Asmanex (Mometasone Furoate): Uses, Dosage, Side Effects & Warnings

Uses

1 INDICATIONS AND USAGE ASMANEX ® TWISTHALER ® is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients 4 years of age and older. Limitations of Use ASMANEX TWISTHALER is not indicated for the relief of acute bronchospasm. ASMANEX TWISTHALER is not indicated in children less than 4 years of age. ASMANEX TWISTHALER is a corticosteroid indicated for maintenance treatment of asthma as prophylactic therapy in patients 4 years of age and older. ( 1 ) Limitations of Use: ASMANEX TWISTHALER is not indicated for the relief of acute bronchospasm ( 1 , 5.2 ) or in children less than 4 years of age ( 1 , 8.4 ).

Dosage and administration

Administration Information Administer ASMANEX TWISTHALER by the orally inhaled route only. Instruct patients to inhale rapidly and deeply. After administration, advise patients to rinse the mouth with water and spit out contents without swallowing. 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. For oral inhalation only. ( 2 ) Instruct patients to inhale rapidly and deeply and, after administration, rinse mouth with water and spit out contents without swallowing. ( 2 ) Recommended Dosages for ASMANEX TWISTHALER Treatment Previous Therapy Recommended Starting Dose Highest Recommended Daily Dose , , , Please refer to section 2.1 for full dosage recommendations and details. Patients ≥12 years who received bronchodilators alone 220 mcg once daily in the evening 440 mcg Patients ≥12 years who received inhaled corticosteroids 220 mcg once daily in the evening 440 mcg Patients ≥12 years who received oral corticosteroids 440 mcg twice daily 880 mcg Children 4-11 years of age 110 mcg once daily in the evening 110 mcg 2.1 Recommended Dosages in Adult and Pediatric Patients 4 Years of Age and Older The recommended starting doses and highest recommended daily dose for ASMANEX TWISTHALER treatment based on prior asthma therapy are provided in Table 1 . Table 1: Recommended Dosages for ASMANEX TWISTHALER Treatment Previous Therapy Recommended Starting Dose Highest Recommended Daily Dose Patients ≥12 years who received bronchodilators alone 220 mcg once daily in the evening When administered once daily, ASMANEX TWISTHALER should be taken only in the evening. 440 mcg The 440 mcg daily dose may be administered in divided doses of 220 mcg twice daily or as 440 mcg once daily. Patients ≥12 years who received inhaled corticosteroids 220 mcg once daily in the evening 440 mcg Patients ≥12 years who received oral corticosteroids For Patients Currently Receiving Chronic Oral Corticosteroid Therapy: Prednisone should be reduced no faster than 2.5 mg/day on a weekly basis, beginning after at least 1 week of ASMANEX TWISTHALER therapy. Monitor patients carefully for signs of asthma instability, including serial objective measures of airflow, and for signs of adrenal insufficiency during steroid taper and following discontinuation of oral corticosteroid therapy [see Warnings and Precautions (5.5) ] . 440 mcg twice daily 880 mcg Children 4-11 years of age Recommended pediatric dosage is 110 mcg once daily in the evening regardless of prior therapy. 110 mcg once daily in the evening 110 mcg

Dosage forms and strengths

Inhalation powder: 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. Inhalation powder: 220 mcg TWISTHALER: delivers 200 mcg mometasone furoate per actuation. ( 3 ) 110 mcg TWISTHALER: delivers 100 mcg mometasone furoate per actuation. ( 3 )

Contraindications

4 CONTRAINDICATIONS ASMANEX TWISTHALER is contraindicated: Status Asthmaticus: in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Hypersensitivity: in patients with known hypersensitivity to milk proteins or any ingredients of ASMANEX TWISTHALER [see Warnings and Precautions (5.3) and Description (11) ]. Patients with status asthmaticus or other acute episodes of asthma where intensive measures are required. ( 4 ) Patients with a known hypersensitivity to milk proteins or any ingredients of ASMANEX TWISTHALER. ( 4 )

Warnings and precautions

Candida albicans infection of the mouth and pharynx. Monitor patients periodically for signs of adverse effects in the mouth and pharynx. After administration, advise patients to rinse mouth with water and spit out contents without swallowing. ( 5.1 ) Deterioration of asthma or acute episodes: ASMANEX TWISTHALER should not be used for relief of acute symptoms. Patients require immediate re-evaluation during rapidly deteriorating asthma. ( 5.2 ) Hypersensitivity reactions including anaphylaxis, angioedema, pruritus, and rash have been reported with the use of ASMANEX TWISTHALER. Discontinue ASMANEX TWISTHALER if such reactions occur. ( 5.3 ) Potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex. More serious or even fatal course of chickenpox or measles in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections. ( 5.4 ) Risk of impaired adrenal function when transferring from oral steroids to inhaled corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to ASMANEX TWISTHALER. ( 5.5 ) Hypercorticism, suppression of hypothalamic-pituitary-adrenal (HPA) function, with very high dosages or at the regular dosage in susceptible individuals. If such changes occur discontinue ASMANEX TWISTHALER slowly. ( 5.6 ) Reduction in bone mineral density with long-term administration. Monitor patients with major risk factors for decreased bone mineral content. ( 5.7 ) Suppression of growth in children. Monitor growth routinely in pediatric patients receiving ASMANEX TWISTHALER. ( 5.8 ) Glaucoma and cataracts. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX TWISTHALER long term. ( 5.9 ) Paradoxical bronchospasm may occur with ASMANEX TWISTHALER. Treat bronchospasm immediately with a fast-acting inhaled bronchodilator and discontinue use of ASMANEX TWISTHALER. ( 5.10 ) Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. Exercise caution when used with ASMANEX TWISTHALER. ( 5.11 ) 5.1 Oropharyngeal Candidiasis In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans occurred in 195 of 3007 patients treated with ASMANEX TWISTHALER. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while remaining on treatment with ASMANEX TWISTHALER therapy, but at times therapy with the ASMANEX TWISTHALER may need to be interrupted. After administration, advise patients to rinse the mouth with water and spit out contents without swallowing. 5.2 Acute Asthma Episodes ASMANEX TWISTHALER is not a bronchodilator and is not indicated for rapid relief of bronchospasm or other acute episodes of asthma. A short acting beta 2 -agonist, such as albuterol, should be available at all times to treat acute asthma symptoms. Instruct patients to contact their physician immediately if episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with ASMANEX TWISTHALER. During such episodes, patients may require therapy with oral corticosteroids. 5.3 Hypersensitivity Reactions Including Anaphylaxis 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 Contraindications (4) and Adverse Reactions (6.2) ]. 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 [see Contraindications (4) and Adverse Reactions (6.2) ]. 5.4 Immunosuppression and Risk of Infections 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. 5.5 Transferring Patients from Systemic Corticosteroid Therapy HPA Suppression/Adrenal Insufficiency 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.

Side effects

The following clinically significant adverse reactions are described elsewhere in the labeling: Oropharyngeal Candidiasis [see Warnings and Precautions (5.1) ] Immunosuppression and Risk of Infections [see Warnings and Precautions (5.4) ] Hypercorticism and Adrenal Suppression [see Warnings and Precautions (5.6) ] Reduction in Bone Mineral Density [see Warnings and Precautions (5.7) ] Growth Effects [see Warnings and Precautions (5.8) and Use in Specific Populations (8.4) ] Glaucoma and Cataracts [see Warnings and Precautions (5.9) ] The most common adverse reactions (incidence ≥5%) are headache, allergic rhinitis, pharyngitis, upper respiratory tract infection, sinusitis, oral candidiasis, dysmenorrhea, musculoskeletal pain, back pain, and dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Organon LLC, a subsidiary of Organon & Co., at 1-844-674-3200 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience 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. Adults and Adolescents 12 Years of Age and Older: The safety results of the 10 trials that were 8 to 12 weeks in duration were pooled because patients with asthma in these studies were previously maintained on bronchodilators and/or inhaled corticosteroids. The safety results of the one 12-week clinical trial in patients with asthma previously treated with oral corticosteroids are presented separately. In the pooled 8- to 12-week clinical trials, adverse reactions were reported in 70% of patients treated with ASMANEX TWISTHALER (n=1750) compared to 65% of patients taking placebo (n=720). Table 2 displays the common adverse reactions (≥3% in any patient group receiving ASMANEX TWISTHALER) that occurred more frequently in patients treated with ASMANEX TWISTHALER compared to patients treated with placebo. Table 2: Adverse Reactions with ≥3% Incidence in 10 Controlled Clinical Trials with ASMANEX TWISTHALER in Patients 12 Years of Age and Older Previously on Bronchodilators and/or Inhaled Corticosteroids (%) of Patients ASMANEX TWISTHALER Adverse Reaction 220 mcg twice daily (n=433) 440 mcg once daily (n=497) 220 mcg once daily in the evening (n=232) Placebo (n=720) Headache 22 17 20 20 Allergic Rhinitis 15 11 14 13 Pharyngitis 11 8 13 7 Upper Respiratory Infection 10 8 15 7 Sinusitis 6 6 5 5 Candidiasis, oral 6 4 4 2 Dysmenorrhea Percentages are based on the number of female patients. 9 4 4 4 Musculoskeletal Pain 8 4 4 5 Back Pain 6 3 3 4 Dyspepsia 5 3 3 3 Myalgia 3 2 3 2 Abdominal Pain 3 2 3 2 Nausea 3 1 3 2 Average Duration of Exposure (Days) 81 70 80 62 The following other adverse reactions occurred in these clinical trials with an incidence of at least 1% but less than 3% and were more common on ASMANEX TWISTHALER therapy than on placebo: Body as a Whole: fatigue, flu-like symptoms, pain Gastrointestinal: gastroenteritis, vomiting, anorexia Hearing, Vestibular: earache Resistance Mechanism: infection Respiratory: dysphonia, epistaxis, nasal irritation, respiratory disorder, throat dry In the 12-week trial in adult asthmatics who previously required oral corticosteroids, the effects of ASMANEX TWISTHALER therapy administered as two 220-mcg inhalations twice daily (n=46) were compared with those of placebo (n=43). Adverse reactions, whether considered drug-related or not by the investigators, reported in more than 3 patients in the ASMANEX TWISTHALER treatment group, and which occurred more frequently than in placebo were (ASMANEX TWISTHALER % vs.

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. Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects. ( 7.1 ) 7.1 Inhibitors of Cytochrome P450 3A4 Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, mometasone furoate and potentially increase the risk for systemic corticosteroid side effects [see Clinical Pharmacology (12.3) ] . Caution should be exercised when considering the coadministration of ASMANEX TWISTHALER with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin). Consider the benefit of coadministration versus the potential risk of systemic corticosteroid effects, in which case patients should be monitored for systemic corticosteroid side effects.

Use in specific populations

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of ASMANEX TWISTHALER in pregnant women. There are clinical considerations with the use of ASMANEX TWISTHALER in pregnant women [see Clinical Considerations ] . In animal reproduction studies with pregnant mice, rats, or rabbits, mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m 2 or AUC basis [see Data ] . However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Data Animal Data In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at an exposure approximately 1/3 of the MRHD (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at an exposure approximately equivalent to the MRHD (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure approximately 1/10 of the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 20 mcg/kg and above). In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 6 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at exposures approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 300 mcg/kg and above). In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure that was approximately 6 times the MRHD (on an area under the curve (AUC) basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings with an exposure approximately 3 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at an exposure approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, mometasone furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at an exposure approximately 1/2 of the MRHD (on an AUC basis with a maternal oral dose of 700 mcg/kg). At an exposure approximately 2 times the MRHD (on an AUC basis with a maternal oral dose of 2800 mcg/kg), most litters were aborted or resorbed. No effects were observed at an exposure approximately 1/10 of the MRHD (on an AUC basis with a maternal oral dose of 140 mcg/kg). 8.2 Lactation Risk Summary There are no available data on the presence of ASMANEX TWISTHALER in human milk, the effects on the breastfed child, or the effects on milk production. Other inhaled corticosteroids, similar to mometasone furoate, are present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ASMANEX TWISTHALER and any potential adverse effects on the breastfed infant from ASMANEX TWISTHALER or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ASMANEX TWISTHALER for maintenance treatment of asthma as prophylactic therapy have been established in children 4 years of age and older. Use of ASMANEX TWISTHALER in pediatric patients 12 years of age and older is supported by evidence from adequate and well-controlled clinical trials in this patient population [see Clinical Studies (14.1) and Adverse Reactions (6.1) ] . 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 [see Clinical Studies (14.1) and Adverse Reactions (6.1) ] . 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.

Pregnancy

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies of ASMANEX TWISTHALER in pregnant women. There are clinical considerations with the use of ASMANEX TWISTHALER in pregnant women [see Clinical Considerations ] . In animal reproduction studies with pregnant mice, rats, or rabbits, mometasone furoate caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m 2 or AUC basis [see Data ] . However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Data Animal Data In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, mometasone furoate produced cleft palate at an exposure approximately 1/3 of the MRHD (on a mcg/m 2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at an exposure approximately equivalent to the MRHD (on a mcg/m 2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure approximately 1/10 of the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 20 mcg/kg and above). In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, mometasone furoate produced fetal umbilical hernia at exposures approximately 6 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at exposures approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 300 mcg/kg and above). In another reproductive toxicity study, pregnant rats were dosed with mometasone furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure that was approximately 6 times the MRHD (on an area under the curve (AUC) basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings with an exposure approximately 3 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 7.5 mcg/kg). Embryofetal development studies were conducted with pregnant rabbits dosed with mometasone furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, mometasone furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at an exposure approximately 3 times the MRHD (on a mcg/m 2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, mometasone furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at an exposure approximately 1/2 of the MRHD (on an AUC basis with a maternal oral dose of 700 mcg/kg). At an exposure approximately 2 times the MRHD (on an AUC basis with a maternal oral dose of 2800 mcg/kg), most litters were aborted or resorbed. No effects were observed at an exposure approximately 1/10 of the MRHD (on an AUC basis with a maternal oral dose of 140 mcg/kg).

Pediatric use

8.4 Pediatric Use The safety and effectiveness of ASMANEX TWISTHALER for maintenance treatment of asthma as prophylactic therapy have been established in children 4 years of age and older. Use of ASMANEX TWISTHALER in pediatric patients 12 years of age and older is supported by evidence from adequate and well-controlled clinical trials in this patient population [see Clinical Studies (14.1) and Adverse Reactions (6.1) ] . 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 [see Clinical Studies (14.1) and Adverse Reactions (6.1) ] . 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.

Geriatric use

8.5 Geriatric Use A total of 175 patients 65 years of age and over (23 of whom were 75 years of age and older) have been treated with ASMANEX TWISTHALER in controlled clinical trials. No overall differences in safety or effectiveness were observed between these and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Overdosage

Chronic overdosage may result in signs/symptoms of hypercorticism [see Warnings and Precautions (5.6) ]. 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.

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 C 27 H 30 Cl 2 O 6 , 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 in vitro 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 in vitro 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). Chemical Structure

Mechanism of action

12.1 Mechanism of Action 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 in vitro 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.

How supplied

How Supplied ASMANEX TWISTHALER 220 mcg: delivers 200 mcg mometasone furoate from the mouthpiece 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. 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”). 14 inhalation units (Institutional Use Only; NDC# 78206-114-03) 30 inhalation units (NDC# 78206-114-04) 60 inhalation units (for more than 1 inhalation daily; NDC# 78206-114-02) 120 inhalation units (for more than 2 inhalations daily; NDC# 78206-114-01) ASMANEX TWISTHALER 110 mcg: delivers 100 mcg mometasone furoate from the mouthpiece 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. 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”). 30 inhalation units (NDC# 78206-115-01) Each inhaler is supplied in a protective foil pouch with Patient’s Instructions for Use. Storage and Handling Store in a dry place at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Discard the inhaler 45 days after opening the foil pouch or when dose counter reads "00", whichever comes first.

Storage

Storage and Handling Store in a dry place at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Discard the inhaler 45 days after opening the foil pouch or when dose counter reads "00", whichever comes first.

Patient information

Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Oropharyngeal Candidiasis Patients should be advised that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing with ASMANEX TWISTHALER therapy, but at times therapy with ASMANEX TWISTHALER may need to be temporarily interrupted under close medical supervision. Rinsing the mouth after inhalation is advised [see Warnings and Precautions (5.1) ] . Acute Asthma Episodes Patients should be advised that ASMANEX TWISTHALER is not a bronchodilator and should not be used to treat status asthmaticus or to relieve acute asthma symptoms. Acute asthma symptoms should be treated with an inhaled, short-acting beta 2 -agonist such as albuterol [see Warnings and Precautions (5.2) ]. Hypersensitivity Reactions Including Anaphylaxis 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 Contraindications (4) , Warnings and Precautions (5.3) , and Adverse Reactions (6.2) ]. 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 [see Contraindications (4) and Adverse Reactions (6.2) ]. Immunosuppression and Risk of Infections Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to consult their physician without delay. Patients should be informed of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex [see Warnings and Precautions (5.4) ] . Hypercorticism and Adrenal Suppression Patients should be advised that ASMANEX TWISTHALER may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, patients should be instructed 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 ASMANEX TWISTHALER [see Warnings and Precautions (5.6) ] . Reduction in Bone Mineral Density Patients who are at an increased risk for decreased BMD should be advised that the use of corticosteroids may pose an additional risk and should be monitored and, where appropriate, be treated for this condition [see Warnings and Precautions (5.7) ] . Reduced Growth Velocity Patients should be informed that orally inhaled corticosteroids, including mometasone furoate inhalation powder, 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 [see Warnings and Precautions (5.8) ] . Use Daily for Best Effect Patients should be advised to use ASMANEX TWISTHALER at regular intervals, since its effectiveness depends on regular use. Maximum benefit may not be achieved for 1 to 2 weeks or longer after starting treatment. If symptoms do not improve in that time frame or if the condition worsens, patients should be instructed to contact their physician. Instructions for Use Patients should be instructed to record the date of pouch opening on the cap label and discard the inhaler 45 days after opening the foil pouch or when the dose counter reads "00" and the final dose has been inhaled, whichever comes first. The inhaler should be held upright while removing the cap. The medication should be taken as directed, breathing rapidly and deeply, and patients should not breathe out through the inhaler. The mouthpiece should be wiped dry and the cap replaced immediately following each inhalation and rotated fully until the click is heard. After administration, the patient should rinse their mouth with water and spit out contents without swallowing. Patients should store the unit as instructed. The dose counter displays the doses remaining. When the dose counter indicates zero, the cap will lock and the unit must be discarded. Patients should be advised that if the dose counter is not working correctly, the unit should not be used and it should be brought to their physician or pharmacist.

Active ingredients

Mometasone Furoate in 2 products

Asmanex NDC products (2)

NDC	Strength & form	Labeler	Type
78206-114	Mometasone Furoate 220 ug/1 Inhalant	Organon LLC	NDA
78206-115	Mometasone Furoate 110 ug/1 Inhalant	Organon LLC	NDA

Asmanex recalls

D-0550-2024 Jun 19, 2024 · Class III · Ongoing
Defective Container
D-0551-2024 Jun 19, 2024 · Class III · Ongoing
Defective Container
D-0169-2024 Jan 3, 2024 · Class II · Terminated
CGMP Deviations: Products were exposed to temperatures outside of the products labeled storage conditions.

Frequently asked questions

What is Asmanex used for?

1 INDICATIONS AND USAGE ASMANEX ® TWISTHALER ® is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients 4 years of age and older. Limitations of Use ASMANEX TWISTHALER is not indicated for the relief of acute bronchospasm. ASMANEX TWISTHALER is not indicated in children less than 4 years of age. ASMANEX TWISTHALER is a corticosteroid indicated…

What are the side effects of Asmanex?

The following clinically significant adverse reactions are described elsewhere in the labeling: Oropharyngeal Candidiasis [see Warnings and Precautions (5.1) ] Immunosuppression and Risk of Infections [see Warnings and Precautions (5.4) ] Hypercorticism and Adrenal Suppression [see Warnings and Precautions (5.6) ] Reduction in Bone Mineral Density [see Warnings and Precautions (5.7) ] Growth… See the full label for the complete list.

Who makes Asmanex?

Asmanex is listed by 1 labeler in the FDA NDC directory, including Organon LLC.

Has Asmanex been recalled?

The FDA enforcement database lists 3 recalls for Asmanex, most recently D-0550-2024 (class iii): Defective Container