A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Serevent Diskus Side Effects, and Drug Interactions - Salmeterol Xinafoate (inhalation powder)
Serevent Diskus Side Effects, and Drug Interactions - Salmeterol Xinafoate (inhalation powder)
SIDE EFFECTS
Adverse reactions to salmeterol are similar in nature to reactions
to other selective
beta2-adrenoceptor agonists, i.e., tachycardia; palpitations; immediate
hypersensitivity reactions, including urticaria,
angioedema, rash,
bronchospasm (see WARNINGS);
headache; tremor; nervousness; and paradoxical bronchospasm
(see WARNINGS).
Two multicenter, 12-week, controlled studies have evaluated twice-daily
doses of SEREVENT inhalation
powder in patients 12
years of age and older with
asthma. The following table
reports the incidence
of adverse events in these two studies.
Table 3: Adverse Experience Incidence in Two Large 12-Week
Adolescent and Adult Clinical Trials
| Adverse
Event Type |
Percent of Patients
|
|
Placebo
n = 152
|
SEREVENT
Inhalation Powder
50 mcg
twice daily
n = 149
|
Albuterol Inhalation
Aerosol
180 mcg
four times daily
n = 150
|
|
Ear, nose, and throat
|
|
| Nasal/ sinus
congestion, pallor |
6
|
9
|
8
|
| Rhinitis |
4
|
5
|
4
|
|
Neurological
|
|
| Headache |
9
|
13
|
12
|
|
Respiratory
|
|
| Asthma |
1
|
3
|
<1
|
| Tracheitis/ bronchitis
|
4
|
7
|
3
|
| Influenza |
2
|
5
|
5
|
The table above includes
all events (whether considered drug-related or nondrug-related by
the
investigator) that occurred at a rate
of ³3% in the SEREVENT inhalation
powder treatment
group and were more common
in the SEREVENT inhalation
powder group
than in the placebo
group.
Pharyngitis, sinusitis,
upper respiratory
tract infection,
and cough occurred at ³3% but were
more
common in the placebo
group. However, throat
irritation has been
described at rates exceeding that of placebo
in other controlled clinical
trials. Other events occurring in the SEREVENT inhalation
powder group
at a frequency of 1% to 3% and at a greater rate
than in placebo were
as follows:
Ear, Nose, and Throat: Sinus headache.
Gastrointestinal: Nausea.
Mouth and Teeth: Oral mucosal abnormality.
Musculoskeletal: Pain in joint.
Neurological: Sleep disturbance, paresthesia.
Skin: Contact dermatitis,
eczema.
Miscellaneous: Localized aches and pains, pyrexia
of unknown origin.
Two multicenter, 12-week, controlled studies have evaluated twice-daily
doses of salmeterol inhalation
powder in patients aged
4 to 11 years with asthma. The following table
includes all events (whether considered drug-related or non-drug
related by the investigator) that occurred at a rate
of ³3% in the SEREVENT inhalation
powder treatment
group and were more common
in the SEREVENT inhalation
powder group
than in the placebo
group.
Table 4: Adverse Experience Incidence in Two Large 12-Week
Pediatric Clinical Trials
| Adverse
Event Type |
Percent of Patients
|
|
Placebo
n = 215
|
SEREVENT
INHALATION
Powder
50 mcg
twice daily
n = 211
|
Albuterol Powder
200 mcg
four times daily
n = 115
|
|
Ear, nose, and throat
|
|
| Ear signs and symptoms |
3
|
4
|
9
|
| Pharyngitis |
3
|
6
|
3
|
|
Neurological
|
|
| Headache |
14
|
17
|
20
|
|
Respiratory
|
|
| Asthma |
2
|
4
|
<1
|
|
Skin
|
|
| Skin rashes |
3
|
4
|
2
|
| Urticaria |
0
|
3
|
2
|
The following events were reported at an incidence
of 1% to 2% (3 to 4 patients) in the salmeterol group
and with a higher incidence
than in the albuterol and placebo
groups: gastrointestinal
signs and symptoms, lower respiratory
signs and symptoms, photodermatitis, and arthralgia
and articular rheumatism.
Observed During Clinical Practice
In extensive United States and worldwide postmarketing experience
with SEREVENT, serious exacerbations of asthma,
including some that have been fatal, have been reported. In
most cases, these have occurred in patients with severe asthma
and/or in some patients in whom asthma
has been acutely deteriorating (see
WARNINGS no. 1), but they have also occurred in a few patients
with less severe asthma as well. It was not possible from these
reports to determine whether SEREVENT contributed to these events
or simply failed to relieve
the deteriorating asthma.
The following events have also been identified during postapproval
use of SEREVENT in clinical
practice. Because they are reported voluntarily from a population
of unknown size, estimates of frequency
cannot be made. These events have been chosen for inclusion
due to a combination of their seriousness, frequency
of reporting, or potential
causal connection to SEREVENT.
Respiratory: Reports of upper airway
symptoms of laryngeal spasm, irritation, or swelling
such as stridor
or choking.
Cardiovascular: Cases of hypertension,
arrhythmias (including atrial fibrillation,
supraventricular
tachycardia, extrasystoles), and anaphylaxis.
DRUG INTERACTIONS
Short-Acting Beta-Agonists
In the two 12-week, repetitive-dose adolescent
and adult clinical
trials (n = 149), the mean
daily need for additional
beta2-agonist use in patients using salmeterol inhalation
powder was approximately
1½ inhalations per day. Twenty-six percent
of the patients in these trials used between 8 and 24 inhalations
of short-acting beta-agonist per
day on one or more occasions. Nine percent
of the patients in these trials averaged over 4 inhalations per
day over the course of the 12-week trials. No
observed increase in frequency
of cardiovascular
events was noted among the 3 patients who used an average
of 8 to 11 inhalations per
day; however, the safety of concomitant
use of more than 8 inhalations per
day of short-acting beta2-agonist with salmeterol inhalation
powder has not been established.
In 29 patients who experienced
worsening of asthma while
receiving salmeterol inhalation powder during these trials, albuterol
therapy administered
via either nebulizer or
inhalation aerosol
(one dose in most cases)
led to improvement in FEV1 and no
increase in occurrence of cardiovascular
adverse events.
Monoamine Oxidase Inhibitors and Tricyclic Antidepressants
Salmeterol should be administered with extreme caution to patients
being treated with monoamine
oxidase inhibitors or
tricyclic antidepressants, or within 2 weeks of discontinuation
of such agents, because
the action of salmeterol on the vascular
system may be potentiated
by these agents.
Corticosteroids and Cromoglycate
In clinical trials,
inhaled corticosteroids and/or inhaled cromolyn sodium did not alter
the safety profile of
SEREVENT when administered concurrently.
Methylxanthines
The concurrent use of intravenously or orally administered methylxanthines
(e.g., aminophylline, theophylline) by patients receiving SEREVENT
has not been completely evaluated. In
one clinical asthma
trial, 87 patients receiving SEREVENT Inhalation Aerosol 42 mcg
twice daily concurrently with a theophylline
product had adverse
event rates similar to those in 71 patients receiving SEREVENT Inhalation
Aerosol without theophylline. Resting heart rates were slightly
higher in the patients on theophylline
but were little affected by therapy
with SEREVENT Inhalation Aerosol.
Beta-adrenergic receptor
blocking agents not
only block the pulmonary
effect of beta-agonists, such
as SEREVENT DISKUS, but may produce severe bronchospasm in asthmatic
patients. Therefore, patients with asthma
should not normally be treated with beta-blockers. However, under
certain circumstances, e.g., as prophylaxis
after myocardial
infarction, there may be no
acceptable alternatives to the use of beta-adrenergic blocking
agents in patients with asthma. In
this setting, cardioselective beta-blockers could be considered,
although they should be administered with caution.
The ECG changes and/or
hypokalemia that
may result from the administration of nonpotassium-sparing diuretics
(such as loop or thiazide
diuretics) can be acutely worsened by beta-agonists, especially
when the recommended dose of the beta-agonist is exceeded. Although
the clinical significance
of these effects is not known, caution is advised in the coadministration
of beta-agonists with nonpotassium-sparing diuretics.
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