ST LOUIS (MD Consult) - On August 13, 2009, King Pharmaceuticals announced that the US Food and Drug Administration (FDA) has approved Embeda (morphine sulfate and naltrexone hydrochloride) extended-release capsules for oral use. Embeda is a long-acting, schedule II, opioid analgesic for the management of moderate to severe pain when a continuous, around-the-clock, opioid analgesic is needed for an extended period of time. A press release by the manufacturer states that Embeda is the first FDA-approved long-acting opioid that is designed to reduce drug liking and euphoria when tampered with by crushing or chewing.

Embeda contains extended-release morphine pellets, each with an inner core of naltrexone hydrochloride, an opioid-receptor antagonist. When the medication is taken as directed, the morphine relieves pain whereas the sequestered naltrexone hydrochloride passes through the body with no intended clinical effect. However, if an Embeda capsule is crushed or chewed, the naltrexone is released and absorbed with the morphine, reversing the morphine's subjective and analgesic effects. The clinical significance of the degree of this reduction has not been established, and no evidence exists to show that the naltrexone in Embeda reduces the drug's abuse liability.

The FDA approval of Embeda was granted on the basis of results from 12 clinical studies, including data demonstrating the drug's efficacy and safety. In a phase 3 study, Embeda therapy provided significant pain relief in patients with moderate to severe pain associated with osteoarthritis of the hip or knee, compared with placebo. Additionally, data from an earlier phase 2 study showed that Embeda was bioequivalent to another marketed extended-release morphine sulfate capsule product.

Phase 3 findings also showed that Embeda was safe and well tolerated in patients treated for up to 12 months, with an overall safety profile consistent with the most common opioid-related adverse events. The most common adverse events reported in the Embeda clinical program were constipation, nausea, and somnolence.

In a separate study of recreational drugs users, Embeda, when crushed and taken orally, was shown to have reduced drug liking and euphoria compared with an equivalent dose of immediate-release morphine sulfate solution. The clinical significance of the degree of reduction in drug liking and euphoria reported in these studies has not yet been established.

Embeda is intended for once- or twice-daily dosing. Because the medication is an extended-release product, it should not be chewed, crushed, or dissolved because a possibility exists that a rapid release and absorption of a potentially fatal dose of morphine could occur. Furthermore, Embeda is not intended for use on an as-needed basis, and it is not indicated for postoperative use.

King Pharmaceuticals intends to launch Embeda in September 2009.

 

 

圣路易斯（MD Consult）——2009年8月13日，国王制药公司（King Pharmaceuticals）宣布，美国食品药品管理局（FDA）已批准Embeda（硫酸吗啡，盐酸纳曲酮）缓释胶囊口服用药。Embeda是一种长效、第II阶梯阿片类止痛药，用以缓解需要日夜不断持续以阿片类止痛药治疗较长期的中度至重度疼痛。生产厂家在召开的新闻发布会上声明，Embeda是首个FDA批准的长效阿片类药物，通过压碎服用或咀嚼服用可减少药物偏爱和欣快感。

 

 Embeda含有缓释吗啡颗粒，各颗粒均有一个盐酸纳曲酮（阿片类受体拮抗剂）内核。当按照说明书服用此药时，吗啡成分可缓解疼痛，而隐藏于内部的盐酸纳曲酮则通过全身，无临床作用。这种减少程度的临床意义尚未得到证实，且尚无证据显示Embeda内的纳曲酮可减少药物滥用潜在可能。

FDA批准Embeda是基于12项临床研究的结果，其中有数据证实了该药的有效性和安全性。在一项3期研究中，与安慰剂对照组相比，Embeda治疗显著缓解髋部或膝部因骨关节炎所致的中度至重度疼痛。此外，一项较早期的2期研究数据表明，Embeda与另一种上市的缓释硫酸吗啡胶囊制剂具有生物等效性。

3期研究结果亦显示，EMbeda是安全的，患者在接受12个月的治疗后仍可很好地耐受此药，其整体安全性与阿片类药物最常见的不良事件一致。Embeda临床计划中报告的最常见的不良事件为便秘、恶心和嗜睡。

在对娱乐毒品使用者单独进行的一项研究中，与等剂量的速效硫酸吗啡溶液相比，Embeda压碎后口服可减少药物偏爱和欣快感。这些研究中报告的Embeda在药物偏爱和欣快感方面的减少程度有何临床意义，对此尚未得到证实。

Embeda适宜1日1～2次用药。鉴于该药为缓释药品，不应咀嚼服用、压碎后服用或溶解后服用，原因在于上述用药途径可能会发生潜在致死剂量的吗啡迅速释放和吸收的情况。此外，Embeda不适宜按需服用，且不适用于术后缓解疼痛。

国王制药公司拟于2009年9月推出Embeda。

 

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