ADVERSE REACTIONS
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).
Asthma
Two multicenter, 12-week, controlled studies have evaluated twice-daily doses of SEREVENT Inhalation Aerosol in patients 12 years of age and older with asthma. Table 3 reports the incidence of adverse events in these 2 studies.
Table 3. Adverse Event Incidence in 2 Large 12-Week Clinical Trials in Patients With Asthma* |
Adverse Event
|
Percent of Patients
|
|
Placebo
(N = 187)
|
SEREVENT Inhalation Aerosol 42 mcg Twice Daily (N = 184)
|
Albuterol Inhalation Aerosol 180 mcg 4 Times Daily (N = 185)
|
|
Ear, nose, and throat
| | | |
|
Upper respiratory tract infection
|
13
|
14
|
16*
|
|
Nasopharyngitis
|
12
|
14
|
11
|
|
Disease of nasal cavity/sinus
|
4
|
6
|
1
|
|
Sinus headache
|
2
|
4
|
<1
|
|
Gastrointestinal
| | | |
|
Stomachache
|
0
|
4
|
0
|
| Neurological | | | |
|
Headache
|
23
|
28
|
27
|
|
Tremor
|
2
|
4
|
3
|
|
Respiratory
| | | |
|
Cough
|
6
|
7
|
3
|
|
Lower respiratory infection
|
2
|
4
|
2
|
* The only adverse event classified as serious was 1 case of upper respiratory tract infection in a patient treated with albuterol.
Table 3 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of over 3% in the group treated with SEREVENT Inhalation Aerosol and were more common in the group treated with SEREVENT Inhalation Aerosol than in the placebo group.
Pharyngitis, allergic rhinitis, dizziness/giddiness, and influenza occurred at 3% or more but were equally common on placebo. Other events occurring in the group treated with SEREVENT Inhalation Aerosol at a frequency of 1% to 3% were as follows:
Cardiovascular
Tachycardia, palpitations.
Ear, Nose, and Throat
Rhinitis, laryngitis.
Gastrointestinal
Nausea, viral gastroenteritis, nausea and vomiting, diarrhea, abdominal pain.
Hypersensitivity
Urticaria.
Mouth and Teeth
Dental pain.
Musculoskeletal
Pain in joint, back pain, muscle cramp/contraction, myalgia/myositis, muscular soreness.
Neurological
Nervousness, malaise/fatigue.
Respiratory
Tracheitis/bronchitis.
Skin
Rash/skin eruption.
Urogenital
Dysmenorrhea.
Data from small dose-response studies show an apparent dose relationship for tremor, nervousness, and palpitations.
In clinical trials evaluating concurrent therapy of salmeterol with inhaled corticosteroids, adverse events were consistent with those previously reported for salmeterol, or might otherwise be expected with the use of inhaled corticosteroids.
Chronic Obstructive Pulmonary Disease
Two multicenter, 12-week, controlled studies have evaluated twice-daily doses of SEREVENT Inhalation Aerosol in patients with COPD. Table 4 reports the incidence of adverse events in these 2 studies.
Table 4. Adverse Event Incidence in 2 Large 12-Week COPD Clinical Trials in Patients With Chronic Obstructive Pulmonary Disease |
Adverse Event
|
Percent of Patients
|
|
Placebo
(N = 278)
|
SEREVENT Inhalation Aerosol 42 mcg Twice Daily (N = 267)
|
Ipratropium Inhalation Aerosol 36 mcg 4 Times Daily (N = 271)
|
|
Ear, nose, and throat
| | | |
| Upper respiratory tract infection |
7
|
9
|
9
|
|
Sore throat
|
3
|
8
|
6
|
|
Nasal sinus infection
|
1
|
4
|
2
|
|
Gastrointestinal
| | | |
|
Diarrhea
|
3
|
5
|
4
|
|
Musculoskeletal
| | | |
|
Back pain
|
3
|
4
|
3
|
|
Neurological
| | | |
|
Headache
|
10
|
12
|
8
|
|
Respiratory
| | | |
|
Chest congestion
|
3
|
4
|
3
|
Table 4 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of over 3% in the group treated with SEREVENT Inhalation Aerosol and were more common in the group treated with SEREVENT Inhalation Aerosol than in the placebo group.
Common cold, rhinorrhea, bronchitis, cough, exacerbation of chest congestion, chest pain, and dizziness occurred at 3% or more but were equally common on placebo. Other events occurring in the group treated with SEREVENT Inhalation Aerosol at a frequency of 1% to 3% were as follows:
Ear, Nose, and Throat
Cold symptoms, earache, epistaxis, nasal congestion, nasal sinus congestion, sneezing.
Gastrointestinal
Nausea, dyspepsia, gastric pain, gastric upset, abdominal pain, constipation, heartburn, oral candidiasis, xerostomia, vomiting, surgical removal of tooth.
Musculoskeletal
Leg cramps, myalgia, neck pain, pain in arm, shoulder pain, muscle injury of neck.
Neurological
Insomnia, sinus headache.
Non-Site Specific
Fatigue, fever, pain in body, discomfort in chest.
Respiratory
Acute bronchitis, dyspnea, influenza, lower respiratory tract infection, pneumonia, respiratory tract infection, shortness of breath, wheezing.
Urogenital
Urinary tract infection.
Electrocardiographic Monitoring in Patients With Chronic Obstructive Pulmonary Disease
Continuous electrocardiographic (Holter) monitoring was performed on 284 patients in 2 large COPD clinical trials during five 24-hour periods. No cases of sustained ventricular tachycardia were observed. At baseline, non-sustained, asymptomatic ventricular tachycardia was recorded for 7 (7.1%), 8 (9.4%), and 3 (3.0%) patients in the placebo, SEREVENT, and ipratropium groups, respectively. During treatment, nonsustained, asymptomatic ventricular tachycardia that represented a clinically significant change from baseline was reported for 11 (11.6%), 15 (18.3%), and 20 (20.8%) patients receiving placebo, SEREVENT, and ipratropium, respectively. Four of these cases of ventricular tachycardia were reported as adverse events (1 placebo, 3 SEREVENT) by 1 investigator based upon review of Holter data. One case of ventricular tachycardia was observed during ECG evaluation of chest pain (ipratropium) and reported as an adverse event.
Observed During Clinical Practice
In extensive US and worldwide postmarketing experience, 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 occurred in a few patients with less severe asthma as well. It was not possible from these reports to determine whether SEREVENT Inhalation Aerosol 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
Rare reports of upper airway symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking; oropharyngeal irritation.
Cardiovascular
Hypertension, arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles).
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