部分中文ASMANEX TWISTHALER处方资料（仅供参考）
ASMANEX TWISTHALER：治疗哮喘的口腔皮质类固醇吸入剂。
美国食品药品管理局（FDA）批准先灵葆雅公司110μg糠酸莫米松（mometasone furoate）吸入式粉末剂（inhalation powder）Asmanex Twisthaler用于预防性治疗4～11岁儿童哮喘患者。FDA于2005年已批准了该药规格为220μg用于12岁及以上哮喘患者。本品规格为110μg是第一个批准用于小至4岁儿童、每天用药1次的吸人性皮质类固醇制剂，为患有轻到中度持续性哮喘的儿童提供了一个重要的治疗选择。本品的给药装置不用抛射剂，而是靠吸入用药，从而消除了用药时需要手揿一吸气协调动作的要求。
先灵葆雅公司2005年3月31日宣布，美国FDA已经批准其220微克糠酸莫米松干粉吸入剂（mometasone furoate inhalation powder，ASMANEX TWISTHALER 220 mcg）作为12岁及以上哮喘患者的预防性治疗，可用于哮喘的一线维持治疗。对于以往接受过支气管扩张剂单药或吸入型糖皮质激素类药物治疗的哮喘患者，ASMANEX是目前获准以一日1次用药为起始的吸入型哮喘控制药物。临床试验显示，ASMANEX能使患者肺功能出现实质性改善，减少急救药物的使用，减少患者夜间醒来次数并显著改善咳嗽、哮鸣等日间症状。
一项为期12周的多中心、随机、双盲、安慰剂对照临床试验证明，与安慰剂比较，ASMANEX能实质性地改善患者肺功能并减少对急救药沙丁胺醇（albuterol）的使用。此项试验共纳入400例以往依赖吸入型糖皮质激素治疗的持续性哮喘患者。在试验终点，治疗组患者在夜间醒来次数、日间症状方面均有显著改善。
ASMANEX由先灵葆雅公司研发部开发，目前已在40多个国家获准治疗哮喘。糠酸莫米松是ASMANEX的活性成分，1987年在美国首次用于皮肤科软膏ELOCON (mometasone furoate ointment)，1997年用于鼻喷雾剂NASONEX (mometasone furoate monohydrate)。
在临床试验中，ASMANEX的不良反应一般为轻至中度，主要为头痛、变应性鼻炎、咽炎、上呼吸道感染、鼻窦炎、口腔念珠菌病、痛经、肌肉骨骼疼痛、背痛、消化不良、腹痛和恶心等。不良反应发生率的统计是基于来自10项安慰剂对照临床试验的双盲资料。这10项临床试验共纳入2809例以往接受过吸入型糖皮质激素和（或）支气管扩张剂维持治疗的哮喘患者，其中男性1140例、女性1669例，患者年龄在12～83岁。在试验中，患者接受为期12周的ASMANEX或安慰剂治疗。
ASMANEX采用了相当便捷的吸入器，不含推进剂，用药时无需患者手和呼吸的配合，并配有数字剂量计算器，为患者直观显示剩余剂量。

【商品名】Asmanex Twisthaler、Nasonex(鼻用)
【药理机制】糠酸莫米松的气道抗炎机制与其它吸入性糖皮质激素相似，其对糖皮质激素受体的结合力与丙酸氟替卡松相似。以常规的Mackenzie血管收缩强度测定了糠酸莫米松的作用强度，发现其作用强度高于二丙酸倍氯米松和布地奈德而稍低于丙酸氟替卡松。体外实验证实在抑制抗IgE诱导的嗜碱细胞释放能力和抑制白细胞介素-5诱导的嗜酸细胞活性方面，糠酸莫米松的作用也大于二丙酸倍氯米松和布地奈德而低于丙酸氟替卡松。

【体内过程】糠酸莫米松是最近Schering-plough 公司开发的一种新型的高脂溶性吸入性糖皮质激素制剂，其脂溶性与丙酸氟替卡松相似。有关糠酸莫米松的药代动力学，已经发现糠酸莫米松的全身生物利用度极低，在0.1-1%之间，与丙酸氟替卡松相似，肝脏首过效应与丙酸氟替卡松均为99%。单剂量吸入糠酸莫米松干粉（Twisthaler）400μg的血浆药物浓度是非常低的。静脉滴注糠酸莫米松400μg后检测到的半衰期为4.5小时，而单剂量吸入糠酸莫米松400μg后的血药浓度持续低于定量限值。

【临床应用】初步观察吸入糠酸莫米松的临床效应和副作用与吸入丙酸氟替卡松的临床疗效是相似的。2003年4月10日Schering-Plough和Novartis公司宣布，两家公司将合作开发一种新型哮喘联合治疗药物，其中成分包括Schering-Plough的糠酸莫米松和Novartis公司的Foradil（福莫特罗）。

【剂量】糠酸莫米松有干粉和MDI两种剂型，成人和16岁以上青少年的起始吸入剂量应在每日200-2000微克之间根据不同的病情严重程度来判断和决定。对于16岁以下少年儿童应根据病情的严重程度和身体发育情况，每日的起始剂量在100-1200微克之间选择，对于6岁以下的哮喘儿童每日的起始吸入剂量可在100-300微克之间确定。在病情控制3-6个月后，应根据患者对吸入糠酸莫米松的反应和医生对患者病情严重程度作出的评价已决定是否逐步降级治疗。

【副作用及其防治】与吸入丙酸氟替卡松相比，在稳态情况下糠酸莫米松对下丘脑-垂体-肾上腺皮质轴的抑制作用要大的多，吸入糠酸莫米松的肺内沉积量也是丙酸氟替卡松的2倍。研究没有发现糠酸莫米松对儿童的生长发育（身高）有影响。有关糠酸莫米松的其他全身和局部副作用及其防治与其它吸入性糖皮质激素相似。

ASMANEX® TWISTHALER® 220mcg
(mometasone furoate) Inhalation Powder

ASMANEX® TWISTHALER® 110mcg
(mometasone furoate) Inhalation Powder

FOR ORAL INHALATION ONLY
DRUG 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 110mcg and 220mcg products are cap-activated, inhalation-driven, multidose dry powder inhalers containing mometasone furoate and anhydrous lactose (which contains milk proteins).
Each actuation of the ASMANEX TWISTHALER 110 mcg or 220 mcg inhaler provides a measured dose of approximately 0.75 or 1.5mgmometasone furoate inhalation powder, containing 110 or 220mcg of mometasone furoate, respectively. This results in delivery of 100 or 200mcgmometasone 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).
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INDICATIONS
Treatment of Asthma
ASMANEX® TWISTHALER® is indicated for the maintenance treatment of asthma as prophylactic therapy in patients 4 years of age and older.
Important 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.
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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.
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HOW SUPPLIED
Dosage Forms And Strengths
ASMANEX TWISTHALER is a dry powder for inhalation that is available in two strengths.
ASMANEX TWISTHALER 220 mcg delivers 200 mcg mometasone furoate per actuation from the mouthpiece.
ASMANEX TWISTHALER 110 mcg delivers 100 mcg mometasone furoate per actuation from the mouthpiece.
Storage And Handling
The ASMANEX TWISTHALER 220 mcg product is comprised of an assembled plastic cap– activated dosing mechanism with dose counter, drug-product storage unit, drug-product formulation (240 mg), and mouthpiece, covered by a white screw cap that bears the product label. The body of the inhaler is white and the turning grip is pink with a clear plastic window indicating the number of doses remaining. The inhaler will not deliver subsequent doses once the counter reaches zero (“00”).
The ASMANEX TWISTHALER 110 mcg product is comprised of an assembled plastic cap– activated dosing mechanism with dose counter, drug-product storage unit, drug-product formulation (135 mg), and mouthpiece, covered by a white screw cap that bears the product label. The body of the inhaler is white and the turning grip is gray with a clear plastic window indicating the number of doses remaining. The inhaler will not deliver subsequent doses once the counter reaches zero (“00”).
The ASMANEX TWISTHALER product is available as:
ASMANEX TWISTHALER 220 mcg, which delivers 200mcg mometasone furoate from the mouthpiece: 14 inhalation units (Institutional Use Only; NDC# 0085-1341-04); 30 inhalation units (NDC# 0085- 1341-03); 60 inhalation units (for more than 1 inhalation daily; NDC# 0085-1341-02); or 120 inhalation units (for more than 2 inhalations daily; NDC# 0085-1341-01).
ASMANEX TWISTHALER 110 mcg, which delivers 100mcgmometasone furoate from the mouthpiece: 7 inhalation units (Institutional Use Only; NDC# 0085-1461-07); 30 inhalation units (NDC# 0085- 1461-02).
Each inhaler is supplied in a protective foil pouch with Patient's Instructions for Use.
Store in a dry place at 25°C (77°F); excursions permitted to 15°-30°C (59°-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.
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SIDE EFFECTS
Systemic and local corticosteroid use may result in the following:
•Candida albicans infection [see WARNINGS AND PRECAUTIONS]
•Immunosuppression [see WARNINGS AND PRECAUTIONS]
•Hypercorticism and adrenal suppression [see WARNINGS AND PRECAUTIONS]
•Growth effects [see WARNINGS AND PRECAUTIONS and Use in Specific Populations]
•Glaucoma and cataracts [see WARNINGS AND PRECAUTIONS]
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 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), 220mcg once daily in the evening (n=232), 220mcg twice daily (n=433), 440mcg 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 110mcg 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.
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.
Long-Term Clinical Trials Experience
12 Years of Age and Older
In 3 long-term safety trials, 475 patients with asthma 12 years of age and older were treated with ASMANEX TWISTHALER 220 mcg twice daily (n=60), 220 mcg once daily in the morning (n=41), 220 mcg once daily in the evening (n=40), 440 mcg once daily in the morning (n=44), 440 once daily in the evening (n=41), 440 mcg twice daily n=62), 880 mcg once daily (n=59), or at variable doses (n=128) for 52 weeks. The safety profile of ASMANEX TWISTHALER in the 52-week trials was similar to the findings in the 8- to 12-week clinical trials. In patients previously on inhaled corticosteroids, cataracts were reported in 3 patients (0.9%) treated with ASMANEX TWISTHALER, compared to 1 patient (1.7%) treated with the active comparator medication. Increased ocular pressure at the end of the study was observed in 2 patients, both on ASMANEX TWISTHALER 880 mcg once daily in the morning. Oral candidiasis, dysphonia, and dysmenorrhea were seen at a higher frequency with long-term administration than in the 8- to 12-week trials.
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 from1 trial are described in Table 3 for ASMANEX TWISTHALER 110mcg once daily in the evening. The safety results from the other 2 trials showed similar findings.
Long-Term Clinical Trials Experience in Children 4 to 11 Years of Age
In a 52-week, active controlled, long-term safety trial, 152 patients with asthma 4 to 11 years of age were treated with ASMANEX TWISTHALER 110mcg twice daily (n=74) or 220mcg once daily (n=78). The safety profile for ASMANEX TWISTHALER in the 52-week trial was similar to the findings in the 12-week clinical trials.
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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.
Inhibitors of Cytochrome P450 3A4
Ketoconazole, a strong inhibitor of cytochrome P450 3A4,may increase plasma levels of mometasone furoate during concomitant dosing [see CLINICAL PHARMACOLOGY].
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WARNINGS
Included as part of the PRECAUTIONS section.
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PRECAUTIONS
Local Effects
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. Advise patients to rinse the mouth after inhalation of ASMANEX TWISTHALER.
Acute Asthma Episodes
ASMANEX TWISTHALER is not a bronchodilator and is not indicated for rapid relief of bronchospasm or other acute episodes of asthma. 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.
Immunosuppression
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.
Transferring Patients from Systemic Corticosteroid Therapy
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 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]. 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 fatigue, lassitude, weakness, nausea and vomiting, and hypotension.
Transfer of patients from systemic corticosteroid therapy to ASMANEX TWISTHALER may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions.
During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function.
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 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.
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 103male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (baseline FEV1 85%-88% predicted), treatment with ASMANEX TWISTHALER 220mcg twice daily resulted in significant reductions in lumbar spine (LS) BMD 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 440mcg 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.
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].
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. Close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
Bronchospasm
As with other inhaled asthma medications, bronchospasm may occur with an immediate increase 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.
Patient Counseling Information
See FDA-Approved Patient Labeling
Oral 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].
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].
Immunosuppression
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].
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].
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].
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].
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, rotated fully until the click is heard. Rinsing of mouth after inhalation is advised. 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 [see FDA-Approved Patient Labeling-Patient's Instructions for Use].
FDA-Approved Patient Labeling
See Patient's Instruction for Use.
Nonclinical Toxicology
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 as say. 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).
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 time 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].
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 and ADVERSE REACTIONS].
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  and ADVERSE REACTIONS].
Controlled clinical studies have shown that inhaled corticosteroids ay 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 110mcg twice daily (n=44), 220mcg once daily in the morning (n=50), 110mcg 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].
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OVERDOSE
Chronic overdosage may result in signs/symptoms of hypercorticism [see WARNINGS AND PRECAUTIONS]. Because of low systemic bioavailability and an absence of acute drug-related systemic findings in clinical studies, acute overdose is unlikely to require any treatment other than observation. Single daily doses as high as 1200mcg per day for 28 days were well tolerated and did not cause a significant reduction in plasma cortisol AUC (94%of placebo AUC). Single oral doses up to 8000mcg have been studied on human volunteers with no adverse reactions reported.
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CONTRAINDICATIONS
Status Asthmaticus
ASMANEX TWISTHALER therapy is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.
Hypersensitivity
ASMANEX TWISTHALER is contraindicated in patients with known hypersensitivity to mometasone or any of the ingredients in ASMANEX TWISTHALER. In the clinical trials and postmarketing experience with ASMANEX TWISTHALER, cases of allergic reaction, facial edema, urticaria, hypersensitivity, and throat tightness have been reported.
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原产地英文商品名:
ASMANEX TWISTHALER 220mcg/dose 120dose/box
原产地英文药品名:
MOMETASONE FUROATE
中文参考商品译名:
ASMANEX TWISTHALER 220微克/剂 120剂/盒
中文参考药品译名:
糠酸莫米松
生产厂家中文参考译名:
先灵葆雅
生产厂家英文名:
Schering-Plough
--------------------------------------------------------------
原产地英文商品名:
ASMANEX TWISTHALER 220mcg/dose 30dose/box
原产地英文药品名:
MOMETASONE FUROATE
中文参考商品译名:
ASMANEX TWISTHALER 220微克/剂 30剂/盒
中文参考药品译名:
糠酸莫米松
生产厂家中文参考译名:
先灵葆雅
生产厂家英文名:
Schering-Plough
--------------------------------------------------------------
原产地英文商品名:
ASMANEX TWISTHALER 110mcg/dose 7dose/inhaler
原产地英文药品名:
MOMETASONE FUROATE
原产地英文化合物名称:
INHALER
中文参考商品译名:
ASMANEX TWISTHALER 110微克/剂 7剂/吸入器
中文参考药品译名:
糠酸莫米松
生产厂家中文参考译名:
先灵葆雅
生产厂家英文名:
Schering-Plough
--------------------------------------------------------------
原产地英文商品名:
ASMANEX TWISTHALER 220mcg/dose 60dose/box
原产地英文药品名:
MOMETASONE FUROATE
中文参考商品译名:
ASMANEX TWISTHALER 220微克/剂 60剂/盒
中文参考药品译名:
糠酸莫米松
生产厂家中文参考译名:
先灵葆雅
生产厂家英文名:
Schering-Plough
--------------------------------------------------------------
原产地英文商品名:
ASMANEX TWISTHALER 110mcg/dose 30dose/inhaler
原产地英文药品名:
MOMETASONE FUROATE
原产地英文化合物名称:
INHALER
中文参考商品译名:
ASMANEX TWISTHALER 110微克/剂 30剂/吸入器
中文参考药品译名:
糠酸莫米松
生产厂家中文参考译名:
先灵葆雅
生产厂家英文名:
Schering-Plough