Drug Detail:Asmanex twisthaler (Mometasone inhalation [ moe-met-a-sone ])
Drug Class: Inhaled corticosteroids
Highlights of Prescribing Information
ASMANEX® TWISTHALER® (mometasone furoate inhalation powder), for oral inhalation use
Initial U.S. Approval: 1987
Recent Major Changes
| Dosage and Administration (2) | 02/2021 |
| Warnings and Precautions (5.1, 5.2) | 02/2021 |
Indications and Usage for Asmanex
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).
Asmanex Dosage and Administration
- 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)
| 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* |
Dosage Forms and Strengths
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
- 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)
Adverse Reactions/Side Effects
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.
Drug Interactions
- Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects. (7.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 6/2021
Full Prescribing Information
1. Indications and Usage for Asmanex
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.
2. Asmanex 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.
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.
| Previous Therapy | Recommended Starting Dose | Highest Recommended Daily Dose |
|---|---|---|
|
||
| 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* |
3. 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.
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)].
5. Warnings and Precautions
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 beta2-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. 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 [see Dosage and Administration (2.1)]. Lung function (FEV1 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.
Unmasking of Allergic Conditions Previously Suppressed by Systemic Corticosteroids
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.
Corticosteroid Withdrawal Symptoms
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.
5.6 Hypercorticism and Adrenal Suppression
ASMANEX TWISTHALER will often help control asthma symptoms with less suppression of HPA function than therapeutically similar oral doses of prednisone. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing ASMANEX TWISTHALER. Particular care should be taken in observing patients postoperatively 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 when ASMANEX TWISTHALER is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of ASMANEX TWISTHALER should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma.
5.7 Reduction in Bone Mineral Density
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 FEV1 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 FEV1 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.
5.8 Effect on Growth
Orally inhaled corticosteroids, including ASMANEX TWISTHALER, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving ASMANEX TWISTHALER routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ASMANEX TWISTHALER, titrate each patient's dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations (8.4)].
5.9 Glaucoma and Cataracts
In clinical trials, glaucoma, increased intraocular pressure, and cataracts have been reported in 8 of 3007 patients following the administration of ASMANEX TWISTHALER. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX TWISTHALER long term.
5.10 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 ASMANEX TWISTHALER, it should be treated immediately with a fast-acting inhaled bronchodilator.
Treatment with ASMANEX TWISTHALER should be discontinued and alternative therapy instituted.
5.11 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors
Caution should be exercised when considering the coadministration of ASMANEX TWISTHALER with ketoconazole, and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systemic exposure to mometasone furoate may occur [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
6. Adverse Reactions/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)]
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.
| (%) 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* | 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. placebo %): musculoskeletal pain (22% vs. 14%), oral candidiasis (22% vs. 9%), sinusitis (22% vs. 19%), allergic rhinitis (20% vs. 5%), upper respiratory infection (15% vs. 14%), arthralgia (13% vs. 7%), fatigue (13% vs. 2%), depression (11% vs. 0%), and sinus congestion (9% vs. 0%). In considering these data, an increased duration of exposure for patients on ASMANEX TWISTHALER treatment (77 days vs. 58 days on placebo) should be taken into account.
Pediatric Patients 4 to 11 Years of Age: In the three 12-week clinical trials in pediatric patients 4 to 11 years of age, patients with asthma were previously maintained on bronchodilators and/or inhaled corticosteroids. The safety results from 1 trial are described in Table 3 for ASMANEX TWISTHALER 110 mcg once daily in the evening. The safety results from the other 2 trials showed similar findings.
Overall adverse reactions were reported with approximately the same frequency by patients treated with ASMANEX TWISTHALER and those receiving placebo. Table 3 displays the common adverse reactions (≥2% in any patient group receiving ASMANEX TWISTHALER) that occurred more frequently in patients 4 to 11 years of age treated with ASMANEX TWISTHALER compared with placebo-treated patients.
| (%) of Patients | ||
|---|---|---|
| ASMANEX TWISTHALER | ||
| Adverse Reaction | 110 mcg once daily in the evening (n=98) | Placebo (n=99) |
| Fever | 7 | 5 |
| Allergic Rhinitis | 4 | 3 |
| Abdominal Pain | 6 | 2 |
| Vomiting | 3 | 2 |
| Urinary Tract Infection | 2 | 1 |
| Bruise | 2 | 0 |
| Average Duration of Exposure (Days) | 72 | 68 |
6.2 Postmarketing Experience
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.
Eye disorders: Vision blurred [see Warnings and Precautions (5.9)].
Immune System Disorders: Immediate and delayed hypersensitivity reactions including rash, pruritus, angioedema and anaphylactic reaction [see Warnings and Precautions (5.3) and Contraindications (4)].
Respiratory, Thoracic and Mediastinal Disorders: Asthma aggravation, which may include cough, dyspnea, wheezing and bronchospasm.
7. 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.
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.
8. Use In Specific Populations
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.
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.
10. 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.
11. 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 C27H30Cl2O6, 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).
12. Asmanex - Clinical Pharmacology
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.
13. Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
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/m2 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/m2 basis).
Mometasone furoate increased chromosomal aberrations in an in vitro Chinese hamster ovary cell assay, but did not have this effect in an in vitro Chinese hamster lung cell assay. Mometasone furoate was not mutagenic in the Ames test or mouse lymphoma assay, and was not clastogenic in an in vivo 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 vivo 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).
16. How is Asmanex 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.
17. Patient Counseling 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 beta2-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.
| Patient Information
ASMANEX® TWISTHALER® (AZ-ma-neks) (mometasone furoate inhalation powder) for oral inhalation use only |
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| This Patient Information has been approved by the U.S. Food and Drug Administration. | Revised Date: 6/2021 | |||||
| What is ASMANEX TWISTHALER?
ASMANEX TWISTHALER is an inhaled corticosteroid (ICS) prescription medicine used as maintenance treatment for the prevention and control of asthma symptoms in people 4 years of age and older.
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Do not use ASMANEX TWISTHALER:
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Before you use ASMANEX TWISTHALER, tell your healthcare provider about all of your medical conditions including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially, tell your healthcare provider if you take antifungal medicines, antibiotic medicines, or anti-HIV medicines such as: |
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Ask your healthcare provider if you are not sure if any of your medicines are the kinds listed above. For some medicines (including medicines for HIV such as ritonavir, cobicistat-containing products, and certain antifungals and antibiotics) your healthcare provider may wish to monitor you carefully. Know the medicines you take. Keep a list and show it to your healthcare provider and pharmacist each time you get a new medicine. |
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| How should I use ASMANEX TWISTHALER? Read the step-by-step instructions for using ASMANEX TWISTHALER in the Instructions for Use.
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| What are the possible side effects of ASMANEX TWISTHALER? ASMANEX TWISTHALER can cause serious side effects, including:
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| The most common side effects reported while using ASMANEX TWISTHALER include: | ||||||
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| Other side effects: Worsening asthma or sudden asthma attacks have been reported with the use of inhaled mometasone furoate. Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the side effects with ASMANEX TWISTHALER. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
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| General information about the safe and effective use of ASMANEX TWISTHALER.
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ASMANEX TWISTHALER for a condition for which it was not prescribed. Do not give your ASMANEX TWISTHALER to other people, even if they have the same condition that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about ASMANEX TWISTHALER that was written for healthcare professionals. For more information about ASMANEX TWISTHALER go to www.ASMANEX.com or to report side effects call 1-844-674-3200. |
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| What are the ingredients in ASMANEX TWISTHALER?
Active ingredient: mometasone furoate Inactive ingredient: anhydrous lactose (which contains trace amounts of milk proteins). |
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Instructions for Use
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It is important that you read this information as the ASMANEX TWISTHALER may work differently from inhalers you have used before.
Read this Instructions for Use before you start using ASMANEX TWISTHALER and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.
TWISTHALER Parts:
See Figures A and B below to become familiar with the TWISTHALER parts.
- Remove the ASMANEX TWISTHALER from its foil pouch and write the date on the cap label.
- Follow Steps 1 and 2 below each time you inhale a dose from your ASMANEX TWISTHALER.
Step 1: Open TWISTHALER
Hold the TWISTHALER straight up (upright position) with the colored portion (the base) on the bottom (see Figure C). It is important that you remove the cap of the TWISTHALER while it is in this upright position to make sure that you get the right amount of medicine with each dose.
Holding the colored base, twist the cap in a counterclockwise direction to remove it (see Figure C). As you lift off the cap, the dose counter on the base will count down by one. Removing the cap loads the TWISTHALER with the medicine that you are now ready to inhale.
Important: The indented arrow (located on the white portion of the TWISTHALER, directly above the colored base) should now be pointing to the dose counter below. (see Figure C).
Step 2: Inhale dose
- Breathe out fully.
- Bring the TWISTHALER up to your mouth or your child’s mouth with the mouthpiece facing toward you or your child.
- Place the mouthpiece in your mouth or your child’s mouth, holding it in a horizontal (on its side) position as shown below (see Figure D).
- Firmly close your lips around the mouthpiece and take in a fast, deep breath. Since the medicine is a very fine powder, you may not be able to taste, smell, or feel it after inhalation.
- Do not cover the ventilation holes while inhaling the dose.
Step 3: Hold breath
- Remove the TWISTHALER from your mouth and hold your breath for about 10 seconds, or as long as you comfortably can.
Important: Do not breathe out (exhale) into the TWISTHALER.
Step 4: Replace Cap and Close TWISTHALER
- After you take your medicine, it is important that you wipe the mouthpiece dry, if needed, and then replace the cap right away, firmly closing the TWISTHALER right away (see Figures E and F).
Be sure that the indented arrow is in line with the dose counter. Put the cap back onto the TWISTHALER and turn it in a clockwise direction, as you gently press down. You will hear a "click" to let you know that the cap is fully closed. This is the only way to be sure that your next dose is loaded the right way.
Step 5: Rinse mouth
- After using your TWISTHALER, rinse your mouth with water. Spit out the water. Do not swallow it.
How should I clean and store the ASMANEX TWISTHALER?
- Store ASMANEX TWISTHALER at room temperature between 68°F to 77°F (20°C to 25°C).
- Keep dry. Avoid contact with liquids.
- Do not wash the ASMANEX TWISTHALER.
- Clean mouthpiece if needed by gently wiping with a dry cloth or tissue.
- Throw away the ASMANEX TWISTHALER 45 days after opening the foil pouch or when the dose counter reads “00” and you have inhaled the final dose, whichever comes first.
- Keep the ASMANEX TWISTHALER and all medicines out of the reach of children.
How to know when the ASMANEX TWISTHALER is empty.
- The TWISTHALER has a dose counter on the colored base, which shows the number of doses left to use.
- As you lift off the cap to take your dose, the dose counter on the base will count down by 1 (if you began with the dose counter reading “30” this will cause the dose counter to now read “29”).
- Read the numbers from top to bottom.
- When the unit reads “01” this means this is the last dose.
- After dose “01” the counter will read “00”.
- When you replace the cap, the unit will lock and then must be thrown away.
- Start using a new ASMANEX TWISTHALER as instructed by your healthcare provider.
This Instructions for Use has been approved by the U.S. Food and Drug Administration
| ASMANEX
mometasone furoate inhalant |
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| ASMANEX
mometasone furoate inhalant |
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| Labeler - Organon LLC (117494753) |
