苯二氮䓬类药物与阿片类药物同时使用可能导致深度镇静、呼吸抑制、昏迷和死亡。当患者对其他治疗选择疗效不足时，方可选择同时给予苯二氮䓬类和阿片类药物。需将剂量和治疗时间降至最低，并密切观察患者是否有呼吸抑制和镇静的症状及体征。
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Benzodiazepines and opioids should only be given together when the patient has not responded adequately to other treatment options. The dose and duration of treatment should be minimized, and the patient should be closely observed for signs and symptoms of respiratory depression and sedation.
【药品名称】  【Drug name】
通用名称：劳拉西泮片  Generic name: Lorazepam tablets
商品名称：佳普乐  Product Name: Jiapule
英文名称：Lorazepam Tablets  English name: Lorazepam Tablets
汉语拼音：Laolaxipan Pian  Chinese Pinyin: Laolaxipan Pian
【成份】  【Ingredients】
本品主要成份为劳拉西泮。  The main ingredient of this product is lorazepam.
化学名称为： $7-$$7-$7-7- 氯－5－（2－氯苯基）—1，3—二氢—3—羟基— $2\mathrm{H}-1$$2\mathrm{H}-1$2H-12 \mathrm{H}-1 ，4—苯并二氮杂䓬—2—酮。
The chemical name is: $7-$$7-$7-7- chloro-5-(2-chlorophenyl)-1,3-dihydro-3-hydroxy- $2\mathrm{H}-1$$2\mathrm{H}-1$2H-12 \mathrm{H}-1 ,4-benzodiazepine-2-one.
化学结构式为：  The chemical structure is:
分子式： ${\mathrm{C}}_{15}{\mathrm{H}}_{10}{\mathrm{Cl}}_2{\mathrm{N}}_2{\mathrm{O}}_2$${\mathrm{C}}_{15}{\mathrm{H}}_{10}{\mathrm{Cl}}_2{\mathrm{N}}_2{\mathrm{O}}_2$C_(15)H_(10)Cl_(2)N_(2)O_(2)\mathrm{C}_{15} \mathrm{H}_{10} \mathrm{Cl}_{2} \mathrm{~N}_{2} \mathrm{O}_{2}  Molecular formula: ${\mathrm{C}}_{15}{\mathrm{H}}_{10}{\mathrm{Cl}}_2{\mathrm{N}}_2{\mathrm{O}}_2$${\mathrm{C}}_{15}{\mathrm{H}}_{10}{\mathrm{Cl}}_2{\mathrm{N}}_2{\mathrm{O}}_2$C_(15)H_(10)Cl_(2)N_(2)O_(2)\mathrm{C}_{15} \mathrm{H}_{10} \mathrm{Cl}_{2} \mathrm{~N}_{2} \mathrm{O}_{2}
分子量： 321.16  Molecular weight: 321.16
辅料：乳糖、微晶纤维素、波拉克林钾（又名：聚克立林钾）、硬脂酸镁。
Excipients: lactose, microcrystalline cellulose, polacrilin potassium (also known as: polycresol potassium), magnesium stearate.
【性状】本品为白色或类白色片，一侧有＂一＂字刻痕。
[Properties] This product is a white or off-white tablet with a "一" mark on one side.

适用于焦虑障碍的治疗或用于缓解焦虑症状及与抑郁症状相关的焦虑的短期治疗。
Indicated for the treatment of anxiety disorders or for short-term treatment of anxiety symptoms and anxiety associated with depressive symptoms.
劳拉西泮长期应用的效果即应用 4 个月以上的效果还未经系统的临床研究评估。医师应定期重新评估该药对个体患者的有效性。
The effects of long-term use of lorazepam, that is, use for more than 4 months, have not been evaluated in systematic clinical studies. Physicians should periodically reassess the effectiveness of this drug for individual patients.

口服用药。为达到最佳疗效，应根据病人的反应对给药剂量、频度及治疗期限进行个体化调整。
Oral medication. To achieve the best therapeutic effect, the dosage, frequency and duration of treatment should be adjusted individually according to the patient's response.
常规的剂量范围是每天 $2\sim 6\mathrm{mg}(2\sim 6$$2\sim 6\mathrm{mg}(2\sim 6$2∼6mg(2∼62 \sim 6 \mathrm{mg} ~(2 \sim 6 片 $)$$)$)) ~ ，分次服用，最大剂量为睡觉前给予，每日剂量可在 $1\sim 10\mathrm{mg}(1\sim 10$$1\sim 10\mathrm{mg}(1\sim 10$1∼10mg(1∼101 \sim 10 \mathrm{mg} ~(1 \sim 10 片）间变动调整。
The usual dosage range is $2\sim 6\mathrm{mg}(2\sim 6$$2\sim 6\mathrm{mg}(2\sim 6$2∼6mg(2∼62 \sim 6 \mathrm{mg} ~(2 \sim 6 tablets per day $)$$)$)) ~ , taken in divided doses, with the maximum dose given at bedtime, and the daily dose can vary between $1\sim 10\mathrm{mg}(1\sim 10$$1\sim 10\mathrm{mg}(1\sim 10$1∼10mg(1∼101 \sim 10 \mathrm{mg} ~(1 \sim 10 tablets).
对于焦虑症状，大部分患者的初始剂量为每天 $2\sim 3\mathrm{mg}$$2\sim 3\mathrm{mg}$2∼3mg2 \sim 3 \mathrm{mg}（ $2\sim 3$$2\sim 3$2∼32 \sim 3 片），每日两次或三次。由于焦虑或暂时性情景压力引起的失眠患者，每日剂量为 $2\sim 4\mathrm{mg}(2\sim 4$$2\sim 4\mathrm{mg}(2\sim 4$2∼4mg(2∼42 \sim 4 \mathrm{mg}(2 \sim 4 片 $)$$)$)) 单次口服，通常安排在入睡前给药。
For anxiety symptoms, the initial dose for most patients is $2\sim 3\mathrm{mg}$$2\sim 3\mathrm{mg}$2∼3mg2 \sim 3 \mathrm{mg} ( $2\sim 3$$2\sim 3$2∼32 \sim 3 tablets) twice or three times daily. For patients with insomnia due to anxiety or temporary situational stress, the daily dose is $2\sim 4\mathrm{mg}(2\sim 4$$2\sim 4\mathrm{mg}(2\sim 4$2∼4mg(2∼42 \sim 4 \mathrm{mg}(2 \sim 4 tablets $)$$)$)) taken orally as a single dose, usually at bedtime.

对于老年患者或者体弱患者，推荐的初始剂量为 $1\sim 2\mathrm{mg}$$1\sim 2\mathrm{mg}$1∼2mg1 \sim 2 \mathrm{mg}（ $1\sim 2$$1\sim 2$1∼21 \sim 2 片）／日，分次服用，可根据需要及患者的耐受性调整用药剂量。
For elderly or frail patients, the recommended initial dose is $1\sim 2\mathrm{mg}$$1\sim 2\mathrm{mg}$1∼2mg1 \sim 2 \mathrm{mg} ( $1\sim 2$$1\sim 2$1∼21 \sim 2 tablets)/day, taken in divided doses. The dose can be adjusted according to needs and patient tolerance.
应在必要时逐渐增加劳拉西泮的给药剂量而勿突然调整以免不良反应发生。当需要增加劳拉西泮的剂量时，在增加白天剂量之前应首先增加晚上的用药剂量。
The dose of lorazepam should be increased gradually when necessary rather than suddenly to avoid adverse reactions. When the dose of lorazepam needs to be increased, the evening dose should be increased first before the daytime dose.

建议患者在增加剂量或突然停药前应咨询医师。  Advise patients to consult their physician before increasing the dose or abruptly stopping the medication.

苯二氮䓬类药物的大多数不良反应，包括中枢神经系统作用和呼吸系统抑制作用在内，呈剂量依赖性，更严重的不良反应发生于高剂量应用时。
Most adverse reactions of benzodiazepines, including central nervous system effects and respiratory depression, are dose-dependent, with more serious adverse reactions occurring at high doses.

劳拉西泮最常见的不良反应是镇静（ $15.9\mathrm{\%}$$15.9\mathrm{\%}$15.9%15.9 \% ），其次是眩晕（ $6.9\mathrm{\%}$$6.9\mathrm{\%}$6.9%6.9 \% ）、乏力（ $4.2\mathrm{\%}$$4.2\mathrm{\%}$4.2%4.2 \% ）和步态不稳（ $3.4\mathrm{\%}$$3.4\mathrm{\%}$3.4%3.4 \% ）。镇静和步态不稳的发生率随着年龄的增长而增加。
The most common adverse reaction to lorazepam is sedation ( $15.9\mathrm{\%}$$15.9\mathrm{\%}$15.9%15.9 \% ), followed by dizziness ( $6.9\mathrm{\%}$$6.9\mathrm{\%}$6.9%6.9 \% ), fatigue ( $4.2\mathrm{\%}$$4.2\mathrm{\%}$4.2%4.2 \% ), and gait disturbance ( $3.4\mathrm{\%}$$3.4\mathrm{\%}$3.4%3.4 \% ). The incidence of sedation and gait disturbance increases with age.

包括劳拉西泮在内的苯二氮䓬类药物的其它不良反应为疲劳、睹睡、遗忘、记忆力损伤、精神错乱、定向力障碍、抑郁、抑郁暴露、脱抑制、欣快感、自杀意念／企图、共济失调、虚弱、锥体外系反应、惊厥／癫痫发作、震颤、眩晕、眼功能／视力障碍（包括复视和视力模糊 ）构音障碍、发音不清、性欲改变、阳䖰、性欲高潮降低；头痛、昏迷、呼吸抑制、呼吸暂停、睡眠呼吸暂停恶化、阻塞性肺病恶化；胃肠道症状包括恶心、食欲改变、便秘、黄疸、胆红素升高、肝脏转氨酶升高、碱性磷酸酯酶升高；高敏反应、过敏性／过敏样反应；皮肤症状、过敏性皮肤反应、脱发；SIADH、低钠血症；血小板减少症、粒细胞缺乏症、各类血细胞减少；低温症；以及自主神经系统表现。可能发生自相矛盾的反应包括焦虑、激动、激越、敌意、攻击性、暴怒、睡眠障碍／失眠、性唤起和幻觉。可能使血压小幅降低或者发生
Other adverse reactions of benzodiazepines, including lorazepam, are fatigue, somnolence, amnesia, memory impairment, confusion, disorientation, depression, depression-unmasking, disinhibition, euphoria, suicidal ideation/attempts, ataxia, weakness, extrapyramidal reactions, convulsions/seizures, tremor, vertigo, eye function/visual disturbances (including diplopia and blurred vision), dysarthria, slurred speech, changes in libido, impotence, decreased orgasm; headache, coma, respiratory depression, apnea, worsening of sleep apnea, worsening of obstructive pulmonary disease; gastrointestinal symptoms including nausea, change in appetite, constipation, jaundice, increased bilirubin, increased liver transaminases, increased alkaline phosphatase; hypersensitivity reactions, allergic/anaphylactoid reactions; skin symptoms, allergic skin reactions, alopecia; SIADH, hyponatremia; thrombocytopenia, agranulocytosis, cytopenias; hypothermia; and autonomic nervous system manifestations. Paradoxical reactions may occur including anxiety, agitation, agitation, hostility, aggression, rage, sleep disturbance/insomnia, sexual arousal, and hallucinations.
低血压症，但通常无临床显著性，可能与应用劳拉西泮产生的抗焦虑作用相关。
Hypotension, but usually not clinically significant, may be related to the anxiolytic effects of lorazepam.
【禁忌】对本品任何成分及苯二氮䓬类药物过敏者、急性闭角型青光眼患者禁用。
[Contraindications] This product is contraindicated for patients who are allergic to any ingredient of this product or benzodiazepines, or patients with acute angle-closure glaucoma.

警告：包括劳拉西泮在内的苯二氮䓬类药物不论是单独应用或与其它中枢抑制剂联合应用均有导致致命性呼吸抑制的潜在危险性。应用包括劳拉西泮在内的苯二氮䓬类药物可能导致生理和心理依赖性。
Warning: Benzodiazepines, including lorazepam, have the potential to cause fatal respiratory depression, whether used alone or in combination with other central nervous system depressants. The use of benzodiazepines, including lorazepam, may lead to physical and psychological dependence.
1．本品按第二类精神药品管理。  1. This product is managed as a Category II psychotropic drug.
2．在包括劳拉西泮在内的苯二氮䓬类药物应用过程中，患者先前已有的抑郁可能出现或加重。本品不作为原发性抑郁障碍或精神疾病的治疗。抑郁患者有自杀的可能，在没有足够的抗抑郁药治疗的情况下不应将苯二氮䓬类药物给予这类患者。
2. During the use of benzodiazepines, including lorazepam, patients' pre-existing depression may reappear or worsen. This product is not used to treat primary depressive disorders or mental illnesses. Depressed patients may commit suicide, and benzodiazepines should not be given to such patients without adequate antidepressant treatment.
3．呼吸功能不全（COPD、睡眠呼吸暂停综合症）患者慎用。
3. Use with caution in patients with respiratory insufficiency (COPD, sleep apnea syndrome).
4．服用本品者不能驾车或操纵重型机器。  4. People taking this product should not drive a car or operate heavy machinery.
5．服用本品者对酒精和其他中枢神经抑制剂的耐受性会降低。
5. People who take this product will have reduced tolerance to alcohol and other central nervous system depressants.
6．通常要求苯二氮䓬类药物的处方量仅为短期应用（例如 $2\sim 4$$2\sim 4$2∼42 \sim 4 周）。应该在延长治疗时间前重新评价持续治疗的必要性。不推荐本品的长期持续性应用。戒断症状（例如反跳性失眠）在短至一周的推荐剂量治疗停药后即可出现。应避免本品的突然停药，长期治疗后应逐渐减少用药量。连续服用本品的患者突然停药，会出现戒断综合症的表现（包括头痛、焦虑、紧张、抑郁、失眠、不安、精神错乱、易激慧、出汗、反跳现象、烦躁不安、头昏、非真实感、人格解体、听觉过敏、麻木／肢端麻刺感、对光和噪音的高敏反应和生理触觉／知觉变化、不随意运动、恶心、呕吐、腹泻、厌食、幻觉／妄想、惊厥／癲痫发作、震颤、腹部痉挛、肌痛、激动不安、心悸、心动过速、惊恐发作、眩晕、反射六进、短期记忆缺失和高热。对于先前患有癫痫的患者或正在服用诸如抗抑郁药类降低惊厥阈值的其它药物的患者惊厥／癲痛发作可能更常见。），因此需停药时应先减量后再逐渐停药。有证据显示服用本品可产生对苯二氮䓬类药物镇静作用的耐受性。
6. Benzodiazepines are usually prescribed for short-term use only (e.g., $2\sim 4$$2\sim 4$2∼42 \sim 4 weeks). The need for continued treatment should be re-evaluated before extending treatment. Long-term continuous use of this product is not recommended. Withdrawal symptoms (e.g., rebound insomnia) can occur after discontinuation of treatment at the recommended dose for as little as one week. Sudden discontinuation of this product should be avoided, and the dosage should be gradually reduced after long-term treatment. Patients who have been taking this drug continuously and suddenly stop taking it may experience symptoms of withdrawal syndrome (including headache, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, sweating, rebound phenomenon, irritability, dizziness, unreality, depersonalization, hyperacusis, numbness/tingling in the extremities, hypersensitivity to light and noise and changes in physical touch/perception, involuntary movements, nausea, vomiting, diarrhea, anorexia, hallucinations/delusions, convulsions/seizures, tremors, abdominal cramps, myalgia, agitation, palpitations, tachycardia, panic attacks, vertigo, hesitant reflexes, short-term memory loss and high fever. Convulsions/seizures may be more common in patients with previous epilepsy or those who are taking other drugs that lower the seizure threshold, such as antidepressants.), so when stopping the drug, the dosage should be reduced first and then gradually stopped. There is evidence that taking this drug can produce tolerance to the sedative effects of benzodiazepines.
7．有药物或酒精依赖倾向的患者服用本品时应严密监测，以防止依赖性产生。
7. Patients with drug or alcohol dependence tendencies should be closely monitored when taking this product to prevent dependence.
8．有些服用本品的患者出现白细胞减少，有些患者的乳酸脱氢酶水平升高，推荐长期用药的患者定期进行血细胞计数检查和肝功能检查。
8. Some patients taking this product have leukopenia, and some patients have elevated lactate dehydrogenase levels. It is recommended that patients taking this product for a long time undergo regular blood cell count and liver function tests.
9．对体弱的患者应酌情减少用量。应不时检査这些患者的情况，按照患者的反应仔细调整其用药剂量，起始剂量不应该超过 2 mg 。偶有苯
9. The dosage should be reduced as appropriate for weak patients. The condition of these patients should be checked from time to time, and the dosage should be carefully adjusted according to the patient's response. The initial dose should not exceed 2 mg.
二氮䓬类药物应用后出现自相矛盾反应的报告，儿童和老年患者更可能产生这类反应，如发生，应停止用药。
There have been reports of paradoxical reactions to the use of diazepam. Children and elderly patients are more likely to experience such reactions. If they occur, the drug should be discontinued.
10．肝功能损害偶可引起本品清除半衰期的延长。对于肾脏或肝脏功能受损的患者应注意观察。与其他苯二氮䓬类药物类似，劳拉西泮可使肝性脑病恶化；因此，有严重肝脏功能不全和／或肝性脑病的患者应慎用本品。对于严重肝脏功能不全的患者，应根据患者的反应仔细调整用药剂量；可能应用低剂量就已足够。
10. Impairment of liver function may occasionally cause a prolongation of the elimination half-life of this product. Patients with impaired kidney or liver function should be carefully observed. Similar to other benzodiazepines, lorazepam can worsen hepatic encephalopathy; therefore, patients with severe liver dysfunction and/or hepatic encephalopathy should use this product with caution. For patients with severe liver dysfunction, the dosage should be carefully adjusted according to the patient's response; a low dose may be sufficient.
11．以 $6\mathrm{mg}/\mathrm{kg}/$$6\mathrm{mg}/\mathrm{kg}/$6mg//kg//6 \mathrm{mg} / \mathrm{kg} / 日的剂量服用劳拉西泮1年以上可引起大鼠食管扩张。不引起扩张的剂量是 $1.25\mathrm{mg}/\mathrm{kg}/$$1.25\mathrm{mg}/\mathrm{kg}/$1.25mg//kg//1.25 \mathrm{mg} / \mathrm{kg} / 日（大约是人最大治疗剂量 $10\mathrm{mg}/$$10\mathrm{mg}/$10mg//10 \mathrm{mg} /日的6倍）。只有在首次观察到此现象的两个月内停止治疗时这种现象才是可逆的。这种现象的临床意义尚不可知。然而，劳拉西泮用于长期治疗以及用于老年人要谨慎，同时应时常监测上消化道疾病症状。
11. Lorazepam administration for more than 1 year at a dose of $6\mathrm{mg}/\mathrm{kg}/$$6\mathrm{mg}/\mathrm{kg}/$6mg//kg//6 \mathrm{mg} / \mathrm{kg} / days caused esophageal dilatation in rats. The dose that did not cause dilatation was $1.25\mathrm{mg}/\mathrm{kg}/$$1.25\mathrm{mg}/\mathrm{kg}/$1.25mg//kg//1.25 \mathrm{mg} / \mathrm{kg} / days (approximately 6 times the maximum therapeutic dose in humans $10\mathrm{mg}/$$10\mathrm{mg}/$10mg//10 \mathrm{mg} / days). This phenomenon was reversible only if treatment was stopped within 2 months of the first observation. The clinical significance of this phenomenon is unknown. However, lorazepam should be used with caution for long-term treatment and in the elderly, and symptoms of upper gastrointestinal disorders should be monitored frequently.

12．苯二氮䓬类和阿片类药物同时使用会增加呼吸抑制的风险，因为药物影响中枢神经系统中控制呼吸的不同受体。苯二氮䓬类影响GAB AA 受体，阿片类药物主要影响 $\mu$$\mu$mu\mu 受体。当苯二氮䓬类和阿片类药物同时使用时，苯二氮䓬类药物可能会令阿片类药物相关的呼吸抑制作用显著增加，因此应将剂量和治疗时间降至最低，并密切观察患者是否有呼吸抑制和镇静的症状和体征。
12. The concurrent use of benzodiazepines and opioids increases the risk of respiratory depression because the drugs affect different receptors in the central nervous system that control breathing. Benzodiazepines affect GAB AA receptors, while opioids primarily affect $\mu$$\mu$mu\mu receptors. When benzodiazepines and opioids are used concurrently, benzodiazepines may significantly increase opioid-related respiratory depression, so the dose and duration of treatment should be minimized, and patients should be closely observed for signs and symptoms of respiratory depression and sedation.
【孕妇及哺乳期妇女用药】  【Use during pregnancy and lactation】
劳拉西泮及其葡萄糖醛酸结合物可通过胎盘屏障。有报道母亲在胎儿出生前几个星期连续摄入苯二氯䓬类药物，婴儿在出生后一段时间有戒断症状。已有报道母亲在妊娠后期或在生产中接受了苯二氮䓬类药物的新生儿有活动减退、肌张力减退、低温、呼吸抑制、窒息、喂养困难和对冷剌激的代谢反应损害的症状发生。
Lorazepam and its glucuronide conjugate can cross the placental barrier. There are reports that mothers who continuously ingest benzodiazepines for several weeks before the birth of the fetus have withdrawal symptoms for a period of time after birth. There have been reports that newborns whose mothers received benzodiazepines in late pregnancy or during delivery have symptoms of hypoactivity, hypotonia, hypothermia, respiratory depression, suffocation, feeding difficulties, and impaired metabolic response to cold stimulation.

人乳汁中可检测到劳拉西泮，因此除非对于妇女的可预期利益超过对于婴儿的潜在危险，否则哺乳期妇女不应服用劳拉西泮。已有哺乳母亲服用苯二氮䓬类药物而出现新生儿镇静和哺乳不能的现象。
Lorazepam can be detected in human breast milk, so unless the expected benefit to the woman outweighs the potential risk to the infant, women who are breastfeeding should not take lorazepam. Neonatal sedation and failure to breastfeed have been reported in breastfeeding mothers taking benzodiazepines.
【儿童用药】12岁以下儿童应用劳拉西泮的安全性和有效性还未确立。
[Use in Children] The safety and effectiveness of lorazepam in children under 12 years of age have not been established.
【老年用药】临床研究结果通常不足以确定 65 岁及以上的老年人与年轻个体对药物的反应不同，但是，可观察到随着年龄的增加镇静和步态不稳的发生增多。
[Use in the Elderly] Clinical study results are generally insufficient to determine whether elderly people aged 65 years and over respond differently to drugs than younger individuals; however, it can be observed that the incidence of sedation and gait instability increases with age.
年龄似乎对劳拉西泮的药代动力学没有显著影响。  Age does not appear to have a significant effect on the pharmacokinetics of lorazepam.
老年患者，通常肝肾功能有所降低，可能对药物更敏感（如镇静作用）。因此老年患者的剂量选择应谨慎，较低剂量可能已经足够。
Elderly patients, who often have reduced liver and kidney function, may be more sensitive to the drug (e.g., sedation). Therefore, dose selection for elderly patients should be cautious, and lower doses may be sufficient.
【药物相互作用】和其他苯二氮䓬类药物一样，本品与其它中枢神经系统抑制剂如酒精、巴比妥类、抗精神病药、镇静／催眠药、抗焦虑药、抗抑郁药、麻醉性镇痛药、镇静性抗组胺药、抗惊厥药和麻醉剂联合应用时可使中枢神经系统抑制剂的作用增强。
[Drug Interactions] Like other benzodiazepines, this product can enhance the effects of central nervous system depressants when used in combination with other central nervous system depressants such as alcohol, barbiturates, antipsychotics, sedatives/hypnotics, anxiolytics, antidepressants, narcotic analgesics, sedative antihistamines, anticonvulsants and anesthetics.

劳拉西泮与氯氮平合用可能产生显著的镇静、过量唾液分泌和运动失调作用。
Concomitant use of lorazepam and clozapine may produce significant sedation, excessive salivation, and ataxia.
劳拉西泮与丙戊酸盐合用可能导致劳拉西泮的血浆药物浓度增加，清除率降低。当与丙戊酸盐合用时，应将劳拉西泮的给药剂量约降低至原来剂量的 $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% 。
Co-administration of lorazepam with valproate may result in increased plasma concentrations of lorazepam and decreased clearance. When co-administered with valproate, the lorazepam dose should be reduced to approximately $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% of the original dose.

劳拉西泮与丙磺舒联合应用时，由于半衰期的延长和总清除率的降低，可能导致劳拉西泮起效更迅速或作用时间延长。当与丙磺舒合用时，需要将劳拉西泮的给药剂量约降低至原来剂量的 $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% 。
When lorazepam is used in combination with probenecid, the half-life is prolonged and the total clearance is reduced, which may lead to a more rapid onset or prolonged duration of action of lorazepam. When used in combination with probenecid, the dosage of lorazepam needs to be reduced to approximately $50\mathrm{\%}$$50\mathrm{\%}$50%50 \% of the original dosage.

应用茶碱或氨茶碱可能降低包括劳拉西泮在内的苯二氮䓬类药物的镇静作用。
Administration of theophylline or aminophylline may reduce the sedative effects of benzodiazepines, including lorazepam.
【药物过量】在药品上市后的应用中，劳拉西泙的过量应用主要发生在与酒精和／或其它药物的联合用药情况。因此，在处理药物过量时应始终谨记患者可能在同时服用多种药物。
[Overdose] In post-marketing applications, lorazepam overdose mainly occurred in combination with alcohol and/or other drugs. Therefore, when dealing with overdose, it should always be kept in mind that the patient may be taking multiple drugs at the same time.

苯二氮䓬类药物的过量症状通常表现在对中枢神经系统不同程度的抑制上，从嗜睡到昏迷。轻度症状包括嗜睡，思维混乱和自相矛盾的反应、构音障碍和昏睡。更严重的症状特别是与其他的药品或酒精同时服用时，症状可能包含运动失调，张力减退，低血压，心血管系统抑制、呼吸抑制、催眠状态，1－3度昏迷和死亡。
Symptoms of benzodiazepine overdose usually manifest in varying degrees of central nervous system depression, ranging from drowsiness to coma. Mild symptoms include drowsiness, confusion and paradoxical responses, dysarthria, and stupor. More severe symptoms, especially when taken with other drugs or alcohol, may include ataxia, hypotonia, hypotension, cardiovascular depression, respiratory depression, hypnotic state, 1-3 degree coma, and death.

对过量的处理推荐常规的支持疗法和对症治疗：监测患者的生命体征和对患者进行密切观察。当有抽吸危险时，不推荐应用催吐治疗。如果给药后不久就有症状的患者，可采用洗胃疗法。服用活性炭也可能减少药物的吸收。低血压，尽管不太可能发生，通常用酒石酸去甲肾上腺素注射剂进行治疗。劳拉西泮的可透析性差。劳拉西泮的非活性代谢产物葡萄糖醛酸劳拉西泮可能具有较高的可透析性。
General supportive and symptomatic treatment is recommended for overdose management: monitor vital signs and observe the patient closely. Inducing vomiting is not recommended when there is a risk of aspiration. Gastric lavage may be used if the patient becomes symptomatic soon after administration. Administration of activated charcoal may also reduce absorption of the drug. Hypotension, although unlikely, is usually treated with injection of norepinephrine tartrate. Lorazepam is poorly dialyzable. The inactive metabolite of lorazepam, lorazepam glucuronide, may be more dialyzable.

苯二氮䓬拮抗剂氟马西尼可以作为住院患者苯二氮䓬类药物过量治疗时的辅助措施，而非作为替代。处方者应该考虑到氟马西尼治疗相关的癫痫发作的危险性，特别是对于长期使用苯二氮䓬类药物的患者和环类抗抑郁药过量使用时，应用氟马西尼前应参考完整的氟马西尼说明书。
The benzodiazepine antagonist flumazenil can be used as an adjunct to the treatment of benzodiazepine overdose in hospitalized patients, not as a replacement. Prescribers should consider the risk of seizures associated with flumazenil treatment, particularly in patients with long-term benzodiazepine use and in cases of overdose with cyclic antidepressants, and should refer to the full flumazenil package insert before using flumazenil.

滥用：劳拉西泮有滥用的可能性，尤其是有药物或酒精依赖倾向的患者。
Abuse: Lorazepam has the potential for abuse, particularly in patients with a history of drug or alcohol dependence.
依赖：使用包括劳拉西泮在内的苯二氮䓬类药物，可能导致生理和心理依赖。依赖性风险随着剂量和持续时间的增加而增加，并且在有药物或酒精依赖倾向或有显著人格障碍的患者中进一步增加。若劳拉西泮剂量适当且用于短期治疗，依赖性风险则降低。易上瘾的患者 （如有药物或酒精依赖倾向者）在接受劳拉西泙或其他精神类药物治疗时，应严密监测。
Dependence: Use of benzodiazepines, including lorazepam, may result in physical and psychological dependence. The risk of dependence increases with dose and duration and is further increased in patients with a predisposition to drug or alcohol dependence or significant personality disorders. The risk of dependence is reduced if lorazepam is used in appropriate doses and for short-term treatment. Patients who are susceptible to addiction (such as those with a predisposition to drug or alcohol dependence) should be closely monitored while receiving lorazepam or other psychotropic medications.

药理作用  Pharmacological Action
临床研究显示，健康志愿者单次服用高剂量劳拉西泮，有中枢镇静作用，对呼吸和心血管系统未见影响。
Clinical studies have shown that a single high-dose dose of lorazepam in healthy volunteers has a central nervous system sedative effect, but has no effect on the respiratory and cardiovascular systems.
毒理研究  Toxicology studies
生殖毒性 在小鼠、大鼠和家兔中进行了生殖毒性试验，家兔中偶见多种异常表现（跗骨、胫骨中骨缩小、四肢转动不良、腹裂、颉骨畸形、小眼球等），但无剂量依赖性。剂量高于 $40\mathrm{mg}/\mathrm{kg}$$40\mathrm{mg}/\mathrm{kg}$40mg//kg40 \mathrm{mg} / \mathrm{kg} 时，出现胎仔吸收，胎仔丢失率增加。
Reproductive toxicity Reproductive toxicity tests were conducted in mice, rats and rabbits. Various abnormalities were occasionally observed in rabbits (tarsal bones, tibia bone reduction, limb rotation malfunction, gastroschisis, antrum deformity, microphthalmia, etc.), but there was no dose dependence. When the dose was higher than $40\mathrm{mg}/\mathrm{kg}$$40\mathrm{mg}/\mathrm{kg}$40mg//kg40 \mathrm{mg} / \mathrm{kg} , fetal resorption occurred and the fetal loss rate increased.

以上发现的临床意义尚不清楚，但有多个研究提示，在妊娠初期使用镇静催眠剂（利眠宁、安定、眠尔通）可使先天畸形发生的危险性增加。由于此类药物通常不用于紧急状态下，因此在妊娠初期应避免使用劳拉西泙。
The clinical significance of the above findings is unclear, but several studies have suggested that the use of sedative hypnotics (chlordiazepoxide, diazepam, meprobamate) in early pregnancy may increase the risk of congenital malformations. Because these drugs are not usually used in emergencies, lorazepam should be avoided in early pregnancy.

致癌作用 在大鼠中进行的给药周期 18 个月的试验中未见致癌作用。
Carcinogenicity No carcinogenicity was observed in rats after an 18-month dosing period.

据国外文献报道：口服劳拉西泮后吸收迅速，绝对生物利用度为 $90\mathrm{\%}$$90\mathrm{\%}$90%90 \% 。血药浓度峰值出现在服药后大约 2 小时。口服 2 mg 劳拉西泮后的血浆药物峰浓度约为 $20\mathrm{ng}/\mathrm{ml}$$20\mathrm{ng}/\mathrm{ml}$20ng//ml20 \mathrm{ng} / \mathrm{ml} 。
According to foreign literature reports: Lorazepam is rapidly absorbed after oral administration, and its absolute bioavailability is $90\mathrm{\%}$$90\mathrm{\%}$90%90 \% . The peak blood concentration occurs about 2 hours after taking the drug. The peak plasma drug concentration after oral administration of 2 mg of lorazepam is approximately $20\mathrm{ng}/\mathrm{ml}$$20\mathrm{ng}/\mathrm{ml}$20ng//ml20 \mathrm{ng} / \mathrm{ml} .

人体血浆中游离的劳拉西泮的平均消除半衰期大约为 12 小时，主要代谢产物葡萄糖醛酸劳拉西泮约为 18 小时。在临床相关的血药浓度水平时，劳拉西泮的血浆蛋白结合率约为 $85\mathrm{\%}$$85\mathrm{\%}$85%85 \% 。劳拉西泮在3—羟基位迅速与葡萄糖醛酸结合形成葡萄糖醛酸盐，然后在尿液中排泄。葡萄糖醛酸劳拉西泮在动物身上未见明显的中枢神经系统活性。
The average elimination half-life of free lorazepam in human plasma is approximately 12 hours, and the major metabolite lorazepam glucuronide is approximately 18 hours. At clinically relevant blood drug concentration levels, the plasma protein binding rate of lorazepam is approximately $85\mathrm{\%}$$85\mathrm{\%}$85%85 \% . Lorazepam rapidly binds to glucuronic acid at the 3-hydroxy position to form glucuronide, which is then excreted in the urine. Lorazepam glucuronide has no significant central nervous system activity in animals.

劳拉西泮的血浆药物水平与给药剂量成比例。没有证据表明服用长达 6 个月会产生过量蓄积作用。
Plasma levels of lorazepam are proportional to the dose administered. There is no evidence of excessive accumulation with administration for up to 6 months.
对年轻和老年受试者进行的比较研究结果显示：年龄的增长对劳拉西泮的药代动力学未见显著影响。但是在一项关于单剂量静脉注射A tivan注射液 $1.5-3\mathrm{mg}$$1.5-3\mathrm{mg}$1.5-3mg1.5-3 \mathrm{mg} 的研究中发现，与 15 例 $19\sim 38$$19\sim 38$19∼3819 \sim 38 岁年龄组比较， 15 例 $60\sim 84$$60\sim 84$60∼8460 \sim 84 岁老年年龄组的劳拉西泮人体平均总清除率降低 $20\mathrm{\%}$$20\mathrm{\%}$20%20 \% 。
Comparative studies of young and elderly subjects have shown that increasing age has no significant effect on the pharmacokinetics of lorazepam. However, in a study of a single dose of intravenous Ativan injection $1.5-3\mathrm{mg}$$1.5-3\mathrm{mg}$1.5-3mg1.5-3 \mathrm{mg} , it was found that the mean total clearance of lorazepam in the elderly group of 15 $60\sim 84$$60\sim 84$60∼8460 \sim 84 years old was reduced compared with that in the 15 $19\sim 38$$19\sim 38$19∼3819 \sim 38 year old group $20\mathrm{\%}$$20\mathrm{\%}$20%20 \% .
【贮藏】密封，不超过 ${25}^{\circ }\mathrm{C}$${25}^{\circ }\mathrm{C}$25^(@)C25^{\circ} \mathrm{C} 保存。  【Storage】Sealed and stored for no more than ${25}^{\circ }\mathrm{C}$${25}^{\circ }\mathrm{C}$25^(@)C25^{\circ} \mathrm{C} years.
【包装】药用铝箔和聚氯乙烯固体药用硬片，外加药用固体纸袋装硅胶干燥剂和聚酯／铝／聚乙烯药品包装用复合膜。
[Packaging] Medicinal aluminum foil and solid polyvinyl chloride medicinal hard tablets, plus medicinal solid paper bags filled with silica gel desiccant and polyester/aluminum/polyethylene composite film for pharmaceutical packaging.
10 片／板／盒、 10 片／板 $\times 2$$\times 2$xx2\times 2 板／盒、 10 片／板 $\times 10$$\times 10$xx10\times 10 板／盒； 12 片／板／盒、 12 片／板 $\times 2$$\times 2$xx2\times 2 板／盒、 12 片／板 $\times 3$$\times 3$xx3\times 3 板／盒、 12 片／板 $\times 4$$\times 4$xx4\times 4 板／盒； 14 片／板／盒、 14 片／板 $\times 2$$\times 2$xx2\times 2 板／盒。
10 pieces/board/box, 10 pieces/board $\times 2$$\times 2$xx2\times 2 board/box, 10 pieces/board $\times 10$$\times 10$xx10\times 10 board/box; 12 pieces/board/box, 12 pieces/board $\times 2$$\times 2$xx2\times 2 board/box, 12 pieces/board $\times 3$$\times 3$xx3\times 3 board/box, 12 pieces/board $\times 4$$\times 4$xx4\times 4 board/box; 14 pieces/board/box, 14 pieces/board $\times 2$$\times 2$xx2\times 2 board/box.
【有效期】 24 个月  【Validity period】 24 months
【执行标准】YBH03892024  【Implementation standard】YBH03892024
【批准文号】国药准字H20060105  【Approval number】National Medicine Standard H20060105
【药品上市许可持有人】  【Drug Marketing Authorization Holder】
名 称：山东信谊制药有限公司  Name: Shandong Xinyi Pharmaceutical Co., Ltd.
注册地址：平原县兴平路 1 号  Registered address: No. 1 Xingping Road, Pingyuan County
邮政编码： 253100  Postal Code: 253100
联系方式：0534－2160269  Contact: 0534-2160269
传 真：0534－2160268  Fax: 0534-2160268
网 址：www．sdsine．com  Website: www.sdsine.com

【生产企业】  【Manufacturer】
企业名称：山东信谊制药有限公司  Company Name: Shandong Xinyi Pharmaceutical Co., Ltd.
生产地址：平原县兴平路 1 号  Production address: No. 1 Xingping Road, Pingyuan County
邮政编码： 253100  Postal Code: 253100
联系方式：0534－2160269  Contact: 0534-2160269
传 真：0534－2160268  Fax: 0534-2160268
网 址：www．sdsine．com  Website: www.sdsine.com

请仔细阅读说明书并在医师指导下使用  Please read the instructions carefully and use under the guidance of a physician
【药品名称】  【Drug name】
通用名称：佐匹克隆片  Generic name: Zopiclone tablets
商品名称：三辰  Product Name: Sanchen
英文名称：Zopiclone Tablets  English name: Zopiclone Tablets
汉语拼音：Zuopikelong Pian  Chinese Pinyin: Zuopikelong Pian
【成份】  【Ingredients】
本品主要成份为佐匹克隆。  The main ingredient of this product is zopiclone.
化学名称为：6－（5－氯吡啶－2－基）－7－［（4－甲基哌嗪－1－基）甲酰氧基］－5，6－二氢吡咯并［3，4－b］吡嗪－5－酮
Chemical name: 6-(5-chloropyridin-2-yl)-7-[(4-methylpiperazin-1-yl)formyloxy]-5,6-dihydropyrrolo[3,4-b]pyrazin-5-one

化学结构式：  Chemical structure:

分子式： ${\mathrm{C}}_{17}{\mathrm{H}}_{17}{\mathrm{ClN}}_6{\mathrm{O}}_3$${\mathrm{C}}_{17}{\mathrm{H}}_{17}{\mathrm{ClN}}_6{\mathrm{O}}_3$C_(17)H_(17)ClN_(6)O_(3)\mathrm{C}_{17} \mathrm{H}_{17} \mathrm{ClN}_{6} \mathrm{O}_{3}  Molecular formula: ${\mathrm{C}}_{17}{\mathrm{H}}_{17}{\mathrm{ClN}}_6{\mathrm{O}}_3$${\mathrm{C}}_{17}{\mathrm{H}}_{17}{\mathrm{ClN}}_6{\mathrm{O}}_3$C_(17)H_(17)ClN_(6)O_(3)\mathrm{C}_{17} \mathrm{H}_{17} \mathrm{ClN}_{6} \mathrm{O}_{3}
分子量： 388.81  Molecular weight: 388.81
【性状】  【Properties】
本品为薄膜衣片，除去包衣后显白色或类白色。  This product is a film-coated tablet, which appears white or off-white after removing the coating.
【适应症】  【Indications】
本品仅限应用在以下严重睡眠障碍的治疗中：  This product is limited to the treatment of the following severe sleep disorders:

【规格】（1） 3.75 mg （2） 7.5 mg
[Specifications] (1) 3.75 mg (2) 7.5 mg
【用法用量】  【Usage and Dosage】
用法：口服  Usage: Oral
剂量：  dose:
年龄低于 65 岁的成年人：每日 7.5 mg 。
Adults under 65 years of age: 7.5 mg daily.
年龄高于65岁的老年人：推荐剂量为每日 3.75 mg ，经评估必要时可以增加至 7.5 mg 。
Elderly people over 65 years old: The recommended dose is 3.75 mg per day, which can be increased to 7.5 mg if necessary after evaluation.

肝脏或呼吸功能损害的患者：推荐剂量为每日 3.75 mg 。
Patients with hepatic or respiratory impairment: The recommended dose is 3.75 mg per day.
肾脏功能不全的患者：推荐起始剂量为每日 3.75 mg 。
Patients with renal impairment: The recommended starting dose is 3.75 mg per day.
超过 65 岁的人群及高风险人群的最佳剂量为 3.75 mg 。量不应超过 7.5 mg 。应在晚上临睡前服药，按单次摄入剂量服用，同一晚不得再次服用。
The optimal dose for people over 65 years of age and those at high risk is 3.75 mg. The dose should not exceed 7.5 mg. The medication should be taken at night before going to bed, as a single intake dose, and should not be taken again on the same night.

本品不用于18岁以下儿童和青少年。  This product is not intended for use in children and adolescents under 18 years of age.
治疗持续时间：  Duration of treatment:
治疗持续时间应该尽可能短，从数天到4周，包括减药期（参见【注意事项】
The duration of treatment should be as short as possible, from a few days to 4 weeks, including a taper period (see Precautions).

必须将治疗持续时间告知患者：  Patients must be informed of the duration of treatment:
短暂性失眠症的治疗持续时间为2－5天（比如，旅行导致的失眠症）。
The duration of treatment for transient insomnia (e.g. travel-induced insomnia) is 2-5 days.
短期失眠症的治疗持续时间为2－3周（比如，发生严重事件而导致的失眠症）
Treatment of short-term insomnia lasts 2-3 weeks (e.g., insomnia caused by a serious incident)

在一些情况下，可能有必要延长治疗持续时间，以至于超过推荐的治疗时间。应对患者的状态进行持续的观察与评估。
In some cases, it may be necessary to prolong the duration of treatment beyond the recommended duration. The patient's condition should be continuously observed and evaluated.
【不良反应】  【Adverse Reactions】
使用时适用如下频率等级：  The following frequency levels apply when used:
十分常见 $\ge 10\mathrm{\%}$$\ge 10\mathrm{\%}$>= 10%\geq 10 \% ；常见 $\ge 1$$\ge 1$>= 1\geq 1 并且 $<10\mathrm{\%}$$<10\mathrm{\%}$< 10%<10 \% ；偶见 $\ge 0.1$$\ge 0.1$>= 0.1\geq 0.1 并且 $<1\mathrm{\%}$$<1\mathrm{\%}$< 1%<1 \% ；罕见 $\ge 0.01$$\ge 0.01$>= 0.01\geq 0.01 并且 $<0.1\mathrm{\%}$$<0.1\mathrm{\%}$< 0.1%<0.1 \% ；十分罕见 $<0.01\mathrm{\%}$$<0.01\mathrm{\%}$< 0.01%<0.01 \% ，未知（不能从已知数据作出评估）。
Very common $\ge 10\mathrm{\%}$$\ge 10\mathrm{\%}$>= 10%\geq 10 \% ; Common $\ge 1$$\ge 1$>= 1\geq 1 and $<10\mathrm{\%}$$<10\mathrm{\%}$< 10%<10 \% ; Uncommon $\ge 0.1$$\ge 0.1$>= 0.1\geq 0.1 and $<1\mathrm{\%}$$<1\mathrm{\%}$< 1%<1 \% ; Rare $\ge 0.01$$\ge 0.01$>= 0.01\geq 0.01 and $<0.1\mathrm{\%}$$<0.1\mathrm{\%}$< 0.1%<0.1 \% ; Very rare $<0.01\mathrm{\%}$$<0.01\mathrm{\%}$< 0.01%<0.01 \% ; Unknown (cannot be estimated from known data).

精神疾病  Mental illness
偶见：梦魘、激动  Occasionally seen: nightmare, excitement
罕见：意识模糊状态、性欲障碍、易激惹、攻击、幻觉
Rare: confusional state, sexual disturbances, irritability, aggression, hallucinations
未知：躁动、妄想、愤怒、异常行为（可能与失忆症有关）以及梦游症、依赖、戒断综合征
Unknown: Agitation, paranoia, anger, unusual behavior (possibly associated with amnesia) and sleepwalking, dependence, withdrawal syndrome

神经系统疾病  Neurological disorders
常见：味觉障碍（苦味）、嗜睡（残余效应）  Common: dysgeusia (bitter taste), drowsiness (residual effect)
偶见：头晕、头痛  Occasionally: dizziness, headache
罕见：顺行性遗忘  Rare: Anterograde amnesia
未知：共济失调、感觉异常、认知障碍如记忆受损、注意障碍和言语障碍呼吸系统、胸及纵隔疾病
Unknown: Ataxia, paresthesias, cognitive impairments such as memory impairment, attention disorders, and speech disorders Respiratory, thoracic, and mediastinal disorders
罕见：呼吸困难  Rare: Dyspnea
未知：呼吸抑制  Unknown: Respiratory depression
皮肤和皮下组织疾病  Skin and subcutaneous tissue disorders
罕见：皮疹、瘙痒症  Rare: rash, pruritus
眼疾病  Eye diseases
未知：复视  Unknown: Double Vision
免疫系统疾病  Immune system disorders
十分罕见：血管性水肿、速发过敏反应  Very rare: Angioedema, anaphylactic reaction
胃肠道疾病  Gastrointestinal disorders
常见：口腔干燥  Common: Dry mouth
偶见：恶心  Occasionally: Nausea
未知：消化不良  Unknown: Indigestion
肝胆疾病  Hepatobiliary diseases
十分罕见：转氨酶升高和／或血碱性磷酸酶升高（轻度至中度）
Very rare: Increased transaminases and/or increased blood alkaline phosphatase (mild to moderate)
肌肉骨骼和结缔组织疾病  Musculoskeletal and connective tissue disorders
未知：肌无力  Unknown: Muscle weakness
全身病症和给药部位反应  Systemic symptoms and administration site reactions
偶见：疲劳  Uncommon: Fatigue
损伤、中毒和手术并发症  Injury, poisoning and surgical complications
罕见：跌倒（主要发生于老年患者）  Rare: Falls (mainly in elderly patients)
佐匹克隆停药有戒断综合征的报道。戒断综合征的表现各异，可包括反跳性失眠症、肌肉痛、焦虑、震颤、出汗、激动、意识模糊、头痛、心悸、心动过速、谵妄、焉梦、易激惹。在重度病例中可能出现下述症状：现实解体、人格解体、听觉过敏、肢体麻木及麻刺感、对光、噪声和身体接触产生超敏反应、幻觉。在十分罕见的病例，可能发生惊厥发作。
Withdrawal syndrome has been reported with discontinuation of zopiclone. Manifestations of withdrawal syndrome vary and may include rebound insomnia, myalgia, anxiety, tremor, sweating, agitation, confusion, headache, palpitations, tachycardia, delirium, nightmares, and irritability. In severe cases, the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of the limbs, hypersensitivity to light, noise, and physical contact, and hallucinations. In very rare cases, convulsive seizures may occur.
【禁忌】  【Taboo】
有以下情况时禁用此药；  This medicine is contraindicated in the following situations;
（1）对佐匹克隆或任何其它成份过敏的患者。  (1) Patients who are allergic to zopiclone or any other ingredients.
（2）重症肌无力患者。  (2) Patients with myasthenia gravis.
（3）严重呼吸功能不全患者。  (3) Patients with severe respiratory insufficiency.
（4）重度睡眠呼吸暂停综合征患者。  (4) Patients with severe sleep apnea syndrome.
（5）严重的急性或慢性肝脏功能不全患者（存在发生肝性脑病的危险
(5) Patients with severe acute or chronic liver dysfunction (who are at risk of developing hepatic encephalopathy)
性）  sex)
（6）对谷蛋白过敏或不耐受的患者。  (6) Patients with gluten allergy or intolerance.
【注意事项】  【Notes】
特别警告要对合并疾病进行评估（需要进行共病诊断评估）
Special warning to evaluate for comorbidities (comorbid diagnostic evaluation required)
建议在有酗酒既往史或其它药物或非药物类依赖的情况下，慎用药物 （见【药物相互作用】）
It is recommended that the drug be used with caution in patients with a history of alcoholism or other drug or non-drug dependence (see [Drug Interactions]).

由于睡眠障碍可能是躯体和／或精神病症的首发症状，因此只有对患者进行仔细的评估后才可以对症治疗失眠。经过7－10天治疗后失眠仍无缓解，表明存在原发性精神和／或内科疾病，应该对其进行评估。失眠加重或出现新的思维或行为异常可能是由一种未被确诊的精神或身体病症引起的。这些发现是在服用镇静／催眠药物（包括佐匹克隆片）治疗的过程中出现的。由于佐匹克隆的一些主要不良反应显示与剂量相关，因此尽可能使用最低的有效剂量（尤其是在老年人服用时）十分重要（参见用法用量）。
Because sleep disturbances may be the first symptom of a medical and/or psychiatric disorder, symptomatic treatment of insomnia should be performed only after careful evaluation of the patient. Insomnia that does not improve after 7-10 days of treatment indicates the presence of a primary psychiatric and/or medical disorder that should be evaluated. Worsening insomnia or new abnormalities in thinking or behavior may be caused by an undiagnosed psychiatric or physical disorder. These findings occur during treatment with sedative/hypnotic medications, including zopiclone tablets. Because some of the major adverse effects of zopiclone appear to be dose-related, it is important to use the lowest effective dose possible, especially when used in the elderly (see Dosage and Administration).

严重过敏性及类过敏反应  Severe allergic and anaphylactoid reactions
极少有患者第一次或随后服用包括佐匹克隆片在内的镇静／催眠药物后会发生累及舌头、声门或喉的血管性水肿的病例报道。部分患者会出现其他一些提示有过敏性反应的症状，如呼吸困难、喉关闭或恶心和呕吐。部分患者需要在急诊科接受治疗。如果血管性水肿累及舌头、声门或喉，患者可能会发生致命性气道阻塞。服用佐匹克隆后发生血管性水肿的患者不能再次服用该药物。
There have been rare case reports of angioedema involving the tongue, glottis, or larynx after a patient took a sedative/hypnotic drug, including Zopiclone, for the first or subsequent time. Some patients have other symptoms suggestive of an allergic reaction, such as difficulty breathing, laryngeal closing, or nausea and vomiting. Some patients have required treatment in the emergency department. If angioedema involves the tongue, glottis, or larynx, the patient may develop a life-threatening airway obstruction. Patients who have developed angioedema after taking Zopiclone should not take the drug again.

异常的思维和行为改变  Unusual changes in thinking and behavior
已有报道多种异常的思维和行为改变与使用镇静／催眠药物有关。（精神／行为）抑制作用下降（例如，出现与性格不符的攻击性和外向性）可能是部分这些改变的特征，这与酒精及其他中枢神经系统抑制剂导致的效应相似。其他一些报道的行为改变包括怪异行为、激动、幻觉和人格解体。
A variety of unusual changes in thinking and behavior have been reported in association with the use of sedative/hypnotic drugs. Decreased inhibition (e.g., inappropriate aggression and extroversion) may characterize some of these changes, similar to the effects of alcohol and other central nervous system depressants. Other reported behavioral changes include bizarre behavior, agitation, hallucinations, and depersonalization.

复杂行为，例如＂梦游驾驶症＂（即服用镇静／催眠药物后尚未完全醒来时驾车，醒来后却忘了发生过这件事）也有报道。从未服用或服用过镇静／催眠药物的人均可发生这些事件。尽管仅服用治疗剂量的佐匹克隆片即可发生如梦游驾驶症等行为，但是在服用佐匹克隆片的同时饮酒及服用其他中枢神经系统抑制剂似乎会增加发生这些行为的风险，而佐匹克隆片的剂量超过最大推荐剂量时也会导致发生这些行为的风险增加。由于这些行为对患者和社区有风险，对于报道发生＂梦游驾驶症＂的患者，应该强烈考虑停用佐匹克隆片。还有报道，服用镇静／催眠药物后没有完全清醒的患者发生了其它复杂行为（例如准备食物和吃食物、打电话或发生性行为）。如发生梦游驾驶症一样，患者通常记不起发生过这些事情。健忘症及其他神经精神症状可能会在无法预测的情况下出现。
Complex behaviors such as "sleepwalking" (i.e., driving while not fully awake after taking sedatives/hypnotic drugs and forgetting that the event occurred after awakening) have also been reported. These events can occur in people who have never taken sedatives/hypnotic drugs or those who have taken them. Although behaviors such as sleepwalking can occur with only therapeutic doses of Zopiclone, the risk of these behaviors appears to be increased with the use of alcohol and other central nervous system depressants while taking Zopiclone, as does the risk of these behaviors when the dose exceeds the maximum recommended dose. Because of the risks to the patient and the community, discontinuation of Zopiclone should be strongly considered in patients who report "sleepwalking." Other complex behaviors (e.g., preparing and eating food, making phone calls, or engaging in sexual activity) have also been reported in patients who have taken sedatives/hypnotic drugs but are not fully awake. As with sleepwalking, patients usually do not remember that these events occurred. Amnesia and other neuropsychiatric symptoms may occur at unpredictable times.

佐匹克隆与酒精和其他中枢神经系统（CNS）镇静剂合用可能增加上述行为风险，佐匹克隆用药剂量超过最大推荐剂量时也会发生类似情况。如果患者出现上述行为，强烈建议其停止用药。
The risk of these behaviors may be increased with the concomitant use of zopiclone with alcohol and other central nervous system (CNS) depressants, as well as with zopiclone doses exceeding the maximum recommended dose. Patients should be strongly advised to discontinue zopiclone if they exhibit these behaviors.

自杀和抑郁症  Suicide and depression
失眠能引起抑郁症状，对此应接受治疗。在持续失眠的情况下，应对患者进行重新评估。
Insomnia can cause depressive symptoms, which should be treated. In cases of persistent insomnia, the patient should be reassessed.

与其它催眠药一样，佐匹克隆不用于抑郁症治疗，并可掩盖其症状。有报道指出原发性抑郁的患者抑郁加重，包括有自杀想法和行为（包括自杀成功）与服用镇静／催眠药物有关。
Zopiclone, like other hypnotics, is not indicated for the treatment of depression and may mask its symptoms. There have been reports of worsening depression, including suicidal thoughts and behaviors (including successful suicides), in patients with primary depression who were taking sedative/hypnotics.

数个流行病学研究表明，伴有或不伴有抑郁症的患者，经苯二氮䓬类和其他催眠药包括佐匹克隆的治疗后，自杀和自杀未遂发生率增加。因果关系尚未确立。很难确定以上列出的特殊异常行为是由药物引起、自发性或是潜在精神疾病或躯体疾病引起的。即使如此，仍要对任何新出现的令人关注的行为体征或症状进行认真而迅速的评估。
Several epidemiologic studies have demonstrated an increased incidence of suicide and suicide attempts in patients with or without depression treated with benzodiazepines and other hypnotics, including zopiclone. A causal relationship has not been established. It is difficult to determine whether the specific abnormal behaviors listed above are drug-induced, spontaneous, or caused by an underlying psychiatric or medical disorder. Even so, any new behavioral signs or symptoms of concern should be carefully and promptly evaluated.

儿童  child
尚未在儿童和 18 岁以下青少年中确定本品的安全有效剂量。因此，不推荐在该人群中使用佐匹克隆。
A safe and effective dose of zopiclone has not been established in children and adolescents under 18 years of age. Therefore, the use of zopiclone in this population is not recommended.

老年及肾功能不全患者  Elderly and patients with renal insufficiency
长期用药后，未证明出现佐匹克隆累积。但是，作为一项预防措施，建议减小一半剂量（见【用法用量】）。
After long-term use, accumulation of zopiclone has not been demonstrated. However, as a precautionary measure, it is recommended to reduce the dose by half (see [Dosage and Administration]).

警告  warn
呼吸功能不全：  Respiratory insufficiency:
催眠药可抑制呼吸动力，因此医生为呼吸功能损害患者开具佐匹克隆处方时应采取适当的预防措施。
Hypnotic drugs can suppress respiratory drive, so physicians should take appropriate precautions when prescribing zopiclone for patients with respiratory compromise.

CNS镇静作用／棈神运动障碍：  CNS Sedation/Psychokinesia:
与其他镇静／催眠药一样，佐匹克隆有中枢神经系统抑制作用。
Like other sedatives/hypnotics, zopiclone has central nervous system depressant effects.
在以下情况下，精神运动障碍包括驾驶能力受损的风险会增加：
The risk of psychomotor impairment, including impaired driving ability, increases in the following situations:
在服用佐匹克隆 12 小时内要进行需要精神集中的活动，服用量超过推荐剂量，或与其他CNS镇静剂、酒精以及其他会升高佐匹克隆血液浓度的药物合用。从事需要高度精神集中或者运动协调的危险职业比如操作机器或者驾车患者在服用佐匹克隆后，尤其是服用后 12 小时内应注意。
Activities requiring mental concentration within 12 hours of taking zopiclone, taking more than the recommended dose, or taking with other CNS depressants, alcohol, or other drugs that increase zopiclone blood levels. Patients who engage in hazardous occupations requiring high mental concentration or motor coordination, such as operating machinery or driving, should exercise caution after taking zopiclone, especially within 12 hours of taking it.

佐匹克隆与其它催眠药一样，当与其它精神药物、抗惊厥药物、抗组胺药物、乙醇及其它本身可引起中枢神经系统抑制的药物同时服用时，可能会导致中枢神经系统抑制的相加效应。服用佐匹克隆片时不能喝酒。佐匹克隆片与其他中枢神经系统抑制剂同时服用时，由于有潜在的相加效应，可能需要调整其剂量。
Zopiclone, like other hypnotics, may cause additive CNS depression when taken concomitantly with other psychotropics, anticonvulsants, antihistamines, ethanol, and other drugs that themselves cause CNS depression. Do not drink alcohol while taking Zopiclone. When Zopiclone is taken concomitantly with other CNS depressants, dose adjustment may be required due to the potential for additive effects.

阿片类药物和苯二氮䓬类药物同时使用的风险：  Risks of concurrent use of opioids and benzodiazepines:
与包括佐匹克隆在内的苯二氮䓬类药物同时使用可能导致镇静、呼吸抑制、昏迷和死亡。由于这些风险，对可选治疗方案不足的患者保留阿片类药物和苯二氮䓬类药物同时使用的处方。
Concomitant use with benzodiazepines, including zopiclone, may result in sedation, respiratory depression, coma, and death. Because of these risks, reserve the prescription of opioids and benzodiazepines for patients for whom alternative treatment options are inadequate.

如果决定同时处方使用佐匹克隆和阿片类药物，需按最低有效剂量和最短同时用药时间处方，且密切随访患者呼吸抑制和镇静的体征和症状。
If the decision is made to prescribe zopiclone and opioids simultaneously, the lowest effective dose and shortest duration of concurrent use should be prescribed, and the patient should be closely monitored for signs and symptoms of respiratory depression and sedation.

本品含有乳糖，因此，本品不建议用于先天性半乳糖血症、葡萄糖或半乳糖吸收不良综合症或乳糖酶缺乏症患者。
This product contains lactose; therefore, it is not recommended for patients with congenital galactosemia, glucose or galactose malabsorption syndrome or lactase deficiency.

耐受性：  Tolerance:
当在数周时间内应用苯二氮䓬及其衍生药物时，尽管应用了相同的给药剂量，但是药物的镇静或催眠效应可能会逐渐下降。在长达 4 周的本品给药期间，在接受治疗的患者中没有观察到任何显著的耐受性事件。
When benzodiazepines and their derivatives are used over a period of several weeks, the sedative or hypnotic effects of the drug may gradually decrease despite the same dose. No significant tolerance events were observed in patients treated with this drug during the 4-week administration period.

依赖性：  Dependencies:
任何的苯二氮䓬及其衍生药物治疗均可以导致生理性和心理性药物依赖或滥用，特别是在长期治疗时。
Any treatment with benzodiazepines or their derivatives can lead to physical and psychological dependence or abuse, especially with long-term treatment.

多种因素似乎可以促进药物依赖性或滥用的出现，这些因素包括：治疗持续时间、给药剂量、具有对药物或其它物质（包括酒精）成癒的病史、与酒精或其他精神药品一起使用、焦虑。
Multiple factors appear to contribute to the development of drug dependence or abuse, including duration of treatment, dose administered, a history of addiction to drugs or other substances (including alcohol), concurrent use of alcohol or other psychotropic drugs, and anxiety.

药物依赖性可以在治疗剂量下出现，和／或在没有特定危险因素的患者中出现。
Drug dependence can occur at therapeutic doses and/or in patients without specific risk factors.

在十分罕见的病例中，已经报道了在治疗剂量下出现佐匹克隆依赖性。
In very rare cases, zopiclone dependence has been reported at therapeutic doses.
在停止治疗时，药物依赖性可以导致戒断症状的出现。
Drug dependence can lead to the onset of withdrawal symptoms when treatment is stopped.
一些症状经常会出现，一般而言症状较轻，这些症状包括：失眠、头痛、明显的焦虑、肌痛、肌肉紧张和易怒。
Some symptoms are common and generally mild and include insomnia, headache, marked anxiety, myalgia, muscle tension, and irritability.

其它症状较为罕见，这些症状包括：焦虑，甚至出现意识模糊；肢体麻木及麻刺感；对光线、噪音和身体接触产生超敏反应；人格解体；现实解体；幻觉；癫痫。
Other symptoms are less common and include: anxiety, even confusion; numbness and tingling in the limbs; hypersensitivity to light, noise and physical contact; depersonalization; derealization; hallucinations; and seizures.

在停止治疗后的数天内，可能会出现戒断症状。当应用短效苯二氮䓬类药物时，特别是在高剂量下进行给药时，戒断症状可能在两次连续给药之间的时间内出现。
Withdrawal symptoms may occur within a few days of stopping treatment. When short-acting benzodiazepines are used, especially when given in high doses, withdrawal symptoms may occur in the time between two consecutive doses.

多种苯二氮䓬类药物的伴随应用可能会增加出现药物依赖的危险性，不管这些苯二氮䓬类药物是用来抗焦虑，还是用来催眠。
The concomitant use of multiple benzodiazepines may increase the risk of drug dependence, regardless of whether these benzodiazepines are used for antianxiety or hypnosis.

也已经报道了一些药物滥用病例。反跳性失眠症：  Some cases of substance abuse have also been reported.