Seretide

1
Seretide Asthma Control through Synergy
2
Seretide Accuhaler One Breath with Symptom-free
Anti-inflammation
3
Synergetic Action of Seretide Fluticasone
Salmeterol
Corticosteroid receptor
C-AMP MAPK
4
Mean change from baseline in morning pre-dose
FEV1 during treatment with Seretide50/100 bd,
Fluticasone, Salmeterol or placebo
FP 250 ?g BID
Change in FEV1 (L)
Placebo
SALM 50 ?g BID
Seretide 50/100 ?g BID
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0.1
1
2
3
4
5
7
9
11
6
8
10
12
Baseline
Endpoint
Weeks
J Allergy Clin Immunol 20001051108-1116
5
Change from bseline in PEFRam during treatment
with Seretide 50/100 bd or Budesonide 400 mcg bd
500
Seretide 50/100
Budesonide 400
100
480
460
p0.006
95
440
420
Percent predicted PEFRam
400
Mean PEFRam (L/min)
90
380
360
85
340
320
300
80
-2
-1
0
1
2
3
4
5
6
7
8
9
10
11
12
Seretide
Budesonide
Weeks of treatment
Mean PEFRam over 12 weeks
Am J Respir crit Care Med 1999159(3 part 2)637-
6
Significantly greater improvement in FEV1 with
Seretide than FP plus montelukast
Seretide 50 / 100 µg bd
Mean PEF am (L/min)
FP 100 µg bd MONT 10 mg od
420

410
400
390
380
370
360
Mean1-12
Run-in
1-2
3-4
5-6
7-8
9-10
11-12
Week
p lt 0.05
Ringdal, ATS, 2001
7
Serial FEV1 after One Week of Treatment with
Seretide, FP, SALM or Placebo
Mean change from baseline in serial FEV1 (L)
Placebo
Seretide 50/250 ?g BID
0.8
SALM 50 ?g BID
FP 250 ?g BID
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
0.1
2
1
3
4
6
8
10
12
Baseline
Time (hours)
Am J Respir Crit Care Med 2000
8
Significantly Less Exacerbation after Seretide
Treatment
Am J Respir Crit Care Med 2000
9
Seretide Control for Patients Means a Change in
Their Quality of Life
Placebo SALM 50µg bd
FP 250µg bd Seretide 50/250µg bd
1.2
1.02
0.8
0.56
Mean change from baseline
0.4
- 0.11
- 0.27
0
(n 90)
(n 86)
(n 84)
(n 83)
-0.4
Reese et al ERJ 1998
10
Significantly Greater Improvement in am PEF with
Seretide vs BUD over 24 Weeks of Treatment
Adjusted mean am PEF (L/min)
420
Seretide
50/250 ?g BID

410



BUD

400
800 ?g BID
390
380
Treatment difference plt0.001
370
360
350
340
14
58
124
1324
912
Baseline
Weeks
Jenkins et al. Respir Med 2000
11
Control of Symptom-free Days Seretide 50/250 vs
budesonide 800
Respir Med 2000 94(7) 715-723
12
Similar Improvement in am PEF with Seretide and
Concurrent SALM FP
Mean am PEF (L/min)
460

450

440

430

420

410

400
Seretide 50/250 ?g BID

390
Concurrent SALM FP

380
0
Weeks
Chapman et al. Can Respir J 1999
13
The Value of Seretide Economic
Outcome measures used to assess cost effectiveness
Definition A week with a mean improvement in
morningpeak expiratory flow of ?5 of the
patientspredicted value compared with baseline
No asthma symptoms during a 24-hour period
Absence of an asthma attack, relief medication,
sleep disturbance or an adverse effect caused by
asthma during a 24-hour period
Outcome measure Successfully treated
week Symptom-free day Episode-free day
PharmacoEconomics 199916(Suppl 2)23-28
14
The value of Seretide economic
Seretide 50/250mcg bd was more cost effective
than budesonide 800mcg bd
Respir Med 2000 94, 724-732
15
SeretideTM (Fluticasone propionate Salmeterol
xinaforate )
gt 12 years and adult 50/ 250 ?g, 1 puff bid
gt 4 years children or adult 50 / 100 ?g, 1 puff
bid
16
Accuhaler (????????) Ease to
use and deliver accurately
17
Accuhaler ??? MDPI
18
Dose Delivered ex-Device During Life of Flixotide
Accuhaler Strips (100 ?g/blister)
120

100
80
label claim
60
40
20
0
Dose number
Prime et al., Pharm. Tech. Eur. 1996
19
Variation in Fine Particle Mass Delivered
ex-Device after Storage at 25 C/60 RH
FP Fluticasone propionate
Prime et al.,Pharm. Tech. Eur. 1996
20
Fine particle mass from Accuhaler inhaler
(salmeterol) vs Turbuhaler (terbutaline)the
effect of humidity
120
100
Accuhaler
(28l/min)
80
60
Fine particle fraction ()
40
Turbuhaler
Turbuhaler (cap removed)
(28l/min)
20
(60l/min)
0
300C/75 RH
0
1
10
20
30
40
50
60
Days
Meakin et al, Int J Pharm 1995
21
Effect of Inspiratory Flow on Delivered Dose (In
Vitro)
of labelled dose
Fluticasone propionate 250?g Accuhaler (n5)
Budesonide 200?g Turbohaler (n5)
Flow rate (L/min)
data from Hill and Slater, Respir. Med. 1996
22
Particle Size and Airway Deposition
No clinical effect. Systemic absorption if
swallowed (not fluticasone propionate)
gt5?m
Clinical effect
2-5 ?m
No clinical effect. Systemic absorption
lt2 ?m
Boyd, Inpharma 1996
23
Fine Particle Mass vs FlowFlixotide Accuhaler
250 mcg
50 40 30 20 10 0
Dose delivered (mcg)
30
40
50
60
70
80
90
100
120
110
Inspiratory flow (l/min)
Bisgaard et al, Am J Resp Crit Care Med, 1996
24
Fine Particle Mass vs Flow Budesonide Turbuhaler
200mcg
60 - 50 - 40 - 30 - 20 - 10 - 0 -
Particles 2 to 5 microns
Fine particles mcg
30
40
50
60
70
80
90
100
Inspiratory flow (l/min)
Bisgaard et al, Am J Resp Crit Care Med, 1996
25
Fine Particle Mass (Particleslt 6?m)
labelled claim lt 6 ?m
28 L/min
60 L/min
Flow Rate
Fluticasone propionate 250?g Accuhaler
Budesonide 200 ?g Turbuhaler
Fuller, J. Aerosol Med. 1995
26
Impact Factors of Turbuhaler

• Total drug in reservoir Not unit-dose
• High channel resistance Inspiratory rate related
• No Lactose

27
Accuhaler ??? Operation
1. ?
2. ??
3. ?
4. ??
28
Overall Preference for AccuhalerTM or
TurbuhalerTM Device
Prefer Accuhaler? to some extent 23 (37
patients)
Overall preference for the Accuhaler? inhaler was
65 plt0.001
Prefer Turbuhaler? to some extent 20 (32
patients)
Strongly prefer Accuhaler? 42 (67 patients)
Strongly prefer Turbuhaler? 14 (23 patients)
Schlaeppi et al., BJCP 1996