ATOZET

What it is

ATOZET is a film-coated tablet containing ezetimibe 10 mg and atorvastatin 10, 20, 40 or 80 mg. ATOZET is a lipid-lowering product that selectively inhibits the intestinal absorption of cholesterol and related plant sterols and inhibits the endogenous synthesis of cholesterol.

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 atorvastatin and in need of additional lowering of LDL-C. — Primary (heterozygous familial and non-familial) hypercholesterolaemia as adjunctive therapy to diet in patients not appropriately controlled with atorvastatin or ezetimibe alone, or already treated with atorvastatin and ezetimibe. — Homozygous familial hypercholesterolaemia.

Dosing overview

This combination product is not indicated for first-line use. For primary hypercholesterolaemia, ATOZET can be administered within the dosage range of 10/10 mg to 10/80 mg as a single daily dose, with a recommended starting dose of 10/10 mg or 10/20 mg once daily. For coronary heart disease, the recommended starting dose in patients already treated with atorvastatin should provide ezetimibe dosed as 10 mg daily and the dose of atorvastatin already being taken. For homozygous familial hypercholesterolaemia, the dosage of ATOZET is 10/40 mg or 10/80 mg daily.

Key safety warnings

Moderate elevations of serum transaminases have been reported following therapy with atorvastatin, with persistent increases in serum transaminases greater than 3 times the upper limit of normal occurring in 0.7% of patients. The incidence of these abnormalities was 0.2, 0.2, 0.6, and 2.3% for 10, 20, 40, and 80 mg respectively. Liver function tests should be performed before the initiation of treatment and periodically thereafter. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with atorvastatin, with a history of renal impairment as a potential risk factor. Such patients merit closer monitoring for skeletal muscle effects. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of creatine kinase. Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing ATOZET. ATOZET therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. A post-hoc analysis of a clinical study in patients without known coronary heart disease who had a recent stroke or transient ischaemic attack showed a higher incidence of haemorrhagic stroke in patients on atorvastatin 80 mg compared to placebo. The potential risk of haemorrhagic stroke should be carefully considered before initiating treatment with ATOZET in patients with recent stroke or transient ischaemic attack.

Contraindications

ATOZET is contraindicated in patients with hypersensitivity to any component of this medication. ATOZET is contraindicated in patients with myopathy secondary to other lipid lowering agents, and in those with active liver disease or unexplained persistent elevations of serum transaminases. ATOZET is contraindicated in pregnancy and lactation, and in women of childbearing potential unless on an effective contraceptive and highly unlikely to conceive. Concomitant use with fusidic acid is contraindicated.

PBS listing

Information regarding PBS listing status, item count, restriction type, and ex-manufacturer price is not available in the provided source documents.

Regulatory history

ATOZET ezetimibe/atorvastatin was first listed on the Australian Register of Therapeutic Goods on 4 February 2015, with registrations for four strength variants: 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg tablet blister packs under licence category RE.