ZIENT

What it is

ZIMYBE is a lipid-lowering product that selectively inhibits the intestinal absorption of cholesterol and related plant sterols and inhibits the endogenous synthesis of cholesterol. ZIMYBE tablets contain 10 mg of ezetimibe as the active ingredient, and 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin as the active ingredient.

Approved indications

**Adults (18 years and over)** — 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-cholesterol. — Adjunctive therapy to diet in patients with primary hypercholesterolaemia or mixed hyperlipidaemia where patients are not appropriately controlled with a statin or ezetimibe alone. — Adjunctive therapy to diet in patients with primary hypercholesterolaemia or mixed hyperlipidaemia who are already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia. **Children and adolescents (10–17 years)** — Adjunctive therapy to diet in adolescent patients with heterozygous familial hypercholesterolaemia where patients are not appropriately controlled with a statin or ezetimibe alone. — Adjunctive therapy to diet in adolescent patients with heterozygous familial hypercholesterolaemia who are already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia in adolescent patients.

Dosing overview

Patients should be placed on a standard cholesterol-lowering diet before receiving ZIMYBE and should continue on this diet during treatment. ZIMYBE should be taken as a single daily dose in the evening, with or without food. The 10/80 mg dose of ZIMYBE 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 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 of 65 years or older, female gender, uncontrolled hypothyroidism, and renal impairment. All patients starting therapy with ZIMYBE, 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. ZIMYBE therapy should be discontinued immediately if myopathy is diagnosed or suspected. **Drug interactions** ZIMYBE is contraindicated with concomitant administration of potent CYP3A4 inhibitors including itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and drugs containing cobicistat. ZIMYBE is contraindicated with concomitant administration of gemfibrozil, ciclosporin, or danazol. In patients taking amiodarone, verapamil, diltiazem or 1 g/day or more of niacin concomitantly with ZIMYBE, the dose of ZIMYBE should not exceed 10/20 mg/day. In patients taking amlodipine concomitantly with ZIMYBE, the dose of ZIMYBE should not exceed 10/40 mg/day.

Contraindications

ZIMYBE is contraindicated in patients with hypersensitivity to the active substances or excipients, active liver disease or unexplained persistent elevations of serum transaminases, pregnancy and lactation, myopathy secondary to other lipid lowering agents, concomitant administration of potent CYP3A4 inhibitors, concomitant administration of gemfibrozil, ciclosporin, or danazol, and concomitant use with fusidic acid hemihydrate.

PBS listing

ZIMYBE 10 mg tablets are listed on the PBS as 2 items with unrestricted and restricted restrictions, with an ex-manufacturer price of A$4.35.

Regulatory history

ZIMYBE (ezetimibe 10 mg tablet) was first listed on the ARTG on 22 December 2015 under licence category RE, sponsored by Organon Pharma.