Q:

4/23/2013
A question has come up during some of my recent discussions with other physicians about the degree of systemic effect of "high-dose'inhaled fluticasone (1000 mcg/day). The specific question relates to what dose of oral prednisone might have similar systemic effects compared to Advair500/50 bid. (I've heard anywhere from 5-9mg/day). What are your thoughts about this? Thank you!

A:

Thank you for your inquiry.

I am going to submit your question to Dr. Stan Szefler who is an international authority on the pharmacokinetics and pharmacodynamics of inhaled corticosteroids. As soon as we hear from Dr. Szefler, we will forward his response to you.

Thank you again for your inquiry.

Sincerely,
Phil Lieberman, M.D.

We have received a response from Dr. Szefler. Thank you again for your inquiry and we hope this response is helpful to you.

Warm regards,
Phil Lieberman, M.D.

Response from Dr. Stanley Szefler:
I will try to answer the best way possible based on my knowledge and provide some references to support my thinking.

1. In regards to fluticasone, it really depends on the delivery device. There is more systemic absorption from MDI versus DPI device. See publication by Whelan et al, JACI 2005. Thus, there would be less concern about DPI then MDI at a dose of 1000 mcg/day. Keep in mind that these were CFC versus a Diskhaer as compared to the current HFA and Discus devices. I suspect the results would be similar when comparing the newer versus older products.

2. To my knowledge there is no direct comparison of fluticasone versus prednisone equivalents. I tried to do that study when we were evaluating this problem in the NHLBI Asthma Clinical Research Network but there was concern about studying oral prednisone, so we chose other models. The best work on this question comes from John Toogood and his landmark publications in the 1970s and 1980s. We just keep verifying his findings with newer steroids. He looked in detail at budesonide. see attached publication. If you look at Figure 2, 1000 mcg/day of budesonide was equivalent to about 8.7 mg/day of prednisone in morning cortisol suppression. This was an MDI formulation, however. So, one would have to account for the delivery device once again to make some comparisons.

3. The two below references are from publications on ICS reviews that might be of interest (Kelly, 2003 and Raissy, 2013)

Potential adverse effects of the inhaled corticosteroids

Inhaled Corticosteroids in Lung Diseases

Therefore, at 1000 mcg per day of fluticasone, I would be less concerned about a DPI formulation than an MDI. With an MDI, I think the estimates regarding prednisone equivalents mentioned with the question below could be in the right ballpark.

Keep in mind that patients vary in regards to their steroid sensitivity.
 
If there is a question about an individual patient and concern about adrenal suppression, I would start with a morning cortisol measure. If that is low, consider a cortrosyn stimulation test or trying to reduce the ICS dose by using non-steroid controllers.

Stan Szefler

AAAAI - American Academy of Allergy Asthma & Immunology