2014年5月2日，葛兰素史克（GSK）慢性阻塞性肺病新药Incruse Ellipta（umeclidinium）获FDA批准，作为一种长期的、每日一次的维持性支气管扩张药物，用于治疗慢性阻塞性肺病（COPD）（包括慢性支气管炎和肺气肿）患者的气流阻塞（airflow obstruction）。GSK预计在2014年第四季度在美国推出该药。
Incruse Ellipta是葛兰素史克首个长效毒蕈碱受体拮抗剂（LAMA）单药疗法，FDA批准的剂量为62.5微克，该药采用新型干粉吸入器Ellipta给药。umeclidinium是一类支气管扩张剂，是一种长效毒蕈碱拮抗剂（LAMA），又名长效抗胆碱能药物，能够影响呼吸道周围的肌肉，阻止肌肉收缩。
Umeclidinium的临床项目包括7项III期临床试验，涉及超过2500例COPD患者。
今年4月18日，Incruse Ellipta获加拿大批准，作为一种长期的、每日一次的维持性支气管扩张药物，用于治疗慢性阻塞性肺病（COPD）（包括慢性支气管炎和肺气肿）患者的气流阻塞（airflow obstruction），该药不适用于COPD急性恶化的缓解，并且不应用于18岁以下患者。这是Incruse Ellipta在全球范围内获得的首个监管批准，
今年4月28日，Incruse Ellipta获欧盟委员会（EC）批准，作为每日一次的维持性支气管扩张剂，用于慢性阻塞性肺病（COPD）成人患者，缓解疾病症状。
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use INCRUSE ELLIPTA safely and effectively. See full prescribing information for INCRUSE ELLIPTA.
INCRUSE ELLIPTA (umeclidinium inhalation powder)
FOR ORAL INHALATION USE
Initial U.S. Approval: 2013
INDICATIONS AND USAGE
INCRUSE ELLIPTA is an anticholinergic indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD). (1)
DOSAGE AND ADMINISTRATION
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For oral inhalation only. (2)
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Maintenance treatment of COPD: 1 inhalation of INCRUSE ELLIPTA once daily. (2)
DOSAGE FORMS AND STRENGTHS
Inhalation Powder. Inhaler containing a double-foil blister strip of powder formulation for oral inhalation. Each blister contains umeclidinium 62.5 mcg. (3)
CONTRAINDICATIONS
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Severe hypersensitivity to milk proteins. ( 4)
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Hypersensitivity to any ingredient. ( 4)
WARNINGS AND PRECAUTIONS
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Do not initiate in acutely deteriorating COPD or to treat acute symptoms. ( 5.1)
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If paradoxical bronchospasm occurs, discontinue INCRUSE ELLIPTA and institute alternative therapy. ( 5.2)
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Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a physician immediately if symptoms occur. ( 5.4)
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Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a physician immediately if symptoms occur. ( 5.5)
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥2% and more common than placebo) include nasopharyngitis, upper respiratory tract infection, cough, arthralgia. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of INCRUSE ELLIPTA with other anticholinergic-containing drugs. (7.1)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 6/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
Sections or subsections omitted from the full prescribing information are not listed.
1 INDICATIONS AND USAGE
INCRUSE® ELLIPTA® is an anticholinergic indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
2 DOSAGE AND ADMINISTRATION
INCRUSE ELLIPTA (umeclidinium 62.5 mcg) should be administered as 1 inhalation once daily by the orally inhaled route only.
INCRUSE ELLIPTA should be taken at the same time every day. Do not use INCRUSE ELLIPTA more than 1 time every 24 hours.
No dosage adjustment is required for geriatric patients, patients with renal impairment, or patients with moderate hepatic impairment [see Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
Inhalation Powder. Disposable light grey and light green plastic inhaler containing a double-foil blister strip with 30 blisters containing powder intended for oral inhalation only. Each blister contains umeclidinium 62.5 mcg. An institutional pack containing a blister strip with 7 blisters is also available.
4 CONTRAINDICATIONS
The use of INCRUSE ELLIPTA is contraindicated in the following conditions:
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Severe hypersensitivity to milk proteins [see Warnings and Precautions (5.3)]
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Hypersensitivity to umeclidinium or any of the excipients [see Warnings and Precautions (5.3), Description (11)]
5 WARNINGS AND PRECAUTIONS
5.1 Deterioration of Disease and Acute Episodes
INCRUSE ELLIPTA should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD. INCRUSE ELLIPTA has not been studied in subjects with acutely deteriorating COPD. The initiation of INCRUSE ELLIPTA in this setting is not appropriate.
INCRUSE ELLIPTA should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. INCRUSE ELLIPTA has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If INCRUSE ELLIPTA no longer controls symptoms of bronchoconstriction; the patient’s inhaled, short-acting beta2-agonist becomes less effective; or the patient needs more short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting a re-eva luation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dose of INCRUSE ELLIPTA beyond the recommended dose is not appropriate in this situation.
5.2 Paradoxical Bronchospasm
As with other inhaled medicines, INCRUSE ELLIPTA can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with INCRUSE ELLIPTA, it should be treated immediately with an inhaled, short-acting bronchodilator; INCRUSE ELLIPTA should be discontinued immediately; and alternative therapy should be instituted.
5.3 Hypersensitivity Reactions
Hypersensitivity reactions may occur after administration of INCRUSE ELLIPTA. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder products containing lactose; therefore, patients with severe milk protein allergy should not use INCRUSE ELLIPTA [see Contraindications (4)].
5.4 Worsening of Narrow-Angle Glaucoma
INCRUSE ELLIPTA should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately if any of these signs or symptoms develops.
5.5 Worsening of Urinary Retention
INCRUSE ELLIPTA should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, painful urination), especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a physician immediately if any of these signs or symptoms develops.
6 ADVERSE REACTIONS
The following adverse reactions are described in greater detail in other sections:
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Paradoxical bronchospasm [see Warnings and Precautions (5.2)]
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Worsening of narrow-angle glaucoma [see Warnings and Precautions (5.4)]
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Worsening of urinary retention [see Warnings and Precautions (5.5)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
A total of 1,663 subjects with COPD across 8 clinical trials (mean age: 62.7 years; 89% white; 65% male across all treatments, including placebo) received at least 1 inhalation dose of umeclidinium at doses of 62.5 or 125 mcg. In the 4 randomized, double-blind, placebo- or active-controlled, efficacy clinical trials, 1,185 subjects received umeclidinium for up to 24 weeks, of which 487 subjects received the recommended dose of umeclidinium 62.5 mcg. In a 12-month, randomized, double-blind, placebo-controlled, long-term safety trial, 227 subjects received umeclidinium 125 mcg for up to 52 weeks [see Clinical Studies (14)].
The incidence of adverse reactions associated with INCRUSE ELLIPTA in Table 1 is based upon 2 placebo-controlled efficacy trials: one 12-week trial and one 24-week trial.
