From 1 December 2013 ezetimibe and atorvastatin composite pack* (Atozet) can be prescribed on the PBS.
This is an Authority required (Streamlined) listing for the treatment of hypercholesterolaemia, in combination with dietary therapy and exercise, in patients whose cholesterol levels are inadequately controlled by a statin and who also have one or more of the following conditions:1
- coronary heart disease (or a family history)
- peripheral vascular disease
- heterozygous familial hypercholesterolaemia
- cerebrovascular disease.
* This fixed-dose combination (FDC) product contains two individual tablets in composite packaging. This is different from an FDC containing two or more active medicines in a single dosage form.
The composite pack contains 30 tablets ezetimibe 10 mg, and 30 tablets atorvastatin 10, 20, 40 or 80 mg.
To fulfil the clinical criteria for inadequate control with a statin the patient must have been treated for at least 3 months at a maximum tolerated dose of the statin in conjunction with dietary therapy and exercise and also have:
- a cholesterol level greater than the initial threshold for PBS subsidy as set out in the General Statement for Lipid-Lowering Drugs2 for patients assessed according to the Statement as not in a very-high-risk category, or
- a cholesterol level in excess of 4 mmol/L for patients assessed according to the General Statement for Lipid-Lowering Drugs2 as in a very-high-risk category.
For patients qualifying according to either of the above criteria, the dose and duration of statin treatment and the cholesterol level that shows inadequate control must be documented in the patient's medical records. The documentation must be no more than 2 months old when ezetimibe with atorvastatin (Azotet) is started.
The PBAC recommended the listing on a cost-minimisation basis compared with corresponding doses of ezetimibe and atorvastatin taken separately.1
Poor adherence with lipid-lowering therapy is associated with increased cardiac events,3 and cardiovascular morbidity and mortality.4,5 Although FDC products comprising two or more active medicines in a single dosage form are associated with a significant improvement in adherence,6-8 improved adherence with composite packs has not been demonstrated.
The composite pack includes dosing instructions and a calendar to indicate the day each dose is to be taken, on the inner packaging. There is some evidence to show reminder packaging improves clinical targets such as blood pressure.9
Reinforcing and reminding patients about their medical treatment may represent a simple method for improving adherence in patients with hypercholesterolaemia.10 There is no evidence of additional clinical or adherence benefit to be gained from using the composite pack formulation over concomitant use of ezetimibe and atorvastatin taken separately.
May be prescribed by nurse practitioners as continuing therapy only
Authorised nurse practitioners may prescribe this medicine. See the PBS website for more information on nurse practitioner PBS prescribing.
Place in therapy
When is the composite pack of ezetimibe with atorvastatin an appropriate choice?
Switching to the composite pack
There is a risk of overdosing if patients take the medicines in this composite pack in addition to the separate medicines that the composite pack replaces, or under-dosing if patients take only one tablet per day from the composite pack. Ensure that patients and carers know the name and dose of the active ingredients, and which medicines are being replaced by the composite product.
- the individual products are no longer required
- each package contains two different medicines and that both tablets need to be taken daily
- the risk of errors is reduced by returning unneeded medicines to a pharmacy for safe disposal.
- Australian Government Department of Health and Ageing. July 2013 PBAC Outcomes – Positive Recommendations. 2013. http://www.pbs.gov.au/info/industry/listing/elements/pbac-meetings/pbac-outcomes/2013-07/positive-recommendations .
- Australian Government Department of Health and Ageing. General Statement for Lipid-Lowering Drugs Prescribed as Pharmaceutical Benefits. 2012. http://www.pbs.gov.au/info/healthpro/explanatory-notes/gs-lipid-lowering-drugs (accessed 1 October 2013).
- Bouchard MH, Dragomir A, Blais L, et al. Impact of adherence to statins on coronary artery disease in primary prevention. Br J Clin Pharmacol 2007;63:698–708. [PubMed]
- Hilleman DE, Monaghan MS, Ashby CL, et al. Physician-prompting statin therapy intervention improves outcomes in patients with coronary heart disease. Pharmacotherapy 2001;21:1415–21. [PubMed]
- Anon. Compliance and adverse event withdrawal: their impact on the West of Scotland Coronary Prevention Study. Eur Heart J 1997;18:1718–24. [PubMed] .
- Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension 2010;55:399–407. [PubMed]
- Bangalore S, Kamalakkannan G, Parkar S, et al. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007;120:713–9. [PubMed]
- Simons LA, Ortiz M, Calcino G. Persistence with a single pill versus two pills of amlodipine and atorvastatin: the Australian experience, 2006-2010. Med J Aust 2011;195:134–7. [PubMed]
- Mahtani KR, Heneghan CJ, Glasziou PP, et al. Reminder packaging for improving adherence to self-administered long-term medications. Cochrane Database Syst Rev 2011:CD005025. [PubMed]
- Schedlbauer A, Davies P, Fahey T. Interventions to improve adherence to lipid lowering medication. Cochrane Database Syst Rev 2010:CD004371. [PubMed]