Included as part of the "PRECAUTIONS" Section
Localized infections with Candida albicans have occurred in the mouth and pharynx in some patients
receiving QVAR. If oropharyngeal candidiasis develops, it should be treated with appropriate local or
systemic (i.e., oral) antifungal therapy while still continuing with QVAR therapy, but at times therapy
with QVAR may need to be temporarily interrupted under close medical supervision. Rinsing the mouth
after inhalation is advised.
Deterioration Of Asthma And Acute Episodes
QVAR 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 beta-2 agonist, not QVAR, should be used to
relieve acute symptoms such as shortness of breath. Instruct patients to contact their physician
immediately if episodes of asthma that are not responsive to bronchodilators occur during the course of
treatment with QVAR. During such episodes, patients may require therapy with oral corticosteroids.
Transferring Patients From Systemic Corticosteroid Therapy
Particular care is needed in patients who are transferred from systemically active corticosteroids to
QVAR 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
hypothalamic-pituitary-adrenal (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completely withdrawn.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 infections (particularly gastroenteritis) or
other conditions with severe electrolyte loss. Although QVAR may provide control of asthmatic
symptoms during these episodes, in recommended doses it supplies less than normal physiological
amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid that is necessary
for coping with these emergencies.
During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic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
warning card indicating that they may need supplementary systemic steroids during periods of stress or
a severe asthma attack.
Patients requiring oral or other systemic corticosteroids should be weaned slowly from oral or other
systemic corticosteroid use after transferring to QVAR. Lung function (FEV1 or PEF), beta-agonist
use, and asthma symptoms should be carefully monitored during withdrawal of oral or other 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,
Transfer of patients from systemic corticosteroid therapy to QVAR may unmask allergic conditions
previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema,
arthritis, and 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, and depression, despite
maintenance or even improvement of respiratory function.
Persons who are on drugs which 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 non-immune children or adults on corticosteroids. In such children or adults who have not had these
diseases or been properly immunized, particular care should be taken to avoid exposure. It is not known
how the dose, route and duration of corticosteroid administration affects the risk of developing a
disseminated infection. Nor is the contribution of the underlying disease and/or prior corticosteroid
treatment 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 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 infection of the respiratory tract; untreated systemic fungal, bacterial, parasitic or viral
infections; or ocular herpes simplex.
Inhaled corticosteroids may produce inhalation induced bronchospasm with an immediate increase in
wheezing after dosing that may be life-threatening. If inhalation induced bronchospasm occurs
following dosing with QVAR, it should be treated immediately with an inhaled, short-acting
bronchodilator. Treatment with QVAR should be discontinued and alternate therapy instituted.
Immediate Hypersensitivity Reactions
Hypersensitivity reactions, such as urticaria, angioedema, rash, and bronchospasm, may occur after
administration of QVAR. Discontinue QVAR if such reactions occur [see CONTRAINDICATIONS]
Hypercorticism And Adrenal Suppression
QVAR will often help control asthma symptoms with less suppression of HPA function than
therapeutically equivalent oral doses of prednisone. Since beclomethasone dipropionate is absorbed
into the circulation and can be systemically active at higher doses, the beneficial effects of QVAR in
minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and
individual patients are titrated to the lowest effective dose.
Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with
QVAR 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, particularly when beclomethasone
dipropionate is administered at higher than recommended doses over prolonged periods of time. If such
effects occur, the dosage of QVAR should be reduced slowly, consistent with accepted procedures
for reducing systemic corticosteroids and for management of asthma symptoms.
Effects On Growth
Reduction In Bone Mineral Density
Glaucoma And Cataracts
Glaucoma, increased intraocular pressure, and cataracts have been reported following the use of longterm
administration of inhaled corticosteroids. Therefore, close monitoring is warranted in patients with
a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts while
Patient Counseling Information
Advise the patients to read the FDA-approved patient labeling (PATIENT INFORMATION and Instructions for
- Risks Associated with Corticosteroid Therapy
Local Effects: Advise patients that localized infections with Candida albicans have occurred in
the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, it should be treated
with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing with QVAR
therapy, but at times therapy with QVAR may need to be temporarily interrupted under close
medical supervision. Rinsing the mouth after inhalation is advised [see WARNINGS AND PRECAUTION].
Immunosuppression: Warn patients who are on immunosuppressant doses of corticosteroids to
avoid exposure to chickenpox or measles and, if exposed, to consult their physician without
delay. Inform patients of potential worsening of existing tuberculosis, fungal, bacterial, viral, or
parasitic infections, or ocular herpes simplex [see WARNINGS AND PRECAUTIONS].
Hypercorticism and Adrenal Suppression: Advise patients that QVAR 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
QVAR [see WARNINGS AND PRECAUTIONS].
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 and that they should be monitored
and, where appropriate, be treated for this condition [see WARNINGS AND PRECAUTIONS].
Reduced Growth Velocity: Inform patients that orally inhaled corticosteroids, including QVAR,
may cause a reduction in growth velocity when administered to pediatric patients. Physicians
should closely follow the growth of pediatric patients taking corticosteroids by any route [see
WARNINGS AND PRECAUTIONS].
Glaucoma and Cataracts: Long-term use of inhaled corticosteroids may increase the risk of some
eye problems (glaucoma or cataracts); regular eye examinations should be considered [see
WARNINGS AND PRECAUTIONS].
- Not for Acute Symptoms
Advise patients that QVAR is not intended for use in the treatment of acute asthma. Acute asthma
symptoms should be treated with an inhaled, short-acting beta-2 agonist such as albuterol. Instruct
the patient to contact their healthcare provider immediately if there is any deterioration of their
asthma [see WARNINGS AND PRECAUTIONS].
- Susceptibility to Infections
Warn persons who are on immunosuppressant doses of corticosteroids to avoid exposure to
chickenpox or measles and, if exposed, to consult their physician without delay. Inform patients of
potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or
ocular herpes simplex[see WARNINGS AND PRECAUTIONS].
- Use Daily for Best Effect
Advise patients to use QVAR at regular intervals, since its effectiveness depends on regular use.
Maximum benefit may not be achieved for 1 week or longer after starting treatment. If symptoms
do not improve after 2 weeks of therapy or if the condition worsens, patients should be instructed
to contact their physician.
- Proper Use and Care of the Inhaler
Priming: Priming is essential to ensure appropriate beclomethasone dipropionate content in each
actuation. Instruct patients to prime the inhaler before using for the first time and in cases where
the inhaler has not been used for more than 10 days by releasing two sprays into the air, away from
Cleaning: For normal hygiene, the mouthpiece of the inhaler should be cleaned weekly with a
clean, dry tissue or cloth. DO NOT WASH OR PUT ANY PART OF THE INHALER IN
Dose Counter: Inform patients that QVAR has a dose counter attached to the actuator. When the
patient receives the inhaler, a black dot will appear in the viewing window until it has been primed
2 times, at which point the total number of actuations will be displayed. The dose counter will
count down each time a spray is released. The dose-counter window displays the number of
sprays left in the inhaler in units of two (e.g., 120, 118, 116, 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 the QVAR inhaler
when the dose counter displays 0 or after the expiration date on the product, whichever comes
- Discontinuing QVAR
Do not stop QVAR use abruptly. Instruct the patient to contact their healthcare provider
immediately if use of QVAR is discontinued.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
The carcinogenicity of beclomethasone dipropionate was evaluated in rats which were exposed for a
total of 95 weeks, 13 weeks at inhalation doses up to 0.4 mg/kg/day and the remaining 82 weeks at
combined oral and inhalation doses up to 2.4 mg/kg/day. There was no evidence of treatment-related
increases in the incidence of tumors in this study at the highest dose, which is approximately 37 and 72
times the maximum recommended daily inhalation dose in adults and children, respectively, on a mg/m2
Beclomethasone dipropionate did not induce gene mutation in bacterial cells or mammalian Chinese
Hamster ovary (CHO) cells in vitro. No significant clastogenic effect was seen in cultured CHO cells in
vitro or in the mouse micronucleus test in vivo.
In rats, beclomethasone dipropionate caused decreased conception rates at an oral dose of 16 mg/kg/day
(approximately 250 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis).
Impairment of fertility, as evidenced by inhibition of the estrous cycle in dogs, was observed following
treatment by the oral route at a dose of 0.5 mg/kg/day (approximately 25 times the maximum
recommended daily inhalation dose in adults on a mg/m2 basis). No inhibition of the estrous cycle in
dogs was seen following 12 months of exposure to beclomethasone dipropionate by the inhalation route
at an estimated daily dose of 0.33 mg/kg (approximately 17 times the maximum recommended daily
inhalation dose in adults on a mg/m2 basis).
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies with QVAR in pregnant women. Animal studies were
conducted with beclomethasone dipropionate in rats, mice, and rabbits. Systemic exposure data were not
determined in the animal studies. In rats exposed to beclomethasone dipropionate by inhalation at doses
greater than 180 times the maximum recommended adult human daily inhalation dose (MRHDID), doserelated
gross injury to the fetal adrenal glands was observed. However, there was no evidence of
external or skeletal malformations or embryolethality in rats at inhalation doses up to 440 times the
MRHDID. Beclomethasone dipropionate was teratogenic (mice and rabbits) and embryolethal (rabbits)
at subcutaneous doses equal to or greater than approximately 0.75 times the MRHDID. Beclomethasone
dipropionate treatment was embryolethal and caused decreased pup survival in mice at subcutaneous
doses equal to or greater than 2.3 times the MRHDID. Beclomethasone dipropionate should be used
during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Disease-Associated Maternal and Fetal Risk
In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased
risk of preeclampsia in the mother and prematurity, low birth weight and small for gestational age for
the neonate. The level of asthma control should be closely monitored in pregnant women and treatment
adjusted as necessary to maintain optimal control.
In an embryofetal development study in pregnant rats, beclomethasone dipropionate administration during
organogenesis from gestation days 6 to 15 at inhaled doses 180 times the MRHDID (0.64 mg/day) in
adults and higher (on a mg/m2 basis at maternal doses of 11.5 and 28.3 mg/kg/day) produced dosedependent
gross injury (characterized by red foci) of the adrenalglands in fetuses. There were no
findings in the adrenal glands of rat fetuses at an inhaled dose that was 40 times the MRHDID in
adults(on a mg/m2 basis at a maternal dose of 2.4 mg/kg/day). There was no evidence of external or
skeletal malformations or embryolethality in rat fetuses at inhaled doses up to 440 times the MRHDID
(on a mg/m2 basis at maternal doses up to 28.3 mg/kg/day).
In an embryofetal development study in pregnant mice, beclomethasone dipropionate administration from
gestation days 1 to 18 at subcutaneous doses equal to and greater than 0.75 times the MRHDID in adults
(on a mg/m2 basis at maternal doses of 0.1 mg/kg/day and higher) produced teratogenic effects
(increased incidence of cleft palate). A no effect dose in mice was not identified. In a second
embryofetal development study in pregnant mice, beclomethasone dipropionate administration from
gestation days 1 to 13 at subcutaneous doses equal to and greater than 2.3 times the MRHDID in adults
(on a mg/m2 basis at a maternal dose of 0.3 mg/kg/day) produced embryolethal effects (increased fetal
resorptions) and decreased pup survival.
In an embryofetal development study in pregnant rabbits, beclomethasone dipropionate administration
during organogenesis from gestation days 7 to 16 at subcutaneous doses equal to and greater than 0.75
times the MRHDID in adults (on a mg/m2 basis at maternal doses of 0.025 mg/kg/day and higher)
produced teratogenic (external and skeletal malformations) and embryolethal effects (increased fetal
resorptions). There were no effects in fetuses of pregnant rabbits administered a subcutaneous dose 0.2
times the MRHDID in adults (on a mg/m2 basis at a maternal dose of 0.006 mg/kg/day).
Corticosteroids are secreted in human milk. Caution should be exercised when QVAR is administered
to a nursing mother.
Eight-hundred and thirty-four children between the ages of 5 and 12 were treated with HFA
beclomethasone dipropionate (HFA-BDP) in clinical trials. The safety and effectiveness of QVAR in
children below 5 years of age have not been established.
Use of QVAR with a spacer device in children less than 5 years of age is not recommended. In vitro
dose characterization studies were performed with QVAR 40 mcg/actuation with the OptiChamber and
AeroChamber Plus® spacer utilizing inspiratory flows representative of children under 5 years old.
These studies indicated that the amount of medication delivered through the spacing device decreased
rapidly with increasing wait times of 5 to 10 seconds as shown in Table 4. If QVAR is used with a
spacer device, it is important to inhale immediately.
Based on the average inspiratory flow rates generated by children 6 months to 5 years old, the projected
daily dose derived from QVAR 40 mcg at one puff per day at various wait times is depicted in Table 4
Table 4 - Average Daily Dose Based on Wait Time in Pediatric Patients
||Wait time, seconds
||Body Weight 50th
percentile, kg† ii
delivered per dose,
mcg/kg‡ iii§ iv
|Age 6 months, Flow rate
|Age 2 years,
|Age 2 years,
|Age 2 years,
|Age 5 years,
|*Summary Report; Pediatric Dose Characterization of QVAR with Spacer; 3M Pharmaceutical Development, July
†CDC Growth charts, developed by the National Center for Health Statistics in collaboration with the National
Center for Chronic Disease Prevention and Health Promotion (2000).
‡Includes an estimated 20% loss in the masks\
§QVAR 4 0mcg in an average adult without using a spacer delivers approximately 0.4 mcg/kg, or bid, 0.8
Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth
velocity in pediatric patients. A 12-month, randomized, controlled clinical trial evaluated the effects of
HFA beclomethasone dipropionate without spacer versus CFC beclomethasone dipropionate with
large-volume spacer on growth in children age 5 to 11. A total of 520 patients were enrolled, of whom
394 received HFA-BDP (100 to 400 mcg/day ex-valve) and 126 received CFC-BDP (200 to 800
mcg/day ex-valve). Similar control of asthma was noted in each treatment arm. When comparing results
at month 12 to baseline, the mean growth velocity in children treated with HFA-BDP was approximately
0.5 cm/year less than that noted with children treated with CFC-BDP via large-volume spacer. The
long-term effects of the reduction in growth velocity associated with orally inhaled corticosteroids,
including the impact on final adult height, are unknown. The potential for "catch-up" growth following
discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied.
The growth of children and adolescents receiving orally inhaled corticosteroids, including QVAR,
should be monitored routinely (e.g., via stadiometry). If a child or adolescent on any corticosteroid
appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect
should be considered. The potential growth effects of prolonged treatment should be weighed against
clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic
effects of orally inhaled corticosteroids, including QVAR, each patient should be titrated to his/her
lowest effective dose [see DOSAGE AND ADMINISTRATION].
Clinical studies of QVAR did not include sufficient numbers of subjects aged 65 and over to determine
whether they respond differently from younger subjects. Other reported clinical experience has not
identified differences in responses between the elderly and 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 therapy.