FORADIL SIDE EFFECTS
- Generic Name: formoterol fumarate inhalation powder
- Brand Name: Foradil Aerolizer
SIDE EFFECTS
Long-acting beta2-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.
Adverse reactions common to LABA drugs include: angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical trials.
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 treatment-emergent adverse reactions 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 treatment-emergent adverse reactions showed dose ordering among tested doses of 6, 12 and 24 mcg administered twice daily; tremor, dizziness and dysphonia.
Number and Frequency of Treatment-Emergent Adverse Reactions in Patients 5 Years of Age and Older from Multiple-Dose Controlled Clinical Trials
| Treatment-Emergent Adverse Reaction |
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) |
| Tonsilitis | 23 | (1.2) | 7 | (0.7) |
| Rash | 22 | (1.1) | 7 | (0.7) |
| Dysphonia | 19 | (1) | 9 | (0.9) |
In patients 5-12 years of age, the numbers and percent of patients who reported treatment-emergent adverse reactions were comparable in the 12 mcg twice daily and placebo groups. In general, the pattern of the treatment-emergent adverse reactions observed in children differed from the usual pattern seen in adults. Treatment-emergent adverse reactions 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).
Serious Asthma Exacerbations in Adolescents and Adults 12 Years of Age and Older
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%) |
| 1patient required intubation 2patients 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. 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%) |
Serious Asthma Exacerbations in Children 5-11 Years of Age
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) |
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. Treatment-emergent adverse reactions reported were similar to those seen in asthmatic patients, but with a higher incidence of COPD-related events in both placebo and formoterol treated patients.
The following table shows treatment-emergent adverse reactions 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 treatment-emergent adverse reactions 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 Treatment-Emergent Adverse Reactions in Adult COPD Patients Treated in Multiple-Dose Controlled Clinical Trials
| Treatment-Emergent Adverse Reaction |
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) |
| 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) |
| Pruritis | 6 | (1.5) | 4 | (1) |
| Sputum increased | 6 | (1.5) | 5 | (1.2) |
| Mouth dry | 5 | (1.2) | 4 | (1) |
Overall, the frequency of all cardiovascular treatment-emergent adverse reactions in the two pivotal studies was6.4% for FORADIL AEROLIZER 12 mcg twice daily, and 6.0% for placebo. There were no frequently-occurring specific cardiovascular treatment-emergent adverse reactions for FORADIL AEROLIZER (frequency greater than or equal to 1% and greater than placebo).
Post Marketing Experience
The following adverse reactions have been identified during post approval use of FORADIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
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, 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.
Immune system disorders: rare reports of anaphylactic reactions, including severe hypotension and angioedema
Metabolism and nutrition disorders: Hypokalemia, hyperglycemia
Respiratory, thoracic and mediastinal disorders: Cough
Skin and subcutaneous tissue disorders: Rash
Cardiac disorders: Atrial fibrillation, angina pectoris, ventricular extrasystoles, tachyarrhythmia
Investigations: Electrocardiogram QT prolonged, blood pressure increased (including hypertension)
SRC: NLM .