部份中文普来纳西处方资料(仅供参考) 商品名：普来纳西 Plenaxis 通用名：注射用阿巴瑞克（abarelix，粉剂和溶剂注射液） 开发与上市厂商 本品由美国Praecis Pharma-ceuticals公司研制，2004年1月首次在美国上市。 适应证 阿巴瑞克(abarelix)获准用于不适宜接受促黄体生成素释放激素（LHRH）激动剂治疗又拒绝手术切除、并有下述一种或几种情况的晚期症状性前列腺癌 (PCA)的姑息治疗：①由于肿瘤转移可能出现神经危害；②由于局部侵犯或转移性疾病出现输尿管或膀胱出口阻塞；③由于肿瘤骨转移而出现严重骨痛需依赖麻醉性镇痛药。 药理作用 本品通过直接抑制黄体生成素 (LH)和促卵泡激素(FSH)分泌而减少睾丸内睾酮的生成。由于本品直接抑制L日的分泌，因此血浆睾酮浓度不会有先升高后降低的现象。 14例健康志愿者（年龄52～75 岁，体重61.6～110.5kg）接受单剂量本品1OOmg肌肉注射治疗，吸收缓慢，Cmax为(43.4±32.3)ng/mL， Tmax为（3.0±2.9）天，AUC0-∞为（500 ±96）ng·d/mL，t1/2为（13.2±3.2）天，CL/F为（208±48）L/d。 本品消除终末期表观分布容积为（4040±1607）L，提示本品在体内广泛分布。肝细胞体外试验（大鼠、猴子、人）和体内试验（大鼠、猴子）显示，本品主要通过肽键水解代谢。尚无证据显示细胞色素P450 参与本品的代谢过程。本品血浆蛋白结合率较高（96％～99％）。 临床肌肉注射15μg/kg本品，约有13％的原形药随尿液排出，尿液中未检出其他代谢产物。本品注射100mg的肾清除率为14.4L/d（或 10 mL/min）。 临床评价 针对接受LHRH激动剂可能出现临床症状恶化的晚期前列腺癌患者的一项临床研究，募集了81例患者。该研究为标签公开的多中心非对照单组临床研究，目的在于明确这类患者通过12周的治疗能否避免施行攀丸切除术。研究中，所有患者至少接受6周治疗，然后决定是否继续后续研究。 在募集的81例患者中，9例患者由于资料不全未能做疗效分析，可进行疗效评价的72例参与该研究的患者为：前列腺癌骨转移引起骨痛31例；前列腺或盆腔肿块导致膀胱颈出口梗阻25例；双侧腹膜后淋巴腺增大并伴有输尿管梗阻9例；脊柱、脊髓或硬膜外转移即将出现神经损害6例；其他1例。平均年龄73 岁（40～94岁）。 给药方案 为第1、15、29天肌肉注偏寸本品1OOmg，每4周重复。12例患者在第169天前中止治疗，原因有：不良反应（2例）、自愿退出（3例）、死亡（4例）和其他（3例）。有60例患者至少接受了24周治疗。有 33例至少治疗了48周，15例至少治疗了96周（中位治疗时间为40周）。 在本研究中，有57例（79％）在第8天达到了药物去势效果（血浆总睾酮浓度≤50 ng/dL），68例(96%) 在第4周达到了药物去势。 虽然本研究的设计目标并不是评估特定临床效果，但可观察到如下结果： ①8例脊椎或硬膜外转移但未出现神经学症状的患者中无，例出现神经损害症状； ②13例因膀胱出口梗阻而插膀胱引流管的患者，10例在12周后拔除了引流管； ③15例骨转移患者治疗12周后疼痛减轻，使用麻醉性镇痛药的药效强度、用量和频率均降低。 不良反应 临床研究显示，本品用于前列腺癌（大部分为晚期无症状性前列腺癌）治疗，可引起急性全身性过敏反应（在给药后30分钟内发生），发生率为1.1％（15例／1397例），其中，14例在注射后8分钟内就出现症状。该风险随治疗时间的延长而增加，在第56、141、365和 676天的累积发生率（95%置信区间）分别为0.51％（0.13%, 0.88%）、 0.80％（0.30％，1.29％）、1.24％（0.43％，2.04％）和2.91％（0.87％， 4.95％）。7例发生低血压和昏厥，发生率为0.5%，第56、141、365 和676天的累积发生率（95%置信区间）分别为0.22%（0.0%, 0.46%）、 0.32％（0.0％，0.64％）、0.61％（0.0％，1.24％）和1.67％（0.07％， 3.28%）。 针对晚期症状性前列腺癌患者，本品不良反应发生率居前的有潮热（79%）、睡眠障（44%）、疼痛（31％）、乳房发育（30%）、胸痛／乳头胀痛（20%）、背部疼痛（17%）、便秘（15%）、和周围水肿（15%）等。 患者注射本品后至少应观察30 分钟。如出现低血压和昏厥，应采取适当的救助措施，如抬高腿部、给氧、静脉输液、给予抗组胺药物、糖皮质激素和肾上腺素等。 个别患者可出现较明显的血浆转氨酶升高。血浆转氨酶超过正常范围上限的2.5倍或＞200U/L的发生率分别为3.1％和0.8%。血红蛋白轻微下降为化学去势后的生理反应。还可出现血浆甘油三酯水平升高（平均达10%）。 注意事项 体重超过102kg（225磅）的患者，应确保严格的血浆睾酮水平监测。患者在开始接受本品治疗前应测定血浆转氨酶水平，并且在治疗期间需定期监测。 本品对儿科患者的安全性和有效性尚未进行研究，另外，其是否在乳汁中有分泌尚不清楚，因此儿科患者和哺乳期妇女禁用。 用法与用量 出于安全考虑，目前本品临床处方尚有一定限制。 本品的推荐方案为第1、15、 29天给予本品100mg肌肉注射，每4周为一疗程。在第29天注射前测定血浆睾酮水平以确定疗效，其后每8周测定一次。 制剂 注射用无菌粉针剂，每瓶含本 ppCMC复合物113mg，临用前加入 2.2mL 0.9%氯化钠溶液溶解，使成 2mL含本品1OOmg（50mg/mL）的一次给药剂量。 abarelix (Plenaxis®)100mg powder and solvent for suspension for injection WARNING Immediate-onset systemic allergic reactions, some resulting in hypotension and syncope, have occurred after administration of Plenaxis™. These immediate-onset reactions have been reported to occur following any administration of Plenaxis™, including after the initial dose. The cumulative risk of such a reaction increases with the duration of treatment (see WARNINGS). Following each injection of Plenaxis™, patients should be observed for at least 30 minutes in the office and in the event of an allergic reaction, managed appropriately. Only physicians who have enrolled in the Plenaxis™ PLUS Program (Plenaxis™ User Safety Program), based on their attestation of qualifications and acceptance of prescribing responsibilities, may prescribe Plenaxis™ (See DOSAGE AND ADMINISTRATION and HOW SUPPLIED). Plenaxis™ is indicated for the palliative treatment of men with advanced symptomatic prostate cancer, in whom LHRH agonist therapy is not appropriate and who refuse surgical castration, and have one or more of the following: (1) risk of neurological compromise due to metastases, (2) ureteral or bladder outlet obstruction due to local encroachment or metastatic disease, or (3) severe bone pain from skeletal metastases persisting on narcotic analgesia. The effectiveness of Plenaxis™ in suppressing serum testosterone to castrate levels decreases with continued dosing in some patients (see CLINICAL PHARMACOLOGY, Pharmacodynamics). Effectiveness beyond 12 months has not been established. Treatment failure can be detected by measuring serum total testosterone concentrations just prior to administration on Day 29 and every 8 weeks thereafter (see WARNINGS). DESCRIPTION Abarelix for injectable suspension (Plenaxis™) is a synthetic decapeptide with potent antagonistic activity against naturally occurring gonadotropin releasing-hormone (GnRH). Plenaxis™ inhibits gonadotropin and related androgen production by directly and competitively blocking GnRH receptors in the pituitary. Abarelix is chemically described as acetyl-D-ß-naphthylalanyl- D-4-chlorophenylalanyl-D-3-pyridylalanyl-L-seryl-L- N-methyl-tyrosyl-D-asparagyl-L-leucyl-L-N(e )-isopropyl-lysyl-L-prolyl-D-alanyl-amide. It is initially manufactured as an acetate water complex and converted to a carboxymethylcellulose (CMC) water complex in manufacturing the drug product. The molecular weight for abarelix anhydrous free base is 1416.06. Abarelix for injectable suspension is supplied as a white to off-white sterile dry powder which, when mixed with the diluent, 0.9% Sodium Chloride Injection, USP, becomes a depot suspension intended for intramuscular (IM) injection. The single-dose vial contains 113 mg of anhydrous free base abarelix peptide (net) supplied in an abarelix CMC complex. This complex also contains 19.1 to 31 mg of CMC. After the vial is reconstituted with 2.2 mL of 0.9% sodium chloride injection, 2 mL is administered to deliver a dose of 100 mg of abarelix (net) as the abarelix CMC complex at a pH of 51. INDICATIONS AND USAGE Plenaxis™ is indicated for the palliative treatment of men with advanced symptomatic prostate cancer, in whom LHRH agonist therapy is not appropriate and who refuse surgical castration, and have one or more of the following: (1) risk of neurological compromise due to metastases, (2) ureteral or bladder outlet obstruction due to local encroachment or metastatic disease, or (3) severe bone pain from skeletal metastases persisting on narcotic analgesia. DOSAGE AND ADMINISTRATION For safety reasons, Plenaxis™ is approved with marketing restrictions. Only physicians who attest to the following qualifications and accept the following responsibilities, and on that basis enroll in PRAECIS PHARMACEUTICALS INCORPORATEDs Plenaxis™ PLUS Program should prescribe Plenaxis™. PRAECIS PHARMACEUTICALS INCORPORATED and its agents will provide Plenaxis™ to physicians enrolled in the Plenaxis™ PLUS Program. To enroll, physicians must attest that they are able and willing to: diagnose and manage advanced symptomatic prostate cancer. diagnose and treat allergic reactions, including anaphylaxis. have access to medication and equipment necessary to treat allergic reactions, including anaphylaxis. have patients observed for development of allergic reactions for 30 minutes following each administration of Plenaxis™. understand the risks and benefits of palliative treatment with Plenaxis™, including information from the Package Insert, Patient Information, and the Physician Attestation. educate the patients on the risks and benefits of treatment with Plenaxis™ and obtain the patients signature on the Patient Information signature page, sign it, and place the original signed form in the patients medical record, and give a copy of the Patient Information leaflet with the signed page to the patient. report serious adverse events, such as any immediate-onset systemic allergic event (including anaphylaxis, hypotension, and syncope) as soon as possible to PRAECIS PHARMACEUTICALS INCORPORATED at 1-866-PLENAXIS (1-866-753-6294) or to the Food and Drug Administrations MedWatch Program at 1-800-FDA-1088. understand that they may withdraw their enrollment in the Plenaxis™ Prescribing Program by a written statement submitted to PRAECIS PHARMACEUTICALS INCORPORATED (contact information below) or that PRAECIS PHARMACEUTICALS INCORPORATED may withdraw physicians from the Plenaxis™ PLUS Program if they do not meet the agreed upon responsibilities. To enroll in the Plenaxis™ Prescribing Program call 1-866-PLENAXIS (1-866-753-6294) or visit www.plenaxisplus.com. Dose: The recommended dose of Plenaxis™ is 100 mg administered intramuscularly to the buttock on Day 1, 15, 29 (week 4) and every 4 weeks thereafter. Treatment failure can be detected by measuring serum testosterone concentrations just prior to Plenaxis™ administration, beginning on Day 29 and every 8 weeks thereafter. Directions for Reconstituting and Administering Plenaxis™ Read the instructions completely before performing reconstitution. The sterile powder for suspension is to be reconstituted in accordance with the following directions: Reconstitution Instructions for 1 Vial of Plenaxis™ to Provide a 100 mg (50 mg/mL) Dose as a Single IM Injection Use aseptic technique throughout. Prior to reconstitution, gently shake the vial of Plenaxis™ (abarelix for injectable suspension). Hold the vial at an angle (45 degrees) and tap lightly on table to break up any caking. Withdraw 2.2 mL of 0.9% Sodium Chloride Inj., USP using the enclosed 18 G x 1 " needle and a 3 cc syringe. Discard the remaining diluent. Keeping the vial upright, insert the needle all the way into the vial and inject the diluent quickly. Before withdrawing the needle, remove 2.2 mL of air. Shake immediately. Shake for approximately 15 seconds. Allow the vial to stand for approximately 2 minutes. Tap the vial to reduce foaming and swirl the vial occasionally. Again, shake for approximately 15 seconds. Allow the vial to stand for approximately 2 minutes. Tap the vial to reduce foaming and swirl the vial occasionally. Do not reinject the air into the vial. Locate a second injection spot on the stopper, and then insert the 18 G needle. Invert the vial and draw up some of the suspension into the syringe and without removing the needle from the vial reinject it at any remaining solids in the vial. Repeat the process until all solids are dispersed. Swirl the vial before withdrawal and withdraw the entire contents (at least 2 mL) by positioning the needle at a 45 degree angle as shown in the picture. Pull the plunger back to recover the residual suspension in the 18 G x1" needle. Exchange the 18 G x 1 " needle with the enclosed 22 G x 1" Safety Glide™ injection needle. Insert the needle at the desired injection site, pull the plunger back to check for back-flow of blood. If blood flows into the syringe, do not inject at this site. Select another injection site. Deliver the entire reconstituted suspension intramuscularly immediately. Observe the patient after injection for 30 minutes for any sign of an allergic-type response. Plenaxis™ does not contain a preservative and should be administered within 1 hour following reconstitution. STORAGE Store at 25C (77F), excursions permitted to 15-30 C (59-86 F), USP Controlled Room Temperature. http://www.kiessig.com/drugs/druginfo.aspx?id=1451 美国FDA批准晚期前列腺癌的新药Plenaxis(通用名：abarelix) 新药阿巴瑞克（通用名：abarelix，商品名：Plenaxis，普来纳西) 及Degarelix属于促性腺激素释放激素(GnRH)受体抑制剂。其作用原理与激动剂相同，但仅是具有拮抗剂作用，它与垂体GnRH受体结合，直接抑制LH和FSH的释放，导致血清睾酮迅速降低到去势水平而无促进作用，其抑制睾酮分泌，不存在血清睾酮的一过性升高和患者病情加重的所谓“Flare 现象”，而延缓前列腺癌的生长和发展。 2003年被美国FDA批准用于临床，2004年1月首次在美国上市。阿巴瑞克：每次100 mg肌肉注射，第15天加用1次，每28天为1周期。 美国食品药品管理局（FDA）推荐阿巴瑞克主要用于晚期前列腺癌的姑息治疗，同时患者也必须满足以下3个条件: ①不适合应用LHRH-a类药物； ②拒绝手术去势治疗； ③患者存在以下情况之一:与肿瘤转移相关的神经压迫危险、肿瘤所致的膀胱和输尿管出口梗阻、骨转移引起的严重骨痛。 本药临床所见最通常的副作用是：热潮红(hot flashes)、睡眠失调、疼痛(包括背痛、胸部增大或疼痛)以及便秘 ------------------------------------- 产地国家： 德国 原产地英文商品名: Plenaxis injection 100mg/vials 1vials/bottle, cold chain product (storage at 2-8 degrees) extra charge for packaging  原产地英文药品名: abarelix  中文参考商品译名: 普来纳西注射混悬液 100毫克/瓶 1瓶/盒 冷链产品（储存在2-8度），需要额外的包装费用 中文参考药品译名: 阿巴瑞克 生产厂家中文参考译名: Praecis 生产厂家英文名: Praecis ------------------------------------- 产地国家： 德国 原产地英文商品名: Plenaxis injection 100mg/vials 3vials/bottle, cold chain product (storage at 2-8 degrees) extra charge for packaging  原产地英文药品名: abarelix 中文参考商品译名: 普来纳西注射混悬液 100毫克/瓶 3瓶/盒 冷链产品（储存在2-8度），需要额外的包装费用 中文参考药品译名: 阿巴瑞克 生产厂家中文参考译名: Praecis 生产厂家英文名: Praecis