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1、Contents目录1.GEMZAR DRUG DESCRIPTION 健择药物说明32. GEMZAR INDICATION & DOSAGE 健择适应症和用量52.1 Indications 适应症52.1.1 Ovarian Cancer 卵巢癌52.1.2 Breast Cancer 乳腺癌52.1.3 Non-Small Cell Lung Cancer 非小细胞肺癌52.1.4 Pancreatic Cancer 胰腺癌52.2 Dosage and Administration 用法用量62.2.1 Ovarian Cancer 卵巢癌62.2.2 Breast Cancer 乳
2、腺癌72.2.3 Non-Small Cell Lung Cancer 非小细胞肺癌82.2.4 Pancreatic Cancer 胰腺癌92.2.5 Preparation and Administration Precautions 制备和使用预防措施102.2.6 Preparation for Intravenous Infusion Administration 制备静脉注射液112.3 How Supplied 如何给药122.3.1 Dosage Forms and Strengths122.3.2 Storage and Handling123.GEMZAR SIDE EFF
3、ECTS & DRUG INTERACTIONS 健择的不良反应和药物的相互作用133.1 Side Effects 不良反应133.2 Drug Interactions 药物相互作用304 GEMZAR WARNINGS & PRECAUTIONS 健择警告和预防措施314.1 Warnings 警告314.2 Precautions 预防措施314.2.1 Infusion Time314.2.2 Hematology314.2.3 Pulmonary314.2.4 Renal314.2.5 Hepatic324.2.6 Pregnancy324.2.7 Laboratory Tests
4、324.2.8 Radiation Therapy334.2.9 Nonclinical Toxicology334.2.10 Use In Specific Populations344.2.10.1 Pregnancy344.2.10.2 Nursing Mothers344.2.10.3 Pediatric Use354.2.10.4 Geriatric Use354.2.10.5 Renal364.2.10.6 Hepatic364.2.10.7 Gender365.GEMZAR OVERDOSAGE & CONTRAINDICATIONS 健择过量和禁忌征候385.1 Overdos
5、age 过量385.2 Contraindications 禁忌征候386. GEMZAR CLINICAL PHARMACOLOGY 健择临床药理学391.Gemzar Drug Description 健择药物说明Brand Name: Gemzar Generic Name: Gemcitabine HclGemzar Drug DescriptionGEMZAR(gemcitabine for injection) Powder, Lyophilized, For Solution For Intravenous UseGemzar (gemcitabine for injection
6、, USP) is a nucleoside metabolic inhibitor that exhibits antitumor activity. Gemcitabine HC1 is 2-deoxy-2,2-difluorocytidine monohydrochloride (-isomer).健择(吉西他滨注射剂)是一种核苷代谢抑制剂，具有抗肿瘤活性。盐酸吉西他滨的化学名是：2-去氧-2,2-二氟胞啶一盐酸 (-异构体).The structural formula is as follows:The empirical formula for gemcitabine HC1 is
7、 C9H11F2N3O4HCl. It has a molecular weight of 299.66.盐酸吉西他滨的实验式是C9H11F2N3O4HCl，分子式是299.66。Gemcitabine HC1 is a white to off-white solid. It is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol and polar organic solvents.盐酸吉西他滨是一种白色至灰白色的固体，溶于水，微溶于甲醇，几乎不溶于乙醇和极性有机溶剂。T
8、he clinical formulation is supplied in a sterile form for intravenous use only. Vials of Gemzar contain either 200 mg or 1 g of gemcitabine HC1 (expressed as free base) formulated with mannitol (200 mg or 1 g, respectively) and sodium acetate (12.5 mg or 62.5 mg, respectively) as a sterile lyophiliz
9、ed powder. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.Last reviewed on RxList: 4/4/2011临床上仅以无菌的注射剂型给药。每瓶健择含200mg或1g盐酸吉西他滨（以游离碱计），200mg或1g甘露醇，12.5 mg or 62.5 mg乙酸钠，用盐酸或氢氧化钠调节pH。2. Gemzar Indication & Dosage 健择适应症和用量2.1 Indications 适应症2.1.1 Ovarian Cancer 卵巢癌Gemzar
10、 (gemcitabine hcl) in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.健择（盐酸吉西他滨）与卡波铂联合应用于治疗（铂类基础治疗后至少6个月）复发性晚期卵巢癌。2.1.2 Breast Cancer 乳腺癌Gemzar (gemcitabine hcl) in com
11、bination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.健择（盐酸吉西他滨）与紫杉醇联合应用于一线治疗（蒽环类抗生素药物辅助化疗失败的）转移性乳腺癌，除非蒽环类抗生素被临床禁忌。2.1.3
12、 Non-Small Cell Lung Cancer 非小细胞肺癌Gemzar (gemcitabine hcl) is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer.健择（盐酸吉西他滨）与顺铂联合应用于一线治疗手术不能治愈的局部晚期（阶段IIIA 或 IIIB)或
13、转移性（阶段IV)非小细胞肺癌。2.1.4 Pancreatic Cancer 胰腺癌Gemzar (gemcitabine hcl) is indicated as first-line treatment for patients with locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. Gemzar (gemcitabine hcl) is indicated for patients previously tre
14、ated with 5-FU.健择（盐酸吉西他滨）一线治疗局部晚期（不能被切除的II期 或 III期）或转移性（IV期）胰腺癌。健择（盐酸吉西他滨）可用于经5-氟脲苷治疗的患者。2.2 Dosage and Administration 用法用量Gemzar (gemcitabine hcl) is for intravenous use only. Gemzar (gemcitabine hcl) may be administered on an outpatient basis.健择（盐酸吉西他滨）只用于静脉注射。健择（盐酸吉西他滨）可用于门诊患者。2.2.1 Ovarian Cance
15、r 卵巢癌Gemzar (gemcitabine hcl) should be administered intravenously at a dose of 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle. Carboplatin AUC 4 should be administered intravenously on Day 1 after Gemzar (gemcitabine hcl) administration. Patients should be monitored prior to each d
16、ose with a complete blood count, including differential counts. Patients should have an absolute granulocyte count 1500 x 106/L and a platelet count 100,000 x 106/L prior to each cycle.健择（盐酸吉西他滨）应静脉注射1000 mg/m2 30分钟（在第1天和第8天），每21天一个周期。在健择（盐酸吉西他滨）注射后1天，静脉注射卡波铂（浓度时间曲线4）。用药前应监测患者完整的血球数，包括差异数。在每一个周期前，患者
17、完全粒细胞数应 1500 x 106/L，血小板数 100,000 x 106/L。2.2.1.1 Dose Modifications 剂量调整Gemzar (gemcitabine hcl) dosage adjustment for hematological toxicity within a cycle of treatment is based on the granulocyte and platelet counts taken on Day 8 of therapy. If marrow suppression is detected, Gemzar (gemcitabine
18、 hcl) dosage should be modified according to guidelines in Table 1.每次治疗周期后，要根据血液毒性（基于治疗的第8天的粒细胞数和血小板数）调整健择（盐酸吉西他滨）剂量。若检测到骨髓抑制，健择（盐酸吉西他滨）用量应根据表1中的方法进行调整。Table 1: Day 8 Dosage Reduction Guidelines for Gemzar (gemcitabine hcl) in Combination with Carboplatin表1:健择（盐酸吉西他滨）与卡波铂联合应用第8天剂量减少指导原则Absolute gran
19、ulocyte count完全粒细胞数(x 106/L) Platelet count血小板数(x 106/L)% of full dose剂量百分比 1500And 100,0001001000-1499and/or75,000-99,99950 1000and/or 75,000HoldIn general, for severe (Grade 3 or 4) non-hematological toxicity, except nausea/vomiting, therapy with Gemzar (gemcitabine hcl) should be held or decrease
20、d by 50% depending on the judgment of the treating physician. For carboplatin dosage adjustment, see manufacturers prescribing information.通常情况下，严重的（3级或4级）非血液毒性（除恶心/呕吐）都可以持续使用健择（盐酸吉西他滨）或根据医嘱减少50%的剂量。对于卡波铂的剂量调整，见制造商的处方信息。Dose adjustment for Gemzar (gemcitabine hcl) in combination with carboplatin for
21、 subsequent cycles is based upon observed toxicity. The dose of Gemzar (gemcitabine hcl) in subsequent cycles should be reduced to 800 mg/m2 on Days 1 and 8 in case of any of the following hematologic toxicities:根据观察到的毒性，调整后期疗程中健择（盐酸吉西他滨）与卡波铂联合使用的剂量。根据如下血液毒性，在第1天和第8天剂量减少为800 mg/m2。 Absolute granuloc
22、yte count 500 x 106/L for more than 5 days 长达5天以上，完全粒细胞数 500 x 106/L Absolute granulocyte count 100 x 106/L for more than 3 days Febrile neutropenia 3天以上，中性粒细胞减少伴发热，完全粒细胞数 100 x 106/L Platelets 25,000 x 106/L 血小板数 75,0001001000-1199Or50,000-75,00075700-999And 50,00050 700Or 50,000HoldIn general, for
23、 severe (Grade 3 or 4) non-hematological toxicity, except alopecia and nausea/vomiting, therapy with Gemzar (gemcitabine hcl) should be held or decreased by 50% depending on the judgment of the treating physician. For paclitaxel dosage adjustment, see manufacturers prescribing information.通常情况下，严重的（
24、3级或4级）非血液毒性（除脱发/恶心/呕吐）都可以持续使用健择（盐酸吉西他滨）或根据医嘱减少50%的剂量。对于紫杉醇的剂量调整，见制造商的处方信息。2.2.3 Non-Small Cell Lung Cancer 非小细胞肺癌Two schedules have been investigated and the optimum schedule has not been determined see Clinical Studies. With the 4-week schedule, Gemzar (gemcitabine hcl) should be administered intra
25、venously at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15 of each 28-day cycle. Cisplatin should be administered intravenously at 100 mg/m2 on Day 1 after the infusion of Gemzar (gemcitabine hcl) . With the 3-week schedule, Gemzar (gemcitabine hcl) should be administered intravenously at 1250 mg/m
26、2 over 30 minutes on Days 1 and 8 of each 21-day cycle. Cisplatin at a dose of 100 mg/m2 should be administered intravenously after the infusion of Gemzar (gemcitabine hcl) on Day 1. See prescribing information for cisplatin administration and hydration guidelines.调查两个时间安排，选出最佳用药时间（见临床研究）。4周一疗程，在第1天
27、、第8天和第15天静脉注射健择（盐酸吉西他滨）1000 mg/m2 30分钟，每28天为一个疗程。健择（盐酸吉西他滨）静脉注射后第1天，静脉注射顺铂100 mg/m2。3周一疗程，在每一个21天的周期中的第1天和第8天静脉注射健择（盐酸吉西他滨）1250 mg/m2。健择（盐酸吉西他滨）注射后的第1天，静脉注射顺铂100 mg/m2。（见顺铂使用和水化指导方法）Dose Modifications 剂量调整Dosage adjustments for hematologic toxicity may be required for Gemzar (gemcitabine hcl) and fo
28、r cisplatin. Gemzar (gemcitabine hcl) dosage adjustment for hematological toxicity is based on the granulocyte and platelet counts taken on the day of therapy. Patients receiving Gemzar (gemcitabine hcl) should be monitored prior to each dose with a complete blood count (CBC), including differential
29、 and platelet counts. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 3. For cisplatin dosage adjustment, see manufacturers prescribing information.要根据血液毒性（基于治疗当天的粒细胞数和血小板数）调整健择（盐酸吉西他滨）和顺铂的剂量。每次用药前应监测完全血细胞数，包括差异数和血小板数。若监测到骨髓抑制，应根据表3中的方法
30、进行剂量调整或暂停使用。对于顺铂的剂量调整，见制造商的处方信息。In general, for severe (Grade 3 or 4) non-hematological toxicity, except alopecia and nausea/vomiting, therapy with Gemzar (gemcitabine hcl) plus cisplatin should be held or decreased by 50% depending on the judgment of the treating physician. During combination thera
31、py with cisplatin, serum creatinine, serum potassium, serum calcium, and serum magnesium should be carefully monitored (Grade 3/4 serum creatinine toxicity for Gemzar (gemcitabine hcl) plus cisplatin was 5% versus 2% for cisplatin alone).通常情况下，即使发生严重的（3级或4级）非血液毒性（除脱发/恶心/呕吐）都可以持续联合使用健择（盐酸吉西他滨）和顺铂，或根据
32、医嘱减少50%的剂量。在与顺铂联合治疗期间，密切监测血清肌酐，血钾，血钙，血镁（健择（盐酸吉西他滨）顺铂联合用药：顺铂（5%：2%），3/4级血清肌酐毒性）。2.2.4 Pancreatic Cancer 胰腺癌Gemzar (gemcitabine hcl) should be administered by intravenous infusion at a dose of 1000 mg/m2 over 30 minutes once weekly for up to 7 weeks (or until toxicity necessitates reducing or holding
33、a dose), followed by a week of rest from treatment. Subsequent cycles should consist of infusions once weekly for 3 consecutive weeks out of every 4 weeks.静脉注射健择（盐酸吉西他滨）1000 mg/m2 30分钟，每周1次，持续7周（或因毒性，减少/暂停用药），然后休息一周。随后的每4周的疗程中，每周注射一次，连续3周。Dose Modifications 剂量调整Dosage adjustment is based upon the de
34、gree of hematologic toxicity experienced by the patient see WARNINGS AND PRECAUTIONS. Clearance in women and the elderly is reduced and women were somewhat less able to progress to subsequent cycles see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY.根据监测到的患者血液毒性程度，调整剂量见警告和预防措施。对妇女和老人减少用药，妇女在随后的疗
35、程中进展不是那么强。见警告和预防措施Patients receiving Gemzar (gemcitabine hcl) should be monitored prior to each dose with a complete blood count (CBC), including differential and platelet count. If marrow suppression is detected, therapy should be modified or suspended according to the guidelines in Table 3.每次使用健择（
36、盐酸吉西他滨）前密切监测完全粒细胞数（CBC），包括差异数和血小板数。若监测到骨髓抑制，应根据表3中的方法进行剂量调整或暂停使用。Table 3: Dosage Reduction Guidelines表3：剂量减少指导Absolute granulocyte count 完全粒细胞数 (x 106/L) Platelet count血小板数(x 106/L)% of full dose计量百分比 1000And 100,000100500-999Or50,000-99,99975 500Or 50,000Hold 暂停Laboratory evaluation of renal and he
37、patic function, including transaminases and serum creatinine, should be performed prior to initiation of therapy and periodically thereafter. Gemzar (gemcitabine hcl) should be administered with caution in patients with evidence of significant renal or hepatic impairment as there is insufficient inf
38、ormation from clinical studies to allow clear dose recommendation for these patient populations.在治疗开始前和治疗后应进行肾脏肝脏功能实验室评价，包括转氨酶、肌酐。对于严重肾脏或肝脏损伤的患者，应谨慎使用健择（盐酸吉西他滨），因为临床研究上，尚没有明确的推荐剂量。Patients treated with Gemzar (gemcitabine hcl) who complete an entire cycle of therapy may have the dose for subsequent
39、cycles increased by 25%, provided that the absolute granulocyte count (AGC) and platelet nadirs exceed 1500 x 106/L and 100,000 x 106/L, respectively, and if non-hematologic toxicity has not been greater than WHO Grade 1. If patients tolerate the subsequent course of Gemzar (gemcitabine hcl) at the
40、increased dose, the dose for the next cycle can be further increased by 20%, provided again that the AGC and platelet nadirs exceed 1500 x 106/L and 100,000 x 106/L, respectively, and that non-hematologic toxicity has not been greater than WHO Grade 1.健择（盐酸吉西他滨）治疗的患者，整个治疗周期结束后，若粒细胞数(AGC)和血小板数分别不低于15
41、00 x 106/L 和 100,000 x 106/L，并且非血液毒性未超过WHO1级，随后的疗程中剂量增加25%。若患者在随后的健择（盐酸吉西他滨）治疗中，能耐受增加的剂量，且粒细胞数(AGC)和血小板数分别不低于1500 x 106/L 和 100,000 x 106/L，并且非血液毒性未超过WHO1级，下一疗程可再增加20%的剂量。2.2.5 Preparation and Administration Precautions 制备和使用预防措施Caution should be exercised in handling and preparing Gemzar (gemcitabi
42、ne hcl) solutions. The use of gloves is recommended. If Gemzar (gemcitabine hcl) solution contacts the skin or mucosa, immediately wash the skin thoroughly with soap and water or rinse the mucosa with copious amounts of water. Although acute dermal irritation has not been observed in animal studies, 2 of 3 rabbits exhibited drug-related systemic toxicities (death, hypoactivity, nasal discharge, shallow breathing) due to dermal absorption.处理和准备健择（盐酸吉西他滨）时要谨慎。建议使用手套。若健
