APO-SIMVASTATIN

What it is

APO-SIMVASTATIN contains simvastatin, a lipid-lowering agent derived synthetically from a fermentation product of Aspergillus terreus. It is available in tablet strengths of 10 mg, 20 mg, 40 mg or 80 mg.

Approved indications

— Treatment of hypercholesterolaemia as an adjunct to diet. — Reduction of the risk of cardiovascular death, major cardiovascular events including stroke, and hospitalisation due to angina pectoris in patients at high risk of coronary heart disease, including patients with diabetes, history of stroke or other cerebrovascular disease, peripheral vessel disease, or with existing coronary heart disease.

Dosing overview

The dosage range for APO-SIMVASTATIN is 10–80 mg per day, given as a single dose in the evening. Adjustments of dosage 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. For patients at high risk of coronary heart disease or with existing coronary heart disease, the usual starting dose is 40 mg per day in the evening. For patients with hypercholesterolaemia or combined hyperlipidaemia who are not in these risk categories, the recommended starting dose is 10 to 20 mg per day in the evening.

Key safety warnings

APO-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), female gender, uncontrolled hypothyroidism, and renal impairment. All patients starting therapy with APO-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. In clinical studies, persistent increases in serum transaminases to more than three times the upper limit of normal have occurred in 1% of adult patients who received simvastatin. When the drug was interrupted or discontinued in these patients, transaminases usually fell slowly to pre-treatment concentration. The increases were not associated with jaundice or other clinical signs or symptoms. Cases of interstitial lung disease have been reported with APO-SIMVASTATIN, especially with long-term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health. If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.

Contraindications

APO-SIMVASTATIN is contraindicated in patients with hypersensitivity to any component of the preparation, active liver disease or unexplained persistent elevations of serum transaminases, pregnancy and nursing, and women of childbearing potential unless on an effective contraceptive and highly unlikely to conceive. Myopathy secondary to other lipid lowering agents is a contraindication. 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 contraindicated. Concomitant use with fusidic acid is contraindicated.

Regulatory history

APO-SIMVASTATIN in strengths of 10 mg, 20 mg, 40 mg and 80 mg was first registered on the Australian Register of Therapeutic Goods on 24 July 2014.