SIMVASTATIN-WGR

What it is

Simvastatin-WGR is available as film-coated tablets in strengths of 5 mg, 10 mg, 20 mg, 40 mg, and 80 mg, each containing the active ingredient simvastatin.

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, with adjustments made at intervals of not less than four weeks to a maximum of 80 mg per day. For adults at high risk of coronary heart disease or with existing CHD, the usual starting dose is 40 mg per day. For hypercholesterolaemia and combined hyperlipidaemia in patients not in high-risk categories, the recommended starting dose is 10 to 20 mg per day. 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 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 should not exceed 10 mg per day. In patients taking amiodarone, verapamil, diltiazem, or products containing elbasvir or grazoprevir, the dose should not exceed 20 mg per day. In patients taking amlodipine, the dose should not exceed 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, and sometimes takes the form of rhabdomyolysis with or without acute renal failure, with rare fatalities. Predisposing factors for myopathy include advanced age (65 years or older), female gender, uncontrolled hypothyroidism, and renal impairment. In a clinical trial database of 41,413 patients, 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 long-term clinical trial (SEARCH) in patients with a history of myocardial infarction treated with simvastatin 80 mg per day over a mean follow-up of 6.7 years, 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 patients starting therapy or whose dose is being increased should be advised of the risk of myopathy and tell their healthcare provider of any unexplained muscle pain, tenderness or weakness; simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. An increased risk of myopathy in Chinese subjects has been identified, with an incidence of approximately 0.24% for Chinese patients compared with 0.05% for non-Chinese patients on simvastatin 40 mg per day; caution should be used when prescribing to Asian patients and the lowest dose necessary should be employed.

Contraindications

Simvastatin-WGR is contraindicated in patients with hypersensitivity to any component, 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 (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, or danazol is contraindicated. Concomitant use with fusidic acid is contraindicated.

Regulatory history

Simvastatin-WGR was first registered on the ARTG on 11 April 2024, with registrations for 10 mg, 20 mg, 40 mg, and 80 mg strengths in blister pack form.