ZIMSTAT

What it is

ZIMSTAT contains simvastatin . The medicine is available in film-coated tablet strengths of 5 mg, 10 mg, 20 mg, 40 mg, and 80 mg .

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 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 . For adults at high risk of coronary heart disease, the usual starting dose is 40 mg per day . For hypercholesterolaemia 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 starting dose is 10 mg once daily, with a dosing range of 10-40 mg per day and a maximum dose of 40 mg per day .

Dose adjustments are required with certain concomitant medications. 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

ZIMSTAT 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, and myopathy can take the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, with rare fatalities occurring . Predisposing factors for myopathy include advanced age of 65 years or more, female gender, uncontrolled hypothyroidism, and renal impairment . 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 . The 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 . An increased risk of myopathy in Chinese subjects has been identified, and caution should be used when prescribing ZIMSTAT to Asian patients with the lowest dose necessary being employed . ZIMSTAT therapy should be discontinued immediately if myopathy is diagnosed or suspected . In most cases, when patients were promptly discontinued from treatment, muscle symptoms and creatine kinase increases resolved .

Contraindications

ZIMSTAT 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 effective contraception and highly unlikely to conceive . Contraindications also include myopathy secondary to other lipid-lowering agents and 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 . ZIMSTAT is also contraindicated with concomitant administration of gemfibrozil, ciclosporin or danazol . Concomitant use with fusidic acid is contraindicated .

PBS listing

ZIMSTAT 5 mg tablets are listed on the PBS as 2 items with unrestricted and restricted access, with an ex-manufacturer price of A$2.50 .

Regulatory history

ZIMSTAT was first registered on the ARTG on 18 July 2003, with 8 product registrations across 5 mg, 10 mg, 20 mg, 40 mg, and 80 mg strengths in blister pack and bottle presentations .