Data from FDA - Curated by Toby Galbraith - Last updated 28 July 2017
4 CONTRAINDICATIONS AEROSPAN is contraindicated in the following conditions: •Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. •Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required (4)
6 ADVERSE REACTIONS Systemic and local corticosteroid use may result in the following: • Candida albicans infection [see Warnings and Precautions (5.1) ] •Immunosuppression, increased risk of infections [see Warnings and Precautions (5.3)] •Hypercorticism and adrenal suppression [see Warnings and Precautions (5.5)] •Reduction in bone mineral density [see Warnings and Precautions (5.6)] •Effects on growth [see Warnings and Precautions (5.7)] •Glaucoma, increased intraocular pressure and cataracts [see Warnings and Precautions (5.8)] •Bronchospasm [see Warnings and Precautions (5.9)] The most common adverse reactions are pharyngitis, rhinitis, headache, sinusitis, and increased cough. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Meda Pharmaceuticals Inc. at 855-653-6325 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 1 shows the adverse reactions that were reported in patients previously receiving bronchodilators and/or orally inhaled corticosteroids in two double-blind, placebo- controlled US clinical trials, in which 519 adult and pediatric patients age 4-78 years (279 males and 240 females) were treated with the AEROSPAN (80 mcg to 320 mcg twice daily for 12 weeks) or placebo. The mean duration of exposure was 76.7, 78.2, 80.5, and 69.4 days for AEROSPAN 80 mcg, 160 mcg, 320 mcg, and placebo, all dosed twice daily, respectively. The table includes all reactions that occurred at a rate of >3% in any AEROSPAN Inhalation Aerosol group. In considering these data, the increased average duration of exposure for AEROSPAN patients should be taken into account, compared with placebo-treated patients. Table 1. Adverse Reactions with >3% incidence reported in controlled clinical studies with AEROSPAN (% of patients) ADVERSE REACTION PLACEBO (n = 220) AEROSPAN Inhalation Aerosol 80 MCG (n = 189) 160 MCG (n = 217) 320 MCG (n = 113) BODY AS A WHOLE Headache 12.7 9.0 13.8 8.8 Allergic Reaction 2.3 4.2 4.6 4.4 Infection, Bacterial 0.9 3.7 0.9 0.9 DIGESTIVE SYSTEM Vomiting 4.1 4.2 4.6 0.0 Dyspepsia 1.4 2.1 3.2 3.5 RESPIRATORY SYSTEM Pharyngitis 13.2 17.5 16.6 16.8 Rhinitis 10.0 9.0 15.7 3.5 Cough Increased 7.7 8.5 5.5 1.8 Sinusitis 5.5 7.4 4.1 8.8 Epistaxis 0.9 3.2 0.9 0.0 UROGENITAL SYSTEM Urinary Tract Infection 0.5 1.1 0.9 3.5 The following other adverse reactions occurred in patients in these clinical trials using AEROSPAN with an incidence of 1 to 3% and were more common in AEROSPAN than in the placebo group. Body As A Whole: abdominal pain, chest pain, infection, neck pain Digestive System: diarrhea, gastroenteritis, nausea, oral moniliasis Metabolic And Nutritional Disorders: edema Musculoskeletal System: myalgia Nervous System: dizziness, insomnia, migraine Respiratory System: bronchitis, laryngitis, voice alteration Skin And Appendages: erythema multiforme Special Senses: conjunctivitis, ear pain, taste perversion Urogenital System: dysmenorrhea, vaginitis Long-Term Clinical Trials Two 52-week open label safety trials of AEROSPAN were conducted in 162 asthma patients 12 to 60 years of age and in 152 asthma patients 4 to 11 years of age. The adverse reaction profile exhibited in these trials was similar to that seen in the two 12-week studies. 6.2 Adverse Reactions from Other Sources The following additional adverse reactions were derived from clinical trials conducted with flunisolide CFC inhalation aerosol with a frequency of ≥1% and not described above: Body as a Whole: flu, decreased appetite, chills, increased appetite, weight gain, malaise, peripheral edema, sweating, weakness Gastrointestinal System: upset stomach, heartburn, constipation, gas, abdominal fullness Cardiovascular System: palpitations, hypertension, tachycardia Nervous System: headache, irritability, shakiness, anxiety, depression, faintness, fatigue, hyperactivity, hypoactivity, moodiness, numbness, vertigo Respiratory System: cold symptoms, nasal congestion, upper respiratory tract infection, chest congestion, hoarseness, runny nose, sinus congestion, sinus drainage, sinus infection, sneezing, sputum, wheezing, chest tightness, bronchospasm, dyspnea, head stuffiness, nasal irritation, pleurisy, pneumonia, sinus discomfort Skin and Appendages: eczema, pruritus, acne, urticaria Special Senses: loss of smell, loss of taste, ear infection, blurred vision, eye discomfort, eye infection Hemic and Lymph: capillary fragility, enlarged lymph nodes Mouth and Throat: sore throat, dry throat, glossitis, mouth irritation, phlegm, throat irritation
Dosing and administration
2 DOSAGE AND ADMINISTRATION For oral inhalation only. Inhaler includes a built-in spacer. Do not use with external spacers or holding chambers. Shake well prior to each inhalation. (2.1) •Starting dosage is based on prior asthma therapy and disease severity. (2.2) • Adults and adolescents 12 years of age and older: The recommended starting dose is 160 mcg twice daily. Do not exceed 320 mcg twice daily. (2.2) • Pediatric Patients 6 to 11 years: The recommended starting dose is 80 mcg twice daily. Do not exceed 160 mcg twice daily. Administer under adult supervision. (2.2) 2.1 Administration Information AEROSPAN should be administered by the orally inhaled route in patients aged 6 years and older. Shake well prior to each inhalation. After inhalation, the patient should rinse his/her mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis. Patients should be instructed on the proper use of their inhaler. AEROSPAN 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. Pediatric patients should administer AEROSPAN under adult supervision. 2.2 Recommended Dosage Adults and Adolescents 12 Years of Age and Older The starting dosage is based on previous asthma therapy and disease severity, including consideration of the patients’ current control of asthma symptoms and risk of future exacerbation. The recommended starting dosage for patients aged 12 years and older who are not on an inhaled corticosteroid is 160 mcg twice daily, approximately 12 hours apart. For other patients, and for patients who do not respond adequately to Aerospan 160 mcg after 2 weeks of therapy, increasing the dosage may provide additional asthma control. The maximum recommended dosage is 320 mcg twice daily. Pediatric Patients 6 to 11 Years The starting dosage is based on previous asthma therapy and disease severity, including consideration of the patients’ current control of asthma symptoms and risk of future exacerbation. The recommended starting dosage for patients aged 6 to 11 years who are not on an inhaled corticosteroid is 80 mcg twice daily, approximately 12 hours apart. For other patients, and for patients who do not respond adequately to Aerospan 80 mcg after 2 weeks of therapy, increasing the dosage may provide additional asthma control. The maximum recommended dosage for patients 6 to 11 years of age is 160 mcg twice daily. General Dosing Recommendations If symptoms arise between doses, an inhaled short-acting beta2-agonist should be used for immediate relief. The onset and degree of symptom relief with orally inhaled corticosteroids is usually apparent within 2-4 weeks after the start of treatment, and varies with individual patients. The time to improvement in asthma control was not evaluated in clinical studies with AEROSPAN. If a dosage regimen of AEROSPAN and additional therapeutic options, e.g., increasing the AEROSPAN dosage, initiating an inhaled corticosteroid and long-acting beta2-agonist (LABA) combination product, or initiating oral corticosteroids, should be considered. After asthma stability has been achieved, titrate to the lowest effective dosage to reduce the possibility of side effects.
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. There are no adequate and well-controlled studies of flunisolide in pregnant women. AEROSPAN 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. 8.3 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 is administered to nursing women. 8.4 Pediatric Use The safety and effectiveness of AEROSPAN has been studied in children 4- 17 years of age. In clinical studies, the efficacy of AEROSPAN was not established in children 4-5 years of age, although the adverse reaction profile observed in patients exposed to AEROSPAN 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 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, 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, 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). 8.5 Geriatric Use Clinical studies of AEROSPAN included 21 patients 65 to 78 years of age exposed to AEROSPAN. 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.
Pregnancy and lactation
8.3 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 is administered to nursing women.
|Agency product number||QK4DYS664X|
|Date Last Revised||02-06-2017|
|Type||HUMAN PRESCRIPTION DRUG|
|Storage and handling||Store at 25 °C (77 °F); excursions permitted to 15 to 30 °C (59 to 86 °F) [see USP Controlled Room Temperature]. For best results, the canister should be at room temperature before use.|
|Marketing authorisation holder||Meda Pharmaceuticals|