英文药名: Sandostatin(octreotide)

中文药名: 善宁（奥曲肽注射剂）

生产厂家: Novartis

药品名称

商品名: 善宁 Sandostatin
通用名: 醋酸奥曲肽注射液
成分: 醋酸奥曲肽 Octreotide acetate
药物分类: 脑垂体激素和相关药物
性状: 醋酸奥曲肽的化学名称为 D-苯丙氨酰-L-半胱氨酰-L-苯丙氨酰-D-色氨酰-L-赖氨酰-L-苏氨酰-L-半胱氨酰-L-苏氨醇环（2→7）二硫化物醋酸盐，分子式：C49H66N10O10S2，nCH3COOH，分子量：1019.3（按游离肽计）。 本品为无色的澄明液体。
药理作用

奥曲肽是人工合成的天然生长抑素的八肽衍生物，其药理作用与生长抑素相似但作用持续时间更长。它抑制生长激素（GH）和胃肠胰（GEP）内分泌系统肽的病理性分泌增加。
在动物体内，奥曲肽在抑制生长激素、胰高糖素和胰岛素释放方面比生长抑素更强，而且对生长激素和胰高糖素选择性更高。
奥曲肽对健康受试者表现出如下的抑制作用：
- 抑制精氨酸、运动或胰岛素诱发的低血糖症引起的生长激素的释放。
- 抑制餐后胰岛素、胰高糖素、胃泌素和GEP系统其它肽类的释放以及精氨酸引起的胰岛素和胰高糖素的释放。
- 抑制由促甲状腺素释放激素（TRH）引起的促甲状腺素（TSH）的释放。
与生长抑素相比，奥曲肽对生长激素分泌的抑制比对胰岛素分泌的抑制更强，而且不引起激素的反弹性高分泌（例如 ：肢端肥大症中的生长激素）。
对肢端肥大症患者，奥曲肽可以降低血浆生长激素和胰岛素样生长因子-1（IGF-1）的浓度。几乎90%的病人的血浆水平下降50%或更多，且半数病例生长激素降至5 ng/mL以下。
多数病人的临床症状有明显减轻，如头痛，皮肤增厚，软组织水肿，多汗，关节疼痛和感觉异常等。此外，奥曲肽可使垂体大腺瘤病人的瘤体缩小。
对功能性GEP内分泌肿瘤的患者，奥曲肽通过其广泛的活性使多种临床症状得到改善。对曾接受过手术、肝动脉栓塞、化疗（链脲霉素或5-氟尿嘧啶等）后仍有与肿瘤相关的严重症状者，奥曲肽可起到良好的改善作用。
奥曲肽对不同肿瘤的作用如下：
*类癌综合征
奥曲肽可改善潮红和腹泻等症状，并使一些患者血浆5-羟色胺浓度下降以及尿中5-羟吲哚乙酸排出减少。
用药后临床症状和实验室检查未改善的病例，奥曲肽的连续用药时间不应超过1周。
*血管活性肠肽瘤（VIP瘤）
此类肿瘤主要的生化特征是血管活性肠肽（VIP）的过量产生。
临床上的主要表现为严重的分泌性腹泻。在大多数病例中，奥曲肽会缓解症状，进而改善病人的生活质量。同时伴随的水电解质失衡（如低钾血症）也会得到缓解，从而可以停止胃肠或胃肠外的替代治疗。一些病人用药后经计算机断层扫描显示肿瘤生长减慢或停止，甚至缩小，特别是某些肝转移患者更为明显。临床好转通常伴有血浆VIP浓度的降低，甚至正常。
*胰高糖素瘤(Glucagonomas)
该病的特征为坏死松解性游走性皮疹，奥曲肽可使大多数患者的该类病症得到明显改善。奥曲肽对该类患者易合并的轻度糖尿病的影响甚微，故通常无需减少胰岛素或口服降糖药用量。本品使那些受影响患者的腹泻减少因而造成相应体重增加。多数情况下奥曲肽会使血浆胰高糖素浓度立即下降，但这种作用并不持久，尽管如此，患者的症状却能继续改善。
*胃泌素瘤（Zollinger-Ellison综合征）
由于慢性胃泌素刺激所致胃酸分泌过多引起的复发性消化性溃疡，并非对质子泵抑制剂或H2受体阻断剂全部有效而且某些明显的腹泻症状也很少缓解。奥曲肽与质子泵抑制剂或H2受体阻断剂合用，可抑制胃酸的过多分泌，使半数此类病人临床症状（包括腹泻）得到改善。并可能缓解其它可能由肿瘤产生的肽类造成的症状（如潮红）。一些病人的血浆胃泌素浓度降低。
*胰岛素瘤（Insulinoma）
奥曲肽可使循环系统中免疫反应性胰岛素水平降低。但这种作用一般比较短暂（约2小时）。对可以手术的肿瘤患者，术前使用奥曲肽有助于获得并维持正常的血糖。某些无法手术的良性或恶性肿瘤患者，即使不伴有血胰岛素浓度的持续降低，奥曲肽也会改善血糖调节。
*生长激素释放因子瘤（GRFoma）
这是一种仅分泌生长激素释放因子（GRF）或同时伴有其他生物活性肽类分泌的少见肿瘤。有两例病人中的1例由于奥曲肽的治疗而改善了肢端肥大样临床症状，其原因可能缘于GRF和GH分泌受到抑制，同时可能使垂体缩小。
*预防胰腺手术后并发症
进行胰腺手术的患者，围手术期和术后使用奥曲肽会减少典型的术后并发症的发生（如胰瘘、脓肿继发脓毒症，急性术后胰腺炎等）。
*食管-胃静脉曲张出血
一项临床研究结果表明，奥曲肽合并硬化剂治疗肝硬化所致的食管-胃静脉曲张出血，会加强对出血的控制并预防早期再出血的发生，从而减少输血量，提高5天存活率。奥曲肽此种作用的确切机制尚不清楚，但有提示认为它通过防止血管活性激素如VIP和胰高糖素等的分泌而减少内脏血流。
药代动力学

吸收:
奥曲肽皮下注射后吸收迅速而完全，30分钟内血浆浓度达峰值。
分布:
分布容积是0.27升/千克，总体廓清率是160毫升/分。血浆蛋白质结合率达65%。与血细胞结合的奥曲肽可忽略不计。
消除:
皮下给药的清除半衰期为100分钟。静脉注射后其消除呈双相，半衰期分别为10分钟和90分钟。大部分经粪便排泄，约32%在尿中以原型排出。
特殊人群
*肾功能衰竭：肾功能损害对皮下给药的奥曲肽总暴露水平（AUC）无影响。
*肝功能衰竭：肝硬化，而非脂肪肝，会使奥曲肽的消除降低30%。
适应症

肢端肥大症:
对手术治疗或放疗失败，或不能、不愿接受手术以及放射治疗尚未生效的间歇期患者，奥曲肽可以控制症状并降低生长激素和胰岛素样生长因子-1的水平。
缓解与功能性功能性胃肠胰内分泌瘤有关的症状和体征：
有充分证据显示，本品对以下肿瘤有效：具有类癌综合征表现的类癌肿瘤；VIP瘤；胰高糖素瘤。
本品对以下肿瘤的有效率约为50%（迄今治疗病例有限）：胃泌素瘤/Zollinger-Ellison综合征（通常与质子泵抑制剂或H2受体阻断剂联用）；胰岛素瘤（术前预防低血糖症和维持正常血糖）；生长激素释放因子瘤，奥曲肽仅可减轻症状和体征，但不能治愈病因；预防胰腺手术后并发症；与内窥镜硬化剂等特殊手段联合用于肝硬化所致的食管-胃静脉曲张出血的紧急治疗。
用法用量

肢端肥大症:
开始每8小时皮下注射1次，每次0.05-0.1毫克，然后每月依循环GH、IGF-1水平和临床反应及耐受性做相应调整（目标 ：GH小于2.5纳克/毫升 ；IGF正常范围）。多数病人每日最适剂量为0.2-0.3毫克。对长期接受同一剂量治疗的病人每6个月测定一次GH浓度。
每日不得超过1.5毫克的最大剂量，通过监测血浆GH 水平，治疗数月后可酌情减量。
如果用药1月后仍无GH水平的降低和无临床反应，应考虑停药。
胃肠胰内分泌肿瘤:
最初皮下注射每日1-2次，每次0.05毫克，依耐受性和疗效（临床反应，肿瘤分泌的激素浓度）渐增至每次0.2毫克，每日3次。个别病例可能需要更高的剂量。维持剂量因个体差异而定。
用药后临床症状和实验室检查未改善时，奥曲肽用药不能超过1周。
预防胰腺手术后并发症:
皮下注射每日3次，每次0.1毫克，连续7天，第1次用药至少在术前1小时进行。
食管-胃静脉曲张出血:
连续静脉滴注0.025毫克/小时，最多治疗5天。奥曲肽可用生理盐水稀释（请参考[使用注意事项下]的"静脉滴注"）。
特殊病人用药剂量:
肝功能不全：肝硬化病人的药物半衰期延长，所以需要改变维持剂量。对肝硬化病人食管-胃静脉曲张出血，持续静脉滴注剂量可达0.05毫克/小时，5天以上，病人耐受良好。
肾功能不全：肾功能不良对皮下给药后的总量露量（AUC）无影响，所以不需调整奥曲肽的用量。
用药须知

*皮下注射给药
对自行用药的病人，医生或护士必须给予正确指导。
药液应达到室温再用，以减少局部不适感。避免同一部位短期多次注射。
直到马上用药前方可打开安瓿。任何剩余不用的药液都应抛弃。
为防止污染，多剂药瓶不应穿刺超过10次。
*静脉滴注
使用前应用肉眼观察是否有颜色改变和颗粒出现。
在无菌生理盐水或5%葡萄糖溶液中奥曲肽可保持理化性质稳定达24小时。但由于奥曲肽会影响葡萄糖体内平衡，故建议使用生理盐水而不用葡萄糖。尽管在25°C以下稀释药液可维持理化活性达24小时，但考虑到微生物的污染，配制好的药液应当立即使用。如果不立即使用，应保存于2-8°C的条件下。使用前药液需达到室温。重新配制药液、用溶媒稀释、冰箱保存直至用药结束时间不应超过24小时。
需静脉滴注奥曲肽时，通常应将0.5毫克奥曲肽溶于60毫升生理盐水中，并用输液泵滴注直到疗程结束。奥曲肽也可低浓度静滴。
不良反应

奥曲肽的主要不良反应包括局部和胃肠道反应。
*局部反应：对奥曲肽的局部反应包括疼痛或注射部位的针刺、麻刺或烧灼感，可伴有红肿。这些作用极少持续15分钟以上，而且可以采取注射前让药液达到室温或减少溶剂用量提高药物浓度的方法来减轻局部不适。
全身反应：
*罕见反应：皮肤过敏反应，暂时性脱发。有过敏反应发生的个别报道。
*心血管系统：心动过缓偶有发生。
*胃肠道系统：食欲不振、恶心、呕吐、痉挛性腹痛，腹胀、胀气、稀便、腹泻和脂肪痢等。虽然大便中脂肪排出会增多，但并无证据表明长期使用奥曲肽会造成吸收不良而导致营养不良。罕见病例中，胃肠道副作用可类似急性肠梗阻伴进行性严重上腹痛、腹部触痛、肌紧张和腹胀。尽量延长用药和吃饭的时间间隔，即在两餐之间或睡觉前用药，会减轻胃肠道副反应的发生。
*胆囊：长期使用奥曲肽可能引起胆石形成（参见“注意事项” ）。
*胰腺：由于奥曲肽对生长激素，胰高糖素和胰岛素分泌的抑制作用，故可能造成血糖调节的紊乱。由于餐后糖耐量受影响，某些长期治疗的病人会导致持续的高血糖症。
*低血糖也有发生。
*个别病例发生急性胰腺炎。通常在奥曲肽开始治疗的几个小时或几天内出现，但会随着停药而逐渐消失。长期应用本品且发生胆石的病人也可能出现胰腺炎。
*肝脏：已有与奥曲肽治疗相关的肝功能不全的个别报道，包括：无胆汁郁积的急性肝炎。停药后转氨酶恢复正常；缓慢发生的高胆红素血症伴碱性磷酸酶、γ-谷氨酰转移酶增高和转氨酶轻度增高。
禁忌症

对奥曲肽或任一赋形剂过敏者禁用。
注意事项

由于分泌GH的垂体瘤可能扩散而引起严重并发症（如视野缺损），所以，应仔细监测所有病人。如果有肿瘤扩散的征兆，应考虑转换其它治疗方法。
用奥曲肽治疗患者的胆石症发生率约为15-30%，而人群发生率为5-20%。故在奥曲肽治疗前和治疗期间每隔6-12个月应做一次胆囊超声检查。 经本品治疗的患者的胆石症大多数没有症状，对有症状的胆石症需采用胆酸溶石治疗或外科手术取石。
少数胃肠胰内分泌肿瘤病人接受奥曲肽治疗时有症状突然失控而导致严重症状复发的报道。
对胰岛素瘤患者，由于奥曲肽对GH和胰高糖素分泌抑制大于对胰岛素分泌的抑制，故有可能增加低血糖的程度和时间。这些病人特别是在治疗开始和改变剂量时应严密监测。
通过较频繁的小剂量用药可控制血糖浓度的明显波动。
奥曲肽可能改变I型糖尿病（胰岛素依赖型）患者对胰岛素的需要量。对非糖尿病和具有部分胰岛素储留的II型糖尿病患者会造成餐后血糖升高。
食管-胃静脉曲张继发出血可增加胰岛素依赖型糖尿病患者的风险性并可引起I型糖尿病患者胰岛素需要量的改变。所以密切观察血糖水平是必要的。
孕妇及哺乳期妇女用药

对雌性大鼠生育力和产前、围产期和产后研究表明：每日皮下注射1毫克/公斤的奥曲肽对生殖和后代发育无副作用。某些年幼动物暂时生长发育迟缓可能是由于药物药理活性引起的生长激素分泌抑制造成的。
对妊娠和哺乳妇女使用奥曲肽的经验有限。这些患者只有在绝对必要时方可用药。
儿童用药

奥曲肽用于儿童的经验有限。
老年患者用药

与其他病人相比，尚无证据表明老年人不能耐受奥曲肽或需要不同的剂量。
药物相互作用

奥曲肽与溴隐亭合用会增加溴隐亭的生物利用度。
仅有少量已出版的数据表明，生长抑素类似物会降低细胞色素P450酶参与代谢物质的清除率。这是由于其抑制生长激素分泌造成的，所以不排除奥曲肽也会有此作用。与其它主要通过CYP 3A4代谢且疗效范围较窄的药物如特啡纳丁合用时应小心。
奥曲肽会减少肠道对环孢素的吸收，也可推迟对西咪替丁的吸收。
药物过量

每日3次、每次皮下注射奥曲肽2.0毫克连续几月仍可很好耐受。急性过量用药后也未 见致命性反应的报道。至今成人最大的单次用量为1毫克静脉推注。所观察到的症状有一过性心率减低，面部潮红，腹部痉挛性疼痛，腹泻，胃部空虚感和恶心等。这些症状会在给药后24小时消失。
有1例患者意外用药过量，持续超量的静脉滴注（0.25毫克/小时，而不是0.025毫克/小时，达48小时）未见不良反应。
对过量用药者应采取对症治疗。
贮藏

保存于2-8°C冰箱中，防冷冻和避光。
需每日使用时，安瓿和多剂药瓶可分别于30°C和25°C以下储存2周。

包装规格：

·1mg/ml 5ml
·500mcg/ml 5支 x 1ml
·0.1mg 1ml
·200mcg/ml 5ml
·50mcg 1ml 

Important note
HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

Monograph title
OCTREOTIDE - INJECTION

Phonetic pronunciation
(ok-TREE-oh-tide)

Common brand name(s)
Sandostatin

Uses
Octreotide is used to treat severe watery diarrhea and sudden reddening of the face and neck caused by certain types of tumors (e.g., carcinoid tumors, vasoactive intestinal peptide tumors) that are found usually in the intestines and pancreas. The symptoms occur when these tumors make too much of certain natural substances (hormones). This medication works by blocking the production of these hormones. By decreasing watery diarrhea, octreotide helps to reduce the loss of body fluids and minerals.Octreotide is also used to treat a certain condition (acromegaly) that occurs when the body makes too much of a certain natural substance called growth hormone. Treating acromegaly helps reduce the risk of serious problems such as diabetes and heart disease. Octreotide works by decreasing the amount of growth hormone to normal levels.This drug is not a cure for these conditions. This medication is usually used with other treatment (e.g., surgery, radiation, other drugs).

How to use
This medication is usually given by injection under the skin, usually 2 to 3 times a day or as directed by your doctor. Depending on your condition, it may be given by injection into a vein by a health care professional.If your doctor directs you to inject this medication under the skin yourself, learn all preparation and usage instructions from your health care professional. Learn how to store and discard needles and medical supplies safely. If you have questions, ask your health care professional.Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Before injecting each dose, clean the injection site with rubbing alcohol. Change the location of the injection site each time to avoid problem areas under the skin.Dosage is based on your medical condition and response to treatment.Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.Tell your doctor if your condition does not improve or if it worsens.

Missed dose
If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Precautions
Before using octreotide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease (e.g., cirrhosis), diabetes, thyroid problems, gallbladder problems (e.g., gallstones), nutrition problems (e.g., decreased fat absorption, vitamin B12 deficiency).This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.Caution is advised when using this drug in children. Use of this medication for long periods (e.g., longer than 1 year) may slow a child's growth rate. However, the growth rate catches up after treatment with the drug is stopped. Consult your doctor for more information.This medication may restore the normal ability to become pregnant in females with acromegaly who have infertility. Females of childbearing age should discuss reliable forms of birth control with the doctor. During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

Side effects
Nausea, vomiting, loose/oily stools, constipation, stomach upset, gas, bloating, dizziness, or headache may occur. Pain and irritation at the injection site may also occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor immediately if any of these unlikely but serious side effects occur: signs of gallbladder/liver problems (e.g., fever, stomach/abdominal pain, severe nausea/vomiting, yellowing eyes/skin, unexplained pain in the back/right shoulder), signs of underactive thyroid (e.g., unexplained weight gain, cold intolerance, slow heartbeat, severe constipation, unusual/extreme tiredness, growth/lump/swelling on the front of the neck), worsening heart condition symptoms (e.g., trouble breathing, slow/fast/irregular heartbeat), numbness/tingling of the arms/legs.This medication may infrequently cause changes in blood sugar, especially if you have diabetes. Symptoms of high blood sugar include increased thirst and urination. Symptoms of low blood sugar include nervousness, shakiness, sweating, fast heartbeat, and hunger. Follow your doctor's instructions to treat low blood sugar (e.g., eat a quick source of sugar such as glucose gel/tablets, table sugar, or honey, or drink fruit juice or non-diet soda). Tell your doctor immediately if you experience symptoms of high or low blood sugar while taking this medication. Monitor your blood sugar levels as directed by your doctor.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Drug interactions
Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: beta-blockers (e.g., metoprolol, propranolol), calcium channel blockers (e.g., diltiazem, verapamil), cyclosporine, drugs to treat diabetes (e.g., glyburide, insulin), nutritional solutions given by vein (e.g., total parenteral nutrition-TPN), pegvisomant, "water pills" (diuretics such as furosemide, hydrochlorothiazide).This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

Overdose
If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes
Do not share this medication with others.Laboratory and/or medical tests (e.g., blood glucose tests, thyroid function tests, hormone levels, vitamin B12 levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

Storage
Store this medication in the refrigerator between 36-46 degrees F (2-8 degrees C) away from light. Allow the medication to come to room temperature before using. This medication is good for 2 weeks if stored at room temperature between 68-86 degrees F (20-30 degrees C) away from light. Multi-use vials should be discarded 2 weeks after opening. Ampules should be opened just before each dose, and any unused portion should be discarded. Do not store in the bathroom. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.