Included as part of the PRECAUTIONS section.
Local Nasal Effects
In clinical trials of 2 to 26 weeks' duration, epistaxis
was observed more frequently in subjects treated with FLONASE Nasal Spray than
those who received placebo [see ADVERSE REACTIONS].
Postmarketing cases of nasal ulceration have been
reported in patients treated with FLONASE Nasal Spray [see ADVERSE REACTIONS].
In clinical trials with fluticasone propionate
administered intranasally, the development of localized infections of the nose
and pharynx with Candida albicans has occurred. When such an infection
develops, it may require treatment with appropriate local therapy and
discontinuation of FLONASE Nasal Spray. Patients using FLONASE Nasal Spray over
several months or longer should be examined periodically for evidence of Candida
infection or other signs of adverse effects on the nasal mucosa.
Nasal Septal Perforation
Postmarketing cases of nasal septal perforation have been
reported in patients treated with FLONASE Nasal Spray [see ADVERSE REACTIONS].
Impaired Wound Healing
Because of the inhibitory effect of corticosteroids on
wound healing, patients who have experienced recent nasal ulcers, nasal
surgery, or nasal trauma should avoid using FLONASE Nasal Spray until healing
Glaucoma And Cataracts
Use of intranasal and inhaled corticosteroids may result
in the development of glaucoma and/or cataracts. Therefore, close monitoring is
warranted in patients with a change in vision or with a history of increased
intraocular pressure, glaucoma, and/or cataracts.
Hypersensitivity Reactions including Anaphylaxis
Hypersensitivity reactions (e.g., anaphylaxis,
angioedema, urticaria, contact dermatitis, and rash) have been reported after
administration of FLONASE Nasal Spray. Discontinue FLONASE
Nasal Spray if such reactions occur [see
CONTRAINDICATIONS]. Rarely, immediate hypersensitivity reactions may occur
after the administration of FLONASE Nasal Spray.
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 children or
adults who have not had these diseases or 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) may be
indicated. If a patient is exposed to measles, prophylaxis with pooled
intramuscular immunoglobulin (IG) may be indicated. (See the complete
prescribing information for VZIG and IG.) If chickenpox develops, treatment
with antiviral agents may be considered.
Intranasal corticosteroids should be used with caution,
if at all, in patients with active or quiescent tuberculous infections of the
respiratory tract; systemic fungal, bacterial, viral, or parasitic infections;
or ocular herpes simplex.
Hypercorticism And Adrenal Suppression
When intranasal corticosteroids are used at higher than
recommended dosages or in susceptible individuals at recommended dosages,
systemic corticosteroid effects such as hypercorticism and adrenal suppression
may appear. If such changes occur, the dosage of FLONASE Nasal Spray should be
discontinued slowly consistent with accepted procedures for discontinuing oral
The replacement of a systemic corticosteroid with a
topical corticosteroid can be accompanied by signs of adrenal insufficiency. In
addition, some patients may experience symptoms of corticosteroid withdrawal
(e.g., joint and/or muscular pain, lassitude, depression). Patients previously
treated for prolonged periods with systemic corticosteroids and transferred to
topical corticosteroids should be carefully monitored for acute adrenal
insufficiency in response to stress. In patients who have asthma or other
clinical conditions requiring long-term systemic corticosteroid treatment,
rapid decreases in systemic corticosteroid dosages may cause a severe
exacerbation of their symptoms.
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, conivaptan,
lopinavir, nefazodone, voriconazole) with FLONASE Nasal Spray is not
recommended because increased systemic corticosteroid adverse effects may occur
[see DRUG INTERACTIONS, CLINICAL PHARMACOLOGY].
Effect On Growth
Intranasal corticosteroids may cause a reduction in
growth velocity when administered to pediatric patients [see Use in Specific
Populations]. Monitor the growth routinely of pediatric patients receiving
FLONASE Nasal Spray. To minimize the systemic effects of intranasal
corticosteroids, including FLONASE Nasal Spray, titrate each patient's dose to
the lowest dosage that effectively controls his/her symptoms [see DOSAGE AND
ADMINISTRATION, Use In Specific Populations].
Patient Counseling Information
Advise the patient to read the FDA-approved patient
labeling (PATIENT INFORMATION and Instructions for Use).
Local Nasal Effects
Inform patients that treatment with FLONASE Nasal Spray
may lead to adverse reactions, which include epistaxis and nasal ulceration. Candida
infection may also occur with treatment with FLONASE Nasal Spray. In addition,
FLONASE Nasal Spray has been associated with nasal septal perforation and
impaired wound healing. Patients who have experienced recent nasal ulcers,
nasal surgery, or nasal trauma should not use FLONASE Nasal Spray until healing
has occurred [see WARNINGS AND PRECAUTIONS].
Glaucoma and Cataracts
Inform patients that glaucoma and cataracts are
associated with nasal and inhaled corticosteroid use. Advise patients to notify
their healthcare providers if a change in vision is noted while using FLONASE
Nasal Spray [see WARNINGS AND PRECAUTIONS].
Hypersensitivity Reactions, including Anaphylaxis
Inform patients that hypersensitivity reactions,
including anaphylaxis, angioedema, urticaria, contact dermatitis, and rash, may
occur after administration of FLONASE Nasal Spray. If such reactions occur,
patients should discontinue use of FLONASE Nasal Spray [see WARNINGS AND
Warn patients who are on immunosuppressant doses of
corticosteroids to avoid exposure to chickenpox or measles and if they are
exposed to consult their healthcare provider without delay. Inform patients of
potential worsening of existing tuberculosis; fungal, bacterial, viral, or
parasitic infections; or ocular herpes simplex [see WARNINGS AND PRECAUTIONS].
Reduced Growth Velocity
Advise parents that FLONASE Nasal Spray may cause a
reduction in growth velocity when administered to pediatric patients.
Physicians should closely follow the growth of children and adolescents taking
corticosteroids by any route [see WARNINGS AND PRECAUTIONS, Pediatric
Use Daily for Best Effect
Inform patients that they should use FLONASE Nasal Spray
on a regular basis. FLONASE Nasal Spray, like other corticosteroids, does not
have an immediate effect on rhinitis symptoms. Maximum benefit may not be
reached for several days. Patients should not increase the prescribed dosage
but should contact their healthcare providers if symptoms do not improve or if
the condition worsens.
Keep Spray Out of Eyes and Mouth
Inform patients to avoid spraying FLONASE Nasal Spray in
their eyes and mouth.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Fluticasone propionate demonstrated no tumorigenic
potential in mice at oral doses up to 1,000 mcg/kg (approximately 20 times the
MRHDID in adults and approximately 10 times the MRHDID in children on a mcg/m² basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg
(approximately 2 times the MRHDID in adults and approximately equivalent to the
MRHDID in children 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 mouse
No evidence of impairment of fertility was observed in
male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 2
times the MRHDID in adults on a mcg/m² basis). Prostate weight was
significantly reduced at a subcutaneous dose of 50 mcg/kg.
Perennial Nonallergic Rhinitis
Three randomized, double-blind, parallel-group, vehicle
placebo-controlled trials were conducted in 1,191 subjects to investigate
regular use of FLONASE Nasal Spray in subjects with perennial nonallergic
rhinitis. These trials evaluated subject-rated total nasal symptom scores
(TNSS) that included nasal obstruction, postnasal drip, rhinorrhea in subjects
treated for 28 days of double-blind therapy and in 1 of the 3 trials for 6
months of open-label treatment. Two of these trials demonstrated that subjects
treated with FLONASE Nasal Spray (100 mcg twice daily) exhibited statistically
significant decreases in TNSS compared with subjects treated with vehicle.
Use In Specific Populations
Pregnancy Category C. There are no adequate and
well-controlled trials with FLONASE Nasal Spray in pregnant women.
Corticosteroids have been shown to be teratogenic in laboratory animals when
administered systemically at relatively low dosage levels. Because animal
reproduction studies are not always predictive of human response, FLONASE Nasal
Spray should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus. Women should be advised to contact their
physicians if they become pregnant while taking FLONASE Nasal Spray.
Mice and rats at fluticasone propionate doses
approximately 1 and 4 times, respectively, the maximum recommended human daily
intranasal dose (MRHDID) for adults (on a mg/m² basis at maternal
subcutaneous doses of 45 and 100 mcg/kg/day, respectively) showed fetal
toxicity characteristic of potent corticosteroid compounds, including embryonic
growth retardation, omphalocele, cleft palate, and retarded cranial
ossification. No teratogenicity was seen in rats at doses up to 3 times the
MRHDID (on a mg/m² basis at maternal inhalation doses up to 68.7
In rabbits, fetal weight reduction and cleft palate were
observed at a fluticasone propionate dose approximately 0.3 times the MRHDID
for adults (on a mg/m² basis at a maternal subcutaneous dose of 4
mcg/kg/day). However, no teratogenic effects were reported at fluticasone
propionate doses up to approximately 20 times the MRHDID for adults (on a mg/m² basis at a maternal oral dose up to 300 mcg/kg/day). No fluticasone
propionate was detected in the plasma in this study, consistent with the
established low bioavailability following oral administration [see CLINICAL
Fluticasone propionate crossed the placenta following
subcutaneous administration to mice and rats and oral administration to
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.
Hypoadrenalism may occur in infants born of mothers receiving
corticosteroids during pregnancy. Such infants should be carefully monitored.
It is not known whether fluticasone propionate is
excreted in human breast milk. However, other corticosteroids have been
detected in human milk. Subcutaneous administration to lactating rats of
tritiated fluticasone propionate at a dose approximately 0.4 times the MRHDID
for adults on a mg/m² basis resulted in measurable radioactivity in
Since there are no data from controlled trials on the use
of intranasal FLONASE Nasal Spray by nursing mothers, caution should be
exercised when FLONASE Nasal Spray is administered to a nursing woman.
The safety and effectiveness of FLONASE Nasal Spray in
children aged 4 years and older have been established [see ADVERSE REACTIONS,
CLINICAL PHARMACOLOGY].Six hundred fifty (650) subjects aged 4 to 11
years and 440 subjects aged 12 to 17 years were studied in US clinical trials
with fluticasone propionate nasal spray. The safety and effectiveness of
FLONASE Nasal Spray in children younger than 4 years have not been established.
Effects on Growth
Controlled clinical trials have shown that intranasal
corticosteroids may cause a reduction in growth velocity when administered to
pediatric patients. This effect was observed in the absence of laboratory
evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting
that growth velocity is a more sensitive indicator of systemic corticosteroid
exposure in pediatric patients than some commonly used tests of HPA axis
function. The long-term effects of this reduction in growth velocity associated
with intranasal corticosteroids, including the impact on final adult height,
are unknown. The potential for “catch-up” growth following discontinuation of
treatment with intranasal corticosteroids has not been adequately studied. The
growth of pediatric patients receiving intranasal corticosteroids, including
FLONASE Nasal Spray, should be monitored routinely (e.g., via stadiometry). The
potential growth effects of prolonged treatment should be weighed against the
clinical benefits obtained and the risks associated with alternative therapies.
To minimize the systemic effects of intranasal corticosteroids, including
FLONASE Nasal Spray, each patient's dosage should be titrated to the lowest
dosage that effectively controls his/her symptoms.
A 1-year placebo-controlled trial was conducted in 150
pediatric subjects (aged 3 to 9 years) to assess the effect of FLONASE Nasal
Spray (single daily dose of 200 mcg) on growth velocity. From the primary
population receiving FLONASE Nasal Spray (n = 56) and placebo (n = 52), the
point estimate for growth velocity with FLONASE Nasal Spray was 0.14 cm/year
lower than placebo (95% CI: -0.54, 0.27 cm/year). Thus, no statistically
significant effect on growth was noted compared with placebo. No evidence of
clinically relevant changes in HPA axis function or bone mineral density was
observed as assessed by 12-hour urinary cortisol excretion and dual-energy
x-ray absorptiometry, respectively.
The potential for FLONASE Nasal Spray to cause growth
suppression in susceptible patients or when given at higher than recommended
dosages cannot be ruled out.
A limited number of subjects aged 65 years and older (n =
129) or 75 years and older (n = 11) have been treated with FLONASE Nasal Spray
in clinical trials. While the number of subjects is too small to permit
separate analysis of efficacy and safety, the adverse reactions reported in
this population were similar to those reported by younger patients. In general,
dose selection for an elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal, or cardiac function, and of concomitant disease or other drug
Formal pharmacokinetic trials using FLONASE Nasal Spray
have not been conducted in subjects 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 trials using FLONASE Nasal Spray
have not been conducted in subjects with renal impairment.