Amlodipine besylate with Valsartan, tablet, 5 mg-80 mg, 5 mg-160 mg, 10 mg-160 mg, Exforge® 5/80, Exforge®5/160, Exforge®10/160, July 2008
Public summary document for Amlodipine besylate with Valsartan, tablet, 5 mg-80 mg, 5 mg-160 mg, 10 mg-160 mg, Exforge® 5/80, Exforge®5/160, Exforge®10/160, July 2008
Page last updated: 31 October 2008
Public Summary Documents
Product: Amlodipine besylate with Valsartan,
tablet, 5 mg-80 mg, 5 mg-160 mg, 10 mg-160 mg, Exforge® 5/80,
Exforge®5/160, Exforge®10/160
Sponsor: Novartis Pharmaceuticals Australia Pty
Ltd
Date of PBAC Consideration: July 2008
1. Purpose of Application
To seek a restricted benefit listing for hypertension in patients
who are not adequately controlled with either amlodipine or
valsartan monotherapy.
2. Background
This combination drug had not previously been considered by the
PBAC. Amlodipine is an unrestricted benefit and has been listed on
the PBS since August 1993, while valsartan has been recommended for
PBS listing on a number of occasions.
3. Registration Status
Exforge was registered by the TGA on 5 February 2008 for the
treatment of hypertension. Treatment should not be initiated with
this fixed dose combination.
4. Listing Requested and PBAC’s View
Restricted Benefit
Hypertension in patients who are not adequately controlled with
either amlodipine or valsartan monotherapy
For PBAC’s view, see Recommendation and
Reasons.
5. Clinical Place for the Proposed Therapy
The combination of valsartan and amlodipine allows more effective blood pressure reduction than the respective monotherapies, and the fixed combination tablet will reduce the tablet burden in patients requiring different types of anti-hypertensive medications
.
6. Comparator
The submission nominated the individual components of the fixed
dose combination, i.e. valsartan and amlodipine as the comparator.
The PBAC considered this was appropriate.
7. Clinical Trials
The submission presented nine randomised trials comparing fixed
dose valsartan/amlodipine (various dose combinations) with
corresponding doses of either valsartan or amlodipine monotherapies
in patients with hypertension. The submission presented two
pharmacokinetic studies comparing fixed combination vs free
components.
The trials published at the time if submission are as follows:
| Trial/Author | Protocol title/Publication title | Publication citation |
| Study 2201 | Two Multicenter, 8-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Studies Evaluating the Efficacy and Tolerability of Amlodipine and Valsartan in Combination and as Monotherapy in Adult Patients with Mild to Moderate Essential Hypertension. | Philipp T ,et al. Clinical Therapeutics 29(4): 563-580 |
| Amlodipine and Valsartan Combined and as Monotherapy in Stage 2, Elderly and Black Hypertensive Patients: Subgroup Analyses of 2 Randomised, Placebo-Controlled Studies. | Smith TR,et al. Journal of Clinical Hypertension 9(5): 355-364 | |
| Study 2307 | A Randomised, Double-Blind, Multi-centre, Multifactorial, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Valsartan (160mg and 320mg) and Amlodipine (10mg) Combined and Alone in Hypertensive Patients. 2005. Novartis Pharmaceuticals. | Same as citations for Study 2201. |
| Fogari et al, 2007 | Effect of Valsartan Addition to Amlodipine on Ankle Oedema and Subcutaneous Tissue Pressure in Hypertensive Patients. | Journal of Human Hypertension 21: 220-224 |
8. Results of Trials
The key results from the trials evaluating the mean change in blood
pressure showed there was a statistically significant difference in
diastolic/systolic blood pressure (D/SBP), favouring
valsartan/amlodipine combination therapy, compared to either drug
alone, which is likely to be clinically important because the
trials were generally powered to detect differences ranging from
2mmHg to 3.5mmHg.
The results from the pharmacokinetic studies showed that the
valsartan/amlodipine combination product, compared to the products
alone could be considered equivalent.
The occurrence of adverse events was low and consistent with the
side effect profiles of the two component monotherapies. The most
common adverse events were oedema and headache.
For PBAC’s comments on these results, see Recommendations
and Reasons.
9. Clinical Claim
The submission claimed the fixed combination is as effective as the
individual components given concomitantly and also claimed superior
efficacy for the combination product compared to constituent
monotherapies.
The PBAC noted that there is currently no evidence to support an
advantage in efficacy, safety or compliance for this combination
product over alternative therapy.
For PBAC’s view, see Recommendations and
Reasons.
10.Economic Analysis
The submission presented a cost minimisation analysis. The
equi-effective doses were estimated as fixed valsartan/amlodipine
combination once daily and concomitant valsartan and amlodipine
once daily.
11. Estimated PBS Usage and Financial Implications
The submission estimated the financial cost per year to the PBS to
be less than $10 million per year in Year 4. The PBAC considered
this to be an underestimate.
12. Recommendation and Reasons
The PBAC recommended listing of amlodipine with valsartan in
accordance with the combination guidelines, on a cost-minimisation
basis compared with its constituent components, amlodipine and
valsartan at equivalent doses.
The PBAC noted that valsartan will be supplied on the PBS from 1
March 2009 and therefore this combination product can only be
listed from that date.
The PBAC also noted that there is currently no evidence to support
an advantage in efficacy, safety or compliance for this combination
product over alternative therapy in accordance with subsection 101
(4AC) of the National Health Act.
Recommendation
AMLODIPINE BESYLATE with VALSARTAN, tablet, 5 mg-80 mg, 5 mg-160
mg, 10 mg-160 mg
Restriction: Restricted Benefit
Hypertension in patients who are not adequately controlled with
either amlodipine or valsartan monotherapy
Maximum quantity: 28
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
The sponsor chose not to comment.
