APX-ROSUVASTATIN

What it is

APX-ROSUVASTATIN contains rosuvastatin calcium in tablet form, available in strengths of 5 mg, 10 mg, 20 mg and 40 mg. Rosuvastatin calcium is a HMG-CoA reductase inhibitor for the treatment of dyslipidaemia and is a fully synthetic competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol.

Approved indications

— Reduction of the risk of nonfatal myocardial infarction in men aged 50 years or older and women aged 60 years or older with no clinically evident cardiovascular disease but with at least two conventional risk factors for cardiovascular disease. — Reduction of the risk of nonfatal stroke in men aged 50 years or older and women aged 60 years or older with no clinically evident cardiovascular disease but with at least two conventional risk factors for cardiovascular disease. — Reduction of the risk of coronary artery revascularisation procedures in men aged 50 years or older and women aged 60 years or older with no clinically evident cardiovascular disease but with at least two conventional risk factors for cardiovascular disease. — Treatment of hypercholesterolaemia, including familial hypercholesterolaemia.

Dosing overview

Prior to initiating APX-ROSUVASTATIN, the patient should be placed on a standard cholesterol-lowering diet. The dose should be individualised according to the goal of therapy and patient response and should take into account the potential risk for adverse reactions. APX-ROSUVASTATIN may be given at any time of the day, with or without food. For Asian patients, initiation of APX-ROSUVASTATIN therapy with 5 mg once daily should be considered, as the potential for increased systemic exposures relative to Caucasians is relevant when considering escalation of dose. In patients taking ciclosporin, APX-ROSUVASTATIN dosage should be limited to 5 mg once daily. If APX-ROSUVASTATIN is used in combination with gemfibrozil, the dose should be limited to 10 mg once daily.

Key safety warnings

APX-ROSUVASTATIN 40 mg is contraindicated in patients with predisposing factors for myopathy and rhabdomyolysis. The incidence of persistent elevations in serum transaminases exceeding 3 times the upper limit of normal in fixed dose studies was low (0.4%, 0%, 0%, and 0.1% at 5, 10, 20, and 40 mg respectively), and in most cases, elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. Liver function tests should be performed before initiation of treatment and periodically thereafter. Patients who develop increased transaminase levels should be monitored until the abnormalities have resolved. Should an increase in ALT or AST of greater than 3 times the upper limit of normal persist, reduction of dose or withdrawal of rosuvastatin is recommended. Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with rosuvastatin. Uncomplicated myalgia has been reported in rosuvastatin-treated patients. Creatine kinase elevations greater than 10 times the upper limit of normal occurred in 0.2% to 0.4% of patients taking rosuvastatin at doses up to 40 mg in clinical studies. Treatment-related myopathy was reported in up to 0.1% of patients taking rosuvastatin doses of up to 40 mg in clinical studies. Patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Rosuvastatin therapy should be discontinued if markedly elevated creatine kinase levels occur or myopathy is diagnosed or suspected. There have been very rare reports of an immune-mediated necrotizing myopathy clinically characterised by persistent proximal muscle weakness and elevated serum creatine kinase during treatment or following discontinuation of statins, including rosuvastatin. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Increases in HbA1c and fasting serum glucose levels have been reported with rosuvastatin. An increased frequency of diabetes mellitus has been reported with rosuvastatin in patients with risk factors for diabetes mellitus. Exceptional cases of interstitial lung disease have been reported with some statins, especially with long-term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health. If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued. Fusidic acid must not be co-administered with statins. There have been reports of rhabdomyolysis, including some fatalities, in patients receiving this combination.

Contraindications

Known hypersensitivity to any of the ingredients. Patients with active liver disease including unexplained, persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3 times the upper limit of normal. During pregnancy, in nursing mothers and in women of childbearing potential, unless they are taking adequate contraceptive precautions. Concomitant use of fusidic acid. APX-ROSUVASTATIN 40 mg is contraindicated in patients with pre-disposing factors for myopathy and rhabdomyolysis, including hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, severe renal impairment (CrCl less than 30 mL/min), Asian patients, and concomitant use of fibrates.

Regulatory history

APX-ROSUVASTATIN was first listed on the Australian Register of Therapeutic Goods on 18 May 2020, with registrations for 5 mg, 10 mg, 20 mg and 40 mg strengths in both blister pack and bottle presentations.