Professional Documents
Culture Documents
P(K)
FAISAL YUNUS
Dept. of Pulmonology and Respiratory Medicine
Faculty of Medicine University of Indonesia
Persahabatan Hospital Jakarta
Introduction
Poor
control
Optimal
control
Time (months, weeks, days)
GINA guidelines
Turbuhaler has characteristics of an
ideal inhaler
Ideal inhaler Turbuhaler
Newman SP (1995)
Turbuhaler delivers more drug to the
lungs than Diskus
Lung deposition
(% of nominal dose)
50
40
30
20
10
0
Pulmicort Flixotide
Turbuhaler Diskus
Thorsson L, et al (2001)
Turbuhaler clinically effective at
standard and low inspiratory flow rates
FEV1 (L)
4.0
Standard inhalation
conditions at peak
inspiratory flow of
84 L/min
Low inspiratory flow
3.5 (rate 30 L/min) through
entire inhalation
3.0
0 0.25 0.5 1 2 4
Cumulative dose of terbutaline (mg)
Adapted from Engel T, et al (1992)
Turbuhaler is an effective delivery
device in acute severe asthmatics in the
emergency setting
60
Formoterol 3 x 18 g
50
Change in FEV 1(%)
via Turbuhaler
40
Salbutamol 3 x 800 g
30 via pMDI + spacer
20
Administration of
10 formoterol and
salbutamol
0
-10
0 40 80 120 160 200 240
Time since administration (minutes)
Boonsawat W, et al (2003)
Is this the solution?
GINA/ NIH Guidelines Define optimum
Asthma Control
The Goal
Increased
Symptoms
Reliever
medication
time
Asthma
control
Decreased
Exacerbation Exacerbation
Factors that induce asthma
variability
Allergens
Cigarette smoke
Respiratory infections
Exercise and hyperventilation
Weather changes
Air pollutants, e.g. sulphur dioxide
Food, additives, drugs
Basic principles behind
adjustable maintenance dosing
Recognition that:
asthma is a variable disease
fixed-dosing regimens do not adequately
address this variability
an ideal treatment approach would allow an early
increase in therapy at the first sign of asthma worsening
providing patients with more flexible and effective
treatment
patients prefer fewer inhalers to control their asthma
thus a single inhaler is also desirable
Asthma is a variable disease
A traditional fixed-dose treatment approach results in
periods of poor control as well as periods of overtreatment
Undertreatment
Excessive rescue use
Courses of inhaled/oral steroids
Poor Asthma
control
control
Fixed
dosing
Optimal
control
Time
(months, weeks, days)
Overtreatment
Unnecessary drug intake
Unnecessary drug costs
+ reliever as needed
Hypothesis :
Asthma control may be improved by providing
the right dose of drug at the right time
drug Asthma
inhalations worsening Asthma control
Quickly
gain
control
Step down to adequate
Maintain dose that maintains control
2 inh. control 4 inh.
bid bid*
1 inh. 1 inh. or 2 inh.
bid bid od
Time
+ reliever as needed (months, weeks, days)
*The dosage 4 inh. bid is within the SPC of the
monocomponents but outside the current SPC for Symbicort inh. = inhalation(s)
Formoterol has a rapid onset of
action similar to salbutamol
Mean FEV 1 Formoterol 9 g
(% change from baseline) Formoterol 4.5 g
30 Salbutamol 200 g
25 Salbutamol 100 g
Placebo
20
15
FEV1 at 3 minutes after
10
inhalation: p<0.001 for
5 all active treatments
compared with placebo
0
0 5 10 15 20 25 30
500
450
400
350
300
0 1 2 3 4 5 6 7 8 9 10 11 12
Time after drug administration (hours)
100
80
60
40
20
0
BUD 400 g bid BUD 100 g bid BUD 100 g
+ placebo qid + BUD 200 g qid + placebo qid
Foresi A, et al (2000)
Formoterol reduces severe exacerbations
more effectively than a higher dose of
budesonide in patients with mild to moderate
asthma Increasing BUD: p=0.069
Adding FORM: p<0.001
BUD 200 g + FORM vs BUD 400 g:
1.0
Exacerbations/patient/year
p<0.001
0.5
0
BUD 200 g BUD 200 g BUD 400 g BUD 400 g
+ FORM + FORM
0.5
0
BUD 200 g BUD 200 g BUD 800 g BUD 800 g
+ FORM + FORM
390
380 Symbicort
Budesonide + formoterol
370
Budesonide
360
350
-10 0 10 20 30 40 50 60 70 80 90
Treatment days
Zetterstrm O, et al (2001)
Symbicort has a faster onset
15 *
10
0
* p<0.001 vs. SeretideTM ** p<0.001 vs. SeretideTM
-5
0 3 5 10 15 0.5 1 2 3
Minutes Hours
Symbicort 160/4.5 g 2 inhalations Seretide 50/250 g 1 inhalation
Symbicort 160/4.5 g 1 inhalation placebo
Maintains Maintains
control control Reduce to
lowest adequate
dose that maintains
control
1x2 1x2
* 2x2 2x2 1x1