Rosuvastatin Calcium, tablets, 5 mg, 10 mg, 20 mg, 40 mg, Crestor®, July 2006
Page last updated: 27 October 2006
Public Summary Document
Product: Rosuvastatin Calcium, tablets, 5 mg, 10 mg, 20 mg, 40 mg, Crestor®
Sponsor: AstraZeneca Pty Ltd
Date of PBAC Consideration: July 2006
1. Purpose of Application
The application sought a restricted benefit listing of rosuvastatin for the treatment
This drug had not previously been considered by the PBAC.
3. Registration Status
Crestor is registered by the TGA as an adjunct to diet when the response to diet and
exercise is inadequate for the treatment of hypercholesterolaemia (including familial
hypercholesterolaemia). Prior to initiating therapy with Crestor, secondary causes
of hypercholesterolaemia (e.g. poorly controlled diabetes mellitus, hypothyroidism,
nephrotic syndrome, dysproteinaemias, obstructive liver disease, other drug therapy,
alcoholism) should be identified and treated.
4. Listing requested and PBAC’s View
A PBS listing comparable to that of the other HMG CoA reductase inhibitors was requested
as shown below.
For use in patients that meet the criteria set out in the General Statement for Lipid Lowering Drugs.
The PBAC’s view was that a NOTE be included in the PBS listing, indicating that the highest strength, 40 mg, should be prescribed with caution as described in the approved Product Information.
For the PBAC’s view see Recommendation and Reasons.
5. Clinical place for the proposed therapy
Rosuvastatin is a member of the HMG CoA reductase inhibitor (statin) class of drugs.
It provides an alternative treatment option to other members of this class for the
lowering of lipid levels.
The submission nominated atorvastatin and simvastatin as the comparators. The PBAC
considered atorvastatin was the most appropriate, as this is the drug that will principally
be replaced in practice.
7. Clinical trials
The submission presented a series of meta-analyses of 29 randomised trials comparing
rosuvastatin with either atorvastatin or simvastatin.
|Trial/First author||Protocol/Publication title||Publication citation|
|SOLAR/ Insull JW et al||Effect of three statins at starting dose on achieving national LDL-C goals in hypercholesterolaemic patients with or without diabetes in a managed-care setting.||Diabetes 2005;54(Suppl:1):1-O.|
|MERCURY II/ Ballantyne CM et al
||Achievement of non-hdl-c and apo B goals in high-risk patients who achieve their atp
III LDL-C goal: mercury II trial.
Effect of switching high- and very high-risk patients to rosuvastatin from atorvastatin or simvastatin on achievement of new ATP III goals: Mercury II.
|Atherosclerosis Supplements 2005;6(1):W16-004.
|STELLAR/ Deedwania PC et al
||Effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on atherogenic
dyslipidemia in patients with characteristics of the metabolic syndrome.
||American Journal of Cardiology 2005 Vol 95(3): 360-366.
|URANUS/ Sorof J et al
||Renal safety of rosuvastatin and atorvastatin in type 2 diabetic patients.
||Atherosclerosis Supplements 2005;(1):W16-083.
|ANDROMEDA/ Betteridge DJ et al||Effect of rosuvastatin and atorvastatin on CRP levels in patients with type 2 diabetes: results from the andromeda study. (abstract)||Atherosclerosis Supplements 2005;6(1):W16-007.|
|DISCOVERY DUTCH/ Bots AFE et al||Achieving lipid goals in real life: the Dutch DISCOVERY Study.||International Journal of Clinical Practice 2005;(12):1387-94.|
|DISCOVERY PENTA/Fonseca FAH et al
||The discovery penta study: A direct statin comparison of LDL-C value - an evaluation
of rosuvastatin therapy compared with atorvastatin.
||Current Medical Research & Opinion 2005 Vol 21(8):1307-1315
|MERCURY I/ Schuster H et al
||Measuring effective reductions in cholesterol using rosuvastatin therapy (MERCURY
I): Achievement of LDL-C goals with updated ATP III recommendations.
|Atherosclerosis Supplements 2005;6(1):W16-079.
|PULSAR/ Clearfield M et al||Efficacy and safety of rosuvastatin 10 mg versus atorvastatin 20 mg: results of the pulsar study.||Atherosclerosis Supplements 2005;6(1):W16-014.|
|RADAR/ Dallinga TM et al
||Effect of rosuvastatin and atorvastatin treatment on LPAI and LPAI:AII in patients
with coronary artery disease and low HDL cholesterol.
||Atherosclerosis Supplements 2005;6(1):49.
|ARIES/ Ferdinand K et al
||Effect of Statin Therapy on C-Reactive Protein Levels Among African American Patients
with Hypercholesterolemia: Results of Aries Trial.
||Journal of the American College of Cardiology 2005;45(3):A437-5.
|DISCOVERY CANADA/ Gupta M et al||Direct statin comparison of LDL-C values: an evaluation of rosuvastatin therapy (discovery - Canada).||Atherosclerosis Supplements 2005;6(1):W16-033.|
|POLARIS/ Leiter LA et al
||Efficacy of rosuvastatin 40 mg versus atorvastatin 80 mg in patients with the metabolic
syndrome: results from a subgroup of the POLARIS study.
|COMETS/ Stalenhoef AFH et al
||A COmparative study with rosuvastatin in subjects with METabolic Syndrome: Results
of the COMETS study.
||European Heart Journal 2005 Vol 26(24): 2664-2672)
|DISCOVERY TRIPLE COUNTRY/ Strandberg TE et al||Discovery: a comparison of efficacy and safety of rosuvastatin and atorvastatin in high-risk subjects with hypercholesterolaemia.||International Journal of Clinical Practice 2005;59(Suppl:148):148.|
|CORALL/ Wolffenbuttel BHR et al||Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes - CORALL study.||Journal of Internal Medicine 2005 Vol 257(6): 531-539).|
8. Results of trials
The submission stated that the results of the meta-analyses supported the conclusion
that rosuvastatin gave rise to a statistically significantly larger % reduction in
LDL-C than twice the strength of atorvastatin and that there was no statistically
significant difference between rosuvastatin and four times the atorvastatin strength.
This analysis suggested that the rosuvastatin: atorvastatin equivalent dose ratio
was greater than 1:2, but less than 1:4. The PBAC agreed that this conclusion appeared
consistent with the results of meta-analyses that were produced during the evaluation.
A meta-analysis comparing rosuvastatin 10 mg and simvastatin 20 mg was also presented. The results of the meta-analysis conducted during the evaluation were consistent with the results of the submission’s meta analysis, that rosuvastatin gave rise to a statistically significantly larger % reduction in LDL-C than twice the strength of simvastatin. No statistically significant heterogeneity was observed across simvastatin trials.
9. Clinical Claim
The submission claimed that rosuvastatin is no worse, in terms of LDL-C lowering efficacy
and safety, than atorvastatin, when compared assuming a therapeutic relativity of
rosuvastatin 1 mg: atorvastatin 3 mg.
10. Economic analysis
A preliminary economic evaluation was presented. The choice of a cost-minimisation
approach was valid. The resources included were drug costs.
A modelled economic evaluation was appropriately not presented.
11. Estimated PBS Usage and Financial Implications:
The overall statin market was not expected to grow more rapidly as a result of listing
12. Recommendations and Reasons
The PBAC recommended listing on a cost-minimisation basis with atorvastatin, with
the ratio of equi-effective doses being rosuvastatin to atorvastatin1:3. This recommendation
is based on the series of meta-analyses presented in the submission of 29 randomised
trials comparing rosuvastatin with atorvastatin or simvastatin. The PBAC agreed that
atorvastatin was the most appropriate comparator, as this is the drug that will principally
be replaced in practice.
The PBAC considered it appropriate that a NOTE be included in the PBS listing, indicating that the highest strength, 40 mg, should be prescribed with caution as described in the approved Product Information. The PBAC requested that the National Prescribing Service considers developing a RADAR article on this product to highlight this issue. The PBAC also requested that the sponsor develop a QUM strategy to address this issue.
Rosuvastatin calcium, tablets, 5 mg, 10 mg, 20 mg, 40 mg
For use in patients that meet the criteria set out in the General Statement for Lipid Lowering Drugs. Note: Doses higher than 20 mg per day should be used with caution. See Product Information.
Maximum quantity: 30
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be subsidised in Australia.
It considers submissions in this context. A PBAC decision not to recommend listing
or not to recommend changing a listing does not represent a final PBAC view about
the merits of the medicine. A company can resubmit to the PBAC or seek independent
review of the PBAC decision.
14. Sponsor’s Comment
Rosuvastatin was the subject of a pre-registration development and safety program, which exceeded that of all the other statins combined. The available evidence shows that rosuvastatin provides superior LDL-C lowering efficacy and the toxicity profile is not different than that of the other listed statins. These data also show that the toxicity profile of the highest dose of rosuvastatin is no different than that of the highest doses of the other statins. All high dose statins should be used with caution.