Ramipril with Felodipine, tablets, 2.5 mg-2.5 mg, 5 mg-5 mg Triasyn®, March 2007
Public summary document for Ramipril with Felodipine, tablets, 2.5 mg-2.5 mg, 5 mg-5 mg Triasyn®, March 2007
Page last updated: 29 June 2007
Public Summary Document
Product: Ramipril with Felodipine, tablets, 2.5
mg-2.5 mg, 5 mg-5 mg Triasyn®
Sponsor: Sanofi-Aventis Australia Pty Ltd
Date of PBAC Consideration: March 2007
1. Purpose of Application:
The submission sought listing for the treatment of hypertension in
patients who are not adequately controlled with either ramipril or
felodipine monotherapy, or who are receiving ramipril and
felodipine concurrently.
2. Background:
This product has not been previously considered by the PBAC.
3. Registration Status:
The product was registered by the TGA on 2 December 1998 for the
treatment of mild to moderate hypertension. This combination should
not be used to commence therapy.
4. Listing requested and PBAC’s View
Restricted benefit
For the treatment of hypertension in patients who are not
adequately controlled with either ramipril or felodipine
monotherapy, or who are receiving ramipril and felodipine
concurrently.
See Recommendation and Reasons for PBAC’s
view.
5. Clinical place for the proposed therapy:
Triasyn will be used predominantly by patients who are currently
treated with felodipine or ramipril (or both concomitantly) for the
treatment of hypertension.
6. Comparator:
The submission nominated ramipril and felodipine extended release
(ER) monotherapies as the appropriate comparators.
7. Clinical trials:
The scientific basis of comparison consisted of four randomised head-to-head studies
comparing the short-term efficacy and safety of ramipril and felodipine combination
therapy to either ramipril or felodipine monotherapy in the treatment of hypertension.
A meta-analysis pooling the results of three of these trials was presented.
The following is the list of trials forming the basis of the submission.
List of trials forming the basis of the submission
| Parallel-group trial | |
| Trial/Author | Title/Source |
| Study B1 HOE/9869/2/303/HT Published as: Scholze J et al. |
Randomised double-blind multicentre study of the efficacy, tolerability and safety of various combinations of ramipril (HOE 498) and felodipine ER in patients with mild to moderate essential hypertension Antihypertensive profiles with ascending dose combinations of ramipril and felodipine ER. Clinical & Experimental Hypertension (New York). 21(8):1447-62, 1999 Nov |
| Study B2 CF -501 |
Efficacy and tolerability of two fixed combinations of felodipine ER and ramipril in hypertensive patients. An international multicentre study |
| Study B3 HOE/9869/2/MN/304/HT Published as: Poisson P et al. |
Randomised double-blind study of the efficacy and safety of the fixed combination 2.5mg ramipril/2.5mg felodipine ER (HOE 9869) compared to the components in hypertensive patients Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy versus combination therapy. Current Medical Research & Opinion. 13(8):445-56, 1996. |
| Study B4 HOE 498/2/B/302/HT |
Randomised double-blind study of the efficacy, safety and tolerability of the combination of 5mg ramipril and 5mg felodipine daily vs. 5mg ramipril daily in subjects suffering from mild to moderate uncomplicated essential hypertension unresponsive to monotherapy with 5mg ramipril daily |
8. Results of trials
Two of the four trials compared the reduction in diastolic blood
pressure (DBP) and systolic blood pressure (SBP) of combination
therapy with felodipine 5mg monotherapy. The results in supine DBP
showed that the contribution of ramipril 5mg varied from –2.3
to –2.7mmHg. The mean differences in reduction of supine SBP
were larger and ranged from –2.8 to –9.5mmHg.
Three of the trials compared the additive effect of felodipine 5mg.
The reductions of supine DBP varied from –3.2 to
–5.8mmHg, greater than the clinically important margin of
2mmHg. The reductions in supine SBP ranged from –4.8 to
–9.5mmHg. The results suggested that the addition of
felodipine 5mg to ramipril 5mg produced a greater reduction in DBP
than the addition of ramipril 5mg to felodipine 5mg, which was also
supported by the results of the meta-analysis.
For the comparisons between felodipine/ramipril 2.5/2.5 mg versus
either felodipine or ramipril monotherapy in doses of 2.5 mg and 5
mg, the mean change in supine DBP ranged from –1.09 to -
2.1mmHg. The reductions of SBP of the combination
(felodipine/ramipril 2.5/2.5 mg) over felodipine 2.5 mg or ramipril
2.5 mg were
–4.3mmHg and –3.3mmHg respectively and were
statistically significant.
Triasyn had similar side effects to the individual components,
ramipril and felodipine. The common side effects were headache, dry
cough, dizziness, and hot flushes.
9. Clinical Claim
On the basis of the results presented, and because a
cost-minimisation approach was most appropriate for this
combination product, the category that best described the proposed
drug is that the drug is considered to be no worse than the main
comparator in terms of effectiveness and toxicity.
See Recommendations and Reasons for PBAC’s
view
10. Economic analysis
The preliminary economic evaluation presented adopted a cost
minimisation approach. The resources included were drug costs
only.
11. Estimated PBS Usage and Financial Implications:
The number of patients was estimated to be < 10,000 in Year
4.
The submission estimated that the financial impact to government is
likely to be modest savings of less than $45,000 per year.
12. Recommendation and Reasons:
The PBAC recommended listing on a cost-minimisation basis compared
with the corresponding strengths of the ramipril and felodipine
components given concomitantly.
The PBAC expressed concern that the combination product does not
provide all the dose possibilities afforded by the single agent
products, with ramipril available in four, and felodipine available
in three strengths, respectively. While this was expected to make
dose titration more difficult in the clinical setting, it did not
constitute a reason for rejection.
Recommendation
RAMIPRIL with FELODIPINE, tablets, 2.5 mg-2.5 mg, 5 mg-5 mg
Restriction: Restricted benefit
Hypertension in a patient not adequately controlled with either
ramipril or felodipine monotherapy. 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
Sanofi-aventis welcomes the PBAC’s positive recommendation of
Triasyn. Sanofi-aventis feels that Triasyn will be a useful
addition in the treatment of hypertension.
