SIMVASTATIN-TIH

What it is

SIMVASTATIN-TIH is available in film-coated tablets containing 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin.

Approved indications

— Adjunct to diet for treatment of hypercholesterolaemia. — Treatment in patients at high risk of coronary heart disease (with or without hypercholesterolaemia) including patients with diabetes, history of stroke or other cerebrovascular disease, peripheral vessel disease, or with existing coronary heart disease 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, aged 10–17 years, with heterozygous familial hypercholesterolaemia.

Dosing overview

The dosage range for simvastatin is 10 to 80 mg daily as a single dose in the evening, with adjustments made at intervals of not less than four weeks to a maximum of 80 mg daily. In patients taking fibrates other than gemfibrozil or fenofibrate, the dose of simvastatin should not exceed 10 mg daily. In patients taking amiodarone, verapamil, diltiazem, or products containing elbasvir or grazoprevir concomitantly, the dose should not exceed 20 mg daily. In patients taking amlodipine concomitantly, the dose should not exceed 40 mg daily.

Key safety warnings

Simvastatin and other HMG-CoA reductase inhibitors 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 (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment. The incidence of myopathy was approximately 0.03%, 0.08% and 0.61% at 20 mg, 40 mg and 80 mg daily, respectively. In a major long-term clinical trial in patients with a history of myocardial infarction treated with simvastatin 80 mg daily, the incidence of myopathy was approximately 1.0% compared with 0.02% for patients on 20 mg daily, with rhabdomyolysis incidence of 0.1 to 0.2% for the 80 mg dose. All patients starting therapy 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. Simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected.

Contraindications

Hypersensitivity to any component of this preparation. Active liver disease or unexplained persistent elevations of serum transaminases. Pregnancy and lactation. Women of childbearing potential, unless on an effective contraceptive and highly unlikely to conceive. 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). Concomitant administration of gemfibrozil, ciclosporin or danazol. Concomitant use with fusidic acid.

Regulatory history

SIMVASTATIN-TIH was first listed on the ARTG on 6 August 2013 in four strengths: 10 mg, 20 mg, 40 mg, and 80 mg tablets.