Included as part of the PRECAUTIONS section.
Localized infections with Candida albicans have occurred
in the mouth and pharynx in some patients receiving QVAR REDIHALER. If
oropharyngeal candidiasis develops, it should be treated with appropriate local
or systemic (i.e., oral) antifungal therapy while still continuing with QVAR
REDIHALER therapy, but at times therapy with QVAR REDIHALER may need to be temporarily
interrupted under close medical supervision. After inhalation, the patient
should rinse his/her mouth with water without swallowing to help reduce the
risk of oropharyngeal candidiasis.
Deterioration Of Asthma And Acute Episodes
QVAR REDIHALER is not indicated for the relief of acute
symptoms, i.e., as rescue therapy for the treatment of acute episodes of
bronchospasm. An inhaled, shortacting
not QVAR REDIHALER, 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 REDIHALER. During such episodes, patients may require
therapy with oral corticosteroids.
Transferring Patients From Systemic Corticosteroid
Particular care is needed in patients who are transferred
from systemically active corticosteroids to QVAR REDIHALER 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 hypothalamicpituitaryadrenal (HPA)
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withdrawn.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 REDIHALER 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
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patients who have been withdrawn from systemic corticosteroids should be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 REDIHALER. Lung function (FEV1 or PEF), betaagonist 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, and hypotension.
Transfer of patients from systemic corticosteroid therapy
to QVAR REDIHALER 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 patients on corticosteroids. In such patients 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 affect the risk of developing a disseminated infection, and 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 inhalationinduced bronchospasm
with an immediate increase in wheezing after dosing that may be
life-threatening. If inhalation induced bronchospasm occurs following dosing
with QVAR REDIHALER, it should be treated immediately with an inhaled, shortacting
bronchodilator. Treatment with QVAR REDIHALER 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
REDIHALER. Discontinue QVAR REDIHALER if such reactions occur [see CONTRAINDICATIONS].
Hypercorticism And Adrenal Suppression
QVAR REDIHALER 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 REDIHALER 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 REDIHALER 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 REDIHALER should be reduced slowly,
consistent with accepted procedures for reducing systemic corticosteroids and
for management of asthma symptoms.
Effects On Growth
Orally inhaled corticosteroids, including QVAR REDIHALER,
may cause a reduction in growth velocity when administered to pediatric
patients. Monitor the growth of pediatric patients receiving QVAR REDIHALER routinely
(e.g., via stadiometry). To minimize the systemic effects of orally inhaled
corticosteroids, including QVAR REDIHALER, titrate each patient's dose to the
lowest dosage that effectively controls his/her symptoms [see Use In Specific
Reduction In Bone Mineral Density
Decreases in bone mineral density (BMD) have been
observed with longterm
administration of products containing inhaled corticosteroids. The clinical
significance of small changes in BMD with regard to longterm outcomes, 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 and corticosteroids)
should be monitored and treated with established standards of care.
Glaucoma, increased intraocular pressure, blurred vision
and cataracts have been reported following the use of long term administration
of inhaled corticosteroids. Therefore, close monitoring is warranted in
patients with a change in vision or with a history of increased intraocular
pressure, blurred vision, glaucoma, and/or cataracts while using QVAR
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 QVAR
REDIHALER, but at times therapy with QVAR REDIHALER 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 thrush.
Status Asthmaticus And Acute Asthma Symptoms
Inform patients that QVAR REDIHALER 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, shortacting beta2agonist 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 QVAR REDIHALER 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 REDIHALER.
Immediate Hypersensitivity Reactions
Advise patients that immediate hypersensitivity reactions
(e.g., urticaria, angioedema, rash, bronchospasm, and hypotension), including
anaphylaxis, may occur after administration of QVAR REDIHALER. Patients should
discontinue QVAR REDIHALER if such reactions occur and contact their healthcare
provider or get emergency medical help.
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 QVAR REDIHALER, 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, glaucoma or blurred vision); consider
regular eye examinations.
Inform patients who are pregnant or nursing that they
should contact their physician about the use of QVAR REDIHALER.
Use Daily For Best Effect
Patients should use QVAR REDIHALER at regular intervals
as directed. The daily dosage of QVAR REDIHALER should not exceed 8 inhalations
per day. Advise patients, if they miss a dose, to take their next dose at the
same time they normally do. 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 QVAR REDIHALER abruptly. Patients should contact their
physicians immediately if they discontinue use of QVAR REDIHALER.
Caring For And Storing The Inhaler
For normal hygiene, the mouthpiece of QVAR REDIHALER
should be cleaned weekly with a clean, dry tissue or cloth. Never was h or
put any part of QVAR REDIHALER in water. Patient should replace QVAR
REDIHALER if washed or placed in water.
Instruct patients to store the inhaler at room
temperature and to avoid exposure to extreme heat and cold.
Inform patients that shaking the inhaler prior to use
is not necessary. Instruct patients not to shake the inhaler with the cap open
to avoid possible actuation of the device.
Instruct patients to never take QVAR REDIHALER apart.
Inform patients that QVAR REDIHALER has a dose counter
attached to the actuator at the rear of the mouth piece. When the patient
receives the inhaler, the number 120 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 healthcare provider for a prescription refill. When the dose
counter reaches 0, the background will change to solid red. Inform patients to
discard QVAR REDIHALER when the dose counter displays 0 or after the expiration
date on the product, whichever comes first.
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 treatmentrelated increases in
the incidence of tumors in this study at the highest dose, which is approximately
37 and 72 times the MRHDID in adults and children, respectively, on a mg/m² basis.
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
MRHDID 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 MRHDID 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 MRHDID in adults on a mg/m² basis).
Use In Specific Populations
There are no adequate and well controlled studies with QVAR REDIHALER
or beclomethasone dipropionate in pregnant women. There are clinical
considerations with the use of inhaled corticosteroids (ICS), including
beclomethasone dipropionate, in pregnant women [see Clinical Considerations].
Also, no published studies, including studies of large birth registries, have
to date related the use of ICS to any increases in congenital malformations or
other adverse perinatal outcomes. Thus, available human data do not establish
the presence or absence of drugassociated
risk to the fetus. In animal reproduction studies, beclomethasone dipropionate
resulted in adverse developmental effects in mice and rabbits at subcutaneous
doses equal to or greater than approximately 0.75 times the maximum recommended
human daily inhalation dose (MRHDID) in adults (0.64 mg/day) [see Data].
In rats exposed to beclomethasone dipropionate by inhalation, doserelated gross injury
to the fetal adrenal glands was observed at doses greater than 180 times the
MRHDID, but there was no evidence of external or skeletal malformations or
embryolethality at inhalation doses of up to 440 times the MRHDID.
The estimated background risk of major birth defects and
miscarriage for the indicated population(s) are unknown. In the US general
population, the estimated risk of major birth defects and miscarriage in clinically
recognized pregnancies is 24%
Disease-Associated Maternal And/Or Embryo/Fetal Risk
The risk of complications to the mother and developing
fetus from inadequate control of asthma must be balanced against the risks from
exposure to beclomethasone dipropionate. 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 to maintain optimal control.
Labor Or Delivery
There are no specific human data regarding any adverse
effects of inhaled beclomethasone dipropionate on labor and delivery.
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 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 adrenal glands 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 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 adverse
developmental 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
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).
There are no data available on the presence of
beclomethasone dipropionate in human milk, the effects on the breastfed child,
or the effects on milk production. However, other inhaled corticosteroids have been
detected in human milk. The developmental and health benefits of breastfeeding
should be considered along with the mother's clinical need for QVAR REDIHALER
and any potential adverse effects on the breastfed child from beclomethasone
dipropionate or from the underlying maternal condition.
Females And Males Of Reproductive Potential
Impairment of fertility was observed in rats and dogs at
oral doses of beclomethasone dipropionate corresponding to 250 and 25 times the
MRHDID for adults on a mg/m² basis, respectively. [see Nonclinical
Five-hundred and one children between the ages of 4 and
11 were treated with at least one dose of QVAR REDIHALER or QVAR MDI in one 12week clinical trial.
The safety and effectiveness of QVAR REDIHALER in children below 4 years of age
have not been established.
Do not use QVAR REDIHALER with as pacer or volume
Controlled clinical studies have shown that inhaled
corticosteroids may cause a reduction in growth velocity in pediatric patients.
randomized, controlled clinical trial evaluated the effects of QVAR MDI versus
beclomethasone dipropionate in a CFC propellantbased
on growth in children age 5 to 11. A total of 520 patients were enrolled, of
whom 394 received QVAR MDI (100 to 400 mcg/day exvalve)
and 126 received CFCBDP
(200 to 800 mcg/day exvalve).
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 QVAR MDI was approximately 0.5 cm/year less than that noted with children
treated with CFCBDP
spacer. The longterm
effects of the reduction in growth velocity associated with orally inhaled
corticosteroids, including the impact on final adult height, are unknown. The
potential for “catchup”
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 REDIHALER, 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
REDIHALER, each patient should be titrated to his/her lowest effective dose [see
DOSAGE AND ADMINISTRATION].
Clinical studies of QVAR REDIHALER did not include
sufficient numbers of patients aged 65 and over to determine whether they
respond differently from younger patients. 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.