APO-ATORVASTATIN

What it is

APO-ATORVASTATIN contains atorvastatin calcium trihydrate and is available in 10 mg, 20 mg, 40 mg and 80 mg tablet strengths. The tablets are white to off-white, elliptical, film-coated tablets. Atorvastatin is a synthetic lipid-lowering agent and an inhibitor of 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. — 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) to reduce the risk of non-fatal myocardial infarction and non-fatal stroke.

Dosing overview

APO-ATORVASTATIN can be administered within the dosage range of 10 mg to 80 mg daily as a single daily dose. Therapy should be individualised according to the target lipid levels, the recommended goal of therapy and the patient's response. The majority of patients with primary hypercholesterolaemia and mixed dyslipidaemia are controlled with 10 mg atorvastatin once a day, 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 following therapy with atorvastatin, with persistent increases greater than 3 times the upper limit of normal occurring in 0.7% of patients in clinical trials, with incidence 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 the initiation of treatment and periodically thereafter. Uncomplicated myalgia has been reported in atorvastatin-treated patients, and 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 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. 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 a clinical study (SPARCL) 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, with increased risk observed particularly in patients 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

APO-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. It is contraindicated in women of childbearing potential, unless on an effective contraceptive and highly unlikely to conceive. Concomitant use with fusidic acid hemihydrate is contraindicated. Treatment with the Hepatitis C antivirals, glecaprevir/pibrentasvir is contraindicated.

Regulatory history

APO-ATORVASTATIN was first listed on the Australian Register of Therapeutic Goods on 23 September 2011, with registrations for 10 mg, 20 mg, 40 mg and 80 mg tablet strengths in bottle format. Blister pack formats for all four strengths were subsequently listed on 1 June 2017.