FLOVENT HFA (Page 2 of 7)

5.5 Hypercorticism and Adrenal Suppression

Fluticasone propionate will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of FLOVENT HFA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing FLOVENT HFA.

Because of the possibility of significant systemic absorption of ICS in sensitive patients, patients treated with FLOVENT HFA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.

It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects. If such effects occur, FLOVENT HFA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of asthma symptoms should be considered.

5.6 Hypersensitivity Reactions, including Anaphylaxis

Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of FLOVENT HFA [see Contraindications (4)].

5.7 Reduction in Bone Mineral Density

Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing ICS. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids), should be monitored and treated with established standards of care.

A 2-year trial in 160 subjects (females aged 18 to 40 years, males 18 to 50) with asthma receiving chlorofluorocarbon (CFC)-propelled fluticasone propionate inhalation aerosol 88 or 440 mcg twice daily demonstrated no statistically significant changes in BMD at any time point (24, 52, 76, and 104 weeks of double-blind treatment) as assessed by dual-energy x-ray absorptiometry at lumbar regions L1 through L4.

5.8 Effect on Growth

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving FLOVENT HFA routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including FLOVENT HFA, titrate each patient’s dosage to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration (2.2), Use in Specific Populations (8.4)].

5.9 Glaucoma and Cataracts

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of ICS, including fluticasone propionate. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use FLOVENT HFA long term.

5.10 Paradoxical Bronchospasm

As with other inhaled medicines, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with FLOVENT HFA, it should be treated immediately with an inhaled, short-acting bronchodilator; FLOVENT HFA should be discontinued immediately; and alternative therapy should be instituted.

5.11 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors

The use of strong cytochrome P450 3A4 (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 [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

5.12 Eosinophilic Conditions and Churg-Strauss Syndrome

In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions. Some of these patients have 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 ICS 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.

6 ADVERSE REACTIONS

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

Oropharyngeal candidiasis infection [see Warnings and Precautions (5.1)]
Immunosuppression and risk of infections [see Warnings and Precautions (5.3)]
Hypercorticism and adrenal suppression [see Warnings and Precautions (5.5)]
Reduction in bone mineral density [see Warnings and Precautions (5.7)]
Growth effects [see Warnings and Precautions (5.8)]
Glaucoma and cataracts [see Warnings and Precautions (5.9)]

6.1 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.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.