Amlodipine Besylate with Atorvastatin Calcium, tablets, 5 mg (base)-10 mg, 5 mg (base)-20 mg, 5 mg (base)-40 mg, 5 mg (base)-80 mg, 10 mg (base)-10 mg, 10 mg (base)-20mg, 10 mg (base)-40 mg, 10 mg (base) – 80 mg, Caduet®, July 2006
Page last updated: 27 October 2006
PDF version of this page (PDF 125 KB)
Public Summary Document
Product: Amlodipine Besylate with Atorvastatin Calcium, tablets, 5 mg (base)-10 mg, 5 mg
(base)-20 mg, 5 mg (base)-40 mg, 5 mg (base)-80 mg, 10 mg (base)-10 mg, 10 mg (base)-20mg,
10 mg (base)-40 mg, 10 mg (base) - 80 mg, Caduet®
Sponsor: Pfizer Australia Pty Limited
Date of PBAC Consideration: July 2006
1. Purpose of Application
The submission sought a restricted benefit listing for a fixed combination of amlodipine
besylate and atorvastatin calcium for a subset of patients with concomitant hypertension
and dyslipidaemia or concomitant angina and dyslipidaemia.
2. Background
This fixed combination had not previously been considered by the PBAC.
3. Registration Status
Caduet was registered on the 14 July 2005 for patients in whom treatment with amlodipine
and atorvastatin is appropriate at the doses presented.
4. Requested Listing and PBAC’s view
Restricted benefit
For use in patients who have hypertension and/or angina and who meet the criteria
set out in the General Statement for Lipid-Lowering Drugs, and:
- Who are currently receiving treatment with a dihydropyridine calcium channel blocker;
OR - Whose blood pressure and/or angina is inadequately controlled with other classes of
antihypertensive and/or anti-anginal agent, and in whom adjunctive therapy with a
dihydropyridine calcium channel blocker would be appropriate;
OR - Who are intolerant of the side effects of other classes of antihypertensive and/or anti-anginal agent, and in whom replacement therapy with a dihydropyridine calcium channel blocker would be appropriate.
For the PBAC’s view, see Recommendation and Reasons
5. Clinical place for the proposed therapy
Caduet will be used predominantly by patients who are currently treated with concomitant
amlodipine and atorvastatin for the treatment of hypertension and dyslipidaemia.
6. Comparator
The submission nominated amlodipine co-administered with atorvastatin as the comparator.
The PBAC accepted this as appropriate.
7. Clinical trials
The submission presented one non-randomised, non-comparative, open-label study of
amlodipine + atorvastatin fixed dose combination tablets 5 mg/10 mg, 5 mg /20 mg,
5 mg/40 mg, 5 mg/80 mg, 10 mg/10mg, 10 mg/20 mg, 10 mg/40 mg and 10 mg/80 mg in patients
with hypertension and dyslipidaemia over 14 weeks (hereafter referred to as the GEMINI
study) and data from eight bioequivalence studies. The Gemini study was published
at the time of the submission as follows:
| Trial/First author | Study Name | Publication citation |
|---|---|---|
| GEMINI/ Blank et al. | Single-pill therapy in the treatment of concomitant hypertension and dyslipidaemia (the amlodipine/atorvastatin Gemini study) | J Clin Hypertens 2005; 7:264-273. |
8. Results of trials
The key results of the GEMINI study are summarised in the table below.
Attainment of lipid and/or blood pressure goals in the GEMINI study
| Outcome | All patients | Group I* | Group II† | Group III‡ |
|---|---|---|---|---|
| ITT population | ||||
| Lipid + blood pressure goals |
692/1199 (57.7%) |
125/162 (77.2%) |
354/465 (76.1%) |
213/572 (37.2%) |
| Blood pressure goal alone |
790/1207 (65.5%) |
126/163 (77.3%) |
373/468 (79.7%) |
291/576 (50.5%) |
| Lipid goal alone |
985/1200 (82.1%) |
158/162 |
437/465 (94.0%) |
390/573 (68.1%) |
| Patients with uncontrolled LDL-C at baseline | ||||
| Lipid + blood pressure goals |
389/749 |
48/67 |
214/281 (76.2%) |
127/401 (31.7%) |
| Blood pressure goal alone |
470/750 |
49/67 |
224/281 (79.7%) |
197/402 (49.0%) |
| Lipid goal alone |
560/750 |
64/67 |
261/281 (92.9%) |
235/402 (58.5%) |
* Group I: hypertension and dyslipidaemia with no additional cardiovascular (CV) risk
factors.
† Group II: hypertension and dyslipidaemia with at least one additional CV risk factor
excluding coronary heart disease (CHD) and diabetes mellitus (DM).
‡ Group III: hypertension and dyslipidaemia with CHD or CHD risk equivalent (DM or
other atherosclerotic disease.
The primary efficacy results were analyses for all patients and by cardiovascular
risk groups. At end point, 57.7% of patients treated with amlodipine + atorvastatin
fixed dose combination tablets attained both their blood pressure and lipid goals.
Attainment of both goals was highest in Group I and II (77.2% and 76.1% respectively)
and lowest in Group III (35.3%) indicating that patients with 0-1 additional cardiovascular
risk factor (excluding coronary heart disease and diabetes) had the highest rate of
attainment. When each treatment goal was considered separately, a similar pattern
was observed, although more patients achieved their lipid goal than blood pressure
goal (82.1% versus 65.5%). When efficacy data on patients with LDL-C uncontrolled
at baseline were analysed separately, results obtained suggest that the pattern of
goal attainment was similar to that observed in the ITT population, although the difference
in the proportion of patients who achieved lipid goal versus proportion of patients
who reached blood pressure goal was smaller.
Results from the eight bioequivalence studies, presented as supportive evidence, suggested
that, in young healthy volunteers, the systemic bioavailability of amlodipine and
atorvastatin components from the combination tablets 5 mg/10 mg, 10 mg/40 mg and 10
mg/80 mg was similar to that from the co-administration of the corresponding monotherapies.
In the GEMINI study 64.1% of patients reported at least one adverse event. The most
commonly reported adverse events were respiratory tract infection (11.9%), peripheral
oedema (8.8%), headache (5.4%) and myalgia (4.2%). The incidence of serious adverse
events during the study appeared to be low (2.7%) with no events attributable to the
study drug. There were no serious events that correlated with myopathy, myositis,
rhabdomyolysis or abnormal/increased in alanine aminotransferase, aspartate aminotransferase
or creatine phosphokinase.
9. Clinical Claim
The submission claimed that the amlodipine + atorvastatin fixed dose combination tablets
are no worse than the corresponding strengths of amlodipine co-administered with atorvastatin
in terms of effectiveness and toxicity.
10. Economic Analysis
The submission presented a cost-minimisation analysis. The PBAC considered the choice
of a cost-minimisation approach valid.
11. Estimated PBS Usage and Financial Implications
The submission estimated that in Year 4 of listing the likely number of patients treated
would be between 10,000 and 50,000 per year and the financial cost per year to the
PBS would be < $10 million.
12. Recommendation and Reasons
The PBAC recommended listing on a cost-minimisation basis compared with the corresponding
strengths of the amlodipine and atorvastatin constituents. The PBAC noted the sponsor
had agreed to remove the Therapeutic Group premium that currently applies to the amlodipine
single agent product from the combination amlodipine with atorvastatin product.
The Committee requested that the DUSC monitor usage.
The PBAC recommended the 20 day safety net rule should apply.
Recommendation
Amlodipine Besylate with Atorvastatin Calcium, tablet, 5 mg (base)-10 mg, 5 mg (base)-20
mg, 5 mg (base)-40 mg, 5 mg (base)-80 mg, 10 mg (base)-10 mg, 10 mg (base)-20mg, 10
mg (base)-40 mg, 10 mg (base) - 80 mg Restriction: Restricted benefit
For use in patients who have hypertension and/or angina and who meet the criteria
set out in the General Statement for Lipid-Lowering Drugs, and:
- who are currently receiving treatment with a dihydropyridine calcium channel blocker;
OR - whose blood pressure and/or angina is inadequately controlled with other classes of
antihypertensive and/or anti-anginal agent, and in whom adjunctive therapy with a
dihydropyridine calcium channel blocker would be appropriate;
OR - who are intolerant of the side effects of other classes of antihypertensive and/or anti-anginal agent, and in whom replacement therapy with a dihydropyridine calcium channel blocker would be appropriate.
Maximum quantity: 30
Repeats: 5
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:
Pfizer Australia (the Sponsor) welcomes the PBAC recommendation to list Caduet on the PBS. The Sponsor believes the availability of the fixed combination will allow prescribers to simplify and integrate the management of a patients overall cardiovascular risk.
