近日，美国食品和药物管理局（FDA）批准静脉注射ELSPAR（Asparaginase）用于急性淋巴细胞白血病（ALL）患者的多药物化疗方案。
批准日期：2014年12月19日 公司：Lundbeck Inc.
ELSPAR（天冬酰胺酶[Asparaginase]）用于注射，静脉注射或肌肉注射
最初的美国批准：1978年
作用机制
Elspar的作用机制被认为是基于由于血浆天冬酰胺耗尽而选择性杀死白血病细胞。 一些白血病细胞是由于缺乏天冬酰胺合成酶而不能合成天冬酰胺，并且依赖于外源天冬酰胺来存活。耗尽
由L-天冬酰胺酶酶处理产生的天冬酰胺可杀死白血病细胞。 然而，由于合成天冬酰胺的可能性，正常细胞受耗尽的影响较小
适应症和用法
Elspar是一种天冬酰胺特异性酶，表明作为治疗急性淋巴细胞白血病（ALL）患者的多药物化疗方案的组成部分
剂量和给药
•每周三次肌肉注射（IM）或静脉注射（IV）6,000国际单位/平方米。
•重新调整适合预期管理的数量：
对于IM管理，重建2mL
对于IV给药，重建5mL
•对于IM管理，将单个注射部位的体积限制为2mL;如果大于2mL，请使用多次注射部位。
•对于IV给药，通过输注氯化钠注射液或葡萄糖注射液5％（D5W）的侧臂超过≥30分钟。
•在8小时内使用重组的Elspar。
剂量形式和强度
•10,000个国际单位，作为冻干粉末使用的小瓶。
禁忌症
•对Elspar或其他大肠杆菌来源的L-天冬酰胺酶的严重过敏反应
先前L-天冬酰胺酶治疗严重血栓形成
•胰腺炎与先前的L-天冬酰胺酶治疗
•先前L-天冬酰胺酶治疗的严重出血事件
警告和注意事项
•过敏反应和其他严重的过敏反应可能发生。在给药后观察患者一小时。在患有严重过敏反应的患者中停用Elspar。
•可能发生严重的血栓形成事件，包括矢状性鼻窦炎。在患有严重血栓形成事件的患者中停用Elspar。
•胰腺炎，在某些情况下暴发性或致命性，可发生。评估腹痛患者的胰腺炎。在胰腺炎患者中停用Elspar。
•葡萄糖不耐受，在某些情况下是不可逆的，可以发生。监测血清葡萄糖。
•可发生凝血功能障碍。执行适当的监控。
•可能发生包括肝功能衰竭在内的肝毒性。进行适当的监测。
不良反应
最常见的不良反应是过敏反应（包括过敏反应），高血糖，胰腺炎，中枢神经系统（CNS）血栓形成，凝血功能障碍，
高胆红素血症和转氨酶升高。
包装提供/存储和处理
剂型
NDC 67386-411-51
10,000个国际单位，作为单剂量小瓶中的冻干粉末，单独包装在纸箱中。
存储和处理
将小瓶冷藏在2-8°C（36-46°F）.Elspar不含防腐剂。 将未使用的重构溶液在2-8°C（36-46°F）下保存，8小时后丢弃，如果变混浊，则应尽快丢弃。
完整说明附件：https://hemonc.org/docs/packageinsert/asparaginase.pdf
Elspar®
By
Class: Chemotherapy
Generic Name: asparaginase (a-SPARE-a-ji-naze), l-asparaginase, erwinia l-asparaginase
Trade Name: Elspar®, Kidrolase®
For which conditions is this drug approved?
Asparaginase is FDA approved for the treatment of acute lymphocytic leukemia. It is recommended that asparaginase be used in conjunction with other agents, if not contraindicated in patients, in a regimen for the induction of remission, not as maintenance therapy for acute lymphocytic leukemia.
What is the mechanism of action?
Asparaginase is an enzyme. Asparaginase produces its anti-cancer effects by “breaking down” asparagine, a substance normally found in the body that is involved in biological processes that are essential for cells to maintain life. Healthy cells are able to create asparagine for themselves; however, cancer cells are not able to create asparagine. Therefore, the depletion of asparagine by asparaginase kills cancer cells, while healthy cells are not as affected.
How is asparaginase typically given (administered)?
Asparaginase may be given in a vein (intravenous) or as an injection into a muscle (intramuscular), and the dose depends on several factors, including the condition being treated, the size of the patient, the particular regimen being used, and the overall health of the patient. Patients will often receive a small “test” dose under the skin (intradermal) prior to therapy to detect an allergic reaction to asparaginase. During administration of asparaginase, patients will be closely monitored as they may experience a serious allergic reaction. If patients experience difficulty in breathing, wheezing, itching, agitation, lightheadedness, or swelling of the face during administration of asparaginase, they should notify their healthcare provider immediately.
How are patients typically monitored?
Patients will usually have scheduled meetings with their healthcare provider while they are being treated with asparaginase. Typically, blood will be drawn to check levels of blood sugar, levels of electrolytes, functions of organs, such as the pancreas, liver and kidneys, function of blood clotting and levels of blood cells. Patients may also undergo physical examinations, scans or other measures to assess side effects and response to therapy.
What are the common (occur in 30% or more of patients) side effects of treatment with asparaginase?
Fever
Chills
Nausea and vomiting
Allergic reaction during administration consisting of difficulty breathing, wheezing, itching, rash, swelling of face, agitation, fever, low blood pressure
Loss of appetite
Abdominal cramping
Excessive fatigue or sleepiness
Depression
Hallucinations
Agitation
Disorientation or confusion
Seizure
What are the less common (occur in 10% to 29% of patients) side effects of treatment with asparaginase?
Mouth sores
Pancreatitis(inflammation of the pancreas) in up to 10% of patients
Increased levels of sugar in the blood
Abnormalities of liver or kidney function tests
Increased risk of bleeding
Increased risk of blood clotting
This is not a complete list of side effects. Some patients may experience other side effects that are not listed here. Patients may wish to discuss with their physician the other less common side effects of this drug, some of which may be serious.
Some side effects may require medical attention. Other side effects do not require medical attention and may go away during treatment. Patients should check with their physician about any side effects that continue or are bothersome.
What can patients do to help alleviate or prevent discomfort and side effects?
Pay careful attention to the physician’s instructions and inform the physician of any side effects.
Maintain adequate rest and nutrition.
Wear sunscreen and protective clothing and try to minimize sun exposure.
Drink plenty of fluids. (Patients should ask their physician about the amount of liquid to consume during a day.)
Eat small meals frequently to help alleviate nausea.
Use a soft toothbrush and an electric razor to prevent cuts on the mouth or skin.
For mouth sores, patients should rinse their mouth three times a day with a salt and sod solution (8 ounces of water mixed with ½ to 1 tsp baking soda and/or ½ to 1 tsp salt) and brush their teeth with a soft toothbrush to help prevent the development of mouth sores.
Are there any special precautions patients should be aware of before starting treatment?
Patients should inform their physician if they are pregnant, breastfeeding or planning a family in the near future. This drug may cause birth defects. It is important to use some kind of birth control while undergoing treatment. Also, patients may want to talk to their physician if they are considering having children in the future, since some drugs may cause fertility problems.
It is important that patients inform their physician of any pre-existing conditions (chicken pox, heart disease, kidney disease, liver disease, lung disease, etc.) as they may worsen with this drug.
Patients should inform their physician of any history of pancreatitis.
Patients should inform their physician of any other medication they are taking (whether prescription or over-the-counter, including vitamins, herbs, etc.) as they may interfere with treatment.
Patients should check with their physician before starting any new drug or nutritional supplement.
Patients should inform their physician of any known drug or food allergies or any reactions to medications they have experienced in the past.
When should patients notify their physician?
Allergic reaction (hives, itching, tightness of chest, difficulty breathing, swelling)
Wheezing
Severe nausea
Prolonged vomiting
Fever or chills
Signs of infection
Prolonged upper abdominal pain or pain that increases after eating
Itching, rash
Abdominal swelling
Severe or prolonged diarrhea
Unusual bleeding or bruising
Swelling, redness and/or pain in one leg or arm
Extreme fatigue
Yellowing of the skin or eyes
Unusual thirst, need to urinate frequently
Confusion, excessive sleepiness, hallucinations, agitation, anxiety, or disorientation
Seizures
What is a package insert?
A package insert is required by the FDA and contains a summary of the essential scientific information needed for the safe and effective use of the drug for healthcare providers and consumers. A package insert typically includes information regarding specific indications, administration schedules, dosing, side effects, contraindications, results from some clinical trials, chemical structure, pharmacokinetics and metabolism of the specific drug. By carefully reviewing the package insert, you will get the most complete and current information about how to safely use this drug. If you do not have the package insert for the drug you are using, your pharmacist or physician may be able to provide you with a copy.
Last updated on 09/16.
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