Belsomra 苏沃雷生 Suvorexant为新一代新型催眠药物
Pharmacological Class:
Orexin receptor antagonist.

Active Ingredient(s):
Suvorexant 5mg, 10mg, 15mg, 20mg; tablets.

Company
Merck & Co., Inc.
Indication(s):
Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

Pharmacology:
The mechanism by which suvorexant exerts its therapeutic effects in insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.

Clinical Trials:
The efficacy of Belsomra was eva luated in 3 clinical trials in patients with insomnia characterized by difficulties with sleep onset and sleep maintenance.

Two similarly designed, 3-month, randomized, double-blind, placebo-controlled, parallel-group studies were conducted (Study 1 and 2). In both studies, non-elderly adults (ages 18–64) were randomized to Belsomra 20mg (n=291) or placebo (n=449), and elderly adults (ages ≥65) were randomized to Belsomra 15mg (n=202) or placebo (n=318).

In Study 1 and Study 2, Belsomra 15mg or 20mg was superior to placebo for sleep latency as assessed both objectively by polysomnography and subjectively by patient-estimated sleep latency. Belsomra 15mg or 20mg was also superior to placebo for sleep maintenance, as assessed both objectively and subjectively.

In a 1-month crossover study (Study 3), non-elderly adults were randomized to placebo (n=249) or Belsomra 10mg (n=62), 20mg (n=61), or up to 80mg. Results showed Belsomra 10mg and 20mg were superior to placebo for sleep latency and sleep maintenance, as assessed by polysomnography.

Belsomra was also eva luated at doses of 30mg and 40mg in the 3-month placebo-controlled trials. The higher doses were found to have similar efficacy to lower doses, but significantly more adverse effects were reported.

For more clinical trials data, see full labeling.

Legal Classification:
CIV

Adults:
Use lowest effective dose. Take within 30 minutes of bedtime if able to get full night’s sleep (≥7 hours) before awakening. 10mg once per night; may increase if ineffective; max 20mg once daily. Concomitant moderate CYP3A inhibitors: 5mg once daily; max 10mg once daily. Effect may be delayed if taken with or soon after a meal.

Children:
Not established.

Contraindication(s):
Narcolepsy.

Warnings/Precautions:
Monitor for somnolence and CNS depression; discontinue or reduce dose if daytime somnolence develops. Risk of next-day impairment (including impaired driving). Monitor for worsening insomnia or abnormal thinking and behavioral changes. Consider discontinuing if any complex sleep behaviors develop. Depression. Monitor for suicidal ideation. Compromised respiratory function (eg, COPD, obstructive sleep apnea). Increased risk of exposure-related effects in obese women. Reeva luate if unresponsive after 7–10 days of treatment. Severe hepatic impairment: not recommended. Drug or alcohol abusers. Pregnancy (Category C). Nursing mothers.

Interaction(s)
Avoid alcohol. Potentiates CNS depression with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol); may need to adjust doses. Concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, conivaptan): not recommended. Concomitant moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil); use reduced dose (see Adults). May be antagonized by strong CYP3A inducers (eg, rifampin, carbamazepine, phenytoin). Monitor digoxin.

Adverse Reaction(s)
Somnolence, headache, dizziness; CNS depression, daytime impairment, complex sleep-related behaviors (eg, sleep-driving), sleep paralysis, hallucinations, cataplexy-like symptoms.

How Supplied:
Blisters—30

LAST UPDATED:
3/27/2015

新型催眠药物suvorexant获FDA批准
美国食品药品管理局（FDA）批准了一种新型催眠药物suvorexant（Belsomra），该药物属于食欲素受体拮抗剂。
Suvorexant是首个获批的食欲素受体拮抗剂，它通过阻断神经肽食欲素A和B与食欲素受体的结合而抑制神经元对唤醒系统的激活作用。
不过，只有在美国缉毒局（DEA）最终确定该药品是否属于管控物质后，该药品才能上市。据suvorexant生产商默克公司称，FDA建议将其列入管控物质，DEA在今年早些时候提议，按照《管控物质法》应纳入IV类管控物质之列。
默克公司预期，suvorexant将在2014年底或2015年初上市。
默克于2012年提交了批准申请。2013年5月，FDA外周与中枢神经系统药品专家委员会对该公司建议的起始剂量的安全性提出质疑。数月后，FDA建议默克公司对大多数患者的起始剂量设定为10 mg。
该公司此前没有准备生产该剂量的制剂，因此重新设计生产了几种新规格制剂。
目前，据FDA药品评价与研究中心药品评价I室主任Ellis Unger博士称，“FDA批准了4种规格—5、10、15和20mg的Belsomra。”Unger博士在声明中指出，“使用最小有效剂量可减少副作用风险，如次日早晨的困倦。”
FDA和默克公司称，每晚仅需在睡前半小时至起床前至少7小时内服用suvorexant 1片，每天不得超过20 mg。
困倦是最常见的副作用。在FDA要求开展的次日驾驶行为研究中，服用20 mg的患者能力受损。FDA称，应警告服用20 mg的患者次日勿从事驾驶或任何需要警觉的活动。
该药物还可能导致FDA所称的“睡眠驾驶和其他在没有完全觉醒的状态下的复杂行为”，包括做饭和饮食、打电话或性行为。如果出现上述行为，患者及其家人应告知医生。
Suvorexant发放时配送一份患者用药指南，其中包括了详细的安全性信息。
FDA称，尽管针对该药开展了3项试验研究，但均未与其他已获批催眠药物进行对比研究，因此，尚不清楚该药物的对比有效性。