EZETORIN

What it is

EZETORIN is available for oral use as tablets containing ezetimibe and simvastatin in the following combinations: 10 mg of ezetimibe and 10 mg of simvastatin (EZETORIN 10/10); 10 mg of ezetimibe and 20 mg of simvastatin (EZETORIN 10/20); 10 mg of ezetimibe and 40 mg of simvastatin (EZETORIN 10/40); and 10 mg of ezetimibe and 80 mg of simvastatin (EZETORIN 10/80). The tablets are light pink to pink coloured with a mosaic appearance, capsule shaped, biconvex, and uncoated, with identifying numbers on one side (335 for 10/10, 336 for 10/20, 337 for 10/40, and 338 for 10/80).

Approved indications —

Coronary heart disease with a history of acute coronary syndrome in patients taking their maximum tolerated dose of simvastatin and in need of additional lowering of LDL-C, in expectation of modest further reduction in the risk of cardiovascular events following at least one year of therapy. — Primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed hyperlipidaemia as adjunctive therapy to diet in patients not appropriately controlled with a statin or ezetimibe alone, or in patients already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia. — Heterozygous familial hypercholesterolaemia in adolescent patients aged 10–17 years (pubertal status: boys Tanner Stage II and above and girls at least one year post-menarche) as adjunctive therapy to diet in patients not appropriately controlled with a statin or ezetimibe alone, or in patients already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia in adolescent patients aged 10–17 years (pubertal status: boys Tanner Stage II and above and girls at least one year post-menarche).

Dosing overview

In patients with primary hypercholesterolaemia or mixed hyperlipidaemia, EZETORIN can be administered within the range of 10/10 mg per day to 10/80 mg per day, with a usual starting dose of 10/10 mg per day to 10/40 mg per day. 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. EZETORIN should be taken as a single daily dose in the evening, with or without food. In patients with coronary heart disease and a history of acute coronary syndrome, the starting dose was 10/40 mg once a day in the evening. In patients with homozygous familial hypercholesterolaemia, the recommended dosage is EZETORIN 10/40 mg per day or 10/80 mg per day in the evening. In patients with chronic kidney disease and estimated glomerular filtration rate less than 60 mL/min/1.73 m², the dose of EZETORIN is 10/20 mg once a day in the evening. In adolescents aged 10–17 years, the recommended usual starting dose is 10/10 mg once a day in the evening, with a recommended dosing range of 10/10 mg to a maximum of 10/40 mg per day.

Key safety warnings

Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above 10 times the upper limit of normal. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. Predisposing factors for myopathy include advanced age (65 years or older), female gender, uncontrolled hypothyroidism, and renal impairment. All patients starting therapy with EZETORIN, 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. EZETORIN therapy should be discontinued immediately if myopathy is diagnosed or suspected. Periodic creatine kinase determinations are recommended for patients titrating to the 10/80 mg dose. An increased risk of myopathy in Chinese subjects has been identified. In a clinical trial, the incidence of myopathy was approximately 0.05% for non-Chinese patients compared with 0.24% for Chinese patients. While the only Asian population assessed was Chinese, caution should be used when prescribing EZETORIN to any Asian patients and the lowest dose necessary should be employed.

Contraindications

EZETORIN is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients. It is contraindicated in active liver disease or unexplained persistent elevations of serum transaminases. EZETORIN is contraindicated in pregnancy and lactation. It is contraindicated in myopathy secondary to other lipid lowering agents. 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, danazol, or fusidic acid is contraindicated.

PBS listing

The provided source documents do not contain information regarding PBS listing status, strength details, item numbers, restriction types, or pricing for EZETORIN.

Regulatory history

EZETORIN was first registered on the ARTG on 15 October 2019, with all four strength variants (10/10, 10/20, 10/40, and 10/80 mg) listed under licence category RE.