The long-acting relievers are sometimes referred to as "symptom controllers" and are
similar to the short-acting bronchodilators like salbutamol and terbutaline except that
their effects last a lot longer. Serevent (salmeterol) and Foradil (formoterol) will be
effective for 12 hours, whereas salbutamol will only be effective for up to 6 hours.
These medications are usually taken twice daily in addition to preventives to achieve
improved control. Like preventive medication, they should NEVER be used to treat
the acute symptoms of asthma.
If the asthma suffer fails to receive clinical benefit from their use after 1 month, the therapy should be withdrawn.
Questions are now being asked about the safety of using long-acting relievers when
there is doubt about the regular use of the short acting ones.
The Benefits
Until recently, systemic side effects of inhaled corticosteroids have been considered
to be of little importance. However doses above 800µg/day usually have little
increased benefit, and the adverse side effects increase dramatically. A study has
shown that people who use very high doses of steroids can cut back to a safer dose by
adding a long-acting beta2 agonist.1 Those taking salmeterol had improved lung
function, improved morning and evening peak flow rates, and less nocturnal asthma.
A second study of asthmatics taking even higher doses of beclomethasone (500µg),
carried out over 24 weeks, found similar results. Combined treatment with BDP
(500µg) plus salmeterol (50µg or 100µg) was more effective than higher doses of
BDP (1000µg) in controlling nocturnal asthma and improving morning and evening
peak flow rates.2
The Risks
Anecdotal evidence revealed twenty deaths reported in the first six months after
salmeterol was introduced to the United States.3 In one nation-wide study it was
noted that the death rate was three times greater in the patients using salmeterol than
those who were using salbutamol.4 People who were elderly or who had severe
asthma were most at risk. These findings have lead some researchers to consider the
safety of beta-agonists in general. However, it is not a clear cut case as underlying
asthma severity, beta-agonist use, co-existing illnesses and other factors may have
played a part.
A further concern with salmeterol is that it may become less effective with prolonged
use. This concern was supported by a number of studies. Cheung et al 5 showed that
salmeterol protection against methacholine challenge fell from ten-fold on day 1 to
only two-fold protection after 4 weeks. Another study showed broncho-protective
effect declined rapidly over 4 days (7 doses) of salmeterol treatment.6 This means
that the asthmatic will need larger doses to maintain the same control.
After four weeks of regular treatment with salmeterol, there was complete loss of
protection against exercise-induced asthma at 6 and 12 h after the dose.7
Finally the broncho-dilating and symptom-relieving effects of salmeterol can mask
increasing inflammation and delay awareness of worsening asthma.8
Five points have come out of these studies:
Watch for an increase in need for short-acting relievers. If you are using four or
more puffs of short-acting relievers each day for two days or 200 doses in eight
weeks as well as salmeterol it indicates your asthma is very poorly controlled
Never introduce long-acting beta-agonists as treatment for acutely deteriorating
asthma
Do not use long-acting beta-agonists to treat acute symptoms
Do not use long-acting beta-agonists as a substitute for oral or inhaled steroids
Do not exceed recommended doses
Weighing up the Options
Current medical opinion suggests that asthmatics who require continued high doses of
inhaled corticosteroids which give adverse side effects, should consider the addition
of long-acting beta2 agonists. This point cannot be precisely quantified and the
decision must be made on an individual basis taking into account the age and size of
the asthmatic, the current dose of inhaled steroids, any adverse effects, and the impact
of the continuing asthma symptoms on lifestyle. As a guide, the addition of
long-acting beta2 agonists should be considered when the dose of inhaled
corticosteroid required for continuing treatment reaches about 800-1000µg/day of
beclomethasone or budesonide and about 500µg/day of fluticasone.
Using salmeterol may make the asthmatic feel better initially, however they should
not stop or reduce steroid therapy unless directed by their doctor. It is unlikely that a
responsible doctor would be inclined to discontinue or quickly reduce steroid therapy,
even though good asthma control is established with salmeterol.
Salmeterol should not be used in place of your short-acting reliever medication. It is
slower to take effect than the rapidly acting medications such as salbutamol or
terbutaline and it is more potent. Carry your short-acting reliever with you and note
how often you need to use it. If the use increases, see your doctor at once.
If you fail to receive clinical benefit from their use after 1 month, the medication should be withdrawn.
The maximum dose of two inhalations twice each day should not be exceeded and
some people may find that they don't need all of these to remain symptom-free. Some
people find that one puff at night is sufficient to prevent night time asthma.
Be aware that there is a trend to combine a fixed dose of long-acting relievers and
steroids in one puffer. This is not recommended because drug intake needs to be
tailored to the individual on any given day.
Because of the concerns about the possible adverse consequences of these long-acting
medications, it has been suggested that only asthmatics who have daily symptoms
despite large doses of inhaled steroids should use these drugs. The safety and
effectiveness of salmeterol has not been established in children under twelve.
References
1. Greening AP, Ind PW. Northfield M et al. Added salmeterol versus higher-dose
corticosteroid in asthma patients with symptoms on existing corticosteroid. Lancet
1997:334:219-24.
2. Woolcock A, Lundback B, Ringdal N et al. Comparison of addition of salmeterol
to inhaled steroids with doubling of the dose of inhaled steroids. Am J Respir Crit
Care Med 1996;143:1481-8
3. Finkelstein FN. Risks of salmeterol? N Engl J Med. 1994;331:1314.
4. Castle W, Fuller R, Hall J, Palmer J. Serevent nationwide surveillance study:
comparison of salmeterol with salbutamol in asthmatic patients who require regular
bronchodilator treatment. BMJ. 1993;306:1034-1037.
5. Cheung D, Timmers MC, Zwinderman AH, et al. Long-term effects of a
long-acting beta2 -adrenoceptor agonist, salmeterol, on airway hyperresponsiveness in
patients with mild asthma. N Engl J Med 1992; 327:1198-203
6. Bhagat R, Kalra S, Swystun VA, et al. Rapid onset of tolerance to the
bronchoprotective effect of salmeterol. Chest 1995; 108:1235-39
7. Ramage L, Lipworth BJ, Ingram CG, et al. Reduced protection against exercise
induced bronchoconstriction after chronic dosing with salmeterol. Respir Med 1994;
88:363-68
8. Mcivor RA. Potential masking effects of salmeterol on airway inflammation in
asthma. Am J Respir Crit Care Med - 1998 Sep; 158(3): 924-30
