APO-EZETIMIBE/SIMVASTATIN

What it is

APO-EZETIMIBE/SIMVASTATIN is a lipid-lowering product that selectively inhibits the intestinal absorption of cholesterol and related plant sterols and inhibits the endogenous synthesis of cholesterol. Each tablet contains 10 mg of ezetimibe and either 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin.

Approved indications

**Adults (18 years and above)** — Prevention of cardiovascular events in patients with coronary heart disease and a history of acute coronary syndrome taking their maximum tolerated dose of simvastatin and in need of additional lowering of LDL-C. — Adjunctive therapy to diet in patients with primary (heterozygous familial and non-familial) hypercholesterolaemia or mixed hyperlipidaemia where use of a combination product is appropriate in patients not appropriately controlled with a statin or ezetimibe alone, or patients already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia. **Children and adolescents (10–17 years)** — Adjunctive therapy to diet in adolescent patients (10–17 years old) with heterozygous familial hypercholesterolaemia where use of a combination product is appropriate in patients not appropriately controlled with a statin or ezetimibe alone, or patients already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia in adolescent patients (10–17 years old).

Dosing overview

Patients should be placed on a standard cholesterol-lowering diet before receiving APO-EZETIMIBE/SIMVASTATIN and should continue on this diet during treatment. APO-EZETIMIBE/SIMVASTATIN should be taken as a single daily dose in the evening, with or without food. The 10/80 mg dose should only be used in patients at high risk for cardiovascular complications who have not achieved their treatment goals on lower doses and when the benefits are expected to outweigh the potential risks.

Key safety warnings

**Myopathy and rhabdomyolysis.** Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with CK above 10 times the upper limit of normal, and myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, with rare fatalities occurring. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. All patients starting therapy with APO-EZETIMIBE/SIMVASTATIN or whose dose is being increased should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness. APO-EZETIMIBE/SIMVASTATIN therapy should be discontinued immediately if myopathy is diagnosed or suspected. **Drug interactions affecting myopathy risk.** In patients taking amiodarone, verapamil, diltiazem or ≥1 g/day of niacin concomitantly with APO-EZETIMIBE/SIMVASTATIN, the dose should not exceed 10/20 mg/day. In patients taking amlodipine concomitantly with APO-EZETIMIBE/SIMVASTATIN, the dose should not exceed 10/40 mg/day. Coadministration of APO-EZETIMIBE/SIMVASTATIN with lipid-modifying doses (≥1 g/day) of niacin-containing products is not recommended in Asian patients due to higher incidence of myopathy in this population.

Contraindications

APO-EZETIMIBE/SIMVASTATIN is contraindicated in patients with hypersensitivity to the active substances or excipients, active liver disease or unexplained persistent elevations of serum transaminases, and in pregnancy and lactation. Myopathy secondary to other lipid lowering agents is a contraindication. Concomitant administration of potent CYP3A4 inhibitors (such as itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and drugs containing cobicistat) is contraindicated. Concomitant administration of gemfibrozil, ciclosporin, or danazol is contraindicated. Concomitant use with fusidic acid hemihydrate is contraindicated.

Regulatory history

APO-EZETIMIBE/SIMVASTATIN was first listed on the ARTG on 15 October 2019 in four strengths: 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg, all in tablet blister pack form.