterolaemia in adolescents aged 10 to 17 years, co-administered with simvastatin.

Dosing overview

The recommended dose of EZETROL is 10 mg once daily, used alone or with a statin for primary hypercholesterolaemia. EZETROL can be administered at any time of the day, with or without food. For patients with coronary heart disease and a history of acute coronary syndrome, EZETROL 10 mg may be administered with a statin with proven cardiovascular benefit. In patients with chronic kidney disease and estimated glomerular filtration rate less than 60 mL/min/1.73 m², the dose of EZETROL is 10 mg and the dose of simvastatin is 20 mg once daily in the evening.

Key safety warnings

There is sufficient evidence to suggest a causal association between ezetimibe monotherapy and drug-induced liver injury. In controlled trials with ezetimibe co-administered with a statin, consecutive transaminase elevations of ≥3 times the upper limit of normal have been observed. When EZETROL is administered alone or with a statin, liver function tests should be performed at initiation of therapy and as indicated or according to the recommendations of the statin. In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with EZETROL compared with the relevant control arm, though myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs. All patients starting therapy with EZETROL should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. EZETROL and any statin that the patient is taking concomitantly should be immediately discontinued if myopathy is diagnosed or suspected. Fibrates may increase cholesterol excretion from the bile, and ezetimibe increased cholesterol in the gallbladder bile in a preclinical study in dogs. Given the potential for cholelithiasis and the numerically higher incidence of cholecystectomies in patients administered ezetimibe and fenofibrate in a clinical study, coadministration of ezetimibe and fenofibrate is not recommended in patients with pre-existing gallbladder disease. Caution should be exercised when initiating ezetimibe in the setting of ciclosporin. Ciclosporin concentrations should be monitored in patients receiving EZETROL and ciclosporin.

Contraindications

EZETROL is contraindicated in patients with hypersensitivity to any component of this medication. EZETROL in combination with fenofibrate is contraindicated in patients with gall bladder disease. Therapy with EZETROL in combination with a statin is contraindicated during pregnancy and lactation. The combination of EZETROL with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in serum transaminases.

Regulatory history

EZETROL ezetimibe 10 mg was first listed on the ARTG on 23 June 2003.