Although not measured, the amounts of inhaled corticosteroids absorbed into the maternal bloodstream and excreted into breastmilk are probably too small to affect a breastfed infant. Expert opinion considers inhaled, nasal and oral corticosteroids acceptable to use during breastfeeding.[1,2] See also Fluticasone, Topical.

Backgroud: A key attribute in selecting an oral inhaler device for chronic obstructive pulmonary disease (COPD) and asthma is its ability to dispense a high degree of pulmonary deposition of the drug at low inspiratory flows. Methods: In this study, the lung deposition of extrafine formulations of beclomethasone dipropionate (BDP) and formoterol fumarate (FF) (pressurized metered-dose inhaler [pMDI] and dry powder inhaler [DPI], NEXThaler) was compared with that of nonextrafine formulations of fluticasone/salmeterol (FP/SAL) Diskus DPI and budesonide/formoterol (BUD/FF) Turbuhaler DPI in 10 patients. Diskus intrathoracic (peripheral and central) lung deposition was estimated at low inhalation flow rates (30 and 40 L/min) via validated functional respiratory imaging (FRI) and computational fluid dynamics (CFD) methods. Results: The BDP/FF NEXThaler and BDP/FF pMDI had the highest median percentages of intrathoracic deposition, with consistent mean values of approximately 50% and 40%, respectively. The median percentage of peripheral deposition from extrafine inhalers was above 30% with BDP/FF NEXThaler and pMDI, 5% or less with the FP/SAL Diskus at both flow rates, and ranged between 12% and 22% with the BUD/FF Turbuhaler DPI at flow rates of 30 and 40 L/min, respectively. Conclusions: Extrafine BDP/FF using NEXThaler and pMDI resulted in greater peripheral deposition of both the inhaled corticosteroid and long-acting beta-agonists moieties than the nonextrafine FP/SAL Discus and BUD/FF DPIs did.

The aim of this study was to analyse the effect of breathing parameters, age, gender and disease status on the lung doses of the two ICS + LABA fixed combination dry powder drugs. Breathing parameters of 113 COPD patients were measured while inhaling through emptied NEXThaler® and Ellipta® inhalers and the corresponding lung doses were calculated. Lung dose of Foster® NEXThaler® was superior to the lung dose of Relvar® Ellipta® in around 85 % of the patients. The average value of the ratio of bronchiolar to bronchial deposition fractions was 5.0 for Foster® NEXThaler® and 2.6 for Relvar® Ellipta®. Lung dose was sensitive to the inhalation parameters, such as peak inhalation flow, inhaled volume and breath-hold time. For both studied drugs the dose to the lungs was relatively high for moderate PIF values, but it declined for low (<35 L/min) and high (>95 L/min) PIFs. The lung dose increased by the increase of the inhaled volume, but saturated over 1.0 L of inhaled air. Longer breath-hold time led to higher lung deposition, but the dependence was drug-specific. FEV1 (%) and FEV1/FVC (%) did not influence the lung dose significantly (p = 0.05). Exacerbating patients had lower lung doses (28.8 ± 5.8 % for Foster® NEXThaler® and 23.7 ± 3.8 % for Relvar® Ellipta®) than their non-exacerbating counterparts (33.7 ± 6.1 % for Foster® NEXThaler® and for 24.9 ± 3.9 % for Relvar® Ellipta®). The exact clinical consequences of the differences between the deposition distributions of the two drugs could be assessed only by systematic clinical trials.

Batch-to-batch variability in inhalation powder has been identified as a potential challenge in the development of generic versions. This study explored the impact of batch-to-batch variability on the probability of establishing pharmacokinetic (PK) bioequivalence (BE) in a two-sequence, two-period (2 × 2) crossover study. A model-based parametric simulation approach was employed, incorporating batch-to-batch variability through the relative bioavailability (RBA) ratio. In the absence of batch variability, recruiting a total of 48 subjects in a 2 × 2 crossover study with the reference formulation resulted in a 95% probability of concluding BE. However, this probability decreased to 80% with a 5% batch difference in RBA and further declined to 30% with a 10% batch difference. With a 10% batch difference, the required number of subjects to achieve an 80% probability of concluding BE increased to 84. When considering product differences between the reference and the test formulations, an additional 10% batch difference reduced the study power from 97% to 30% for a T/R bioavailability ratio of 100% in a 2 × 2 crossover study with 48 subjects. As a result, the substantial impact of batch-to-batch variability on the study power and type I error of the PK BE study may pose significant challenges for the development of generic Advair Diskus due to its degree of PK batch-to-batch variability. Therefore, alternative PK BE study designs and guidelines are needed to adequately address the influence of batch-to-batch variability in products like Advair Diskus.