Aerospan tm (flunisolide hfa, 80 mcg) Inhalation Aerosol For Oral Inhalation Only Rx Only description

Disposition and Elimination:
Twice daily inhalation administration of flunisolide 
hemihydrate for up to 14 days did not result in appreciable accumulation of flunisolide.
Upon multiple dosing with 160 mcg and 320 mcg, the C
max
values were 1.0 ng/mL and 
2.1 ng/mL, respectively. The corresponding AUC
0-12hr
values were 1.2 ng.hr/mL and 2.5 
ng.hr/mL. 
Flunisolide is rapidly cleared from the body, independent of route of administration or 
dose administered. Flunisolide is not detectable in plasma twelve hours post-dose. After 
administration of 320 mcg of AEROSPAN Inhalation Aerosol the elimination half-life 
ranges from 1.3 to 1.7 hours. After a single 320 mcg dose, mean oral clearance values, 
not adjusted for bioavailability, range from 83 to 167 L/hr. 
 
Special Populations
: There were no gender differences for flunisolide after single and 
multiple dose administration of the AEROSPAN Inhalation Aerosol. Formal 
pharmacokinetic studies using flunisolide were not carried out in any other special 
populations. 
Pharmacodynamics:
Dose finding for AEROSPAN Inhalation Aerosol was based on 
comparability of systemic exposure to flunisolide CFC inhalation aerosol. The effect of 
flunisolide CFC inhalation aerosol and AEROSPAN Inhalation Aerosol on 
pharmacokinetics and 12-hour plasma cortisol levels was investigated in two studies. In 
both studies, the Cmax and AUC of flunisolide, 6
β
-OH flunisolide, and 12-hour plasma 
cortisol measurements were comparable for 1000 mcg of flunisolide CFC inhalation 
aerosol and 320 mcg of AEROSPAN Inhalation Aerosol. The first was a parallel arm 
study in 31 subjects. Pharmacokinetics and plasma cortisol levels were determined after 
single and multiple doses of flunisolide CFC inhalation aerosol 1000 µg and 
AEROSPAN Inhalation Aerosol 160 µg or 320 µg administered twice daily for 13.5 
days. At steady state, flunisolide mean peak plasma concentrations from flunisolide CFC 
inhalation aerosol 1000 mcg and AEROSPAN Inhalation Aerosol 320 mcg were found to 
be 2.6 ng/mL and 3.4 ng/mL, respectively. The corresponding mean AUC values for the 
12-hr dosing interval were 5.7 ng.hr/mL and 4.7 ng.hr/mL, respectively. At steady state, 
the mean peak plasma concentrations of 6
β
-OH flunisolide from flunisolide CFC 
inhalation aerosol 1000 mcg and AEROSPAN Inhalation Aerosol 320 mcg were found to 
be 0.9 ng/mL and 0.3 ng/mL, respectively. The corresponding mean AUC values for the 
12-hr dosing interval were 3.8 ng.hr/mL and 1.1 ng.hr/mL, respectively. The second was 
a crossover study in 11 subjects after single doses of flunisolide CFC inhalation aerosol 
1000 mcg or AEROSPAN Inhalation Aerosol 320 mcg. The mean peak plasma 

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concentrations of flunisolide from the flunisolide CFC inhalation aerosol 1000 mcg and 
AEROSPAN Inhalation Aerosol 320 mcg were found to be 2.5 ng/mL and 3.3 ng/mL, 
respectively. The corresponding mean AUC values were 5.1 ng.hr/mL and 5.8 ng.hr/mL, 
respectively. The mean peak plasma concentrations of 6
β
-OH flunisolide from 
flunisolide CFC inhalation aerosol 1000 mcg and AEROSPAN Inhalation Aerosol 320 
μ
g were found to be 0.8 ng/mL and 0.3 ng/mL, respectively. The corresponding mean 
AUC values were 3.8 ng.hr/mL and 2.3 ng.hr/mL, respectively.
Controlled clinical studies with flunisolide CFC inhalation aerosol included over 500 
treated asthma patients, among them 150 children aged 6 years and older. Open label 
studies of two years or more duration included more than 120 treated patients. No 
significant adrenal suppression attributed to flunisolide was seen in these studies.
The potential effects of AEROSPAN Inhalation Aerosol and flunisolide CFC inhalation 
aerosol on the hypothalamic-pituitary-adrenal (HPA) axis were studied in 2 placebo- and 
active-controlled studies and 2 active-controlled, open label, long-term studies (see 
CLINICAL TRIALS). In the placebo-controlled studies, the ability to increase cortisol 
production in response to stress was assessed by the 60 minute cosyntropin (ACTH) 
stimulation test. For adult and adolescent patients treated with AEROSPAN Inhalation 
Aerosol 80 mcg, 160 mcg, 320 mcg, or placebo twice daily for 12 weeks, 92% (22/24), 
93% (26/28), 93% (26/28), and 92% (22/24) of patients, normal at baseline, respectively, 
continued to have a normal stimulated cortisol response (peak cortisol 
≥
18 mcg/dL and 
an increase in plasma cortisol 
≥
7 mcg/dL within 60 minutes after cosyntropin injection) 
at trial’s end. All patients had peak cortisol levels 
≥
18mcg/dL. There was no significant 
suppression of 24 hour urinary cortisol, and 100% (96/96) of patients treated with 
AEROSPAN Inhalation Aerosol had normal morning serum cortisol levels at the end of 
study. For pediatric patients treated with the AEROSPAN Inhalation Aerosol, 80 mcg 
and 160 mcg or placebo twice daily for 12 weeks, 91% (31/34), 97% (28/29), and 89% 
(24/27) of patients, respectively, continued to have a normal stimulated cortisol response 
(as defined above) at trial’s end. No suppression of 24-hour urinary cortisol was noted.
In these studies, comparable results were obtained in patients treated with flunisolide 
CFC inhalation aerosol. 
In the active-controlled, open label, long-term studies, 99.4% (161/162) of adult and 
adolescent patients and 98.4% (126/128) pediatric patients treated with AEROSPAN 
Inhalation Aerosol had normal morning serum cortisol levels (
≥
5 mcg/dL) after 12 or 52 
weeks of treatment, respectively. For patients treated with AEROSPAN Inhalation 
Aerosol, 92.5% (99/107) continued to have a normal stimulated plasma cortisol response 
to cosyntropin at trial’s end with all having peak cortisol levels 
≥
18mcg/dL. In these 
studies, no suppression of 24-hour urinary cortisol was noted, and comparable results 
were obtained in patients treated with flunisolide CFC inhalation aerosol.