ADVAIR DISKUS SIDE EFFECTS
- Generic Name: fluticasone propionate
- Brand Name: Advair Diskus
- Drug Class: Respiratory Inhalant Combos, COPD Agents, Respiratory Inhalant Combos
SIDE EFFECTS
LABA, such as salmeterol, one of the active ingredients in ADVAIR DISKUS, increase the risk of asthma-related death. Data from a large placebo-controlled U.S. trial that compared the safety of salmeterol or placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.
Systemic and local corticosteroid use may result in the following:
- Candida albicans infection
- Pneumonia in patients with COPD
- Immunosuppression
- Hypercorticism and adrenal suppression
- Reduction in bone mineral density
- Growth effects
- Glaucoma and cataracts
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience In Asthma
Adult And Adolescent Subjects Aged 12 Years And Older
The incidence of adverse reactions associated with ADVAIR DISKUS in Table 2 is based upon two 12-week, placebo-controlled, U.S. clinical trials (Trials 1 and 2). A total of 705 adult and adolescent subjects (349 females and 356 males) previously treated with salmeterol or inhaled corticosteroids were treated twice daily with ADVAIR DISKUS (100/50-or 250/50-mcg doses), fluticasone propionate inhalation powder (100-or 250-mcg doses), salmeterol inhalation powder 50 mcg, or placebo. The average duration of exposure was 60 to 79 days in the active treatment groups compared with 42 days in the placebo group.
Table 1: Adverse Reactions with ADVAIR DISKUS with ≥ 3% Incidence and More Common than Placebo in Adult and Adolescent Subjects with Asthma
| Adverse Event | ADVAIR DISKUS 100/50 (n = 92) % |
ADVAIR DISKUS 250/50 (n = 84) % |
Fluticasone Propionate 100 mcg (n = 90) % |
Fluticasone Propionate 250 mcg (n = 84) % |
Salmeterol 50 mcg (n = 180) % |
Placebo (n = 175) % |
| Ear, nose, and throat | ||||||
| Upper respiratory tract infection | 27 | 21 | 29 | 25 | 19 | 14 |
| Pharyngitis | 13 | 10 | 7 | 12 | 8 | 6 |
| Upper respiratory inflammation | 7 | 6 | 7 | 8 | 8 | 5 |
| Sinusitis | 4 | 5 | 6 | 1 | 3 | 4 |
| Hoarseness/dysphonia | 5 | 2 | 2 | 4 | < 1 | < 1 |
| Oral candidiasis | 1 | 4 | 2 | 2 | 0 | 0 |
| Lower respiratory | ||||||
| Viral respiratory infections | 4 | 4 | 4 | 10 | 6 | 3 |
| Bronchitis | 2 | 8 | 1 | 2 | 2 | 2 |
| Cough | 3 | 6 | 0 | 0 | 3 | 2 |
| Neurology | ||||||
| Headaches | 12 | 13 | 14 | 8 | 10 | 7 |
| Gastrointestinal | ||||||
| Nausea and vomiting | 4 | 6 | 3 | 4 | 1 | 1 |
| Gastrointestinal discomfort and pain | 4 | 1 | 0 | 2 | 1 | 1 |
| Diarrhea | 4 | 2 | 2 | 2 | 1 | 1 |
| Viral gastrointestinal infections | 3 | 0 | 3 | 1 | 2 | 2 |
| Non-site specific | ||||||
| Candidiasis unspecified site | 3 | 0 | 1 | 4 | 0 | 1 |
| Musculoskeletal | ||||||
| Musculoskeletal pain | 4 | 2 | 1 | 5 | 3 | 3 |
Additional Adverse Reactions
Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with asthma treated with ADVAIR DISKUS compared with subjects treated with placebo include the following: lymphatic signs and symptoms; muscle injuries; fractures; wounds and lacerations; contusions and hematomas; ear signs and symptoms; nasal signs and symptoms; nasal sinus disorders; keratitis and conjunctivitis; dental discomfort and pain; gastrointestinal signs and symptoms; oral ulcerations; oral discomfort and pain; lower respiratory signs and symptoms; pneumonia; muscle stiffness, tightness, and rigidity; bone and cartilage disorders; sleep disorders; compressed nerve syndromes; viral infections; pain; chest symptoms; fluid retention; bacterial infections; unusual taste; viral skin infections; skin flakiness and acquired ichthyosis; disorders of sweat and sebum.
Pediatric Subjects Aged 4 To 11 Years
The safety data for pediatric subjects aged 4 to 11 years is based upon 1 U.S. trial of 12 weeks’ treatment duration. A total of 203 subjects (74 females and 129 males) who were receiving inhaled corticosteroids at trial entry were randomized to either ADVAIR DISKUS 100/50 or fluticasone propionate inhalation powder 100 mcg twice daily. Common adverse reactions (greater than or equal to 3% and greater than placebo) seen in the pediatric subjects but not reported in the adult and adolescent clinical trials include: throat irritation and ear, nose, and throat infections.
Laboratory Test Abnormalities
Elevation of hepatic enzymes was reported in greater than or equal to 1% of subjects in clinical trials. The elevations were transient and did not lead to discontinuation from the trials. In addition, there were no clinically relevant changes noted in glucose or potassium.
Clinical Trials Experience In Chronic Obstructive Pulmonary Disease
Short-Term (6 Months to 1 Year) Trials
The short-term safety data are based on exposure to ADVAIR DISKUS 250/50 twice daily in one 6-month and two 1-year clinical trials. In the 6-month trial, a total of 723 adult subjects (266 females and 457 males) were treated twice daily with ADVAIR DISKUS 250/50, fluticasone propionate inhalation powder 250 mcg, salmeterol inhalation powder, or placebo. The mean age of the subjects was 64, and the majority (93%) was Caucasian. In this trial, 70% of the subjects treated with ADVAIR DISKUS reported an adverse reaction compared with 64% on placebo. The average duration of exposure to ADVAIR DISKUS 250/50 was 141.3 days compared with 131.6 days for placebo. The incidence of adverse reactions in the 6-month trial is shown in Table 2.
Table 2: Overall Adverse Reactions with ADVAIR DISKUS 250/50 with ≥ 3% Incidence in Subjects with Chronic Obstructive Pulmonary Disease Associated with Chronic Bronchitis
| Adverse Event | ADVAIR DISKUS 250/50 (n = 178) % |
Fluticasone Propionate 250 mcg (n = 183) % |
Salmeterol 50 mcg (n = 177) % |
Placebo (n = 185) % |
| Ear, nose, and throat | ||||
| Candidiasis mouth/throat | 10 | 6 | 3 | 1 |
| Throat irritation | 8 | 5 | 4 | 7 |
| Hoarseness/dysphonia | 5 | 3 | < 1 | 0 |
| Sinusitis | 3 | 8 | 5 | 3 |
| Lower respiratory | ||||
| Viral respiratory infections | 6 | 4 | 3 | 3 |
| Neurology | ||||
| Headaches | 16 | 11 | 10 | 12 |
| Dizziness | 4 | < 1 | 3 | 2 |
| Non-site specific | ||||
| Fever | 4 | 3 | 0 | 3 |
| Malaise and fatigue | 3 | 2 | 2 | 3 |
| Musculoskeletal | ||||
| Musculoskeletal pain | 9 | 8 | 12 | 9 |
| Muscle cramps and spasms | 3 | 3 | 1 | 1 |
The incidence of pneumonia was higher in subjects older than 65 years, 9% in the subjects treated with ADVAIR DISKUS compared with 4% in the subjects treated with ADVAIR DISKUS younger than 65 years. In the subjects treated with salmeterol, the incidence of pneumonia was the same (3%) in both age-groups.
Long-Term (3 Years) Trial
The safety of ADVAIR DISKUS 500/50 was evaluated in a randomized, double-blind, placebo-controlled, multicenter, international, 3-year trial in 6,184 adult subjects with COPD (4,684 males and 1,500 females). The mean age of the subjects was 65 years, and the majority (82%) was Caucasian. The distribution of adverse events was similar to that seen in the 1-year trials with ADVAIR DISKUS 250/50. In addition, pneumonia was reported in a significantly increased number of subjects treated with ADVAIR DISKUS 500/50 and fluticasone propionate 500 mcg (16% and 14%, respectively) compared with subjects treated with salmeterol 50 mcg or placebo (11% and 9%, respectively). When adjusted for time on treatment, the rates of pneumonia were 84 and 88 events per 1,000 treatment-years in the groups treated with fluticasone propionate 500 mcg and with ADVAIR DISKUS 500/50, respectively, compared with 52 events per 1,000 treatment-years in the salmeterol and placebo groups. Similar to what was seen in the 1-year trials with ADVAIR DISKUS 250/50, the incidence of pneumonia was higher in subjects older than 65 years (18% with ADVAIR DISKUS 500/50 versus 10% with placebo) compared with subjects younger than 65 years (14% with ADVAIR DISKUS 500/50 versus 8% with placebo).
Additional Adverse Reactions
Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with COPD treated with ADVAIR DISKUS compared with subjects treated with placebo include the following: syncope; ear, nose, and throat infections; ear signs and symptoms; laryngitis; nasal congestion/blockage; nasal sinus disorders; pharyngitis/throat infection; hypothyroidism; dry eyes; eye infections; gastrointestinal signs and symptoms; oral lesions; abnormal liver function tests; bacterial infections; edema and swelling; viral infections.
Laboratory Abnormalities
There were no clinically relevant changes in these trials. Specifically, no increased reporting of neutrophilia or changes in glucose or potassium was noted.
Postmarketing Experience
In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of any formulation of ADVAIR, fluticasone propionate, and/or salmeterol regardless of indication. 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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to ADVAIR DISKUS, fluticasone propionate, and/or salmeterol or a combination of these factors.
Cardiac Disorders
Arrhythmias (including atrial fibrillation, extrasystoles, supraventricular tachycardia), ventricular tachycardia.
Endocrine Disorders
Cushing’s syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism.
Eye Disorders
Glaucoma.
Gastrointestinal Disorders
Abdominal pain, dyspepsia, xerostomia.
Immune System Disorders
Immediate and delayed hypersensitivity reaction (including very rare anaphylactic reaction). Very rare anaphylactic reaction in patients with severe milk protein allergy.
Infections And Infestations
Esophageal candidiasis.
Metabolic and Nutrition Disorders
Hyperglycemia, weight gain.
Musculoskeletal, Connective Tissue, And Bone Disorders
Arthralgia, cramps, myositis, osteoporosis. Nervous System Disorders Paresthesia, restlessness.
Psychiatric Disorders
Agitation, aggression, depression. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.
Reproductive System And Breast Disorders
Dysmenorrhea.
Respiratory, Thoracic, And Mediastinal Disorders
Chest congestion; chest tightness; dyspnea; facial and oropharyngeal edema, immediate bronchospasm; paradoxical bronchospasm; tracheitis; wheezing; reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking.
Skin And Subcutaneous Tissue Disorders
Ecchymoses, photodermatitis.
Vascular Disorders
Pallor.
SRC: NLM .