Included as part of the PRECAUTIONS section.
Local Effects Of Inhaled Corticosteroids
In clinical trials, the development of localized
infections of the mouth and pharynx with Candida albicans has occurred in
subjects treated with ARMONAIR RESPICLICK. When such an infection develops, it
should be treated with appropriate local or systemic (i.e., oral) antifungal therapy
while treatment with ARMONAIR RESPICLICK continues, but at times therapy with
ARMONAIR RESPICLICK may need to be interrupted. Advise the patient to rinse
his/her mouth with water without swallowing following inhalation to help reduce
the risk of oropharyngeal candidiasis.
Acute Asthma Episodes
ARMONAIR RESPICLICK is not indicated for the relief of
acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of
bronchospasm. An inhaled, short-acting beta2agonist, not ARMONAIR RESPICLICK,
should be used to relieve acute symptoms such as shortness of breath. When
prescribing ARMONAIR RESPICLICK, the physician must provide the patient with an
inhaled, short-acting beta2-agonist (e.g., albuterol) for treatment of acute
symptoms, despite regular twice-daily use of ARMONAIR RESPICLICK. Instruct
patients to contact their physicians immediately if episodes of asthma not
responsive to bronchodilators occur during the course of treatment with
ARMONAIR RESPICLICK. During such episodes, patients may require therapy with oral
Persons who are using 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 using
corticosteroids. In such patients who have not had these diseases or who have
not been properly immunized, particular care should be taken to avoid exposure.
How the dose, route and duration of corticosteroid administration affect 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 a patient is exposed to chickenpox, prophylaxis with
varicella-zoster immune globulin (VZIG) or pooled intravenous immunoglobulin
(IVIG) may be indicated. If a patient is exposed to measles, prophylaxis with
pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective
package inserts for complete VZIG and IG prescribing information.) If
chickenpox develops, treatment with antiviral agents may be considered.
Inhaled corticosteroids should be used with caution, if
at all, in patients with active or quiescent tuberculosis infections of the
respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic
infections; or ocular herpes simplex.
Transferring Patients From Systemic Corticosteroid
Particular care is needed for patients who are
transferred from systemically active corticosteroids to inhaled corticosteroids
because deaths due to adrenal insufficiency have occurred in patients with
asthma 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
hypothalamic-pituitary-adrenal (HPA) function.
Patients who have been previously maintained on 20 mg or
more 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 ARMONAIR RESPICLICK may improve control of asthma
symptoms during these episodes, in recommended doses it supplies less than
normal physiological amounts of corticosteroid systemically and does NOT
provide the mineralocorticoid that is necessary for coping with these
During periods of stress or a severe asthmatic attack, patients
who have been withdrawn from systemic corticosteroids should be instructed to
resume oral corticosteroids (in large doses) immediately and to contact their
physician for further instruction. These patients should also be instructed to
carry a medical identification warning card indicating that they may need
supplementary systemic corticosteroids during periods of stress or a severe
Patients requiring systemic corticosteroids should be
weaned slowly from systemic corticosteroid use after transferring to ARMONAIR
RESPICLICK. Prednisone reduction can be accomplished by reducing the daily
prednisone dose by 2.5 mg on a weekly basis during therapy with ARMONAIR
RESPICLICK. Lung function (mean forced expiratory volume in 1 second [FEV1] or
morning peak expiratory flow [AM PEF]), beta-agonist use, and asthma symptoms
should be carefully monitored during withdrawal of systemic 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 ARMONAIR RESPICLICK may unmask allergic conditions previously suppressed by
the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema,
arthritis, eosinophilic conditions).
During withdrawal from oral corticosteroids, some
patients may experience symptoms of systemically active corticosteroid
withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite
maintenance or even improvement of respiratory function.
Hypercorticism And Adrenal Suppression
ARMONAIR RESPICLICK will often help control asthma
symptoms with less suppression of HPA function than therapeutically equivalent
oral doses of prednisone. Since ARMONAIR RESPICLICK is absorbed into the
circulation and can be systemically active at higher doses, the beneficial
effects of ARMONAIR RESPICLICK 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
Because of the possibility of significant systemic
absorption of inhaled corticosteroids, patients treated with ARMONAIR
RESPICLICK 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
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, the dosage of ARMONAIR RESPICLICK should be reduced slowly,
consistent with accepted procedures for reducing systemic corticosteroids, and
for management of asthma symptoms.
Hypersensitivity Reactions, Including Anaphylaxis
Immediate hypersensitivity reactions (e.g., urticaria,
angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur
after administration of ARMONAIR RESPICLICK. There have been reports of
anaphylactic reactions in patients with severe milk protein allergy after
inhalation of other powder products containing lactose; therefore, patients
with severe milk protein allergy should not use ARMONAIR RESPICLICK [see CONTRAINDICATIONS].
Reduction In Bone Mineral Density
Decreases in bone mineral density (BMD) have been
observed with long-term administration of products containing inhaled
corticosteroids. 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, 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.
Effect On Growth
Orally inhaled corticosteroids, including ARMONAIR
RESPICLICK, may cause a reduction in growth velocity when administered to
pediatric patients. Monitor the growth of pediatric patients receiving ARMONAIR
RESPICLICK routinely (e.g., via stadiometry). To minimize the systemic effects
of orally inhaled corticosteroids, including ARMONAIR RESPICLICK, titrate each
patient's dosage to the lowest dosage that effectively controls his/her
symptoms [see DOSAGE AND ADMINISTRATION, Use In Specific Populations].
Glaucoma And Cataracts
Glaucoma, increased intraocular pressure, and cataracts
have been reported in patients following the long-term administration of
inhaled corticosteroids, including fluticasone propionate. Therefore, close
monitoring is warranted in patients with a change in vision or with a history
of increased intraocular pressure, glaucoma, and/or cataracts.
As with other inhaled medicines, bronchospasm may occur
with an immediate increase in wheezing after dosing. If bronchospasm occurs
following dosing with ARMONAIR RESPICLICK, it should be treated immediately
with an inhaled, short-acting bronchodilator; ARMONAIR RESPICLICK should be
discontinued immediately; and alternative therapy should be instituted.
Drug Interactions With Strong Cytochrome P450 3A4
The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors
(e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole,
nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with ARMONAIR
RESPICLICK is not recommended because increased systemic corticosteroid adverse
effects may occur [see DRUG INTERACTIONS, CLINICAL PHARMACOLOGY].
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 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.
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (PATIENT INFORMATION and Instructions for Use).
Patients should be given the following information:
Inform patients that localized infections with Candida
albicans occurred in the mouth and pharynx in some patients. If oropharyngeal
candidiasis develops, treat it with appropriate local or systemic (i.e., oral)
antifungal therapy while still continuing therapy with ARMONAIR RESPICLICK, but
at times therapy with ARMONAIR RESPICLICK may need to be temporarily
interrupted under close medical supervision. Rinsing the mouth with water
without swallowing after inhalation is advised to help reduce the risk of
Status Asthmaticus And Acute Asthma Symptoms
Inform patients that ARMONAIR RESPICLICK is not a
bronchodilator and is not intended for use as rescue medicine for acute asthma
exacerbations. Advise patients to treat acute asthma symptoms with an inhaled,
short-acting beta2-agonist such as albuterol. Instruct the patient to contact
their physicians immediately if there is deterioration of their asthma.
Warn patients who are on immunosuppressant doses of
corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to
consult their physicians without delay. Inform patients of potential worsening
of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or
ocular herpes simplex.
Hypercorticism And Adrenal Suppression
Advise patients that ARMONAIR RESPICLICK may cause
systemic corticosteroid effects of hypercorticism and adrenal suppression.
Additionally, instruct patients that deaths due to adrenal insufficiency have
occurred during and after transfer from systemic corticosteroids. Patients
should taper slowly from systemic corticosteroids if transferring to ARMONAIR
Immediate Hypersensitivity Reactions
Advise patients that immediate hypersensitivity reactions
(e.g., urticaria, angioedema, rash, bronchospasm, and hypotension), including
anaphylaxis, may occur after administration of ARMONAIR RESPICLICK. Patients
should discontinue ARMONAIR RESPICLICK if such reactions occur and contact
their healthcare provider or get emergency medical help. There have been
reports of anaphylactic reactions in patients with severe milk protein allergy
after inhalation of powder products containing lactose; therefore, patients
with severe milk protein allergy should not take ARMONAIR RESPICLICK.
Reduction In Bone Mineral Density
Advise patients who are at an increased risk for
decreased BMD that the use of corticosteroids may pose an additional risk.
Reduced Growth Velocity
Inform patients that orally inhaled corticosteroids,
including ARMONAIR RESPICLICK, may cause a reduction in growth velocity when
administered to pediatric patients. Physicians should closely follow the growth
of adolescents taking corticosteroids by any route.
Long-term use of inhaled corticosteroids may increase the
risk of some eye problems (cataracts or glaucoma); consider regular eye
Inform patients who are pregnant or nursing that they
should contact their physician about the use of ARMONAIR RESPICLICK.
Use Daily for Best Effect
Patients should use ARMONAIR RESPICLICK at regular
intervals as directed. The daily dosage of ARMONAIR RESPICLICK should not
exceed 1 inhalation twice a day. Advise patients, if they miss a dose, to take
their next dose at the same time they normally do and to not take 2 doses at
one time. Individual patients will experience a variable time to onset and
degree of symptom relief and the full benefit may not be achieved until
treatment has been administered for 1 to 2 weeks or longer. Patients should not
increase the prescribed dosage but should contact their physicians if symptoms
do not improve or if the condition worsens. Instruct patients to not stop use
of ARMONAIR RESPICLICK abruptly. Patients should contact their physicians
immediately if they discontinue use of ARMONAIR RESPICLICK.
Caring For And Storing The Inhaler
Instruct patients to not open their inhaler unless
they are taking a dose. Repeated opening and closing the cover without
taking medication will waste medication and may damage the inhaler.
Advise patients to keep their inhaler dry and clean at
all times. Never wash or put any part of the inhaler in water. Patient
should replace inhaler if washed or placed in water.
Advise patients to immediately replace inhaler if
mouthpiece cover is damaged or broken.
Gently wipe the mouthpiece with a dry cloth or tissue as
Instruct patients to store the inhaler at room
temperature and to avoid exposure to extreme heat, cold, or humidity.
Instruct patients to never take the inhaler apart.
Inform patients that ARMONAIR RESPICLICK has a dose
counter attached to the actuator. When the patient receives the inhaler, the
number 60 will be displayed. The dose counter will count down each time the
mouthpiece cap is opened and closed. The dose-counter window displays the
number of actuations left in the inhaler in units of two (e.g., 60, 58, 56,
etc.). When the counter displays 20, the color of the numbers will change to
red to remind the patient to contact their pharmacist for a refill of
medication or consult their physician for a prescription refill. When the dose
counter reaches 0, the background will change to solid red. Inform patients to
discard ARMONAIR RESPICLICK when the dose counter displays 0, 30 days after
opening the foil pouch or after the expiration date on the product, whichever
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Fluticasone propionate demonstrated no tumorigenic
potential in mice at oral doses up to 1,000 mcg/kg (approximately 10 times the
MRHDID for adults on a mcg/m² basis) for 78 weeks or in rats at inhalation
doses up to 57 mcg/kg (approximately equivalent to the MRHDID for adults on a
mcg/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 in vivo mouse
Fertility and reproductive performance were unaffected in
male and female rats at subcutaneous doses up to 50 mcg/kg (approximately
equivalent to the MRHDID for adults on a mcg/m² basis).
Use In Specific Populations
There are no randomized clinical studies of ARMONAIR
RESPICLICK in pregnant women. There are clinical considerations with the use of
ARMONAIR RESPICLICK in pregnant women [see Clinical Considerations]. In
animals, teratogenicity characteristic of corticosteroids, decreased fetal body
weight, and/or skeletal variations in rats, mice, and rabbits were observed
with subcutaneously administered maternal toxic doses of fluticasone propionate
less than the maximum recommended human daily inhaled dose (MRHDID) on a mcg/m²
basis [see Data]. However, fluticasone propionate administered via
inhalation to rats decreased fetal body weight, but did not induce
teratogenicity at a maternal toxic dose approximately 2 times the MRHDID on a
mcg/m² basis [see Data]. Experience with oral corticosteroids suggests
that rodents are more prone to teratogenic effects from corticosteroids than
humans. The estimated risk of major birth defects and miscarriage for the
indicated population is unknown. In the U.S. general population, the estimated
risk of major birth defects and miscarriage in clinically recognized
pregnancies is 2% to 4% and 15% to 20%, respectively.
Disease-Associated Maternal And/Or Embryo/Fetal Risk
In women with poorly or moderately controlled asthma,
there is an increased risk of several perinatal adverse outcomes such as
preeclampsia in the mother and prematurity, low birth weight, and small for
gestational age for the neonate. Pregnant women with asthma should be closely
monitored and medication adjusted as necessary to maintain optimal asthma
In embryo/fetal development studies with pregnant rats
and mice dosed by the subcutaneous route throughout the period of
organogenesis, fluticasone propionate was teratogenic in both species.
Omphalocele, decreased body weight, and skeletal variations were observed in
rat fetuses, in the presence of maternal toxicity, at a dose approximately 2
times the MRHDID (on a mcg/m² basis with a maternal subcutaneous dose of 100
mcg/kg/day). The rat no observed adverse effect level (NOAEL) was observed at
approximately 0.6 times the MRHDID (on a mcg/m² basis with a maternal
subcutaneous dose of 30 mcg/kg/day). Cleft palate and fetal skeletal variations
were observed in mouse fetuses at a dose approximately 0.5 times the MRHDID (on
a mcg/m² basis with a maternal subcutaneous dose of 45 mcg/kg/day). The mouse
NOAEL was observed with a dose approximately 0.16 times the MRHDID (on a mcg/m²
basis with a maternal subcutaneous dose of 15 mcg/kg/day).
In an embryo/fetal development study with pregnant rats
dosed by the inhalation route throughout the period of organogenesis,
fluticasone propionate produced decreased fetal body weights and skeletal
variations, in the presence of maternal toxicity, at a dose approximately 0.5
times the MRHDID (on a mcg/m² basis with a maternal inhalation dose of 25.7
mcg/kg/day); however, there was no evidence of teratogenicity. The NOAEL was
observed with a dose approximately 0.1 times the MRHDID (on a mcg/m² basis with
a maternal inhalation dose of 5.5 mcg/kg/day).
In an embryofetal development study in pregnant rabbits
that were dosed by the subcutaneous route throughout organogenesis, fluticasone
propionate produced reductions of fetal body weights, in the presence of
maternal toxicity at doses approximately 0.02 times the MRHDID and higher (on a
mcg/m² basis with a maternal subcutaneous dose of 0.57 mcg/kg/day).
Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at
a dose approximately 0.2 times the MRHDID (on a mcg/m² basis with a maternal
subcutaneous dose of 4 mcg/kg/day). The NOAEL was observed in rabbit fetuses
with a dose approximately 0.004 times the MRHDID (on a mcg/m² basis with a
maternal subcutaneous dose of 0.08 mcg/kg/day).
Fluticasone propionate crossed the placenta following
subcutaneous administration to mice and rats and oral administration to
In a pre-and post-natal development study in pregnant
rats dosed from late gestation through delivery and lactation (Gestation Day 17
to Postpartum Day 22), fluticasone propionate was not associated with decreases
in pup body weight, and had no effects on developmental landmarks, learning,
memory, reflexes, or fertility at doses up to approximate equivalence to the
MRHDID (on a mcg/m² basis with maternal subcutaneous doses up to 50
There are no available data on the presence of
fluticasone propionate in human milk, the effects on the breastfed child, or
the effects on milk production. Other corticosteroids have been detected in
human milk. However, fluticasone propionate concentrations in plasma after
inhaled therapeutic doses are low and therefore concentrations in human breast
milk are likely to be correspondingly low [see CLINICAL PHARMACOLOGY]. The
developmental and health benefits of breastfeeding should be considered along with
the mother's clinical need for ARMONAIR RESPICLICK and any potential adverse
effects on the breastfed child from ARMONAIR RESPICLICK or from the underlying
Subcutaneous administration of tritiated fluticasone propionate
at a dose in lactating rats approximately 0.2 times the MRHDID for adults (on a
mcg/m² basis) resulted in measurable levels in milk.
The safety and effectiveness of ARMONAIR RESPICLICK in
pediatric patients below the age of 12 years have not been established.
Effects On Growth
Orally inhaled corticosteroids may cause a reduction in
growth velocity when administered to pediatric patients. A reduction of growth
velocity in children or teenagers may occur as a result of poorly controlled
asthma or from use of corticosteroids, including inhaled corticosteroids. The
effects of long-term treatment of children and adolescents with inhaled
corticosteroids, including fluticasone propionate, on final adult height are
No overall differences in safety or efficacy were
observed in data collected in 135 subjects aged 65 years and older versus
younger subjects who were treated with ARMONAIR RESPICLICK in
placebo-controlled Phase 2 and 3 studies.
Formal pharmacokinetic studies using ARMONAIR RESPICLICK
have not been conducted in patients with hepatic impairment. Since fluticasone
propionate is predominantly cleared by hepatic metabolism, impairment of liver
function may lead to accumulation of fluticasone propionate in plasma.
Therefore, patients with hepatic disease should be closely monitored.
Formal pharmacokinetic studies using ARMONAIR RESPICLICK
have not been conducted in patients with renal impairment.