mg of radiolabeled salmeterol (as salmeterolxinafoate) orally, approximately 25% and 60% of the radiolabeled salmeterol was eliminatedin urine and feces, respectively, over a period of 7 days.
Specific Populations
A population pharmacokinetic analysis was performed for fluticasone propionate and salmeterolutilizing data from 9 controlled clinical trials that included 350 subjects with asthma aged 4 to77 years who received treatment with another fluticasone propionate and salmeterol MDPIproduct, the combination of HFA-propelled fluticasone propionate and salmeterol inhalationaerosol, fluticasone propionate MDPI, HFA-propelled fluticasone propionate inhalation aerosol,or CFC-propelled fluticasone propionate inhalation aerosol. The population pharmacokineticanalyses for fluticasone propionate and salmeterol showed no clinically relevant effects of age,gender, race, body weight, body mass index, or percent of predicted FEV1 on apparent clearanceand apparent volume of distribution. AirDuo Digihaler is not approved in pediatric patientsyounger than 12 years.
Geriatric and Pediatric Patients: No pharmacokinetic studies have been performed with AirDuoDigihaler in pediatric or geriatric patients. A subgroup analysis was conducted to comparepatients aged 12-17 (n=15) and ≥18 (n=23) years following administration of 232/14 mcg fluticasone propionate/salmeterol MDPI. No overall differences in fluticasone propionate andsalmeterol pharmacokinetics were observed.
Male and Female Patients: A subgroup analysis was conducted to compare male (n=21) andfemale (n=16) patients following administration of 232/14 mcg fluticasone propionate/salmeterolMDPI. No overall differences in fluticasone propionate and salmeterol pharmacokinetics wereobserved.
Patients with Renal Impairment: The effect of renal impairment of the pharmacokinetics ofAirDuo Digihaler has not been eva luated.
Patients with Hepatic Impairment: Formal pharmacokinetic studies using AirDuo Digihaler havenot been conducted in patients with hepatic impairment. However, since both fluticasonepropionate and salmeterol are predominantly cleared by hepatic metabolism, impairment of liverfunction may lead to accumulation of fluticasone propionate and salmeterol in plasma [see Usein Specific Populations (8.6)].
Drug Interaction Studies
In a single-dose trial, the presence of salmeterol did not alter fluticasone propionate exposure.
No studies have been performed with AirDuo Digihaler to investigate the effect of fluticasonepropionate on salmeterol pharmacokinetics when given in combination.
Drug Interaction Studies with Another Fluticasone Propionate/Salmeterol MDPI Product:The population pharmacokinetic analysis from 9 controlled clinical trials in 350 subjects withasthma showed no significant effects on fluticasone propionate or salmeterol pharmacokineticsfollowing co-administration with beta2-agonists, corticosteroids, antihistamines, or theophyllines.
Strong CYP3A4 Inhibitors: Fluticasone propionate is a substrate of CYP3A4.
Coadministration of fluticasone propionate and ritonavir, a strong CYP3A4 inhibitor, is notrecommended based upon a multiple-dose, crossover drug interaction trial in 18 healthysubjects [see Drug Interactions (7.1)]. Plasma fluticasone propionate concentrationsfollowing fluticasone propionate aqueous nasal spray alone were undetectable (<10 pg/mL)i |
