Recommended Topic Related To:

Aerospan HFA

"The U.S. Food and Drug Administration will complete its phase-out of all inhaler medical products containing chlorofluorocarbons (CFCs) by Dec. 31, 2013. This effort is to comply with an international treaty to protect the ozone layer by phasing "...

Aerospan HFA

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Local Infections

In clinical studies with flunisolide, localized infections with Candida albicans or Aspergillus niger have occurred in the mouth and pharynx and occasionally in the larynx. If oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing with AEROSPAN Inhalation Aerosol therapy, but at times therapy with AEROSPAN Inhalation Aerosol may need to be temporarily interrupted under close medical supervision. Rinsing the mouth after inhalation is advised. [see ADVERSE REACTIONS] .

Acute Asthma Episodes

AEROSPAN Inhalation Aerosol is not a bronchodilator and is not indicated for rapid relief of bronchospasm. Instruct patients to contact their physician immediately when episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with AEROSPAN Inhalation Aerosol. During such episodes, patients may require therapy with systemic corticosteroids.

Immunosuppression

Patients 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 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. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and 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 respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.

Because of the potential for worsening infections, use inhaled corticosteroids with caution, if at all, in patients with untreated active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, parasitic or viral infections; or ocular herpes simplex.

Transfer from Systemic Corticosteroids

Particular care is needed in patients who are transferred from systemically active corticosteroids to AEROSPAN Inhalation Aerosol 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 associated with severe electrolyte loss. Although AEROSPAN Inhalation Aerosol may provide control of asthmatic symptoms during these episodes, in recommended doses it supplies less than the physiologic amounts of glucocorticoid (cortisol) systemically and does NOT provide the mineralocorticoid activity 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 systemic steroids immediately and to contact their physician for further instruction. Instruct these patients to carry a warning card indicating that they may need supplementary systemic steroids during periods of stress or a severe asthma attack.

Wean patients requiring oral corticosteroids slowly from systemic corticosteroid use after transferring to AEROSPAN Inhalation Aerosol. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg/day on a weekly basis [see DOSAGE AND ADMINISTRATION . Lung function (forced expiratory volume in one second [FEV1] or morning peak expiratory flow rate [AM PEF]), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, observe patients 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 AEROSPAN Inhalation Aerosol 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 or muscular pain, lassitude and depression, despite maintenance or even improvement of respiratory function.

Hypercorticism and Adrenal Suppression

In responsive patients, flunisolide may permit control of asthmatic symptoms with less suppression of HPA axis function than therapeutically equivalent oral doses of prednisone. Since flunisolide is absorbed into the circulation and can be systemically active, the beneficial effects of AEROSPAN Inhalation Aerosol in minimizing or preventing HPA axis dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing AEROSPAN Inhalation Aerosol.

Because of the possibility of systemic absorption of inhaled corticosteroids, observe patients treated with AEROSPAN Inhalation Aerosol carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients post-operatively or during periods of stress for evidence of inadequate adrenal response.

It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear in a small number of patients, particularly at higher doses. If such changes occur, reduce the AEROSPAN Inhalation Aerosol dose slowly, consistent with accepted procedures for management of asthma symptoms and for tapering of systemic corticosteroids.

Reduction in Bone Mineral Density

Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids, including flunisolide. The clinical significance of small changes in BMD with regard to long-term outcomes is unknown. Monitor patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) and treat with established standards of care.

Effects on Growth

Orally inhaled corticosteroids, including flunisolide, may cause a reduction in growth velocity when administered to pediatric patients [see Use In Specific Populations] . Monitor the growth of children and adolescents receiving AEROSPAN Inhalation Aerosol. To minimize the systemic effects of orally inhaled corticosteroids, including AEROSPAN Inhalation Aerosol, each titrate each patient to his/her lowest effective dose [see DOSAGE AND ADMINISTRATION] .

Glaucoma and Cataracts

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids, including flunisolide. Monitor patients closely, especially patients with a change in vision or with a history of increased intraocular pressure, glaucoma, or cataracts.

Paradoxical Bronchospasm

As with other inhaled asthma medications, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with AEROSPAN Inhalation Aerosol, treat immediately with a fast-acting inhaled bronchodilator. Discontinue treatment with AEROSPAN Inhalation Aerosol immediately and institute alternative therapy.

Patient Counseling Information

See FDA-approved Patient Labeling (Patient Information and Instructions for Use).

Oral Candidiasis

Advise patients that localized fungal infections occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing with AEROSPAN Inhalation Aerosol therapy, but at times therapy with AEROSPAN Inhalation Aerosol may need to be temporarily interrupted under close medical supervision. Rinsing the mouth after inhalation is advised.

Status Asthmaticus and Acute Asthma Symptoms

Advise patients that AEROSPAN Inhalation Aerosol is not a bronchodilator and is not intended to be used to treat status asthmaticus or to relieve acute asthma symptoms. Treat acute asthma symptoms with an inhaled, short-acting beta-2 agonist such as albuterol. Instruct patients to contact their physicians immediately if there is deterioration of their asthma.

Immunosuppression

Warn patients who are on immunosuppressant doses of AEROSPAN Inhalation Aerosol 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.

Hypercorticism and Adrenal Supression

Advise patients that AEROSPAN Inhalation Aerosol 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. Taper patients slowly from systemic corticosteroids if transferring to AEROSPAN Inhalation Aerosol.

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. Monitor patients and, where appropriate, treat for this condition.

Reduced Growth Velocity

Inform patients that orally inhaled corticosteroids, including AEROSPAN Inhalation Aerosol, 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.

Ocular Effects

Long-term use of inhaled corticosteroids, including AEROSPAN Inhalation Aerosol, may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations.

Use Daily for Best Effect

Advise patients to use AEROSPAN Inhalation Aerosol at regular intervals as directed, since its effectiveness depends on regular use. 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 2 to 4 weeks. If symptoms do not improve in that time frame or if the condition worsens, patients should not increase dosage, but should contact the physician immediately.

Advise patients not to stop Aerospan Inhalation Aerosol or change the dose without talking with a healthcare provider. Advise patients that if they miss a dose to take the next scheduled dose when it is due.

Instructions for Use

Aerospan Inhalation Aerosol contains a built-in spacer. Do not use with any external spacer or holding chamber devices. Instruct patients to prepare the inhaler for use by pulling the built-in purple actuator out from the gray spacer and snapping into an “L” shape prior to use. With use, the appearance of a white ring on the orifice of the actuator and inside the spacer is normal. The performance of AEROSPAN Inhalation Aerosol is not affected by this residue. No cleaning is required.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 22 month study in Swiss mice, flunisolide at oral doses up to 500 mcg/kg/day (approximately 3 and 4 times the maximum recommended daily inhalation dose [MRDID] in adults and children on a mg/m² basis) did not demonstrate any carcinogenic effects.

In a two year study in Sprague Dawley rats, administration of flunisolide in the diet at a dose of 2.5 mcg/kg/day (less than MRDID in adults or children on a mg/m² basis) resulted in an increased incidence of mammary gland adenomas and islet cell adenomas of the pancreas in females. The significance of these findings for humans is unknown. There were no significant increases in the incidence of any tumor type in female rats at a dose of 1.0 mcg/kg/day (less than MRDID in adults or children on a mg/m² basis), or in male rats at a dose of 2.5 mcg/kg/day (less than MRDID in adults or children on a mg/m² basis).

Flunisolide showed no mutagenic activity when tested in in vitro bacterial assay systems (Ames Assay and the Rec-assay) and no clastogenic activity when tested in the in vitro chromosomal aberration assay using Chinese Hamster CHL cells and in the in vivo mouse bone marrow chromosomal aberration assay.

Studies on the effects of flunisolide on fertility in female rats showed that flunisolide, at an oral dose of 200 mcg/kg/day (approximately 3 times MRDID on a mg/m² basis) impaired fertility, but was devoid of such effects at doses up to 40 mcg/kg/day (less than MRDID on a mg/m² basis).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of flunisolide in pregnant women. AEROSPAN Inhalation Aerosol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

As with other corticosteroids, flunisolide has been shown to be teratogenic and fetotoxic in rabbits and rats at approximately 1 and 3 times the maximum recommended daily inhalation dose on a mg/m² basis, respectively (doses of 40 and 200 mcg/kg/day, respectively).

Experience with oral corticosteroids since their introduction in pharmacologic, as opposed to physiological, doses suggests that rodents are more prone to teratogenic effects from corticosteroids than humans.

Nonteratogenic Effects

Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.

Nursing Mothers

It is not known whether flunisolide is excreted in human milk. Because other corticosteroids are excreted in human milk, caution should be exercised when AEROSPAN Inhalation Aerosol is administered to nursing women.

Pediatric Use

The safety and effectiveness of AEROSPAN Inhalation Aerosol has been studied in children 4-17 years of age. In clinical studies, the efficacy of AEROSPAN Inhalation Aerosol was not established in children 4-5 years of age, although the adverse reaction profile observed in patients exposed to AEROSPAN Inhalation Aerosol was similar between the 4-5 year age group (n=21), the 6-11 year age group (n=210), the 12-17 year age group (n=30), and those patients 18 years of age and older (n=258). The safety and effectiveness of AEROSPAN Inhalation Aerosol has not been studied in patients less than 4 years of age.

Effects on Growth

Controlled clinical studies have shown that orally inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. In these studies, the mean reduction in growth velocity was approximately one cm per year (range 0.3 to 1.8 cm per year) and appears to depend upon the dose and duration of exposure. 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 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 pediatric patients receiving orally inhaled corticosteroids, including AEROSPAN Inhalation Aerosol, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks/benefits of treatment alternatives. To minimize the systemic effects of orally inhaled corticosteroids, including AEROSPAN Inhalation Aerosol, each patient should be titrated to the lowest dose that effectively controls his/her symptoms.

The potential effect of AEROSPAN on growth rates in children was assessed in a 52 week randomized, placebo controlled study conducted in 242 prepubescent children age 4 to 9.5 years (145 males, 97 females) with mild persistent asthma. Treatment groups were AEROSPAN 160 mcg twice daily and placebo. Growth velocity was estimated for each patient using the slope of the linear regression of height over time using observed data in the intent to treat population who had at least 3 height measurements. The mean growth velocities were 6.19 cm/year in the placebo group and 6.01 cm/year in the AEROSPAN treated group (difference from placebo -0.17 cm/year; 95% CI: -0.58, 0.24).

Geriatric Use

Clinical studies of AEROSPAN Inhalation Aerosol included 21 patients 65 to 78 years of age exposed to AEROSPAN Inhalation Aerosol. These studies did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from 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.

Last reviewed on RxList: 9/11/2013
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Allergies & Asthma

Improve treatments & prevent attacks.