8th December 17:38
serevent w/steroid vs. double the steroid (singulair)
In a previous post, CBI continued to question combining servent with lower
levels of steroid, suggesting using twice as much steroid, even at systemic
levels, and/or adding other alternatives like singulair and theopyline.
For those interested, studies suggest that the reduction in steroid by using
serevent could be as high as 60%. See J Allergy Clin Immunol 2003
Jan;111(1):57-65 (60% reduction)
As to generally the state of the studies, see the following:
Pharmacotherapy 2002 Feb;22(2):212-26 (ISSN: 0277-0008)
Stoloff S; Poinsett-Holmes K; Dorinsky PM
University of Nevada School of Medicine, Reno, USA.
"Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of
drugs with different mechanisms of action that are commonly used to provide
effective long-term control of persistent asthma. Scientific and clinical data
support the complementary mechanisms of action of the inhaled corticosteroids
and the long-acting beta2-agonists in achieving a superior level of asthma
control. In addition, evidence supports significant reductions in exacerbations
and effective control of airway inflammation with an inhaled corticosteroid and
a long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or
combinations of other the****utic agents with an inhaled corticosteroid.
Finally, there are distinct economic advantages to combining an inhaled
corticosteroid and a long-acting beta2-agonist in the treatment of asthma
relative to other treatment regimens."
I have no love of the drug company producing servent. I think it was unethical
for the company to discontinue servent mdi cfc in the US before it received
approval to market the HFA version, which is widely distributed in Canada and
throughout the world. However, while CBI raises good theoretical points about
the long term benefit and potential impact of servent on the heart and lungs,
points that should be considered given the recent FDA warning, the state of the
current scientific studies should be also made clear. Since that warning could
merely be affirming what was well known about serevent, which is, it cannot be
misused as a rescue medicine, and the failure to use it properly could
adversely affect a large population's asthma, which could also cause impacts to
heart and lung, one must consider all sides.
I also think we need to consider carefully his argument that salmeterol is
merely a manipulated molecule of albuterol. Manipulating molecules may mean
nothing or a lot, depending upon the molecule and how it is manipulated.
That's why we do studies. CBI perhaps could cite some to support his view,
other than simply saying that the burden is on the drug companies. It is, but
there is a lot of data suggested by the above cites (only two of many) that
supports the use of servent.
Obviously for the individual patient, a discussion with a knowledgable
physician regarding their individual needs is the best way to resolve this
issue. I cite the above to prompt the inquiry, not to end it.
8th December 17:38
serevent w/steroid vs. double the steroid (albuterol)
I'm not sure what, exactly, you want me to support. That Serevent is a
manipulation of the albuterol molecule is a fact. Furthermore, the specific
manipulation is that they added a lipophilic tail to the molecule which
results in slower clearance from the system but does not affect "the
business end". There is no reason to suspect that the receptor is seeing any
difference between salmeterol and albuterol. That standing doses of
albuterol are associated with an increased risk of death is also a well
established fact that I doubt few here would debate. If you really are
questioning either of these issues then let me know and perhaps I, or
someone else, will dig up the studies but they are old and not debated much
If you are asking me to cite support for my suspicion that sameterol might
be delerious then I would say that you are making an unfair request. I have
always been careful to present my concerns as theoretical and, until now,
have never claimed that there was clinical evidence. I again assert that
since such a similar agent was shown to be deleterious the burden is on the
drug company to show that they are different. This is all the more so now
that there is some clinical data to suggest a problem that seem to confirm
the theoretical suspicions.
To be clear about the present study: It does not suggest that salmeterol is
dangerous only to people who misuse it. No such ****ysis was presented. In
the study in question salmeterol was simply added to the usualltherapy of
the asthmatics and they were otherwise treated as usual. Presumably they
still had, and used, their normal relievers. At least there is no indication
that the results were due to use other than as intended. It showed that
salmeterol is clearly deleterious to those who are not taking an inhaled
steroid and possibly is deleterious to blacks and those with more severe
asthma. Not much can be infered reagrding whites taking an inhaled steroid.
Whether the addition of an inhaled steroid would have blunted or negated
this deleterious effect is an interesting, and as yet unanswered, question
that does have some theoretical support. Unfortunately, the study was
stopped because it would not have allowed for this type of subgroup ****ysis
to be done.
Fist of all - I am not broadly against Serevent. I do prescribe it, although
not as much as the drug company would have me do. I generally favor adding
or increasing an anti-inflammatory over adding Serevent, however, do find a
use for Serevent in several situations.
As for the state of the current studies: They show that adding Serevent is
roughly as effective as doubling the dose of inhaled steroid in terms of
short term clinical outcomes (exacerbations etc). What has not yet been
adequately studied is either longer term clinical outcomes or the
physiologic effects on the lungs. Only inhaled steroids have the support of
that kind of data.
10th December 06:43
serevent w/steroid vs. double the steroid (theophylline)
This was a widely referenced meta-****ysis that came out fairly strongly in
favor of using the combination of steroid and salmeterol. They basically
frame the argument as the two of us have framed it here. They say it is
better because the clinical end points show more immediate improvement with
this strategy than with adding other agents. I feel that long term safety
concerns have not been adequately addressed.
The relevant passage to this reads, " Clinicians frequently question what
actions should be taken for a patient who is symptomatic while receiving
inhaled corticosteroids: increase the dosage of the inhaled corticosteroid,
add theophylline, add a leukotriene modifier, or add a long-acting
ß2-agonist. The following published data from clinical trials that
specifically evaluated the long-acting ß2-agonist therapy compared with
other therapies suggest that the addition of a long-acting ß2-agonist
bronchodilator provides greater improvement in lung function and asthma
symptom control than do the other the****utic options."
Again, I would point out that short term symptom control may not be the best
standard to judge and that longer term data would be helpful - particularly
showing a lack of tachyphylaxis (the benefit wearing off over time) and a
halt to the loss of lung function over longer period of time.
I would also point out that the authors list themselves as employees of
The full article can be accessed for free at: