【药品名称】 　　
通用名: 咪达唑仑注射液 　　
英文名:Midazolam Injection 　　
汉语拼音名:Midazolun Zhusheye 　　
本品主要成分: 咪达唑仑盐酸盐(马来酸盐)
化学名称: 8-氯-6-(2-氟苯基)-1-甲基-4H-咪唑并[1,5-a][1,4]苯并二氮杂卓 　　
分子式： 盐酸盐C18H13ClFN3· HCl 分子量： 362.2 　　

分子式： 马来酸盐C18H13ClFN3· C4H4O4 分子量： 441.8 　　

【性状】无色至淡黄色的澄明液体。 　　
【药理毒理】动物试验结果表明，本品具有明显的镇静、肌松、抗惊厥、抗焦虑药理作用。小鼠急性毒性结果，静脉LD50，雄91.32mg/kg、雌93.26mg/kg；腹腔LD50、雄240.05mg/kg、雌212.82mg/kg。 　　
【药代动力学】 据文献报道，本品肌肉给药吸收迅速完全，生物利用度高达90%以上。本品在体内完全被代谢，主要代谢物为羟基咪达唑仑，然后迅速与葡萄糖醛酸结合，呈无活性的代谢物。60%～70%剂量由肾脏排出体外。静脉给药的稳态分布容积可达50～60升，血浆蛋白结合率约95%，血中廓清率300～400ml/分，半衰期为1.5～2.5小时。 　　
【适应症】 　　
1．麻醉前给药。 　　
2．全麻醉诱导和维持。 　　
3．椎管内麻醉及局部麻醉时辅助用药。 　　
4．诊断或治疗性操作(如心血管造影、心律转复、支气管镜检查、消化道内镜检查等)时病人镇静。 　　
5． ICU病人镇静。 　　
【用法用量】本品为强镇静药,注射速度宜缓慢,剂量应根据临床需要、病人生理状态、年龄和伍用药物情况而定。 　　
1．肌内注射 用0.9%氯化钠注射液稀释。 静脉给药 用0.9%氯化钠注射液、5％或10%葡萄糖注射液、5%果糖注射液、林格氏液稀释。 　　
2．麻醉前给药 在麻醉诱导前20-60分钟使用,剂量为0.05-0.075mg/kg肌内注射,老年患者剂量酌减;全麻诱导常用5-10mg(0.1-0.15mg/kg)。 　　
3．局部麻醉或椎管内麻醉辅助用药,分次静脉注射0.03-0.04mg/kg。 　　
4．ICU病人镇静,先静注2-3mg,继之以0.05mg/(kg· h)静脉滴注维持。 　　
【不良反应】 　　
1．较常见的不良反应为嗜睡、镇静过度、头痛、幻觉、共济失调、呃逆和喉痉挛： 　　
2．静脉注射还可发生呼吸抑制及血压下降,极少数可发生呼吸暂停、停止或心跳骤停。有时可发生血栓性静脉炎； 　　
3．直肠给药,一些病人可有欣快感。 　　
【禁忌症】对苯二氮卓过敏的病人、重症肌无力患者、精神分裂症患者、严重抑郁状态患禁用; 　　
【注意事项】 　　
1．用作全麻诱导术后常有较长时间再睡眠现象,应注意保持病人气道通畅。 　　
2．本品不能用6%葡聚糖注射液或碱性注射液稀释或混合。 　
3．长期静脉注射咪达唑仑,突然撤药可引起戒断综合症,推荐逐渐减少剂用量。 　　
4．肌内或静脉注射咪达唑仑后至少3个小时不能离开医院或诊室,之后应有人伴随才能离开。至少12个小时内不得开车或操作机器等。 　　
5．慎用于体质衰弱者或慢性病、肺阻塞性疾病、慢性肾衰、肝功能损害或充血性心衰病人,若使用咪达唑仑应减小剂量并进行生命体征的监测。 　　
【孕妇及哺乳期妇女用药】 　　
1．咪达唑仑不能用于孕妇,在分娩过程中应用须特别注意,单次大剂量注射可致新生儿呼吸抑制,肌张力减退,体温下降以及吸吮无力。 　　
2．咪达唑仑可随乳汁分泌,通常不用于哺乳期妇女。 　　
【老年患者用药】60岁以上老人为高风险病人之列。 　　
【药物相互作用】 　　
1．咪达唑仑可增强催眠药、镇静药、抗焦虑药、抗抑郁药、抗癫痫药、麻醉药和镇静性抗组胺药的中枢抑制作用。 　　
2．一些肝酶抑制药,特别是细胞色素P450 3A抑制药物,可影响咪达唑仑的药代动力学,使其镇静作用延长。 　　
3．酒精可增强咪达唑仑的镇静作用。 　　
【药物过量】 　　
1．过量一般主要表现是药理作用的增强:中枢抑制—从过度镇静到昏迷、精神失常、昏睡、肌肉松弛或异常兴奋。
在大多数情况下,只需注意监测生命体征即可。 　　
2．严重过量可导致昏迷、反射消失、呼吸循环抑制和窒息,需采取相应的措施(人工呼吸、循环支持),以及采用苯二氮卓类受体拮抗剂如氟马西尼逆转。 　　　　
【贮藏】本品不宜冷冻贮存以防冻裂。

【原产地英文商品名】MIDAZOLAM HCL 2mg/2ml/vial 10vial/box
【原产地英文药品名】MIDAZOLAM HCL
【中文参考商品译名】
注：以下产品是不同的规格和价格，购买时请以电话咨询为准！
·MIDAZOLAM HCL 2毫克/ 2毫升/支 10支/盒
·MIDAZOLAM HCL 5毫克/ 5毫升/支 5支/盒
【中文参考药品译名】咪达唑仑注射液
【生产厂家中文参考译名】巴克斯特国际公司
【生产厂家英文名】Baxter Healthcare Corporation

Chemistry - An imidazobenzodiazepine, midazolam occurs as a white to light yellow crystalline powder with a pKa of 6.15. Midazolam HCl’s aqueous solubility is pH depen­dent. At 25°C and a pH of 3.4, 10.3 mg are soluble in 1 ml of water. The pH of the com­mercially prepared injection is approximately 3.

Storage/Stability/Compatibility - It is recommended to store midazolam injection at room temperature (15°-30°C) and protect from light. After being frozen for 3 days and allowed to thaw at room temperature, the injectable product was physically stable. Midazolam is stable at a pH from 3-3.6.

Midazolam is reportedly compatible when mixed with the following products: D5W, normal saline, lactated Ringer’s, atropine sulfate, fentanyl citrate, glycopyrrolate, hydrox­yzine HCl, ketamine HCl, meperidine HCl, morphine sulfate, nalbuphine HCl, promet­hazine HCl, sufantanil citrate, and scopolamine Hbr. Compatibility is dependent upon fac­tors such as pH, concentration, temperature, and diluents used and it is suggested to con­sult specialized references for more specific information.

Pharmacology - Midazolam exhibits similar pharmacologic actions as other benzodi­azepines (refer to the diazepam monograph for more information). Its unique solubility characteristics (water soluble injection but lipid soluble at body pH) give it a very rapid onset of action after injection.

Uses/Indications - In humans, midazolam has been suggested to be used as a premedicant before surgery, and when combined with potent analgesic/anesthetic drugs (e.g., ketamine or fentanyl), as a conscious sedative. In humans, midazolam reduces the incidences of “dreamlike” emergence reactions and increases in blood pressure and cardiac rate that ke­tamine causes.

When compared to the thiobarbiturate induction agents (e.g., thiamylal, thiopental), mi­dazolam has less cardiopulmonary depressant effects, is water soluble, can be mixed with several other agents, and does not tend to accumulate in the body after repeated doses. There is much interest in using the drug alone as an induction agent. Several veterinary anesthesiologists are studying the clinical applications of this agent in veterinary medicine and additional information regarding its use should be forthcoming.

Pharmacokinetics - Following IM injection, midazolam is rapidly and nearly completely (91%) absorbed. Although no oral products are being marketed, midazolam is well absorbed after oral administration, but because of a rapid first-pass effect, bioavailibilities suffer (31-72%). The onset of action following IV administration is very rapid due to the high lipophilicity of the agent. In humans, the loss of the lash reflex or counting occurs within 30-97 seconds of administration.

The drug is highly protein bound (94-97%) and rapidly crosses the blood-brain barrier. Because only unbound drug will cross into the CNS, changes in plasma protein concentra­tions and resultant protein binding may significantly alter the response to a given dose.

Midazolam is metabolized in the liver, principally by microsomal oxidation. An active metabolite (alpha-hydroxymidazolam) is formed, but because of its very short half-life and lower pharmacologic activity, it probably has negligible clinical effects. The serum half-life and duration of activity of midazolam in humans is considerably shorter than that of diazepam. Elimination half-lives measured in humans average approximately 2 hours (vs. approx. 30 hrs for diazepam).

Contraindications/Precautions - The manufacturer lists the following contraindications for use in humans: hypersensitivity to benzodiazepines, or acute narrow-angle glaucoma. Additionally, intra-carotid artery injections must be avoided.

Use cautiously in patients with hepatic or renal disease and in debilitated or geriatric pa­tients. Patients with congestive heart failure may eliminate the drug more slowly. The drug should be administered to patients in coma, shock or having significant respiratory de­pression very cautiously.

Although midazolam has not been demonstrated to cause fetal abnormalities, in humans other benzodiazepines have been implicated in causing congenital abnormalities if admin­istered during the first trimester of pregnancy. Infants born of mothers receiving large doses of benzodiazepines shortly before delivery have been reported to suffer from apnea, impaired metabolic response to cold stress, difficulty in feeding, hyperbilirubinemia, hypo­tonia, etc. Withdrawal symptoms have occurred in infants whose mothers chronically took benzodiazepines during pregnancy. The veterinary significance of these effects is unclear, but the use of these agents during the first trimester of pregnancy should only occur when the benefits clearly outweigh the risks associated with their use. It is unknown if midazo­lam is distributed into milk, but other benzodiazepines and their metabolites are distributed into milk and may cause CNS effects in nursing neonates.

Adverse Effects/Warnings - Few adverse effects have been reported in human patients receiving midazolam. Most frequently effects on respiratory rate, cardiac rate and blood pressure have been reported. Respiratory depression has been reported in patients who have received narcotics or have COPD. The following adverse effects have been reported in more than 1%, but less than 5% of patients receiving midazolam: pain on injection, lo­cal irritation, headache, nausea, vomiting, and hiccups.

The principle concern in veterinary patients is the possibility of respiratory depression occurring.

Overdosage - Very limited information is currently available. The IV LD50 in mice has been reported to be 86 mg/kg. It is suggested that accidental overdoses be managed in a supportive manner, similar to diazepam.

Drug Interactions - Use with barbiturates or other CNS depressants may increase the risk of respiratory depression occurring. Narcotics (including Innovar®) may increase the hypnotic effects of midazolam and hypotension has been reported when used with meperidine. Midazolam may decrease the dosages required for inhalation anesthetics or thiopental.

Doses -

Horses:

As a preoperative agent: 0.011 - 0.0.44 mg/kg IV (Mandsager 1988)

Monitoring Parameters -

1)   Level of sedation

2)   Respiratory and cardiac signs

Client Information - This agent should be used in an inpatient setting only or with direct professional supervision where cardiorespiratory support services are available.

Dosage Forms/Preparations -

Veterinary-Approved Products: None

Human-Approved Products:

Midazolam HCl for Injection 1mg/ml in 2, 5, & 10 ml vials; 5 mg/ml in 1, 2, 5, &

10 ml vials, 2 ml syringes; Versed®  (Roche); (Rx)

Midazolam is a Class-IV controlled substance.