VYTORIN

What it is

VYTORIN is available as tablets containing 10 mg of ezetimibe and either 10 mg, 20 mg, 40 mg, or 80 mg of simvastatin.

Approved indications

— Prevention of cardiovascular disease in patients with coronary heart disease and a history of acute coronary syndrome taking their maximum tolerated dose of simvastatin and in need of additional lowering of LDL-C. — Adjunctive therapy to diet in patients with primary (heterozygous familial and non-familial) hypercholesterolaemia or mixed hyperlipidaemia where use of a combination product is appropriate, including patients not appropriately controlled with a statin or ezetimibe alone and patients already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia. — Adjunctive therapy to diet in adolescent patients aged 10–17 years with heterozygous familial hypercholesterolaemia where use of a combination product is appropriate, including patients not appropriately controlled with a statin or ezetimibe alone and patients already treated with a statin and ezetimibe. — Homozygous familial hypercholesterolaemia in adolescent patients aged 10–17 years.

Dosing overview

Patients should be placed on a standard cholesterol-lowering diet before receiving VYTORIN and should continue on this diet during treatment. VYTORIN should be taken as a single daily dose in the evening, with or without food. The 10/80 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.

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. 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 older, female gender, uncontrolled hypothyroidism, and renal impairment. All patients starting therapy with VYTORIN, 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. VYTORIN therapy should be discontinued immediately if myopathy is diagnosed or suspected. An increased risk of myopathy in Chinese subjects has been identified, and caution should be used when prescribing VYTORIN to any Asian patients and the lowest dose necessary should be employed. The incidence of consecutive elevations in serum transaminases (≥3 times the upper limit of normal) was 1.7% overall in 12-week trials and 1.8% in controlled long-term extensions. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment. It is recommended that liver function tests be performed before treatment with VYTORIN begins and periodically thereafter when clinically indicated. Patients titrated to the 10/80 mg dose should receive an additional test prior to titration, 3 months after titration to the 10/80 mg dose, and periodically thereafter for the first year of treatment. Cases of interstitial lung disease have been reported with some statins, including simvastatin especially with long-term therapy, presenting with dyspnoea, non-productive cough and deterioration in general health. If it is suspected that a patient has developed interstitial lung disease, statin therapy should be discontinued.

Contraindications

VYTORIN is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients, active liver disease or unexplained persistent elevations of serum transaminases, pregnancy and lactation. VYTORIN is contraindicated in 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 contraindicated. Concomitant use with fusidic acid is contraindicated.

PBS listing

No source documents provide information regarding PBS listing, strength restrictions, authority requirements, or ex-manufacturer pricing for VYTORIN.

Regulatory history

VYTORIN was first registered on the ARTG on 7 January 2005 across four strength variants: 10/10 mg (ARTG 98100), 10/20 mg (ARTG 98111), 10/40 mg (ARTG 98115), and 10/80 mg (ARTG 98117).