ATORVASTATIN MLPL

What it is

ATORVASTATIN is available as film-coated tablets containing atorvastatin calcium trihydrate equivalent to 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin. Atorvastatin is a synthetic lipid-lowering agent that inhibits HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate, a precursor of sterols, including cholesterol.

Approved indications

— Treatment of patients with hypercholesterolaemia as an adjunct to diet. — Reduction of the risk of non-fatal myocardial infarction and non-fatal stroke in hypertensive patients with multiple risk factors for coronary heart disease, which may include diabetes, history of stroke or other cerebrovascular disease, peripheral vascular disease or existing asymptomatic coronary heart disease.

Dosing overview

ATORVASTATIN can be administered within the dosage range of 10 mg to 80 mg per day as a single daily dose. Therapy should be individualised according to target lipid levels and the patient's response, with lipid levels re-analysed within 4 weeks of initiation or titration and dosage adjusted accordingly. The majority of patients with primary hypercholesterolaemia and mixed dyslipidaemia are controlled with 10 mg atorvastatin once daily, with a therapeutic response evident within two weeks and maximum response usually achieved within four weeks. Atorvastatin can be taken at any time of the day, with or without food.

Key safety warnings

Moderate elevations of serum transaminases have been reported with atorvastatin therapy, with persistent increases greater than 3 times the upper limit of normal occurring in 0.7% of patients in clinical trials, with incidences of 0.2%, 0.2%, 0.6% and 2.3% for 10 mg, 20 mg, 40 mg and 80 mg doses respectively. Liver function tests should be performed before initiation of treatment and periodically thereafter, with patients who develop increased transaminase levels monitored until abnormalities resolve, and dose reduction or withdrawal recommended if an increase in ALT or AST of greater than 3 times the upper limit of normal persists. Myopathy, defined as muscle ache or muscle weakness in conjunction with increases in creatine kinase values greater than 10 times the upper limit of normal, should be considered in patients 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, and atorvastatin therapy should be discontinued if markedly elevated creatine kinase levels occur or if myopathy is diagnosed or suspected. Atorvastatin must not be co-administered with fusidic acid, as there have been reports of rhabdomyolysis (including some fatalities) in patients receiving concomitant fusidic acid and statins. A post-hoc analysis of the SPARCL 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 (2.3%) compared to placebo (1.4%), with increased risk observed particularly in patients who entered the study with prior haemorrhagic stroke or prior lacunar infarct. The potential risk of haemorrhagic stroke should be carefully considered before initiating treatment with atorvastatin in patients with recent (1–6 months) stroke or transient ischaemic attack.

Contraindications

ATORVASTATIN is contraindicated in patients with hypersensitivity to any component of the medication, active liver disease or unexplained persistent elevations of serum transaminases, and in pregnancy and lactation. Women of childbearing potential are contraindicated unless on an effective contraceptive and highly unlikely to conceive. Concomitant use with fusidic acid hemihydrate and treatment with the hepatitis C antivirals glecaprevir/pibrentasvir are contraindicated.

PBS listing

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

Regulatory history

ATORVASTATIN was first approved on 13 September 2011. Multiple ARTG registrations were listed from September 2011, with additional film-coated tablet formulations registered from December 2020.