APO-EZETIMIBE

What it is

APO-EZETIMIBE contains 10 mg ezetimibe per tablet. Ezetimibe is a lipid-modifying compound that inhibits the intestinal absorption of cholesterol and related 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.

Approved indications

— Primary hypercholesterolaemia in adults (≥18 years), administered alone or with a statin, as adjunctive therapy to diet in patients with primary (heterozygous familial and non-familial) hypercholesterolaemia. — Homozygous familial hypercholesterolaemia in adults, administered with a statin. — Homozygous sitosterolaemia (phytosterolaemia) in adults, for the reduction of elevated sitosterol and campesterol levels. — Prevention of cardiovascular disease in adults with coronary heart disease and a history of acute coronary syndrome, in combination with the maximum tolerated dose of a statin with proven cardiovascular benefit, in patients in need of additional lowering of LDL cholesterol. — Heterozygous familial hypercholesterolaemia in adolescents aged 10–17 years (pubertal status: boys Tanner Stage II and above and girls who are at least one year post-menarche), co-administered with simvastatin (doses up to 40 mg) as adjunctive therapy to diet. — Homozygous familial hypercholesterolaemia in adolescents aged 10–17 years (pubertal status: boys Tanner Stage II and above and girls who are at least one year post-menarche), co-administered with simvastatin (doses up to 40 mg).

Dosing overview

The recommended dose of APO-EZETIMIBE for patients with primary hypercholesterolaemia is 10 mg once daily, used alone or with a statin. APO-EZETIMIBE 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, APO-EZETIMIBE 10 mg may be administered with a statin with proven cardiovascular benefit. In patients with renal impairment, no dosage adjustment of ezetimibe is necessary when given as monotherapy. No dosage adjustment is required for elderly patients.

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 and a statin, consecutive transaminase elevations (≥3 times the upper limit of normal) have been observed. When ezetimibe 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. All patients starting therapy with ezetimibe should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. APO-EZETIMIBE and any statin that the patient is taking concomitantly should be immediately discontinued if myopathy is diagnosed or suspected. 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 ezetimibe and ciclosporin.

Contraindications

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

Regulatory history

APO-EZETIMIBE was first registered on the ARTG on 5 October 2016 in two pack variants: a bottle pack (ARTG 263217) and a blister pack (ARTG 263212).