AKM-EZETIMIBE SIMVASTATIN

What it is

AKM EZETIMIBE SIMVASTATIN contains the active ingredients ezetimibe and simvastatin. The medicine is supplied as tablets. AKM EZETIMIBE SIMVASTATIN is available in four strengths: 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg, with each tablet containing 10 mg of ezetimibe combined with 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin respectively.

Approved indications

— 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 LDL-C. — Primary hypercholesterolaemia as 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 in patients already treated with a statin and ezetimibe. — Homozygous Familial Hypercholesterolaemia (HoFH) in patients who may also receive adjunctive treatments such as LDL apheresis. — Heterozygous Familial Hypercholesterolaemia (HeFH) as adjunctive therapy to diet in adolescent patients (10-17 years old) where use of a combination product is appropriate in patients not appropriately controlled with a statin or ezetimibe alone or in patients already treated with a statin and ezetimibe. — Homozygous Familial Hypercholesterolaemia (HoFH) in adolescent patients (10-17 years old) who may also receive adjunctive treatments such as LDL apheresis.

Dosing overview

In patients with primary hypercholesterolaemia or mixed hyperlipidaemia, AKM EZETIMIBE SIMVASTATIN can be administered within the range of 10/10 mg/day to 10/80 mg/day, with the usual starting dose being 10/10 mg/day to 10/40 mg/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. AKM EZETIMIBE SIMVASTATIN 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. The recommended dosage for patients with homozygous familial hypercholesterolaemia is AKM EZETIMIBE SIMVASTATIN 10/40 mg/day or 10/80 mg/day in the evening, with the 10/80 mg dose only used when the benefits are expected to outweigh the potential risks. In patients with mild renal insufficiency (estimated GFR ≥60 mL/min/1.73 m²) no dosage adjustment is necessary. No dosage adjustment is required for elderly patients.

Key safety warnings

Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with CK 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), female gender, uncontrolled hypothyroidism, and renal impairment. All patients starting therapy with AKM 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. An increased risk of myopathy in Chinese subjects has been identified, with the incidence approximately 0.24% for Chinese patients compared with 0.05% for non-Chinese patients. Caution should be used when prescribing AKM EZETIMIBE SIMVASTATIN to any Asian patients and the lowest dose necessary should be employed.

Contraindications

AKM EZETIMIBE SIMVASTATIN is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients. Active liver disease or unexplained persistent elevations of serum transaminases are contraindications. Pregnancy and lactation are contraindications. Concomitant administration of potent CYP3A4 inhibitors (including 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.

Regulatory history

AKM EZETIMIBE SIMVASTATIN was first registered on the ARTG on 18 February 2019 in eight formulations (10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg strengths in both bottle and blister pack formats), sponsored by Pharmacor.