rials, no significant differences were observed in the pharmacodynamic effects ofsalmeterol (pulse rate, blood pressure, QTc interval, potassium, and glucose) whether thesalmeterol was given as fluticasone propionate and salmeterol DPI, concurrently with fluticasonepropionate from separate inhalers, or as salmeterol alone. The systemic pharmacodynamiceffects of salmeterol were not altered by the presence of fluticasone propionate in the otherfluticasone propionate and salmeterol DPI product.
Other Salmeterol Products in Subjects with Asthma:
Inhaled salmeterol, like other beta-adrenergic agonist drugs, can produce dose-related CV effectsand effects on blood glucose and/or serum potassium [see Warnings and
Precautions (5.11, 5.17)]. The CV effects (heart rate, blood pressure) associated with salmeterolinhalation aerosol occurred with similar frequency, and are of similar type and severity, as thosenoted following albuterol administration.
The effects of rising inhaled doses of salmeterol and standard inhaled doses of albuterol werestudied in volunteers and in subjects with asthma. Salmeterol doses up to 84 mcg administered asinhalation aerosol resulted in heart rate increases of 3 to 16 beats/minute, about the same asalbuterol dosed at 180 mcg by inhalation aerosol (4 to 10 beats/minute). Adult and adolescentsubjects receiving 50 mcg doses of salmeterol MDPI (N=60) underwent continuouselectrocardiographic monitoring during two 12-hour periods after the first dose and after 1 monthof therapy, and no clinically significant dysrhythmias were noted.
Concomitant Use of Fluticasone Propionate/Salmeterol Inhalation MDPI with OtherRespiratory Medications:
Short-Acting Beta2-Agonists: In clinical trials in subjects with asthma, the mean daily needfor albuterol by 166 adult and adolescent subjects aged 12 years and older using anotherfluticasone propionate/salmeterol DPI product was approximately 1.3 inhalations/day andranged from 0 to 9 inhalations/day (0 to about 4.5 times the maximum approved salmeteroldosage for that DPI per dosing interval). Five percent (5%) of subjects using anotherfluticasone propionate/salmeterol DPI product in these trials averaged 6 or more inhalationsper day (3 times the maximum approved salmeterol dosage for that DPI per dosing interval)over the course of the 12-week trials. No increase in frequency of CV adverse events wasobserved among subjects who averaged 6 or more inhalations per day.
Methylxanthines: In clinical trials in subjects with asthma, 39 subjects receiving anotherfluticasone propionate/salmeterol MDPI product, fluticasone propionate 100 mcg andsalmeterol 50 mcg, fluticasone propionate 250 mcg and salmeterol 50 mcg, or fluticasonepropionate 500 mcg and salmeterol 50 mcg twice daily concurrently with a theophyllineproduct had adverse event rates similar to those in 304 subjects receiving another fluticasonepropionate/salmeterol product without theophylline. Similar results were observed in subjects receiving salmeterol 50 mcg plus fluticasone propionate 500 mcg twice daily concurrently
with a theophylline product (n = 39) or without theophylline (n = 132).
12.3 Pharmacokinetics
Absorption
Fluticasone Propionate:
AirDuo Digihaler acts locally in the lung; therefore, plasma levels may not predict therapeuticeffect. Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oralsystemic bioavailability of flut |
