【药品名称】
通用名称：硫酸妥布霉素注射液
英文名称：Tobramycin Sulfate Injection
【成份】本品主要成分为硫酸妥布霉素。
化学名称：O-3-氨基-3-脱氧-α-O-葡吡喃糖基-(1→6)-O-[2,6-二氨基- 2,3,6-三脱氧-α-D-核-己吡喃糖基-(1→4)]-2-脱氧-D-链霉胺
化学结构式：
分子式：C18H37N5O9
分子量：467.52
【适 应 症】本品适用于铜绿假单胞菌、变形杆菌属、大肠埃希菌、克雷伯菌属、肠杆菌属、沙雷菌属所致的新生儿脓毒症、败血症、中枢神经系统感染（包括脑膜炎）、泌尿生殖系统感染、肺部感染、胆道感染、腹腔感染及腹膜炎、骨骼感染、烧伤、皮肤软组织感染、急性与慢性中耳炎、鼻窦炎等，或与其他抗菌药物联合用于葡萄球菌感染（耐甲氧西林菌株无效）。本品用于铜绿假单胞菌脑膜炎或脑室炎时可鞘内注射给药；用于支气管及肺部感染时可同时气溶吸入本品作为辅助治疗。本品对多数D组链球菌感染无效。
【用法用量】肌内注射或静脉滴注。
1．成人 按体重一次1～1.7mg/kg，每8小时1次，疗程7～14日。
2．小儿 按体重，早产儿或出生0～7日小儿：一次2mg/kg，每12～24小时1次；其他小儿：一次2mg/kg，每8小时1次。
【不良反应】
1．全身给药合并鞘内注射可能引起腿部抽搐、皮疹、发热和全身痉挛等。
2．发生率较多者有听力减退、耳鸣或耳部饱满感（耳毒性）、血尿、排尿次数显著减少或尿量减少、食欲减退、极度口渴（肾毒性）、步履不稳、眩晕（耳毒性、影响前庭、肾毒性）。发生率较低者有呼吸困难、嗜睡、极度软弱无力（神经肌肉阻滞或肾毒性）。本品引起肾功能减退的发生率较庆大霉素低。
3．停药后如发生听力减退、耳鸣或耳部饱满感，须注意耳毒性。
【禁忌症】
1．对本品或其他氨基糖苷类过敏者、本人或家族中有人因使用链霉素引起耳聋或其他耳聋者禁用。
2．肾衰竭者禁用。
【注意事项】
1．肾功能不全、肝功能异常、前庭功能或听力减退者、失水、重症肌无力或帕金森病及老年患者慎用。
2．本品1个疗程不超过7～14日。
3．交叉过敏：对一种氨基糖苷类抗生素如链霉素、庆大霉素过敏的患者，可能对本品过敏。
4．对患者（尤其对肾功能减退者、早产儿、新生儿、婴幼儿或老年患者、休克、心力衰竭、腹水或严重失水等患者）应注意监测：
①听电图：对老年患者须在用药前、用药过程中定期及长期用药后用以检测高频听力损害；
②温度刺激试验：在用药前、用药过程中定期及长期用药后用以检测前庭毒性；
③尿常规检查和肾功能测定，在用药前、用药过程上中定期测定肾功能，以防止严重肾毒性反应。
④在用药过程中应注意监测本品的血清浓度，一般于静脉滴注后30分钟到1小时测血清峰浓度，于下次用药前测血清谷浓度，当峰浓度超过12μg/ml、谷浓度超过2μg/ml时易出现毒性反应。
5．肌酐清除率在70ml/分钟以下者其维持剂量须根据测得的肌酐清除率进行调整。
6．本品静脉滴注时必须经充分稀释。可将每次用量加入50～200ml5%葡萄糖注射液或氯化钠注射液稀释成浓度为1mg/ml（0.1%）的溶液，在30～60分钟内滴完（滴注时间不可少于20分钟），小儿用药时稀释的液量应相应减少。
7．本品不能静脉注射，以免产生神经肌肉阻滞和呼吸抑制作用。不宜皮下注射，因可引起疼痛。
8．长期应用本品可能导致耐药菌过度生长。
9．应给患者补充足够的水分，以减少肾小管损害。
10．对实验室检查指标的干扰：本品可使丙氨酸氨基转移酶、门冬氨酸氨基转移酶、血清胆红素浓度及血清乳酸脱氢酶浓度的测定值增高；血钙、镁、钾、钠浓度的测定值可能降低。
【孕妇与哺乳期妇女用药】
1．本品可穿过胎盘，在脐带血中达到的浓度约与母血中相近，据报道氨基糖苷类曾引致人类胎儿听力损害，故孕妇禁用。
2．本品亦可在人乳中少量分泌，故哺乳期妇女慎用或用药期间暂停哺乳。
【儿童用药】年龄对于本品的血药浓度有显著影响。剂量相同时，5岁以下小儿的平均血药峰浓度约为成人的一半，5～10岁儿童约为成人的2/3。按体表面积计算给药剂量可消除年龄造成的差异。小儿应慎用本品。在小儿使用过程中，要注意监测听力和肾功能，以防本品产生的肾毒性和耳毒性。
【老年患者用药】老年患者应用本品后可产生各种毒性反应，因此在疗程中监测肾功能极为重要。肾功能正常者用药后亦可能产生听力减退。此外，老年患者应采用较小剂量或延长给药间隔，以与其年龄、肾功能和第8对脑神经的功能相适应。
【药物相互作用】
1．本品与其他氨基糖苷类合用或先后连续局部或全身应用，可增加耳毒性、肾毒性以及神经肌肉阻滞作用。可能发生听力减退，停药后仍可能进展至耳聋；听力损害可能恢复或呈永久性。神经肌肉阻滞作用可导致骨骼肌软弱无力、呼吸抑制或呼吸麻痹（呼吸暂停），用抗胆碱酯酶药或钙盐有助于阻滞作用恢复。
2．本品与神经肌肉阻滞药合用，可加重神经肌肉阻滞作用，导致肌肉软弱、呼吸抑制或呼吸麻痹（呼吸暂停）。与代血浆类药如右旋糖酐、海藻酸钠，利尿药如依他尼酸、呋塞米及卷曲霉素、顺铂、万古霉素等合用，或先后连续局部或全身应用，可增加耳毒性与肾毒性，可能发生听力损害，且停药后仍可能发展至耳聋，听力损害可能恢复或呈永久性。
3．本品与头孢噻吩局部或全身合用可能增加肾毒性。
4．本品与多粘菌素类合用，或先后连续局部或全身应用，因可增加肾毒性和神经肌肉阻滞作用，后者可导致骨骼肌软弱无力，呼吸抑制或呼吸麻痹（呼吸暂停）。
5．本品不宜与其他肾毒性或耳毒性药物合用或先后应用，以免加重肾毒性或耳毒性。
6．本品与β-内酰胺类（头孢菌素类或青霉素类）合用常可获得协同作用。
7．本品与β-内酰胺类（头孢菌素类或青霉素类）混合可导致相互失活，需联合应用时必须分瓶滴注。本品亦不宜与其他药物同瓶滴注。
【药物过量】本品过量的严重程度与剂量大小、患者的肾功能、脱水状态、年龄以及是否同时使用有类似毒性作用的药物等有关。成人一天用量超过5mg/kg，儿童一天用量超过7.5mg/kg或用药疗程过长以及对肾功能不全患者的用药剂量未作调整均可引起本品的毒性。毒性发作可发生在用药后10天。毒性作用主要表现为肾功能损害以及前庭神经和听神经的损害，也可发生神经肌肉阻滞和呼吸麻痹。
本品无特异性对抗药，过量或引起毒性反应时，主要用对症疗法和支持疗法。血液透析或腹膜透析有助于从血中清除本品。新生儿也可考虑换血疗法。
【药理毒理】本品属氨基糖苷类抗生素。抗菌谱与庆大霉素近似，对大肠埃希菌、产气杆菌、克雷白杆菌、奇异变形杆菌、某些吲哚阳性变形杆菌、铜绿假单胞菌、某些奈瑟菌、某些无色素沙雷杆菌和志贺菌等革兰阴性菌有抗菌作用；本品对铜绿假单胞菌的抗菌作用较庆大霉素强3～5倍，对庆大霉素中度敏感的铜绿假单胞菌对本品高度敏感。革兰阳性菌中，金黄色葡萄球菌（包括产b-内酰胺酶株）对本品敏感；链球菌（包括化脓性链球菌、肺炎球菌、粪链球菌等）均对本品耐药。厌氧菌（拟杆菌属）、结核杆菌、立克次体、病毒和真菌亦对本品耐药。
本品的作用机制是与细菌核糖体30S亚单位结合，抑制细菌蛋白质的合成
【药代动力学】本品肌内注射后吸收迅速而完全。主要分布在细胞外液，其中5%～15%再分布到组织中，在肾皮质细胞中蓄积。本品可穿过胎盘。分布容积（Vd）为0.26L/kg。尿液中药物浓度高，肌内注射本品1mg/kg后尿中浓度可达75～100mg/L。滑膜液内可达有效浓度，在支气管分泌液、脑脊液、胆汁、粪便、乳汁、房水中浓度低。肌内注射本品1mg/kg后血药浓度约为4mg/L；1小时内静脉滴注本品1mg/kg，所得血药浓度与肌内注射相似。血消除衰期（t1/2b）为1.9～2.2小时，蛋白结合率很低。
本品在体内不代谢，经肾小球滤过排出。24小时排出给药量的85%～93%。本品可经血液透析或腹膜透析清除。
【贮 藏】密闭，在凉暗处（不超过20℃）保存。
【原产地英文商品名】TOBRAMYCIN SULF 1.2g/vial
【原产地英文药品名】TOBRAMYCIN SULFATE
【中文参考商品译名】硫酸妥布霉素 1.2克/瓶
【中文参考药品译名】硫酸妥布霉素
该药品相关信息网址1:
http://www.rxlist.com/tobramycin-injection-drug.htm
该药品相关信息网址2:
http://www.drugs.com/monograph/tobramycin-sulfate.html
该药品相关信息网址3:
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a681003.html
Tobramycin Sulfate Injection
IMPORTANT WARNING:
Tobramycin can cause severe hearing and kidney problems. Before administering tobramycin, tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially diuretics ('water pills'), cisplatin (Platinol), amphotericin (Amphotec, Fungizone), other antibiotics, and vitamins.
If you experience any of the following symptoms, call your health care provider immediately: dizziness, vertigo, ringing in the ears, hearing loss, numbness, muscle twitching or weakness, difficulty breathing, decreased urination, rash, itching, or sore throat.
About your treatment
Your doctor has ordered tobramycin, an antibiotic, to help treat your infection. The drug will be either injected into a large muscle (such as your buttock or hip) or added to an intravenous fluid that will drip through a needle or catheter placed in your vein for at least 30 minutes, one to three times a day.
Tobramycin eliminates bacteria that cause many kinds of infections, including lung, skin, bone, joint, stomach, blood, and urinary tract infections. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
Your health care provider (doctor, nurse, or pharmacist) may measure the effectiveness and side effects of your treatment using laboratory tests and physical examinations. It is important to keep all appointments with your doctor and the laboratory. The length of treatment depends on how your infection and symptoms respond to the medication.
Precautions
Before administering tobramycin,
tell your doctor and pharmacist if you are allergic to amikacin, gentamicin (Garamycin), kanamycin (Kantrex), neomycin, netilmicin (Netromycin), streptomycin, tobramycin, or any other drugs.
tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially diuretics ('water pills'), cisplatin (Platinol), amphotericin (Amphotec, Fungizone), other antibiotics, and vitamins.
tell your doctor if you have or have ever had kidney disease, vertigo, hearing loss, ringing in the ears, myasthenia gravis, or Parkinson's disease.
tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking tobramycin, call your doctor immediately. Tobramycin can harm the fetus.
Administering your medication
Before you administer tobramycin, look at the solution closely. It should be clear and free of floating material. Gently squeeze the bag or observe the solution container to make sure there are no leaks. Do not use the solution if it is discolored, if it contains particles, or if the bag or container leaks. Use a new solution, but show the damaged one to your health care provider.
It is important that you use your medication exactly as directed. Do not stop your therapy on your own for any reason because your infection could worsen and result in hospitalization. Do not change your dosing schedule without talking to your health care provider. Your health care provider may tell you to stop your infusion if you have a mechanical problem (such as a blockage in the tubing, needle, or catheter); if you have to stop an infusion, call your health care provider immediately so your therapy can continue.
Side effects
Tobramycin occasionally causes side effects. To reduce this risk, your health care provider may adjust your dose based on your blood test results. Follow the directions in the IMPORTANT WARNING section for the symptoms listed there and tell your health care provider if any of the following symptoms are severe or do not go away:
upset stomach
vomiting
fatigue
pale skin
If you experience any of the following symptoms, call your doctor immediately:
severe rash
difficulty breathing
Storing your medication
Your health care provider probably will give you a several-day supply of tobramycin at a time. If you are receiving tobramycin intravenously (in your vein), you probably will be told to store it in the refrigerator or freezer.
Take your next dose from the refrigerator 1 hour before using it; place it in a clean, dry area to allow it to warm to room temperature.
If you are told to store additional tobramycin in the freezer, always move a 24-hour supply to the refrigerator for the next day's use.
Do not refreeze medications.
If you are receiving tobramycin intramuscularly (in your muscle), your health care provider will tell you how to store it properly.
Store your medication only as directed. Make sure you understand what you need to store your medication properly.
Keep your supplies in a clean, dry place when you are not using them, and keep all medications and supplies out of reach of children. Your health care provider will tell you how to throw away used needles, syringes, tubing, and containers to avoid accidental injury.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Signs of infection
If you are receiving tobramycin in your vein or under your skin, you need to know the symptoms of a catheter-related infection (an infection where the needle enters your vein or skin). If you experience any of these effects near your intravenous catheter, tell your health care provider as soon as possible:
tenderness
warmth
irritation
drainage
redness
swelling
pain