英文药名: Elspar (Asparaginase Vials) 中文药名: 天门冬酰胺酶注射剂 生产厂家：Lundbeck公司 药品简介 此药也叫:Leunase. 别名 天门冬酰胺酶, 左旋门冬酰胺酶,爱施巴, L-天门冬酰胺酶, 门冬酰胺酶 外文名 L-Asparaginase , ASP, L-ASP, Elspar, Asparaginase, Leunase. 适应症 对急性粒细胞型白血病和急性单核细胞白血病也有一定疗效。对恶性淋巴瘤也有较好的疗效。其优点是对于常用药物治疗后复发的病例也有效，缺点是单独应用不仅缓解期短，而且很易产生耐药性，故目前大多与其他药物合并应用。对机体免疫有抑制作用，因而有人用来治疗皮肌炎等。 用法用量 可用于静注、静滴、肌注和鞘内注射。一般剂量：每千克体重20～5000单位或每平方米体表面积10000～15000单位，每周3～7次。以每日每千克体重500～100单位较佳。亦可每周应用１次，每次每千克体重2500单位，一般以3～4周为1疗程。总剂量应根据所用药物的纯度和毒性而定。静注以等渗盐水20～40ml稀释，静滴以5%葡萄糖液或等渗盐水500ml稀释。 注意事项 1.大肠杆菌门冬酰胺酶含有内毒素，故可引起发热现象。此外，还常有食欲减退、恶心、呕吐、腹泻等不良反应，有的病人有头痛、头昏、嗜睡、精神错乱等。由于门冬酰胺酶能影响蛋白质的合成和干扰脂质代谢，有的病人有血浆蛋白低下，血脂质过高或过低，氮质血症和肝功能损害。约1/3～1/2病人有骨髓抑制，表现为白细胞和血小板下降，有的病人可有贫血、凝血障碍、局部出血、感染等。有人报告有的病人有心血管系统症状、脱发、蛋白尿等，极少数病人且可发生胰腺炎。 2.可引起过敏反应，故用药前必须先用过敏试验，如有红肿、斑块，则为过敏反应。有过敏史的病人应十分小心或不用。 3.不同药厂、不同批号的产品，其纯度和过敏反应均有差异，使用时必须慎重。 4.有致畸胎作用，故妊娠早期应禁用。 5.肝、肾功能严重损害者忌用。 6.溶解后不宜长时间放置，以免丧失活力。 Generic Name: Asparaginase (a-SPARE-a-ji-naze), L-asparaginase, Erwinia L-asparaginase Elspar (Asparaginase)-Indications and Dosage INDICATIONS AND USAGE ELSPAR is indicated in the therapy of patients with acute lymphocytic leukemia. This agent is useful primarily in combination with other chemotherapeutic agents in the induction of remissions of the disease in pediatric patients. ELSPAR should not be used as the sole induction agent unless combination therapy is deemed inappropriate. ELSPAR is not recommended for maintenance therapy. DOSAGE AND ADMINISTRATION This drug may have toxic properties and must be handled and administered with care. Special handling procedures should be reviewed prior to handling and followed diligently during reconstitution and administration. Inhalation of dust or aerosols and contact with skin or mucous membranes, especially those of the eyes, must be avoided. (See DOSAGE AND ADMINISTRATION, Special Handling.) As a component of selected multiple agent induction regimens, ELSPAR may be administered by either the intravenous or the intramuscular route. When administered intravenously this enzyme should be given over a period of not less than thirty minutes through the side arm of an already running infusion of Sodium Chloride Injection or Dextrose Injection 5% (D5 W). ELSPAR has little tendency to cause phlebitis when given intravenously. Anaphylactic reactions require the immediate use of epinephrine, oxygen, and intravenous steroids. When administering ELSPAR intramuscularly, the volume at a single injection site should be limited to 2 ml. If a volume greater than 2 ml is to be administered, two injection sites should be used. Unfavorable interactions of ELSPAR with some antitumor agents have been demonstrated. It is recommended therefore, that ELSPAR be used in combination regimens only by physicians familiar with the benefits and risks of a given regimen. During the period of its inhibition of protein synthesis and cell replication ELSPAR may interfere with the action of drugs such as methotrexate which require cell replication for their lethal effect. ELSPAR may interfere with the enzymatic detoxification of other drugs, particularly in the liver. Recommended Induction Regimens: When using chemotherapeutic agents in combination for the induction of remissions in patients with acute lymphocytic leukemia, regimens are sought which provide maximum chance of success while avoiding excessive cumulative toxicity or negative drug interactions. One of the following combination regimens incorporating ELSPAR is recommended for acute lymphocytic leukemia in pediatric patients: In the regimens below, Day 1 is considered to be the first day of therapy. Regimen I Prednisone 40 mg/square meter of body surface area per day orally in three divided doses for 15 days, followed by tapering of the dosage as follows: 20mg/square meter for 2 days, 10 mg/square meter for 2 days, 5 mg/square meter for 2 days, 2.5 mg/square meter for 2 days and then discontinue. Vincristine sulfate 2 mg/square meter of body surface area intravenously once weekly on Days 1, 8, and 15 of the treatment period. The maximum single dose should not exceed 2.0 mg. Asparaginase 1,000 I.U./kg/day intravenously for ten successive days beginning on Day 22 of the treatment period. Regimen II Prednisone 40 mg/square meter of body surface area per day orally in three divided doses for 28 days (the total daily dose should be to the nearest 2.5 mg), following which the dosage of prednisone should be discontinued gradually over a 14 day period. Vincristine sulfate 1.5 mg/square meter of body surface area intravenously weekly for four doses, on Days 1, 8, 15, and 22 of the treatment period. The maximum single dose should not exceed 2.0 mg. Asparaginase 6,000 I.U./square meter of body surface area intramuscularly on Days 4, 7, 10, 13, 16, 19, 22, 25, and 28 of the treatment period. When a remission is obtained with either of the above regimens, appropriate maintenance therapy must be instituted. ELSPAR should not be used as part of a maintenance regimen. The above regimens do not preclude a need for special therapy directed toward the prevention of central nervous system leukemia. It should be noted that ELSPAR has been used in combination regimens other than those recommended above. It is important to keep in mind that ELSPAR administered intravenously concurrently with or immediately before a course of vincristine and prednisone may be associated with increased toxicity. Physicians using a given regimen should be thoroughly familiar with its benefits and risks. Clinical data are insufficient for a recommendation concerning the use of combination regimens in adults. Asparaginase toxicity is reported to be greater in adults than in pediatric patients. Use of ELSPAR as the sole induction agent should be undertaken only in an unusual situation when a combined regimen is inappropriate because of toxicity or other specific patient-related factors, or in cases refractory to other therapy. When ELSPAR is to be used as the sole induction agent for pediatric patients or adults the recommended dosage regimen is 200 I.U./kg/ day intravenously for 28 days. When complete remissions were obtained with this regimen, they were of short duration, 1 to 3 months. ELSPAR has been used as the sole induction agent in other regimens. Physicians using a given regimen should be thoroughly familiar with its benefits and risks. Patients undergoing induction therapy must be carefully monitored and the therapeutic regimen adjusted according to response and toxicity. Such adjustments should always involve decreasing dosages of one or more agents or discontinuation depending on the degree of toxicity. Patients who have received a course of ELSPAR, if retreated, have an increased risk of hypersensitivity reactions. Therefore, retreatment should be undertaken only when the benefit of such therapy is weighed against the increased risk. Intradermal Skin Test: Because of the occurrence of allergic reactions, an intradermal skin test should be performed prior to the initial administration of ELSPAR and when ELSPAR is given after an interval of a week or more has elapsed between doses. The skin test solution may be prepared as follows: Reconstitute the contents of a 10,000 I.U. vial with 5.0 ml of diluent. From this solution (2,000 I.U./ml) withdraw 0.1 ml and inject it into another vial containing 9.9 ml of diluent, yielding a skin test solution of approximately 20.0 I.U./ml. Use 0.1 ml of this solution (about 2.0 I.U.) for the intradermal skin test. The skin test site should be observed for at least one hour for the appearance of a wheal or erythema either of which indicates a positive reaction. An allergic reaction even to the skin test dose in certain sensitized individuals may rarely occur. A negative skin test reaction does not preclude the possibility of the development of an allergic reaction. Desensitization: Desensitization should be performed before administering the first dose of ELSPAR on initiation of therapy in positive reactors, and on retreatment of any patient in whom such therapy is deemed necessary after carefully weighing the increased risk of hypersensitivity reactions. Rapid desensitization of the patient may be attempted with progressively increasing amounts of intravenously administered ELSPAR provided adequate precautions are taken to treat an acute allergic reaction should it occur. One reported schedule begins with a total of 1 I.U. given intravenously and doubles the dose every 10 minutes, provided no reaction has occurred, until the accumulated total amount given equals the planned doses for that day. For convenience the following table is included to calculate the number of doses necessary to reach the patient's total dose for that day: For example: a patient weighing 20 kg who is to receive 200 I.U./kg (total dose 4000 I.U.) would recieve injections 1 through 12 during desensitization.  Directions for Reconstitution This drug may have toxic properties and must be handled and administered with care. Inhalation of dust or aerosols and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Appropriate protective equipment should be worn when handling ELSPAR. (See Special Handling.) Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. When reconstituted, ELSPAR should be a clear, colorless solution. If the solution becomes cloudy, discard. For Intravenous Use Reconstitute with Sterile Water for Injection or with Sodium Chloride Injection. The volume recommended for reconstitution is 5 ml for the 10,000 unit vials. Ordinary shaking during reconstitution does not inactivate the enzyme. This solution may be used for direct intravenous administration within an eight hour period following restoration. For administration by infusion, solutions should be diluted with the isotonic solutions, Sodium Chloride Injection or Dextrose Injection 5%. These solutions should be infused within eight hours and only if clear. Occasionally, a very small number of gelatinous fiber-like particles may develop on standing. Filtration through a 5.0 micron filter during administration will remove the particles with no resultant loss in potency. Some loss of potency has been observed with the use of a 0.2 micron filter. For Intramuscular Use When ELSPAR is administered intramuscularly according to the schedule cited in the induction regimen, reconstitution is carried out by adding 2 ml Sodium Chloride Injection to the 10,000 unit vial. The resulting solution should be used within eight hours and only if clear. Special Handling L-asparaginase may be irritating to eyes, skin and the upper respiratory tract. It has also been shown to be embryo-toxic and teratogenic by the intravenous route in animal studies. Due to the drug's potential toxic properties, appropriate precautions including the use of appropriate safety equipment are recommended for the preparation of ELSPAR for administration. Inhalation of dust or aerosols and contact with skin or mucous membranes, especially those of the eyes, must be avoided. The National Institutes of Health presently recommends that the preparation of injectable anti-neoplastic drugs should be performed in a Class II laminar flow biological safety cabinet. Personnel preparing drugs of this class should wear chemical resistant, impervious gloves, safety goggles, outer garments and shoe covers. Additional body garments should be used based upon the task being performed (e.g., sleevelets, apron, gauntlets, disposable suits) to avoid exposed skin surfaces and inhalation of vapors and dust. Appropriate techniques should be used to remove potentially contaminated clothing. Several other guidelines for proper handling and disposal of antineoplastic drugs have been published and should be considered. Accidental Contact Measures Should accidental eye contact occur, copious irrigation for at least 15 minutes with water, normal saline or a balanced salt ophthalmic irrigating solution should be instituted immediately, followed by prompt ophthalmologic consultation. Should accidental skin contact occur, the affected part should be washed immediately with soap and water. Medical attention should be sought. If inhaled, remove from exposure and seek medical attention. (See PRECAUTIONS, General and DOSAGE AND ADMINISTRATION.) HOW SUPPLIED No. 4612 -- ELSPAR is a white lyophilized plug or powder supplied as follows: NDC 0006-4612-00 in a sterile 10 ml vial containing 10,000 I.U. of asparaginase and 80 mg mannitol, an inactive ingredient (6505-01-153-9650 10 mL vial). STORAGE Store at 2-8°C (36-46°F). ELSPAR does not contain a preservative. Unused, reconstituted solution should be stored at 2-8°C (36-46°F) and discarded after eight hours, or sooner if it becomes cloudy.