EzSimva GH

What it is

EzSimva GH contains ezetimibe and simvastatin. The medicine is available as oral tablets in four strengths: 10 mg ezetimibe with 10 mg simvastatin, 10 mg ezetimibe with 20 mg simvastatin, 10 mg ezetimibe with 40 mg simvastatin, and 10 mg ezetimibe with 80 mg simvastatin.

Approved indications

**Adults (18 years and above)** — Prevention of cardiovascular disease 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 low-density lipoprotein cholesterol. — 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. — Homozygous familial hypercholesterolaemia. **Children and adolescents (10–17 years)** — Adjunctive therapy to diet in adolescent patients 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. — Homozygous familial hypercholesterolaemia in adolescent patients.

Dosing overview

Patients should be placed on a standard cholesterol-lowering diet before receiving EzSimva GH and should continue on this diet during treatment. In patients with primary hypercholesterolaemia or mixed hyperlipidaemia, EzSimva GH 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. EzSimva GH should be taken as a single daily dose in the evening, with or without food. After initiation or titration, lipid levels may be analysed after 2 or more weeks and dosage adjusted if needed. 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. For patients with homozygous familial hypercholesterolaemia, the recommended dosage is 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 EzSimva GH is 10/20 mg once a day in the evening. For adolescents aged 10 to 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 and above), female gender, uncontrolled hypothyroidism, and renal impairment. All patients starting therapy with EzSimva GH, 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. Periodic creatine kinase determinations may be considered in patients starting therapy with EzSimva GH or whose dose is being increased, and are recommended for patients titrating to the 10/80 mg dose. An increased risk of myopathy in Chinese subjects has been identified, with an incidence of approximately 0.24 per cent for Chinese patients compared with 0.05 per cent for non-Chinese patients. Caution should be used when prescribing EzSimva GH to any Asian patients and the lowest dose necessary should be employed.

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. Concomitant administration of potent cytochrome P450 3A4 inhibitors, including 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.

PBS listing

No information on PBS listing is available in the provided source documents.

Regulatory history

EzSimva GH was registered on the Australian Register of Therapeutic Goods on 15 October 2019 in four strengths (10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg), each in the form of tablet blister packs, under licence category RE.