Asmanex

Name: Asmanex

About mometasone inhaler

Type of medicineA corticosteroid (steroid) inhaler
Used forAsthma
Also calledAsmanex®
Available asDry powder inhaler

Inhalers are the main treatment for asthma. The medicine inside the inhaler goes straight into your airways when you breathe in. This means that your airways and lungs are treated, but little of the medicine gets into the rest of your body.

Mometasone is a preventer inhaler. You must use it regularly every day to prevent your symptoms from developing. Steroids like mometasone work by reducing the inflammation in your airways. When the inflammation has gone, your airways are much less likely to become narrow and cause symptoms such as wheezing.

Before using a mometasone inhaler

Some medicines are not suitable for people with certain conditions, and sometimes a medicine can only be used if extra care is taken. For these reasons, before you start using a mometasone inhaler it is important that your doctor knows:

  • If you are pregnant, trying for a baby or breast-feeding. This is because it is particularly important that your asthma should be well controlled if you are expecting a baby, and your doctor will want to advise you about your care.
  • If you have ever had pulmonary tuberculosis (TB).
  • If you are taking or using any other medicines. This includes any medicines you are taking which are available to buy without a prescription, such as herbal and complementary medicines.
  • If you have ever had an allergic reaction to a medicine.

Asmanex Drug Class

Asmanex is part of the drug class:

  • OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS

Uses for Asmanex

Asthma

Long-term prevention of bronchospasm in patients with asthma.1 2

In corticosteroid-dependent patients, may permit a substantial reduction in the daily maintenance dosage or discontinuance of the systemic corticosteroid.1 6

Do not use for rapid relief of bronchospasm.1 2 8

Advice to Patients

  • Importance of providing the patient a copy of the manufacturer's patient information.1

  • Importance of adequate understanding of proper storage, preparation, and inhalation techniques, including use of the Twisthaler device.1 8

  • Importance of pediatric patients receiving oral inhalation therapy under adult supervision.8

  • Importance of rinsing the mouth after oral inhalation.1 2 8

  • Importance of advising patients that mometasone furoate oral inhalation must be used at regular intervals to be therapeutically effective.1 8

  • Importance of adherence to prescribed dosage regimen; do not increase the frequency of administration without consulting a clinician.8

  • Importance of advising patients that at least 1–2 weeks of continuous therapy may be required for optimum effects to be achieved.1 8 Importance of contacting a clinician if asthma symptoms do not improve in such a time frame.1 8

  • Importance of advising patients that orally inhaled mometasone should not be used as a bronchodilator and that the drug is not indicated for emergency use (e.g., relief of acute bronchospasm).1 8

  • Importance of availability and use of a short-acting β2-adrenergic agonist for relief of acute asthma symptoms.1 8 12

  • Importance of contacting a clinician immediately if asthmatic attacks that are not controlled by bronchodilator therapy occur.1

  • Importance of gradual withdrawal from systemic corticosteroids during transfer to orally inhaled mometasone and of monitoring by a clinician during such transfer of therapy.8 (See Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids under Dosage and Administration.)

  • Importance of advising patients being transferred from systemic corticosteroid to mometasone oral inhalation therapy to carry special identification (e.g., card, bracelet) indicating the need for supplementary systemic corticosteroids during periods of stress or severe exacerbation of asthma.1 Importance of advising patients to immediately resume therapy with large doses1 of systemic corticosteroids and contact their clinician for further instructions during stressful periods (e.g., stress, severe asthmatic attack, surgery, trauma, infection).1 8

  • Importance of informing patients that corticosteroids may decrease bone mineral density.1 8 (See Musculoskeletal Effects under Cautions.)

  • Risk of localized candidal infections of mouth and pharynx.1 8 (See Infections under Cautions.)

  • Risk of systemic corticosteroid effects (e.g., hypercorticism, potentially life-threatening adrenal suppression).1 Importance of informing a clinician of fatigue, weakness, nausea, vomiting, dizziness, or fainting.1 8 (See Systemic Corticosteroid Effects under Cautions.)

  • Risk of reduction in growth velocity with orally inhaled corticosteroids.1 (See Pediatric Use under Cautions.)

  • Importance of informing patients that long-term use of inhaled corticosteroids may increase the risk for development of some eye problems (e.g., cataracts, glaucoma).1 (See Ocular Effects under Cautions.)

  • Importance of immunosuppressed patients avoiding exposure to chickenpox or measles, and, if exposed, of immediately consulting a clinician.1 8 (See Immunosuppressed Patients under Cautions.)

  • Importance of advising immunosuppressed patients of potential worsening of existing tuberculosis, fungal, bacterial, parasitic, or viral infections, or ocular herpes simplex.1 Importance of immunosuppressed patients informing clinician of a history of infections.8

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., infections).1 8

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Asmanex Dosage and Administration

Administer Asmanex TWISTHALER by the orally inhaled route only. Instruct patients to inhale rapidly and deeply. Advise patients to rinse the mouth after inhalation. Individual patients will experience a variable time to onset and degree of symptom relief. Maximum benefit may not be achieved for 1 to 2 weeks or longer after initiation of treatment. After asthma stability has been achieved, it is desirable to titrate to the lowest effective dosage to reduce the possibility of side effects. For patients ≥12 years of age who do not respond adequately to the starting dose after 2 weeks of therapy, higher doses may provide additional asthma control. The safety and efficacy of Asmanex TWISTHALER when administered in excess of recommended doses have not been established.

Recommended Dosages in 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
* When administered once daily, Asmanex TWISTHALER should be taken only in the evening. † The 440 mcg daily dose may be administered in divided doses of 220 mcg twice daily or as 440 mcg once daily. ‡ 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)]. § Recommended pediatric dosage is 110 mcg once daily in the evening regardless of prior therapy.
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*

Use in specific populations

Pregnancy

Pregnancy Category C:

There are no adequate and well-controlled studies of Asmanex TWISTHALER use in pregnant women. Animal reproduction studies in mice, rats, and rabbits revealed evidence of teratogenicity. Asthma is a serious and potentially life-threatening condition. Poorly controlled asthma during pregnancy is associated with adverse outcomes for mother and fetus. Asmanex TWISTHALER should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There is a natural increase in corticosteroid production during pregnancy; therefore, most women require a lower exogenous corticosteroid dose and may not need corticosteroid treatment during pregnancy. Infants born to mothers taking substantial oral corticosteroid doses during pregnancy should be monitored for signs of hypoadrenalism.

When administered to pregnant mice, rats, and rabbits, mometasone furoate increased fetal malformations and decreased fetal growth (measured by lower fetal weights and/or delayed ossification). Dystocia and related complications were also observed when mometasone furoate was administered to rats late in gestation. However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans.

In a mouse reproduction study, subcutaneous mometasone furoate produced cleft palate at approximately one-third of the maximum recommended daily human dose (MRHD) for adults on an mcg/m2 basis and decreased fetal survival at approximately 1 times the MRHD. No toxicity was observed at approximately one-tenth of the MRHD.

In a rat reproduction study, mometasone furoate produced umbilical hernia at topical dermal doses approximately 6 times the MRHD and delays in ossification at approximately 3 times the MRHD.

In another study, rats received subcutaneous doses of mometasone 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 a dose that was approximately 6 times the MRHD for adults on an area under the curve (AUC) basis. Similar effects were not observed at approximately 3 times the MRHD.

In rabbits, mometasone furoate caused multiple malformations (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at topical dermal doses approximately 3 times the maximum recommended daily inhalation dose in adults on an mcg/m2 basis. In an oral study, mometasone furoate increased resorptions and caused cleft palate and/or head malformations (hydrocephaly and domed head) at a dose less than the MRHD for adults based on AUC. At a dose approximately 2 times the MRHD in adults based on AUC, most litters were aborted or resorbed [see Nonclinical Toxicology (13.2)].

Nursing Mothers

Systemic absorption of a single inhaled 400 mcg mometasone dose was less than 1%. It is not known if mometasone furoate is excreted in human milk. Because other corticosteroids are excreted in human milk, caution should be used when Asmanex TWISTHALER is administered to nursing women.

Pediatric Use

The safety and effectiveness of Asmanex TWISTHALER have been established in children 4 years of age and older. Use of Asmanex TWISTHALER in children 12 years of age and older is supported by evidence from adequate and well-controlled clinical trials in this patient population [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

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.

Hepatic Impairment

Concentrations of mometasone furoate appear to increase with severity of hepatic impairment [see Clinical Pharmacology (12.3)].

Clinical Studies

Asthma

Adults and Adolescents 12 Years of Age and Older: The efficacy of Asmanex TWISTHALER in patients with asthma 12 years and older was evaluated in ten 8- to 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trials. These trials included 1750 patients ranging from 12 to 83 years of age; 38% male and 62% female; 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). The results of the clinical trials are presented based upon previous asthma therapy.

Patients ≥12 Years of Age Previously Maintained on Bronchodilators Alone: Asmanex TWISTHALER was studied in three 12-week, double-blind trials in 737 patients with mild to moderate asthma (mean baseline FEV1≅2.6 L, 72% of predicted normal) who were maintained on short-acting beta2-agonists alone. The first 2 trials evaluated doses of 440 mcg administered as 2 inhalations once daily in the morning and 1 of these studies also evaluated 220 mcg twice daily. In both trials, AM predose FEV1 was significantly improved at endpoint (last observation) following treatment with 440 mcg Asmanex TWISTHALER once daily in the morning as compared to placebo (14% vs. 2.5%, respectively, in 1 trial and 16% vs. 5.5% in the other). There was also a significant improvement in AM predose FEV1 at endpoint following treatment with Asmanex TWISTHALER 220 mcg twice daily. Other measures of lung function (AM and PM PEFR) also showed improvement compared to placebo. Patients receiving Asmanex TWISTHALER treatment had reduced frequency of beta2-agonist rescue medication use compared to those on placebo (mean reductions at endpoint 2.2 and 0.5 puffs per day, respectively, from a baseline of 4.1 puffs/day). Additionally, fewer patients receiving Asmanex TWISTHALER 440 mcg once daily experienced asthma worsening than did patients receiving placebo.

In the third trial, 195 asthmatic patients were treated with Asmanex TWISTHALER 220 mcg once daily in the evening or placebo. The AM FEV1 at endpoint was significantly improved compared to placebo (mean change at endpoint 0.43 L or 16.8% vs. 0.16 L or 6%, respectively, see Figure 1). Evening PEF increased 24.96 L/min (7%) from baseline in the Asmanex TWISTHALER group compared to 8.67 L/min (4%) in placebo.

Patients ≥12 Years of Age Previously Maintained on Inhaled Corticosteroids: The efficacy and safety of Asmanex TWISTHALER in doses ranging from 110 mcg twice daily to 440 mcg twice daily was evaluated in 3 trials in 1072 patients previously maintained on inhaled corticosteroids. In the first 2 trials, asthmatic patients (mean baseline FEV1 ~2.6 L, 76% predicted) were previously on either beclomethasone dipropionate [84–1200 mcg/day], flunisolide [100–2000 mcg/day], fluticasone propionate [110–880 mcg/day], or triamcinolone acetonide [300–2400 mcg/day]. The first trial included 307 patients who were treated in an open-label fashion with Asmanex TWISTHALER 220 mcg (110 mcg × 2 inhalations) twice daily for 2 weeks followed by 12 weeks of double-blind treatment with Asmanex TWISTHALER 440 mcg once daily in the morning or placebo. The second trial involved 365 patients who continued on their previous dose of inhaled corticosteroids during a 2-week screening period before being switched to Asmanex TWISTHALER 440 mcg twice daily, 220 mcg twice daily, 110 mcg twice daily, beclomethasone dipropionate 168 mcg twice daily, or placebo for 12 weeks.

In the first trial, AM predose FEV1 was effectively maintained (-1.4% change from baseline to endpoint) over the 12 weeks in the patients who were randomized to Asmanex TWISTHALER 440 mcg once daily in the morning, while decreasing 10% at endpoint in those switched to placebo. In addition, fewer patients treated with Asmanex TWISTHALER experienced worsening of asthma compared to placebo.

In the second trial, AM predose FEV1 was significantly increased at endpoint when patients were switched to Asmanex TWISTHALER 220 mcg twice daily (7% increase) or 440 mcg twice daily (6.2% increase) as compared to a decrease of 7% when switched to placebo. Additionally, beta2-agonist rescue medication use was decreased for patients who received Asmanex TWISTHALER treatment relative to those on placebo (mean reduction from baseline to endpoint 1.1 puffs/day vs. increase of 0.7 puffs/day). Fewer patients receiving Asmanex TWISTHALER treatment experienced asthma worsening than did patients receiving placebo.

The third trial evaluated the efficacy and safety of Asmanex TWISTHALER compared to placebo in 400 asthmatic patients (mean FEV1 67% predicted at baseline) previously maintained on beclomethasone dipropionate (hydrofluoroalkane [HFA] or chlorofluorocarbon [CFC]) 168–600 mcg/day, budesonide 200–1200 mcg/day, flunisolide 500–2000 mcg/day, fluticasone propionate 88–880 mcg/day, or triamcinolone acetonide 400–1600 mcg/day. Following a 28-day inhaled corticosteroid dose-reduction phase, patients were randomized to Asmanex TWISTHALER 440 mcg once daily in the evening, 220 mcg once daily in the evening, 220 mcg twice daily, or placebo. At endpoint, patients who received Asmanex TWISTHALER 220 mcg once daily in the evening, 440 mcg once daily in the evening, or 220 mcg twice daily had a significant improvement in AM FEV1 [0.41 L (19%), 0.49 L (22%), and 0.51 L (24%) in the 220 mcg once daily in the evening, 440 mcg once daily in the evening, and 220 mcg twice daily treatment group, respectively] compared to placebo [0.16 L (8%)] (see Figure 2). Evening PEF increased 15.65 L/min (4.1%) with the 220 mcg once daily in the evening dose, 39.26 L/min (10.7%) with the 440 mcg once daily in the evening dose, and 36.7 L/min (10.8%) with the 220 mcg twice daily dose, respectively, compared to a 1.4 L/min (1%) increase with placebo. Patients receiving all doses of Asmanex TWISTHALER treatment had reduced frequency of beta-agonist rescue medication use compared to those on placebo (mean reductions at endpoint of 1.4–1.8 puffs/day from a baseline of more than 3 puffs/day compared to an increase in use by 0.5 puffs/day for placebo). In addition, fewer patients receiving Asmanex TWISTHALER experienced asthma worsening than did those on placebo.

Patients ≥12 Years of Age Previously Maintained on Oral Corticosteroids: The efficacy of Asmanex TWISTHALER 440 mcg and 880 mcg twice daily was evaluated in one 12-week, double-blind trial in patients previously maintained on oral corticosteroids. A total of 132 patients requiring oral prednisone (baseline mean daily oral prednisone requirement approximately 12 mg; baseline FEV1 of 1.8 L, 59% of predicted normal), most of whom were also on inhaled corticosteroids (baseline inhaled steroid: beclomethasone dipropionate [168–840 mcg/day], budesonide [800–1600 mcg/day], flunisolide [1000–2000 mcg/day], fluticasone propionate [440–1760 mcg/day], or triamcinolone acetonide [400–2400 mcg/day]) were studied. Patients who received Asmanex TWISTHALER 440 mcg twice daily had a significant reduction in their oral prednisone (46%) as compared to placebo (164% increase in oral prednisone dose). Additionally, 40% of patients on Asmanex TWISTHALER 440 mcg twice daily were able to completely discontinue their use of prednisone, whereas 60% of patients on placebo had an increase in daily prednisone use. Patients on Asmanex TWISTHALER had significant improvement in lung function (14% increase) compared to a 12% decrease in FEV1 in the placebo group. Additionally, mean rescue beta2-agonist use was reduced to approximately 3 puffs/day from a baseline of 4–5 puffs/day with Asmanex TWISTHALER treatment, compared to an increase of 0.3 puffs/day on placebo. Patients who received Asmanex TWISTHALER 880 mcg twice daily experienced no additional benefit beyond that seen with 440 mcg twice daily.

Pediatric Patients 4 to 11 Years of Age: The efficacy of Asmanex TWISTHALER in patients with asthma 4 to 11 years of age was evaluated in three 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trials. These trials included 630 patients receiving Asmanex TWISTHALER, ranging from 4 to 11 years of age; 63% male and 37% female; 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). The results for 1 clinical trial are described below. The other 2 clinical trials support the efficacy of Asmanex TWISTHALER.

A 12-week, placebo-controlled trial of 296 patients 4 to 11 years of age with asthma of at least 6 months duration (mean % predicted FEV1 at baseline ranging from 77.3%–79.7%) was conducted to demonstrate the efficacy of the Asmanex TWISTHALER in the treatment of asthma. Patients were treated with Asmanex TWISTHALER 110 mcg once daily in the evening (n=98) or placebo (n=99) for 12 weeks. Assessment of efficacy was based upon morning predose FEV1. The primary endpoint was the mean change from baseline to endpoint in percent-predicted FEV1. For the primary endpoint, improvement in the Asmanex TWISTHALER 110 mcg once daily in the evening treatment group (4.73) was statistically significant compared to placebo (-1.77). Figure 3 displays the results for % predicted FEV1 change from baseline at endpoint.

In this study, secondary endpoints of morning and evening peak expiratory flow and rescue medication use were supportive of efficacy of Asmanex TWISTHALER.

Before using Asmanex

You should not use Asmanex if you are allergic to mometasone, or to milk proteins.

To make sure Asmanex is safe for you, tell your doctor if:

  • you have glaucoma or cataracts; or

  • you have been sick or had an infection of any kind.

It is not known whether Asmanex will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether mometasone passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Asmanex can affect growth in children. Talk with your doctor if you think your child is not growing at a normal rate while using this medication.

Do not give Asmanex to a child younger than 4 years old without medical advice.

Long-term use of steroids may lead to bone loss (osteoporosis), especially if you smoke, if you do not exercise, if you do not get enough vitamin D or calcium in your diet, or if you have a family history of osteoporosis. Talk with your doctor about your risk of osteoporosis.

What should I avoid?

Asmanex can weaken your immune system. This can make it easier for you to get sick from being around others who are ill.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using Asmanex.

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