Flovent HFA

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Oropharyngeal candidiasis infection [see WARNINGS AND PRECAUTIONS]
• Immunosuppression and risk of infections [see WARNINGS AND PRECAUTIONS]
• Hypercorticism and adrenal suppression [see WARNINGS AND PRECAUTIONS]
• Reduction in bone mineral density [see WARNINGS AND PRECAUTIONS]
• Growth effects [see WARNINGS AND PRECAUTIONS]
• Glaucoma and cataracts [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

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.

The incidence of common adverse reactions in Table 1 is based upon 2 placebo-controlled U.S. clinical trials in which 812 adult and adolescent subjects (457 females and 355 males) previously treated with as-needed bronchodilators and/or ICS were treated twice daily for up to 12 weeks with 2 inhalations of FLOVENT HFA 44 mcg, FLOVENT HFA 110 mcg, FLOVENT HFA 220 mcg (dosages of 88, 220, or 440 mcg twice daily), or placebo.

Table 1. Adverse Reactions with FLOVENT HFA with >3% Incidence and More Common than Placebo in Subjects Aged 12 Years and Older with Asthma

Adverse Event	FLOVENT HFA 88 mcg Twice Daily (n = 203) %	FLOVENT HFA 220 mcg Twice Daily (n = 204) %	FLOVENT HFA 440 mcg Twice Daily (n = 202) %	Placebo (n = 203) %
Ear, nose, and throat
Upper respiratory tract infection	18	16	16	14
Throat irritation	8	8	10	5
Upper respiratory inflammation	2	5	5	1
Sinusitis/sinus infection	6	7	4	3
Hoarseness/dysphonia	2	3	6	<1
Gastrointestinal
Candidiasis mouth/throat and non-site specific	4	2	5	<1
Lower respiratory
Cough	4	6	4	5
Bronchitis	2	2	6	5
Neurological
Headache	11	7	5	6

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 HFA and were more common than in the placebo group. Less than 2% of subjects discontinued from the trials because of adverse reactions. The average duration of exposure was 73 to 76 days in the active treatment groups compared with 60 days in the placebo group.

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 FLOVENT HFA compared with subjects treated with placebo include the following: rhinitis, rhinorrhea/post-nasal drip, nasal sinus disorders, laryngitis, diarrhea, viral gastrointestinal infections, dyspeptic symptoms, gastrointestinal discomfort and pain, hyposalivation, musculoskeletal pain, muscle pain, muscle stiffness/tightness/rigidity, dizziness, migraines, fever, viral infections, pain, chest symptoms, viral skin infections, muscle injuries, soft tissue injuries, urinary infections.

Fluticasone propionate inhalation aerosol (440 or 880 mcg twice daily) was administered for 16 weeks to 168 subjects with asthma requiring oral corticosteroids (Trial 3). Adverse reactions not included above but reported by more than 3 subjects in either group treated with FLOVENT HFA and more commonly than in the placebo group included nausea and vomiting, arthralgia and articular rheumatism, and malaise and fatigue.

In 2 long-term trials (26 and 52 weeks), the pattern of adverse reactions in subjects treated with FLOVENT HFA at dosages up to 440 mcg twice daily was similar to that observed in the 12-week trials. There were no new and/or unexpected adverse reactions with long-term treatment.

Pediatric Subjects Aged 4 To 11 Years

FLOVENT HFA has been evaluated for safety in 56 pediatric subjects who received 88 mcg twice daily for 4 weeks. Types of adverse reactions in these pediatric subjects were generally similar to those observed in adults and adolescents.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of fluticasone propionate. 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 fluticasone propionate or a combination of these factors.

Ear, Nose, And Throat

Aphonia, facial and oropharyngeal edema, and throat soreness and irritation.

Endocrine And Metabolic

Cushingoid features, growth velocity reduction in children/adolescents, hyperglycemia, osteoporosis, and weight gain.

Eye

Cataracts.

Gastrointestinal Disorders

Dental caries and tooth discoloration.

Immune System Disorders

Immediate and delayed hypersensitivity reactions, including urticaria, anaphylaxis, rash, and angioedema and bronchospasm, have been reported.

Infections and Infestations

Esophageal candidiasis.

Psychiatry

Agitation, aggression, anxiety, depression, and restlessness. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.

Respiratory

Asthma exacerbation, chest tightness, cough, dyspnea, immediate and delayed bronchospasm, paradoxical bronchospasm, pneumonia, and wheeze.

Skin

Contusions, cutaneous hypersensitivity reactions, ecchymoses, and pruritus.

DRUG INTERACTIONS

Inhibitors Of Cytochrome P450 3A4

Fluticasone propionate is a substrate of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with FLOVENT HFA is not recommended because increased systemic corticosteroid adverse effects may occur.

Ritonavir

A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see CLINICAL PHARMACOLOGY]. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression.

Ketoconazole

Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under the curve (AUC), but had no effect on urinary excretion of cortisol.

Read the entire FDA prescribing information for Flovent HFA (Fluticasone Propionate HFA)