| 1. Does the formoterol
component of Symbicort mask exacerbations of asthma? |
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Tattersfield et al (1999) provided a detailed analysis of the
changes before and after exacerbations in relation to the treatment
with and without a long-acting ß2-agonist. The study was
an extension of the original publication of the FACET study. Study
results provided an reassurance that the exacerbations that occurred
in patients taking formoterol did not differ in severity or in
response to treatment compared with exacerbations in patients
not taking formoterol.
The one-year study found when the components of Symbicort were
given concomitantly via separate inhalers, changes in PEF and
symptom scores seen during a severe exacerbation were similar
to those seen with inhaled corticosteroid (budesonide) alone.
Thus, addition of formoterol to budesonide decreased the number
of exacerbations without changing the time-course or severity
of exacerbations. So, exacerbations could still be detected and
treated as needed, even when regular long-acting ß2-agonist
is part of daily asthma therapy, hence there is no masking of
exacerbations of asthma.
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| 2. Does Symbicort mask underlying inflammation of asthma? |
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Formoterol, the ß2-agonist component of Symbicort,
does not mask the underlying inflammation.
Kips (2000) compared the effects of low dose budesonide (Pulmicort®
200µg bid) + formoterol (Oxis® 9µg bid) with high
dose budesonide (Pulmicort 400µg bid) alone over a 12 month
period. No significant changes in underlying airway inflammation
were seen, as measured by the proportion of eosinophils and EG2
positive cells (EG2+) found in induced sputum. Thus, when the components
of Symbicort were given concomitantly via separate inhalers for
12 months, no masking of the underlying airway inflammation was
seen. |
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| 3. Is the formoterol component of Symbicort as safe as a traditional, short-acting reliever bronchodilator? |
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Repeated, high doses of formoterol, the long-acting ß2-agonist
component of Symbicort, given over a 3-day period in doses up to
90 µg/day, were as well-tolerated as high doses of a short-acting
ß2-agonist, terbutaline (Tötterman, 1998). Increases
in the QTc interval on ECG and reductions in serum potassium that
occur after inhalation of high doses of ß2-agonist, were less
marked with high doses of formoterol than with high doses of the
short-acting ß2-agonist terbutaline. |
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| 4. What happens if a patient inhales more doses of Symbicort than prescribed? |
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| The tolerability of a high dose of Symbicort (10 extra inhalations of Symbicort
160/4.5 µg) has been investigated in 14 asthmatic patients
already receiving maintenance treatment with two inhalations twice
daily Symbicort 160/4.5 (Ankerst, 2001). The study (1600/45µg
+ 320/9µg) was designed to resemble the situation where a
patient might use Symbicort instead of a short-acting ß2-agonist
to relieve the symptoms of an acute asthma attack.
Expected ß2-agonist class effects were seen with Symbicort
in pulse, blood pressure assessments, QT and QTc intervals and
in potassium, glucose, and lactate measurements. Neither individual
nor mean effects constituted any safety concerns.
Treatment effects of 10 extra doses of Symbicort® were
consistent with those expected after inhalation of a high dose
of formoterol
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Heart rate (bpm) |
Syst./diast. Blood pressure (mmHg) |
QTc (ms) |
Serum K+ (mmol/L) |
Blood glucose (mmol/L) |
Plasma lactate (mmol/L) |
| Symbicort® vs. Placebo |
+5.4* |
+2.5*/-3.3* |
+17.1* |
-0.16* |
+0.44* |
+0.19* |
| Symbicort® vs. Formoterol |
+3.7* |
-0.2/-1.1 |
+2.1 |
-0.02 |
+0.09 |
-0.08 |
*p<0.05 |
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| 5. Is long term
treatment with Symbicort safe and effective? |
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| The results from an open, 12-month randomized study,
involving 321 asthma patients, designed to compare the long-term
safety and efficacy of Symbicort with Pulmicort® + Oxis®,
were recently presented (Rosenhall, 2001). This study confirmed
that in long term asthma management, Symbicort is at least as effective
as the monocomponents given separately. One important result was
when patients were treated with Symbicort, they were less likely
to withdraw from the study. This difference increased over time
and was statistically significant at 12 months (p=0.008). Reasons
for withdrawal included asthma worsening, non-compliance and adverse
events. This suggests that Symbicort® may increase adherence
to therapy, thereby improving asthma control beyond that which can
be achieved when patients must use two inhalers. |
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