FDA批准每日1次复方吸入剂治疗COPD

12月18日，美国食品药品管理局(FDA) 批准了Anoro Ellipta用于慢性阻塞性肺病(COPD)气流阻塞的长期维持性治疗。该药物为每日1次的复方吸入剂，含有抗胆碱能药物umeclidinium 62.5 μg和β受体激动剂维兰特罗 25 μg 。

制造商葛兰素史克声明指出，该公司计划在2014年第一季度推出该药物。

根据葛兰素提交的临床试验数据，FDA审评专家一致同意该吸入剂可为患者带来有临床意义的受益，不过对严重心脏病患者的安全性表示忧虑。在主要有效性试验中观察到的缺血性相关事件数量的不均衡性在长期安全性研究中并没有出现，心脏安全性数据是否可外推至严重心脏病患者也令人担忧，因为排除标准已将更为严重的先脏病患者排除在外。

葛兰素在声明中指出，该药物“应慎用于心血管疾病患者，尤其是冠脉功能不全、心律失常和高血压患者。维兰特罗等β2受体激动剂用于正在接受或2周前接受已知可延长QTc间期药物治疗的患者更应高度慎重。”

还建议，Anoro Ellipta在与长效酮康唑及其他已知高活性细胞色素P450 3A4抑制剂联用时应慎重，因为这可能增加心血管不良发应。

FDA还指出，心血管效应属于“严重副作用”，还包括矛盾性支气管痉挛、狭角性青光眼以及尿潴留恶化。

常见副作用包括咽炎、鼻窦炎、下呼吸道感染、便秘、腹泻、剧痛、肌肉痉挛、颈痛和胸痛。

该产品附有患者用药指南，标签中含有一项黑框警告，提醒长效β2受体激动剂维兰特罗可增加哮喘相关死亡风险。该复方吸入剂的另一成分umeclidinium属于抗胆碱能药物。

葛兰素指出，“AnoroEllipta不应在COPD快速恶化或发生潜在致死性发作期间开始用药，也不应作为支气管痉挛急性发作的抢救治疗药，在这种情况下应使用吸入性短效β2受体激动剂治疗。”

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By: M. ALEXANDER OTTO, Cardiology News Digital Network

The Food and Drug Administration on Dec. 18 approvedAnoroEllipta (umeclidinium 62.5 mcg/vilanterol 25 mcg), an anticholinergic/beta2-agonist, once-daily combination inhaler for long-term maintenance treatment of airflow obstruction in chronic obstructive pulmonary disease.

Manufacturer GlaxoSmithKline plans to launch the product during the first quarter of 2014, the company said in a statement.

FDA’s review panel unanimously agreed that the inhaler provided clinically meaningful benefits, based on Glaxo’s clinical trials, but panelists were concerned about its safety in patients with severe heart disease. There were numerical imbalances in ischemia-related events in primary efficacy trials that were not seen in a long-term safety study. Generalizability of the cardiac safety data was also a concern because trial exclusion criteria may have eliminated patients with more severe heart disease.

Glaxo noted in its statement that the drug "should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. ... Beta2-agonists, such as vilanterol, should be administered with extreme caution to patients being treated with drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents."

Caution also was advised when AnoroEllipta is considered for coadministration "with long-term ketoconazole and other known strong cytochrome P450 3A4 inhibitors because increased cardiovascular adverse effects may occur," the company said.

The FDA also noted cardiovascular effects among "serious side effects," as well as

paradoxical bronchospasm, narrow-angle glaucoma, and worsening of urinary retention.

More common side effects include pharyngitis, sinusitis, lower respiratory tract infection, constipation, diarrhea, extremity pain, muscle spasms, neck pain, and chest pain.

The product will come with a patient medication guide and carry a boxed warning that long-acting beta2-adrenergic agonists like vilanterol increase the risk of asthma-related death. Umeclidinium, the other drug in the combination inhaler, is an anticholinergic.

"AnoroEllipta should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm, which should be treated with an inhaled, short-acting beta2-agonist," Glaxo noted.

Frontline Medical News reporter Elizabeth Mechcatie contributed to this report.