ADVAIR DISKUS ADVAIR - GlaxoSmithKline

Over the 3 year treatment period of study SCO30003, FEV 1 values were also higher in
patients treated with ADVAIR ® DISKUS ® 50/500 mcg than for those treated with
placebo (average difference over 3 years 92 mL, 95% CI: 75 to 108 mL; p < 0.001).
ADVAIR ® DISKUS ® was also more effective than salmeterol or fluticasone propionate
in improving FEV 1 (average difference over 3 years 50 mL, p < 0.001 for salmeterol and
44 mL, p < 0.001 for fluticasone propionate). Averaged over the 3 years of the study,
patients treated with ADVAIR ® DISKUS ® showed a +29 mL increase from baseline in
post-bronchodilator FEV 1 while the placebo, salmeterol and fluticasone propionate
groups demonstrated a decline of -62 mL, -21 mL, and -15 mL, respectively.
TOXICOLOGY
Note: For complete information on the toxicology of the individual compounds
salmeterol xinafoate and fluticasone propionate, please refer to the SEREVENT ® and
FLOVENT ® Product Monographs.
Acute Toxicity
The experimental details of single dose studies are presented below:
Species
(strain)
Route of
Administration
Nominal Exposure
Concentrations (mcg/L)
(Salmeterol xinafoate:
Fluticasone propionate)
Initial
Group
M
F
Duration
of Treatment
(Days)
Rat
(Wistar)
Inhalation
(dry powder)
0:0
75:40
0:0
10:20
20:40
10 10
10 10
5 5
5 5
5 5
1
Rat
(Wistar)
Inhalation
(dry powder)
0:0
1:2
2:4
5:10
10:20
20:40
7 7
7 7
7 7
7 7
7 7
7 7
1
Rat
(Wistar)
Inhalation
(dry power)
0:0
75:0
75:40
10 0
10 0
10 0
1
High single inhaled doses of combinations of salmeterol xinafoate and fluticasone
propionate were well-tolerated by rats. With one exception (mild atrial myocarditis), all
findings were expected at the doses of salmeterol xinafoate and fluticasone propionate
administered.
Mild atrial myocarditis occurred at combination doses of 28 mcg/kg salmeterol with
73 mcg/kg fluticasone propionate, or higher, at which plasma drug concentrations were at
least 30 times (salmeterol) or 26 times (fluticasone propionate) greater than peak levels in
July 29, 2014
Page 48 of 67