ST LOUIS (MD Consult) - On March 18, 2010, Somaxon Pharmaceuticals announced that the US Food and Drug Administration (FDA) has approved Silenor for the treatment of insomnia characterized by difficulty with sleep maintenance. It is a low-dose (3 mg, 6 mg) tablet formulation of doxepin. Silenor is approved for the treatment of both transient and chronic insomnia in adults, including older adults.

According to Somaxon, sleep-maintenance difficulty, defined as waking frequently during the night and/or waking too early and being unable to return to sleep, is the most commonly reported nighttime symptom of insomnia. In clinical trials, Silenor demonstrated maintenance of sleep into the 7th and 8th hours of the night, with no meaningful evidence of next-day residual effects.

The FDA granted approval for Silenor on the basis of data from clinical trials that included more than 1,000 participants. In trials, Silenor was found to have a favorable safety and tolerability profile. The overall incidence of adverse events with the use of Silenor was comparable with that of placebo, and patients demonstrated no evidence of withdrawal, tolerance, amnesia, or complex sleep behaviors (eg, sleep driving, sleep eating).

Silenor has not been designated as a controlled substance by the US Drug Enforcement Administration because of its demonstrated lack of abuse potential. In addition, in the Silenor clinical development program, no withdrawal effects or other adverse events were observed that were indicative of physical dependence.

Silenor binds with high affinity to histamine receptors. This is believed to be the mechanism by which Silenor promotes the maintenance of sleep.

Health care professionals should be aware that sleep disturbances may be caused by underlying physical and/or psychiatric disorders and that symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated.

Patients should take Silenor only when they are prepared to get a full night's sleep, and the medication should be taken within 30 minutes of bedtime. Patients should be instructed to refrain from drinking alcoholic beverages and taking other drugs that cause drowsiness with Silenor. In addition, they should be told to avoid engaging in hazardous activities such as operating a motor vehicle at night after taking Silenor, and should be cautioned about potential impairment in the performance of such activities that may occur during the day after Silenor ingestion.

Silenor should not be prescribed for patients with untreated narrow-angle glaucoma, severe urinary retention, and severe sleep apnea.

Doxepin, the active ingredient in Silenor, is part of the hypnotic class of medications, according to the drug's prescribing information. Doxepin, at doses 10 to 100 times higher than that contained in Silenor, is used as an antidepressant. In primarily depressed patients, worsening of depression, including suicidal thoughts and actions, has been reported in association with the use of hypnotics. Because a theoretical risk for psychiatric events exists in patients taking hypnotics, clinicians should question their patients about mental illness, suicidal thoughts, and depression before prescribing Silenor.

Somaxon plans to launch Silenor in the United States during the second half of 2010.

 

圣路易斯(MD Consult)——2010年3月18日，Somaxon制药公司(Somaxon Pharmaceuticals)宣布，美国食品药品管理局(FDA)已批准Silenor用于治疗以睡眠维持困难为特征的失眠症。Silenor是一种低剂量(3 mg、6 mg)多塞平片剂，现已获准用于治疗成人(包括老年人)暂时性和慢性失眠症。

 

睡眠维持困难定义为夜间经常觉醒和(或)觉醒过早而无法再次入睡。据Somaxon公司称，该症状是最常报道的夜间失眠症状。临床试验证实，Silenor可使夜间睡眠达到7~8 h且次日无明显的后遗效应表现。

FDA批准Silenor是依据相关的临床试验数据，这些临床试验共纳入受试者逾1,000例。临床试验表明，Silenor有着极优的安全性和耐受性。Silenor治疗组不良事件的总发生率与安慰剂对照组相当，患者无停药反应、耐受、遗忘或复杂的睡眠行为(如梦游驾驶症、梦游饮食症)等表现。

鉴于Silenor经证实不具备滥用可能，美国缉毒局(US Drug Enforcement Administration)一直未将其列为受管制药品。另外，在Silenor的临床研发项目中，未观察到显示躯体依赖的停药反应或其他不良事件。

Silenor与组胺受体具有较高的亲和力。研究认为，该药通过与组胺受体结合这一机制促进睡眠的维持。

医护人员应知道，睡眠紊乱可能由潜在的躯体疾病和(或)精神失常所致，应在对患者进行仔细评估后，方开始失眠症对症治疗。治疗失眠7~10天后无效可能意味着存在原发性精神和(或)医学疾病，应对这类疾病进行评估。

患者应仅在准备好获得整晚睡眠时服用Silenor，而且应在睡前30 min服用。应指导患者在服药期间戒除酒精饮料或停用其他可产生睡意的药物。另外，还应告诉患者避免从事危险作业，如夜间服用Silenor后骑摩托车等，而且应告诫患者白天服用Silenor后从事这类活动可能会带来危害。

对存在未治疗的窄角型青光眼、重度尿潴留及重度睡眠呼吸暂停的患者不应开具Silenor处方。

根据该药品的处方说明，Silenor的活性成分多塞平是催眠类药物的组成部分。多塞平用作抗抑郁药时的剂量较Silenor中的高10~100倍。有研究报道，原发性抑郁症患者抑郁加重(包括自杀意念和行为)与服用催眠药有关。由于服用催眠药的患者理论上存在精神病事件风险，故医生在开具Silenor处方前应询问患者有关精神病、自杀意念和抑郁等情况。

Somaxon公司拟于2010年下半年将Silenor推向美国市场。