ZIMYBE

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 is available in four strengths: 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg, each containing 10 mg of ezetimibe and 10, 20, 40, or 80 mg of simvastatin respectively.

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-C. — Adjunctive therapy to diet in patients with primary hypercholesterolaemia or mixed hyperlipidaemia where use of a combination product is appropriate, including patients not appropriately controlled with a statin or ezetimibe alone and patients already treated with a statin and ezetimibe. — Treatment of homozygous familial hypercholesterolaemia. **Children and adolescents (10–17 years)** — Adjunctive therapy to diet in adolescent patients aged 10–17 years with heterozygous familial hypercholesterolaemia where use of a combination product is appropriate, including patients not appropriately controlled with a statin or ezetimibe alone and patients already treated with a statin and ezetimibe. — Treatment of homozygous familial hypercholesterolaemia in adolescent patients aged 10–17 years.

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. **Adults with primary hypercholesterolaemia or mixed hyperlipidaemia** ZIMYBE can be administered within the range of 10/10 mg per day to 10/80 mg per day, with the usual starting dose being 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. **Patients with coronary heart disease and acute coronary syndrome** The starting dose is 10/40 mg once a day in the evening. **Patients with homozygous familial hypercholesterolaemia** The recommended dosage is ZIMYBE 10/40 mg per day or 10/80 mg per day in the evening. **Special populations** In patients with mild renal insufficiency (estimated GFR ≥60 mL/min/1.73 m²) no dosage adjustment is necessary, but in patients with chronic kidney disease and estimated glomerular filtration rate <60 mL/min/1.73 m², the dose is 10/20 mg once a day in the evening. For adolescents aged 10–17 years, the recommended usual starting dose is 10/10 mg once a day in the evening, with a dosing range of 10/10 to a maximum of 10/40 mg per day.

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, and myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, with rare fatalities having occurred. Predisposing factors for myopathy include advanced age (65 years and over), 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** In patients taking amiodarone, verapamil, diltiazem or 1 g per day or more of niacin concomitantly with ZIMYBE, the dose of ZIMYBE should not exceed 10/20 mg per day. In patients taking amlodipine concomitantly with ZIMYBE, the dose of ZIMYBE should not exceed 10/40 mg per day. The concomitant use of ZIMYBE and fibrates should be avoided.

Contraindications

Hypersensitivity to the active substances or to any of the 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 such as itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and drugs containing cobicistat. Concomitant administration of gemfibrozil, ciclosporin, or danazol. Concomitant use with fusidic acid hemihydrate.

PBS listing

No source document provides information on PBS listing for ZIMYBE.

Regulatory history

ZIMYBE 10/10, 10/20, 10/40, and 10/80 tablet formulations were first registered on the Australian Register of Therapeutic Goods on 11 January 2021 under licence category RE, sponsored by Alphapharm.