Asmanex Information
Asmanex () Dosage And Administration
Administer Asmanex () TWISTHALER by the orally inhaled route only. Instruct patients to inhale rapidly and deeply. Advise patients to rinse the mouth after inhalation. Individual patients will experience a variable time to onset and degree of symptom relief. Maximum benefit may not be achieved for 1 to 2 weeks or longer after initiation of treatment. After asthma stability has been achieved, it is desirable to titrate to the lowest effective dosage to reduce the possibility of side effects. For patients ≥12 years of age who do not respond adequately to the starting dose after 2 weeks of therapy, higher doses may provide additional asthma control. The safety and efficacy of Asmanex () TWISTHALER when administered in excess of recommended doses have not been established.
Asmanex () Dosage Forms And Strengths
Asmanex () TWISTHALER is a dry powder for inhalation that is available in two strengths.
Asmanex () TWISTHALER 220 mcg delivers 200 mcg mometasone furoate per actuation from the mouthpiece.
Asmanex () TWISTHALER 110 mcg delivers 100 mcg mometasone furoate per actuation from the mouthpiece.
Asmanex () Contraindications
Asmanex () TWISTHALER is contraindicated in patients with hypersensitivity to milk proteins or any ingredients of Asmanex () TWISTHALER.
Asmanex () Warnings And Precautions
Hypersensitivity reactions including rash, pruritus, angioedema, and anaphylactic reaction have been reported with use of Asmanex () TWISTHALER. Discontinue Asmanex () TWISTHALER if such reactions occur
Asmanex () TWISTHALER contains small amounts of lactose, which contains trace levels of milk proteins. In postmarketing experience with Asmanex () TWISTHALER, anaphylactic reactions in patients with milk protein allergy have been reported
Persons 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 susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or who are not properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not 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, viral, or parasitic infections; or ocular herpes simplex.
Particular care is needed for patients who are transferred from systemically active corticosteroids to Asmanex () TWISTHALER 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 infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although Asmanex () TWISTHALER may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity necessary for coping with these emergencies.
During periods of stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe asthma attack.
Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Asmanex () TWISTHALER. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during treatment with Asmanex () TWISTHALER []. Lung function (FEV or PEFR), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral 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 Asmanex () TWISTHALER 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.
Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids, including mometasone furoate. The clinical significance of small changes in BMD with regard to long-term outcomes 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.
In a 2-year double-blind study in 103 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (baseline FEV 85%–88% predicted), treatment with Asmanex () TWISTHALER 220 mcg twice daily resulted in significant reductions in lumbar spine (LS) BMD at the end of the treatment period compared to placebo. The mean change from baseline to endpoint in the lumbar spine BMD was -0.015 (-1.43%) for the Asmanex () TWISTHALER group compared to 0.002 (0.25%) for the placebo group. In another 2-year double-blind study in 87 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (baseline FEV 82%–83% predicted), treatment with Asmanex () TWISTHALER 440 mcg twice daily demonstrated no statistically significant changes in lumbar spine BMD at the end of the treatment period compared to placebo. The mean change from baseline to endpoint in the lumbar spine BMD was -0.018 (-1.57%) for the Asmanex () TWISTHALER group compared to -0.006 (-0.43%) for the placebo group.
As with other inhaled asthma medications, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with Asmanex () TWISTHALER, it should be treated immediately with a fast-acting inhaled bronchodilator.
Treatment with Asmanex () TWISTHALER should be discontinued and alternative therapy instituted.
Asmanex () Adverse Reactions
Systemic and local corticosteroid use may result in the following:
The safety data described below reflect exposure to Asmanex () TWISTHALER in 2380 patients with asthma exposed for 8 to 12 weeks and 627 patients with asthma exposed for 1 year in a total of 17 clinical trials.
In adult and adolescent patients 12 years of age and older, Asmanex () TWISTHALER was studied in 10 placebo-controlled clinical trials of 8 to 12 weeks duration with a total of 1750 patients receiving Asmanex () TWISTHALER. There were also 3 trials with a total of 475 patients receiving Asmanex () TWISTHALER for 1 year. In the 8- to 12-week clinical trials, the population was 12 to 83 years of age, 38% males and 62% females, and 83% Caucasian, 8% black, 6% Hispanic, and 3% other race/ethnicity. Patients received Asmanex () TWISTHALER 110 mcg twice daily (n=133), 220 mcg once daily in the morning (n=209), 220 mcg once daily in the evening (n=232), 220 mcg twice daily (n=433), 440 mcg once daily in the morning (n=419), 440 mcg once daily in the evening (n=250), or 440 mcg twice daily (n=74). In 3 long-term safety trials (two 9-month extensions of efficacy trials and one 52-week active-controlled safety trial), 475 patients with asthma (12 – 83 years of age, 44% males, 56% females, 87% Caucasian, 8% black, 4% Hispanic, and 1% other race/ethnicity) received various doses of Asmanex () TWISTHALER for 1 year.
In pediatric patients 4 to 11 years of age, Asmanex () TWISTHALER was studied in 3 placebo-controlled clinical trials of 12 weeks duration with a total of 630 patients receiving Asmanex () TWISTHALER and a 52-week, active-controlled safety trial with a total of 152 patients receiving Asmanex () TWISTHALER. In the 12-week clinical trials, the population was 4 to 11 years of age, 63% males and 37% females, and 67% Caucasian, 13% black, 17% Hispanic, and 3% other race/ethnicity. Patients received Asmanex () TWISTHALER 110 mcg once daily in the evening (n=98), 110 mcg once daily in the morning (n=181), 110 mcg twice daily (n=179), or 220 mcg once daily in the morning (n=172). In the long-term active-controlled safety trial (n=152), patients with asthma (4 to 11 years of age, 60% males and 40% females, 84% Caucasian, 11% Black, and 5% Hispanic) received Asmanex () TWISTHALER 110 mcg twice daily or 220 mcg once daily in the morning for 52 weeks.
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.
The following adverse reactions have been reported during post-approval use of Asmanex () TWISTHALER. Because they are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Respiratory, Thoracic and Mediastinal Disorders:
Asmanex () Drug Interactions
In clinical studies, the concurrent administration of Asmanex () TWISTHALER and other drugs commonly used in the treatment of asthma was not associated with any unusual adverse reactions.
Asmanex () Use In Specific Populations
The safety and effectiveness of Asmanex () TWISTHALER have been established in children 4 years of age and older. Use of Asmanex () TWISTHALER in children 12 years of age and older is supported by evidence from adequate and well-controlled clinical trials in this patient population [].
Use of Asmanex () TWISTHALER in pediatric patients 4 to 11 years of age is supported by evidence from adequate and well-controlled clinical trials of 12 weeks duration in 630 patients 4 to 11 years of age receiving Asmanex () TWISTHALER and one 52-week safety trial in 152 patients [].
Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth in pediatric patients. In these studies, the mean reduction in growth velocity was approximately 1 cm per year (range: 0.3–1.8 per year) and appears to depend upon dose and duration of exposure. This effect was observed in the absence of laboratory evidence of 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 children and adolescents (4 years of age and older) receiving orally inhaled corticosteroids, including Asmanex () TWISTHALER, should be monitored routinely (e.g., via stadiometry).
A 52-week, placebo-controlled, parallel-group study was conducted to assess the potential growth effects of Asmanex () TWISTHALER in 187 prepubescent children (131 males and 56 females) 4 to 9 years of age with asthma who were previously maintained on an inhaled beta-agonist. Treatment groups included Asmanex () TWISTHALER 110 mcg twice daily (n=44), 220 mcg once daily in the morning (n=50), 110 mcg once daily in the morning (n=48), and placebo (n=45). For each patient, an average growth rate was determined using an individual regression approach. The mean growth rates, expressed as least-squares mean in cm per year, for Asmanex () TWISTHALER 110 mcg twice daily, 220 mcg once daily in the morning, 110 mcg once daily in the morning, and placebo were 5.34, 5.93, 6.15, and 6.44, respectively. The differences from placebo and the corresponding 2-sided 95% CI of growth rates for Asmanex () TWISTHALER 110 mcg twice daily, 220 mcg once daily in the morning, and 110 mcg once daily in the morning were -1.11 (95% CI: -2.34, 0.12), -0.51 (95% CI: -1.69, 0.67), and -0.30 (95% CI: -1.48, 0.89), respectively.
The potential growth effects of prolonged treatment with orally inhaled corticosteroids should be weighed against clinical benefits obtained and the availability of safe and effective noncorticosteroid treatment alternatives. To minimize the systemic effects of orally inhaled corticosteroids, including Asmanex () TWISTHALER, each patient should be titrated to his/her lowest effective dose.
Asmanex () Overdosage
Chronic overdosage may result in signs/symptoms of hypercorticism []. Because of low systemic bioavailability and an absence of acute drug-related systemic findings in clinical studies, acute overdose is unlikely to require any treatment other than observation. Single daily doses as high as 1200 mcg per day for 28 days were well tolerated and did not cause a significant reduction in plasma cortisol AUC (94% of placebo AUC). Single oral doses up to 8000 mcg have been studied on human volunteers with no adverse reactions reported.
Asmanex () Description
Mometasone furoate, the active component of the Asmanex () TWISTHALER product, is a corticosteroid with the chemical name 9,21-dichloro-11(Beta),17-dihydroxy-16(alpha)-methylpregna-1,4-diene-3,20-dione 17-(2-furoate) and the following chemical structure:
Mometasone furoate is a white powder with an empirical formula of CHClO, and molecular weight of 521.44 Daltons.
The Asmanex () TWISTHALER 110 mcg and 220 mcg products are cap-activated, inhalation-driven, multidose dry powder inhalers containing mometasone furoate and anhydrous lactose (which contains trace amounts of milk proteins).
Each actuation of the Asmanex () TWISTHALER 110 mcg or 220 mcg inhaler provides a measured dose of approximately 0.75 or 1.5 mg mometasone furoate inhalation powder, containing 110 or 220 mcg of mometasone furoate, respectively. This results in delivery of 100 or 200 mcg mometasone furoate from the mouthpiece, respectively, based on testing at flow rates of 30 L/min and 60 L/min with constant volume of 2 L. The amount of mometasone furoate emitted from the inhaler does not differ significantly for flow rates ranging from 28.3 L/min to 70 L/min at a constant volume of 2 L. However, the amount of drug delivered to the lung will depend on patient factors such as inspiratory flow and peak inspiratory flow through the device. In adult and adolescent patients (aged ≥12 years) with varied asthma severity, mean peak inspiratory flow rate through the device was 69 L/min (range: 54–77 L/min). In pediatric patients (aged 5–12 years) diagnosed with asthma, mean peak inspiratory flow rate in the 5- to 8-year-old subgroup was >50 L/min (minimum of 46 L/min) and for the 9- to 12-year-old subgroup was >60 L/min (minimum of 48 L/min).
Asmanex () Clinical Pharmacology
Mometasone furoate is a corticosteroid demonstrating potent anti-inflammatory activity. The precise mechanism of corticosteroid action on asthma is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation and in the asthmatic response. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma.
Mometasone furoate has been shown to exhibit a binding affinity for the human glucocorticoid receptor, which is approximately 12 times that of dexamethasone, 7 times that of triamcinolone acetonide, 5 times that of budesonide, and 1.5 times that of fluticasone. The clinical significance of these findings is unknown.
Though effective for the treatment of asthma, corticosteroids do not affect asthma symptoms immediately. Maximum improvement in symptoms following inhaled administration of mometasone furoate may not be achieved for 1 to 2 weeks or longer after starting treatment. When corticosteroids are discontinued, asthma stability may persist for several days or longer.
Asmanex () Nonclinical Toxicology
In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 67 mcg/kg (approximately 8 times the maximum recommended daily inhalation dose in adults on an AUC basis and 2 times the maximum recommended daily inhalation dose in pediatric patients based on an mcg/m basis). In a 19-month carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no statistically significant increase in the incidence of tumors at inhalation doses up to 160 mcg/kg (approximately 10 times the maximum recommended daily inhalation dose in adults on an AUC basis and 2 times the maximum recommended daily inhalation dose in pediatric patients based on an mcg/m basis).
Mometasone furoate increased chromosomal aberrations in an Chinese hamster ovary cell assay, but did not have this effect in an Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an mouse micronucleus assay, a rat bone marrow chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration assay. Mometasone furoate also did not induce unscheduled DNA synthesis in rat hepatocytes.
In reproductive studies in rats, impairment of fertility was not produced by subcutaneous doses up to 15 mcg/kg (approximately 6 times the maximum recommended daily inhalation dose in adults on an AUC basis).
Asmanex () How Supplied/storage And Handling
The Asmanex () TWISTHALER 220 mcg product is comprised of an assembled plastic cap–activated dosing mechanism with dose counter, drug-product storage unit, drug-product formulation (135 mg for the 14 and 30 inhalation units and 240 mg for the 60 and 120 inhalation units), and mouthpiece, covered by a white screw cap that bears the product label. The body of the inhaler is white and the turning grip is pink with a clear plastic window indicating the number of doses remaining. The inhaler will not deliver subsequent doses once the counter reaches zero ("00").
The Asmanex () TWISTHALER 110 mcg product is comprised of an assembled plastic cap–activated dosing mechanism with dose counter, drug-product storage unit, drug-product formulation (135 mg), and mouthpiece, covered by a white screw cap that bears the product label. The body of the inhaler is white and the turning grip is gray with a clear plastic window indicating the number of doses remaining. The inhaler will not deliver subsequent doses once the counter reaches zero ("00").
The Asmanex () TWISTHALER product is available as:
Asmanex () TWISTHALER 220 mcg, which delivers 200 mcg mometasone furoate from the mouthpiece: 14 inhalation units (Institutional Use Only; NDC# 0085-1341-04); 30 inhalation units (NDC# 0085-1341-03); 60 inhalation units (For more than 1 inhalation daily; NDC# 0085-1341-02); or 120 inhalation units (For more than 2 inhalations daily; NDC# 0085-1341-01).
Asmanex () TWISTHALER 110 mcg, which delivers 100 mcg mometasone furoate from the mouthpiece: 7 inhalation units (Institutional Use Only; NDC# 0085-1461-07); 30 inhalation units (NDC# 0085-1461-02).
Each inhaler is supplied in a protective foil pouch with Patient's Instructions for Use.
Asmanex () Patient Counseling Information
See
Hypersensitivity reactions including rash, pruritus, angioedema and anaphylactic reaction have been reported with use of Asmanex () TWISTHALER. Discontinue Asmanex () TWISTHALER if such reactions occur
see accompanying
Asmanex ()
Asmanex ()
Asmanex ()
Asmanex ()
