CONTRAINDICATIONS
Fluticasone propionate is contraindicated in the primary treatment of status asthmaticus or other
acute episodes of asthma where intensive measures are required.
Hypersensitivity to any of the ingredients of these preparations contraindicates their use.
WARNINGS
Particular care is needed for patients who are transferred from systemically active
corticosteroids to fluticasone propionate because deaths due to adrenal insufficiency
have occurred in asthmatic patients during and after transfer from systemic
corticosteroids to less systemically available inhaled corticosteroids. After withdrawal
from systemic corticosteroids, a number of months are required for recovery of HPA
function.
Patients who have been previously maintained on 20 mg or more per day of prednisone
(or its equivalent) may be most susceptible, particularly when their systemic
corticosteroids have been almost completely withdrawn. During this period of HPA
suppression, patients may exhibit signs and symptoms of adrenal insufficiency when
exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions
associated with severe electrolyte loss. Although fluticasone propionate inhalation
powder and aerosol may provide control of asthma symptoms during these episodes, in
recommended doses they supply less than normal physiological amounts of
corticosteroid systemically and do NOT provide the mineralocorticoid activity that is
necessary for coping with these emergencies.
During periods of stress or a severe asthma attack, patients who have been withdrawn
from systemic corticosteroids should be instructed to resume oral corticosteroids (in
large doses) immediately and to contact their physicians for further instruction. These
patients should also be instructed to carry a warning card indicating that they may need
supplementary systemic corticosteroids during periods of stress or a severe asthma
attack.
Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use
after transferring to fluticasone propionate inhalation powder or aerosol. In a clinical trial of 96
patients, prednisone reduction was successfully accomplished by reducing the daily prednisone dose
by 2.5 mg on a weekly basis during transfer to inhaled fluticasone propionate. Successive reduction
of prednisone dose was allowed only when lung function, symptoms, and as-needed beta-agonist
use were better than or comparable to that seen before initiation of prednisone dose reduction. Lung
function (FEV1 or AM PEFR), beta-agonist use, and asthma symptoms should be carefully
monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and
symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as
fatigue, lassitude, weakness, nausea and vomiting, and hypotension.
Transfer of patients from systemic corticosteroid therapy to fluticasone propionate inhalation
powder or aerosol may unmask conditions previously suppressed by the systemic corticosteroid
therapy, e.g., rhinitis, conjunctivitis, eczema, and arthritis.
Persons who are on drugs that suppress the immune system are more susceptible to infections than
healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal
course in susceptible children or adults on corticosteroids. In such children or adults who have not
had these diseases, particular care should be taken to avoid exposure. How the dose, route, and
duration of corticosteroid administration affects the risk of developing a disseminated infection is not
known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is
also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG)
may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG)
may be indicated. (See complete prescribing information for IG and VZIG.) If chickenpox develops,
treatment with antiviral agents may be considered.
Fluticasone propionate inhalation powder and aerosol are not to be regarded as bronchodilators and
are not indicated for rapid relief of bronchospasm.
As with other inhaled asthma medications, bronchospasm may occur with an immediate increase in
wheezing after dosing. If bronchospasm occurs following dosing with fluticasone propionate, it
should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with inhaled
fluticasone propionate should be discontinued and alternative therapy instituted.
Patients should be instructed to contact their physicians immediately when episodes of asthma that
are not responsive to bronchodilators occur during the course of treatment with fluticasone
propionate inhalation powder or aerosol. During such episodes, patients may require therapy with
oral corticosteroids.
PRECAUTIONS
General
During withdrawal from oral corticosteroids, some patients may experience symptoms of
systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and
depression, despite maintenance or even improvement of respiratory function.
Fluticasone propionate will often permit control of 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
fluticasone propionate inhalation powder or aerosol 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 fluticasone propionate inhalation
powder or aerosol.
Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with
these drugs 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
may appear in a small number of patients, particularly at higher doses. If such changes occur,
fluticasone propionate inhalation powder or aerosol should be reduced slowly, consistent with
accepted procedures for reducing systemic corticosteroids and for management of asthma
symptoms.
A reduction of growth velocity in children or teenagers may occur as a result of inadequate control
of chronic diseases such as asthma or from use of corticosteroids for treatment. Physicians should
closely follow the growth of children and adolescents taking corticosteroids by any route, and weigh
the benefits of corticosteroid therapy against the possibility of growth suppression if growth appears
slowed. Patients should be maintained on the lowest dose of inhaled corticosteroid that effectively
controls their asthma. Additional Information for Inhalation Powder Only: A 52-week
placebo-controlled study to assess the potential growth effects of fluticasone propionate inhalation
powder at 50 and 100 mg twice daily was conducted in the U.S. in 325 prepubescent children (244
males and 81 females), 4 to 11 years of age. The mean growth velocities at 52 weeks observed in
the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the
50-mg group (n = 98), and 5.66 cm/year in the 100-mg group (n = 89). An imbalance in the
proportion of children entering puberty between groups and a higher dropout rate in the placebo
group due to poorly controlled asthma may be confounding factors in interpreting these data. A
separate subset analysis of children who remained prepubertal during the study revealed growth
rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mg group (n
= 74), and 5.67 cm/year in the 100-mg group (n = 79). The clinical significance of these growth data
is not certain. In children 8.5 years of age, the mean age of children in this study, the range for
expected growth velocity is: boys—3rd percentile = 3.8 cm/year, 50th percentile = 5.4 cm/year, and
97th percentile = 7.0 cm/year; girls—3rd percentile = 4.2 cm/year, 50th percentile = 5.7 cm/year,
and 97th percentile = 7.3 cm/year. The effects of long-term treatment of children with inhaled
corticosteroids, including fluticasone propionate, on final adult height are not known.
The long-term effects of fluticasone propionate in human subjects are not fully known. In particular,
the effects resulting from chronic use of fluticasone propionate on developmental or immunologic
processes in the mouth, pharynx, trachea, and lung are unknown. Some patients have received
inhaled fluticasone propionate on a continuous basis for periods of 3 years or longer. In clinical
studies with patients treated for nearly 2 years with inhaled fluticasone propionate, no apparent
differences in the type or severity of adverse reactions were observed after long- versus short-term
treatment.
Rare instances of glaucoma, increased intraocular pressure, and cataracts have been reported
following the inhaled administration of corticosteroids, including fluticasone propionate.
In clinical studies with inhaled fluticasone propionate, the development of localized infections of the
pharynx with Candida albicans has occurred. When such an infection develops, it should be
treated with appropriate local or systemic (i.e., oral antifungal) therapy while remaining on
treatment with fluticasone propionate inhalation powder or aerosol, but at times therapy with
fluticasone propionate may need to be interrupted.
Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent
tuberculous infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic
infections; or ocular herpes simplex.
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 ADVERSE
REACTIONS).
Information for Patients
Patients being treated with fluticasone propionate should receive the following information and
instructions. This information is intended to aid them in the safe and effective use of this medication.
It is not a disclosure of all possible adverse or intended effects.
Patients should use fluticasone propionate at regular intervals as directed. Results of clinical trials
indicated significant improvement may occur within the first day or two of treatment; however, the
full benefit may not be achieved until treatment has been administered for 1 to 2 weeks or longer.
The patient should not increase the prescribed dosage but should contact the physician if symptoms
do not improve or if the condition worsens.
Patients should be warned to avoid exposure to chickenpox or measles and, if they are exposed, to
consult their physicians without delay.
For the proper use of fluticasone propionate inhalation powder or aerosol and to attain maximum
improvement, the patient should read and follow carefully the accompanying Patient's Instructions
for Use.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Inhalation Powder
Fluticasone propionate demonstrated no tumorigenic potential in studies of oral doses up to 1000
mg/kg (approximately 2 times the maximum recommended daily inhalation dose in adults [and for
powder approximately 10 times the maximum recommended daily inhalation dose in children on a
mg/m2 basis]) for 78 weeks in the mouse or inhalation of up to 57 mg/kg (approximately ¼ the
maximum recommended daily inhalation dose in adults [and for powder comparable to the
maximum recommended daily inhalation dose in children] on a mg/m2 basis) for 104 weeks.
Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No
significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the
mouse micronucleus test when administered at high doses by the oral or subcutaneous routes.
Furthermore, the compound did not delay erythroblast division in bone marrow.
No evidence of impairment of fertility was observed in reproductive studies conducted in rats dosed
simultaneously with up to 50 mg/kg (approximately 1/5 [for powder] and ¼ [for aerosol] the
maximum recommended daily inhalation dose in adults on a mg/m2 basis) in males and females.
However, prostate weight was significantly reduced in rats.
Pregnancy, Teratogenic Effects, Pregnancy Category C
Subcutaneous studies in the mouse and rat at 45 and 100 mg/kg, respectively, (approximately 1/10
and 1/3 [for inhalation powder; ½ for inhalation aerosol] the maximum recommended human daily
inhalation dose based on a mg/m2 respectively), revealed fetal toxicity characteristic of potent
corticosteroid compounds, including embryonic growth retardation, omphalocele, cleft palate, and
retarded cranial ossification.
In the rabbit, fetal weight reduction and cleft palate were observed following subcutaneous doses of
4 mg/kg (approximately 1/30 [for inhalation powder] and 1/25 [for inhalation aerosol] the maximum
recommended human daily inhalation dose based on mg/m2). However, following oral administration
of up to 300 mg/kg (approximately 2 times [for inhalation powder] and 3 times [for aerosol] the
maximum human daily inhalation dose based on mg/m2) of fluticasone propionate to the rabbit, there
were no maternal effects nor increased incidence of external, visceral, or skeletal fetal defects. No
fluticasone propionate was detected in the plasma in this study, consistent with the established low
bioavailability following oral administration (see CLINICAL PHARMACOLOGY).
Fluticasone propionate crossed the placenta (less than 0.008% of the administered dose for
inhalation aerosol) following oral administration of 100 mg/kg to rats or 300 mg/kg to rabbits
(approximately 1/3 and 2 times [for inhalation powder] and ½ and 3 times [for inhalation aerosol],
respectively, the maximum recommended daily inhalation dose in adults on a mg/m2 basis).
There are no adequate and well-controlled studies in pregnant women. Fluticasone propionate
should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to
physiologic, doses suggests that rodents are more prone to teratogenic effects from corticosteroids
than humans. In addition, because there is a natural increase in corticosteroid production during
pregnancy, most women will require a lower exogenous corticosteroid dose and many will not need
corticosteroid treatment during pregnancy.
Nursing Mothers
It is not known whether fluticasone propionate is excreted in human breast milk. Subcutaneous
administration of 10 mg/kg tritiated drug to lactating rats (approximately 1/25 [for inhalation powder]
and 1/20 [for inhalation aerosol] the maximum recommended daily inhalation dose on a mg/m2 basis)
resulted in measurable radioactivity in milk (for inhalation aerosol, both plasma and milk). Because
other corticosteroids are excreted in human milk, caution should be exercised when fluticasone
propionate inhalation powder or aerosol is administered to a nursing woman.
Pediatric Use
Inhalation Powder: Two hundred fourteen (214) patients 4 to 11 years of age and 142 patients 12
to 16 years of age were treated with fluticasone propionate inhalation powder in U.S. clinical trials.
The safety and effectiveness of fluticasone propionate inhalation powder in children below 4 years
of age have not been established.
Inhaled corticosteroids, including fluticasone propionate, may cause a reduction in growth in children
and adolescents (see PRECAUTIONS). If a child or adolescent on any corticosteroid appears to
have growth suppression, the possibility that they are particularly sensitive to this effect of
corticosteroids should be considered. Patients should be maintained on the lowest dose of inhaled
corticosteroid that effectively controls their asthma.
Inhalation Aerosol: One hundred thirty-seven (137) patients between the ages of 12 and 16 years
were treated with fluticasone propionate inhalation aerosol in the U.S. pivotal clinical trials. The
safety and effectiveness of fluticasone propionate inhalation aerosol in children below 12 years of
age have not been established. Oral corticosteroids have been shown to cause a reduction in growth
velocity in children and teenagers with extended use. If a child or teenager on any corticosteroid
appears to have growth suppression, the possibility that they are particularly sensitive to this effect
of corticosteroids should be considered (see PRECAUTIONS).
Geriatric Use
One hundred seventy-three (173) [574 for inhalation aerosol] patients 65 years of age or older have
been treated with fluticasone propionate inhalation powder and aerosol in U.S. and non-U.S. clinical
trials. There were no differences in adverse reactions compared to those reported by younger
patients.