SIMVAR

What it is

SIMVAR contains simvastatin , a lipid-lowering medicine available in tablet form.

Approved indications

— Adjunct to diet for treatment of hypercholesterolaemia. — Treatment of patients at high risk of coronary heart disease (CHD) with or without hypercholesterolaemia, including patients with diabetes, history of stroke or other cerebrovascular disease, peripheral vessel disease, or with existing CHD to reduce the risk of cardiovascular death, major cardiovascular events including stroke, and hospitalisation due to angina pectoris. — Adjunct to diet in adolescent boys and girls who are at least one year post-menarche, 10–17 years of age, with heterozygous familial hypercholesterolaemia (HeFH).

Dosing overview

The dosage range for simvastatin is 10 to 80 mg per day, given as a single dose in the evening. Adjustments of dosage, if required, should be made at intervals of not less than four weeks, to a maximum of 80 mg per day given as a single dose in the evening. The usual starting dose of simvastatin is 40 mg per day given as a single dose in the evening in patients at high risk of CHD (with or without hypercholesterolaemia), including patients with diabetes, history of stroke or other cerebrovascular disease, peripheral vessel disease, or with existing CHD. For hypercholesterolaemia and combined hyperlipidaemia in other patients, the recommended starting dose is 10 to 20 mg per day given in the evening. For paediatric patients aged 10–17 years with heterozygous familial hypercholesterolaemia, the recommended usual starting dose is 10 mg once daily in the evening, with a recommended dosing range of 10–40 mg per day and a maximum recommended dose of 40 mg per day. In patients taking fibrates other than gemfibrozil or fenofibrate, the dose of SIMVAR should not exceed 10 mg per day. In patients taking amiodarone, verapamil, diltiazem, or products containing elbasvir or grazoprevir concomitantly with simvastatin, the dose should not exceed 20 mg per day. In patients taking amlodipine concomitantly with simvastatin, the dose should not exceed 40 mg per day.

Key safety warnings

SIMVAR and other inhibitors of HMG-CoA reductase occasionally cause 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 over, female gender, uncontrolled hypothyroidism, and renal impairment. In a clinical trial database in which 41,413 patients were treated with SIMVAR, the incidence of myopathy was approximately 0.03%, 0.08% and 0.61% at 20, 40 and 80 mg per day, respectively. In a major large long-term clinical trial (SEARCH) in which patients with a history of myocardial infarction were treated with simvastatin 80 mg per day, the incidence of myopathy was approximately 1.0% compared with 0.02% for patients on 20 mg per day, with rhabdomyolysis incidence of 0.1 to 0.2%, all allocated to simvastatin 80 mg per day. An increased risk of myopathy in Chinese subjects has been identified. In a clinical trial in which patients at high risk of cardiovascular disease were treated with simvastatin 40 mg per day, 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 in this clinical trial was Chinese, caution should be used when prescribing SIMVAR to Asian patients and the lowest dose necessary should be employed. All patients starting therapy with SIMVAR, 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.

Contraindications

SIMVAR is contraindicated in patients with hypersensitivity to any component of this preparation, active liver disease or unexplained persistent elevations of serum transaminases, pregnancy and lactation, and women of childbearing potential unless on an effective contraceptive and highly unlikely to conceive. It is also contraindicated in patients with 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 or danazol is also contraindicated. Concomitant use with fusidic acid is contraindicated.

PBS listing

SIMVAR is listed on the PBS in 10 mg, 20 mg and 80 mg tablet strengths. The 10 mg and 20 mg tablets have two PBS items each with both restricted and unrestricted restrictions, with an ex-manufacturer price of A$2.50 per item. The 80 mg tablet has two PBS items with both restricted and unrestricted restrictions, with an ex-manufacturer price of A$3.50 per item.

Regulatory history

SIMVAR was first registered on the ARTG on 26 November 2003, with listings for 10 mg, 20 mg, 40 mg and 80 mg tablet strengths under licence category RE.