CADUET

What it is

CADUET contains the active ingredients amlodipine besilate and atorvastatin calcium trihydrate. CADUET is a combination of atorvastatin, a HMG-CoA reductase inhibitor (statin) and amlodipine, a calcium channel blocker (CCB). CADUET is a combination product targeting two distinct cardiovascular risk factors, hypertension and dyslipidaemia. CADUET, amlodipine besilate/atorvastatin calcium trihydrate tablets, are formulated for oral administration and are available in combinations of 5 mg/10 mg, 5 mg/20 mg, 5 mg/40 mg, 5 mg/80 mg, 10 mg/10 mg, 10 mg/20 mg, 10 mg/40 mg and 10 mg/80 mg.

Approved indications

— Hypertension: amlodipine is indicated for the first line treatment of hypertension and can be used as the sole agent to control blood pressure in the majority of patients. — Angina: amlodipine is indicated for the first line treatment of chronic stable angina. — Atorvastatin is indicated as an adjunct to diet for the treatment of patients with hypercholesterolaemia. — Atorvastatin is indicated in hypertensive patients with multiple risk factors for coronary heart disease (CHD) which may include diabetes, history of stroke or other cerebrovascular disease, peripheral vascular disease or existing asymptomatic CHD to reduce the risk of non-fatal myocardial infarction and non-fatal stroke.

Dosing overview

CADUET is to be taken once-daily and may be taken at any time of the day with or without food. The starting dose and maintenance doses of CADUET should be individualised according to goals consistent with current treatment guidelines and patient response. After initiation of CADUET, lipid levels should be analysed and blood pressure measured after approximately 4 to 6 weeks, and dosage adjusted accordingly.

Key safety warnings

Rarely patients, particularly those with severe obstructive coronary artery disease, have developed documented increased frequency, duration and/or severity of angina on starting calcium channel blocker therapy or at the time of dosage increase. Mild to moderate peripheral oedema was the most common adverse event in amlodipine clinical trials. The incidence of peripheral oedema was dose dependent and ranged in frequency from 3.0% to 10.8% in the 5 mg to 10 mg dose range. Uncomplicated myalgia has been reported in atorvastatin-treated patients. Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine kinase (CK) values >10 x ULN, should be considered in any patient with diffuse myalgias, muscle tenderness or weakness and/or marked elevation of CK. Patients should be advised to report promptly unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Following therapy with other lipid-lowering agents of the same class as atorvastatin, moderate (>3 x upper limit of normal [ULN]) elevations of serum transaminases have been reported. Persistent increases in serum transaminases >3 x ULN occurred in 0.7% of patients who received atorvastatin in clinical trials. Liver function tests should be performed before the initiation of treatment and periodically thereafter. 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 (TIA), showed a higher incidence of haemorrhagic stroke in patients on atorvastatin 80 mg (55/2365, 2.3%) compared to placebo (33/2366, 1.4%), (p=0.02).

Contraindications

CADUET is contraindicated in patients with a known hypersensitivity to any component of this medication. CADUET contains atorvastatin calcium trihydrate and is, therefore, contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases. CADUET is contraindicated during pregnancy, while breastfeeding and in women of child-bearing potential, unless on an effective contraceptive and highly unlikely to conceive. Concomitant use with fusidic acid hemihydrate is also contraindicated due to the atorvastatin component. CADUET is contraindicated in patients being treated with the Hepatitis C antivirals, glecaprevir/pibrentasvir.

Regulatory history

CADUET was first listed on the ARTG on 20 July 2005 with eight registered strengths: 5/10 mg, 5/20 mg, 5/40 mg, 5/80 mg, 10/10 mg, 10/20 mg, 10/40 mg and 10/80 mg tablets in blister pack presentations.