ADVERSE REACTIONS
Long-acting beta
2
-adrenergic agonists (LABA), including formoterol, the active ingredient in FORADIL AEROLIZER, increase the risk of asthma-related death and may increase the risk of asthma-related hospitalizations in pediatric and adolescent patients. Clinical trials with FORADIL AEROLIZER suggested a higher incidence of serious asthma exacerbations in patients who received FORADIL AEROLIZER than in those who received placebo. (See WARNINGS)
Experience in Pediatric, Adolescent and Adult Patients with Asthma
Of the 5,824 patients in multiple-dose controlled clinical trials, 1,985 were treated with FORADIL AEROLIZER at the recommended dose of 12 mcg twice daily. The following table shows adverse events where the frequency was greater than or equal to 1% in the FORADIL twice daily group and where the rates in the FORADIL group exceeded placebo. Three adverse events showed dose ordering among tested doses of 6, 12 and 24 mcg administered twice daily; tremor, dizziness and dysphonia.
NUMBER AND FREQUENCY OF ADVERSE EXPERIENCES IN PATIENTS 5 YEARS OF AGE AND OLDER FROM MULTIPLE-DOSE CONTROLLED CLINICAL TRIALS
Adverse Event |
FORADIL AEROLIZER 12 mcg twice daily |
Placebo |
| n |
(%) |
n |
(%) |
Total Patients |
1985 |
(100) |
969 |
(100) |
|
|
|
|
|
Infection viral |
341 |
(17.2) |
166 |
(17.1) |
Bronchitis |
92 |
(4.6) |
42 |
(4.3) |
Chest infection |
54 |
(2.7) |
4 |
(0.4) |
Dyspnea |
42 |
(2.1) |
16 |
(1.7) |
Chest pain |
37 |
(1.9) |
13 |
(1.3) |
Tremor |
37 |
(1.9) |
4 |
(0.4) |
Dizziness |
31 |
(1.6) |
15 |
(1.5) |
Insomnia |
29 |
(1.5) |
8 |
(0.8) |
Tonsillitis |
23 |
(1.2) |
7 |
(0.7) |
Rash |
22 |
(1.1) |
7 |
(0.7) |
Dysphonia |
19 |
(1.0) |
9 |
(0.9) |
In two 12-week controlled trials with combined enrollment of 1095 patients 12 years of age and older, FORADIL AEROLIZER 12 mcg twice daily was compared to FORADIL AEROLIZER 24 mcg twice daily, albuterol 180 mcg four times daily, and placebo. Serious asthma exacerbations (acute worsening of asthma resulting in hospitalization) occurred more commonly with FORADIL AEROLIZER 24 mcg twice daily than with the recommended dose of FORADIL AEROLIZER 12 mcg twice daily, albuterol, or placebo. The results are shown in the following table.
NUMBER AND FREQUENCY OF SERIOUS ASTHMA EXACERBATIONS IN PATIENTS 12 YEARS OF AGE AND OLDER FROM TWO 12-WEEK CONTROLLED CLINICAL TRIALS
|
Foradil 12 mcg twice daily
|
Foradil 24 mcg twice daily
|
Albuterol 180 mcg four times daily
|
Placebo
|
Trial #1
|
Serious asthma exacerbations
|
0/136 (0) |
4/135 (3.0%)1
|
2/134 (1.5%) |
0/136 (0) |
Trial #2
|
Serious asthma exacerbations
|
1/139 (0.7%) |
5/136 (3.7%)2
|
0/138 (0) |
2/141 (1.4%) |
1 1 patient required intubation
2 2 patients had respiratory arrest; 1 of the patients died |
In a 16-week, randomized, multi-center, double-blind, parallel-group trial, patients who received either 24 mcg twice daily or 12 mcg twice daily doses of FORADIL AEROLIZER experienced more serious asthma exacerbations than patients who received placebo (see CLINICAL TRIALS). The results are shown in the following table.
NUMBER AND FREQUENCY OF SERIOUS ASTHMA EXACERBATIONS IN PATIENTS 12 YEARS OF AGE AND OLDER FROM A 16-WEEK TRIAL
|
Foradil 12 mcg twice daily
|
Foradil 24 mcg twice daily
|
Placebo
|
Serious asthma exacerbations
|
3/527 (0.6%) |
2/527 (0.4%) |
1/514 (0.2%) |
Experience in Children with Asthma
The safety of FORADIL AEROLIZER 12 mcg twice daily compared to FORADIL AEROLIZER 24 mcg twice daily and placebo was investigated in one large, multicenter, randomized, double-blind, 52-week clinical trial in 518 children with asthma (ages 5-12 years) in need of daily bronchodilators and anti-inflammatory treatment. More children who received FORADIL AEROLIZER 24 mcg twice daily than children who received FORADIL AEROLIZER 12 mcg twice daily or placebo experienced serious asthma exacerbations, as shown in the next table.
NUMBER AND FREQUENCY OF SERIOUS ASTHMA EXACERBATIONS IN PATIENTS 5-12 YEARS OF AGE FROM A 52-WEEK TRIAL
|
Foradil 12 mcg twice daily
|
Foradil 24 mcg twice daily
|
Placebo
|
Serious asthma exacerbations
|
8/171 (4.7%) |
11/171 (6.4%) |
0/176 (0) |
The numbers and percent of patients who reported adverse events were comparable in the 12 mcg twice daily and placebo groups. In general, the pattern of the adverse events observed in children differed from the usual pattern seen in adults. The adverse events that were more frequent in the formoterol group than in the placebo group reflected infection/inflammation (viral infection, rhinitis, tonsillitis, gastroenteritis) or abdominal complaints (abdominal pain, nausea, dyspepsia).
Experience in Adult Patients with COPD
Of the 1634 patients in two pivotal multiple-dose Chronic Obstructive Pulmonary Disease (COPD) controlled trials, 405 were treated with FORADIL AEROLIZER 12 mcg twice daily. The numbers and percent of patients who reported adverse events were comparable in the 12 mcg twice daily and placebo groups. Adverse events (AE's) experienced were similar to those seen in asthmatic patients, but with a higher incidence of COPD-related AE's in both placebo and formoterol treated patients.
The following table shows adverse events where the frequency was greater than or equal to 1% in the FORADIL AEROLIZER group and where the rates in the FORADIL AEROLIZER group exceeded placebo. The two clinical trials included doses of 12 mcg and 24 mcg, administered twice daily. Seven adverse events showed dose ordering among tested doses of 12 and 24 mcg administered twice daily; pharyngitis, fever, muscle cramps, increased sputum, dysphonia, myalgia, and tremor.
NUMBER AND FREQUENCY OF ADVERSE EXPERIENCES IN ADULT COPD PATIENTS TREATED IN MULTIPLE-DOSE CONTROLLED CLINICAL TRIALS
Adverse Event |
FORADIL AEROLIZER 12 mcg twice daily |
Placebo |
| n |
(%) |
n |
(%) |
|
|
|
|
|
Total patients |
405 |
(100) |
420 |
(100) |
|
|
|
|
|
Upper respiratory tract infection |
30 |
(7.4) |
24 |
(5.7) |
Pain back |
17 |
(4.2) |
17 |
(4.0) |
Pharyngitis |
14 |
(3.5) |
10 |
(2.4) |
Pain chest |
13 |
(3.2) |
9 |
(2.1) |
Sinusitis |
11 |
(2.7) |
7 |
(1.7) |
Fever |
9 |
(2.2) |
6 |
(1.4) |
Cramps leg |
7 |
(1.7) |
2 |
(0.5) |
Cramps muscle |
7 |
(1.7) |
0 |
|
Anxiety |
6 |
(1.5) |
5 |
(1.2) |
Pruritus |
6 |
(1.5) |
4 |
(1.0) |
Sputum increased |
6 |
(1.5) |
5 |
(1.2) |
Mouth dry |
5 |
(1.2) |
4 |
(1.0) |
Overall, the frequency of all cardiovascular adverse events in the two pivotal studies was low and comparable to placebo (6.4% for FORADIL AEROLIZER 12 mcg twice daily, and 6.0% for placebo). There were no frequently-occurring specific cardiovascular adverse events for FORADIL AEROLIZER (frequency greater than or equal to 1% and greater than placebo).
Other adverse reactions to FORADIL AEROLIZER are similar in nature to other selective beta2-adrenoceptor agonists; e.g., angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia.
Post Marketing Experience
In extensive worldwide marketing experience with FORADIL, serious exacerbations of asthma, including some that have been fatal, have been reported. While most of these cases have been in patients with severe or acutely deteriorating asthma (see WARNINGS), a few have occurred in patients with less severe asthma. It is not possible to determine from these individual case reports whether FORADIL AEROLIZER contributed to the events.
Rare reports of anaphylactic reactions, including severe hypotension and angioedema, have also been received in association with the use of formoterol fumarate inhalation powder.
|
REPORTS OF SUSPECTED FORADIL SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Foradil. The information is not vetted and should not be considered as verified clinical evidence.
Possible Foradil side effects / adverse reactions in 90 year old female
Reported by a individual with unspecified qualification from Dominican Republic on 2011-10-03
Patient: 90 year old female
Reactions: Death
Adverse event resulted in: death
Suspect drug(s):
Foradil
Possible Foradil side effects / adverse reactions in 69 year old female
Reported by a individual with unspecified qualification from Dominican Republic on 2011-10-05
Patient: 69 year old female
Reactions: Death, Diabetes Mellitus, Hypertension
Adverse event resulted in: death, hospitalization
Suspect drug(s):
Foradil
Other drugs received by patient: Loratadine; Enalapril Maleate; Insulin; Hydrochlorothiazide; Daflon (Diosmin); Metformin HCL
Possible Foradil side effects / adverse reactions in 79 year old female
Reported by a physician from United States on 2011-10-13
Patient: 79 year old female
Reactions: Vitreous Floaters, Visual Impairment, Macular Degeneration
Suspect drug(s):
Foradil
Other drugs received by patient: Probiotics; Vitamin A
|