ADVERSE REACTIONS
The incidence of common adverse events in Table 1 is based upon 7 placebo-controlled US clinical trials in which 1,176 pediatric, adolescent, and adult patients (466 females and 710 males) previously treated with as-needed bronchodilators and/or inhaled corticosteroids were treated with FLOVENT DISKUS (doses of 50 to 500 mcg twice daily for up to 12 weeks) or placebo.
Table 1. Overall Adverse Events With >3% Incidence in US Controlled Clinical Trials With FLOVENT DISKUS in Patients With Asthma Previously Receiving Bronchodilators and/or Inhaled Corticosteroids | Adverse Event | Placebo (n = 543)
% | FLOVENT DISKUS 50 mcg Twice Daily (n = 178)
% | FLOVENT DISKUS 100 mcg Twice Daily (n = 305)
% | FLOVENT DISKUS 250 mcg Twice Daily (n = 86)
% | FLOVENT DISKUS 500 mcg Twice Daily (n = 64)
% |
| Ear, nose, and throat | | | | | |
| Upper respiratory tract infection | 16 | 20 | 18 | 21 | 14 |
| Throat irritation | 8 | 13 | 13 | 3 | 22 |
| Sinusitis/sinus infection | 6 | 9 | 10 | 6 | 6 |
| Upper respiratory inflammation | 3 | 5 | 5 | 0 | 5 |
| Rhinitis | 2 | 4 | 3 | 1 | 2 |
| Oral candidiasis | 7 | <1 | 9 | 6 | 5 |
| Gastrointestinal | | | | | |
| Nausea and vomiting | 4 | 8 | 4 | 1 | 2 |
| Gastrointestinal discomfort and pain | 3 | 4 | 3 | 2 | 2 |
| Viral gastrointestinal infection | 1 | 4 | 3 | 3 | 5 |
| Non-site specific | | | | | |
| Fever | 4 | 7 | 7 | 1 | 2 |
| Viral infection | 2 | 2 | 2 | 0 | 5 |
| Lower respiratory | | | | | |
| Viral respiratory infection | 4 | 4 | 5 | 1 | 2 |
| Cough | 4 | 3 | 5 | 1 | 5 |
| Bronchitis | 1 | 2 | 3 | 0 | 8 |
| Neurological | | | | | |
| Headache | 7 | 12 | 12 | 2 | 14 |
| Musculoskeletal and trauma | | | | | |
| Muscle injury | 1 | 2 | 0 | 1 | 5 |
| Musculoskeletal pain | 2 | 4 | 3 | 2 | 5 |
| Injury | <1 | 2 | <1 | 0 | 5 |
| Average duration of exposure (days) | 56 | 76 | 73 | 79 | 78 |
Table 1 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of over 3% in any of the groups treated with FLOVENT DISKUS and were more common than in the placebo group. In considering these data, differences in average duration of exposure should be taken into account.
These adverse events were mostly mild to moderate in severity, with <2% of patients discontinuing the studies because of adverse events. Rare cases of immediate and delayed hypersensitivity reactions, including rash and other rare events of angioedema and bronchospasm, have been reported.
Other adverse events that occurred in the groups receiving FLOVENT DISKUS in these studies with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo were:
Cardiovascular
Palpitations.
Drug Interaction, Overdose, and Trauma
Soft tissue injuries, contusions and hematomas, wounds and lacerations, postoperative complications, burns, poisoning and toxicity, pressure-induced disorders.
Ear, Nose, and Throat
Ear signs and symptoms; rhinorrhea/postnasal drip; hoarseness/dysphonia; epistaxis; tonsillitis; nasal signs and symptoms; laryngitis; unspecified oropharyngeal plaques; otitis; ear, nose, throat, and tonsil signs and symptoms; ear, nose, and throat polyps; allergic ear, nose, and throat disorders; throat constriction.
Endocrine and Metabolic
Fluid disturbances, weight gain, goiter, disorders of uric acid metabolism, appetite disturbances.
Eye
Keratitis and conjunctivitis, blepharoconjunctivitis.
Gastrointestinal
Diarrhea, gastrointestinal signs and symptoms, oral ulcerations, dental discomfort and pain, gastroenteritis, gastrointestinal infections, abdominal discomfort and pain, oral erythema and rashes, mouth and tongue disorders, oral discomfort and pain, tooth decay.
Hepatobiliary Tract and Pancreas
Cholecystitis.
Lower Respiratory
Lower respiratory infections.
Musculoskeletal
Muscle pain, arthralgia and articular rheumatism, muscle cramps and spasms, musculoskeletal inflammation.
Neurological
Dizziness, sleep disorders, migraines, paralysis of cranial nerves.
Non-Site Specific
Chest symptoms; malaise and fatigue; pain; edema and swelling; bacterial infections; fungal infections; mobility disorders; cysts, lumps, and masses.
Psychiatry
Mood disorders.
Reproduction
Bacterial reproductive infections.
Skin
Skin rashes, urticaria, photodermatitis, dermatitis and dermatosis, viral skin infections, eczema, fungal skin infections, pruritus, acne and folliculitis.
Urology
Urinary infections.
Three (3) of the 7 placebo-controlled US clinical trials were pediatric studies. A total of 592 patients 4 to 11 years were treated with FLOVENT DISKUS (dosages of 50 or 100 mcg twice daily) or placebo; an additional 174 patients 4 to 11 years received FLOVENT ROTADISK at the same doses. There were no clinically relevant differences in the pattern or severity of adverse events in children compared with those reported in adults.
In the first 16 weeks of a 52-week clinical trial in adult patients with asthma who previously required oral corticosteroids (daily doses of 5 to 40 mg oral prednisone), the effects of FLOVENT DISKUS 500 mcg twice daily (n = 41) and 1,000 mcg twice daily (n = 36) were compared with placebo (n = 34) for the frequency of reported adverse events. Adverse events, whether or not considered drug related by the investigators, reported in more than 5 patients in the group taking FLOVENT DISKUS and that occurred more frequently with FLOVENT DISKUS than with placebo are shown below (percent FLOVENT DISKUS and percent placebo). In considering these data, the increased average duration of exposure for patients taking FLOVENT DISKUS (105 days for FLOVENT DISKUS versus 75 days for placebo) should be taken into account.
Ear, Nose, and Throat
Hoarseness/dysphonia (9% and 0%), nasal congestion/blockage (16% and 0%), oral candidiasis (31% and 21%), rhinitis (13% and 9%), sinusitis/sinus infection (33% and 12%), throat irritation (10% and 9%), and upper respiratory tract infection (31% and 24%).
Gastrointestinal
Nausea and vomiting (9% and 0%).
Lower Respiratory
Cough (9% and 3%) and viral respiratory infections (9% and 6%).
Musculoskeletal
Arthralgia and articular rheumatism (17% and 3%) and muscle pain (12% and 0%).
Non-Site Specific
Malaise and fatigue (16% and 9%) and pain (10% and 3%).
Skin
Pruritus (6% and 0%) and skin rashes (8% and 3%).
Observed During Clinical Practice
In addition to adverse events reported from clinical trials, the following events have been identified during postapproval use of fluticasone propionate 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 either their seriousness, frequency of reporting, or causal connection to fluticasone propionate or a combination of these factors.
Ear, Nose, and Throat
Aphonia, facial and oropharyngeal edema, and throat soreness.
Endocrine and Metabolic
Cushingoid features, growth velocity reduction in children/adolescents, hyperglycemia, and osteoporosis.
Eye
Cataracts.
Psychiatry
Agitation, aggression, anxiety, depression, and restlessness. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.
Non-Site Specific
Very rare anaphylactic reaction, very rare anaphylactic reaction in patients with severe milk protein allergy.
Respiratory
Asthma exacerbation, bronchospasm, chest tightness, dyspnea, immediate bronchospasm, pneumonia, and wheeze.
Skin
Contusions and ecchymoses.
Eosinophilic Conditions
In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions, with some patients presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established (see PRECAUTIONS: Eosinophilic Conditions).
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