General: Because of the relatively high molar dose of flunisolide per
activation in this preparation, and because of the evidence suggesting higher
levels of systemic absorption with flunisolide than with other comparable inhaled
corticosteroids (see CLINICAL PHARMACOLOGY
section), patients treated with AEROBID (flunisolide) should be observed carefully
for any evidence of systemic corticosteroid effect, including suppression of
bone growth in children. Particular care should be taken in observing patients
post-operatively or during periods of stress for evidence of a decrease in adrenal
function. During withdrawal from oral steroids, some patients may experience
symptoms of systemically active steroid withdrawal, e.g. joint and/or muscular
pain, lassitude and depression, despite maintenance or even improvement of respiratory
function. (See DOSAGE AND ADMINISTRATION
In responsive patients, flunisolide may permit control of asthmatic symptoms without suppression of HPA function. Since flunisolide is absorbed into the circulation and can be systemically active, the beneficial effects of AEROBID Inhaler in minimizing or preventing HPA dysfunction may be expected only when recommended dosages are not exceeded.
The long-term local and systemic effects of AEROBID (flunisolide) in human
subjects are still not fully known. In particular, the effects resulting from
chronic use of AEROBID on developmental or immunologic processes in the mouth,
pharynx, trachea, and lung are unknown.
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
Pulmonary infiltrates with eosinophilia may occur in patients on AEROBID Inhaler therapy.
Although it is possible that in some patients this state may become manifest
because of systemic steroid withdrawal when inhalational steroids are administered,
a causative role for the drug and/or its vehicle cannot be ruled out.
Information for Patients:
Since the relief from AEROBID Inhaler depends on its regular use and on proper
inhalation technique, patients must be instructed to take inhalations at regular
intervals. They should also be instructed in the correct method of use. (See
Patient Instruction Leaflet.)
Patients whose systemic corticosteroids have been reduced or withdrawn should
be instructed to carry a warning card indicating they may need supplemental
systemic steroids during periods of stress or a severe asthmatic attack that
is not responsive to bronchodilators.
Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chicken pox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.
An illustrated leaflet of patient instructions for proper use accompanies each AEROBID Inhaler System.
CONTENTS UNDER PRESSURE
Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F (49°C) may cause container to explode. Never throw container into fire or incinerator. Keep out of reach of children.
Carcinogenesis: Long-term studies were conducted in mice and
rats using oral administration to evaluate the carcinogenic potential of the
drug. There was an increase in the incidence of pulmonary adenomas in mice,
but not in rats.
Female rats receiving the highest oral dose had an increased incidence of mammary adenocarcinoma compared to control rats. An increased incidence of this tumor type has been reported for other corticosteroids.
Impairment of Fertility: Female rats receiving high doses of
flunisolide (200 mcg/kg/ day) showed some evidence of impaired fertility. Reproductive
performance in the low- (8 mcg/kg/day) and mid-dose (40 mcg/kg/day) groups was
comparable to controls.
Pregnancy: Pregnancy Category C. As with other corticosteroids,
flunisolide has been shown to be teratogenic in rabbits and rats at doses of
40 and 200 mcg/kg/day respectively. It was also fetotoxic in these animal reproductive
studies. There are no adequate and well-controlled studies in pregnant women.
Flunisolide should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
Nursing Mothers: It is not known whether this drug is excreted
in human milk. Because other corticosteroids are excreted in human milk, caution
should be exercised when flunisolide is administered to nursing women.
Pediatric Use: Safety and effectiveness have not been established
in children below the age of 6. Oral corticoids have been shown to cause growth
suppression in children and adolescents, particularly with higher doses over
extended periods. If a child or adolescent on any corticoid appears to have
growth suppression, the possibility that they are particularly sensitive to
this effect of steroids should be considered.