FDA于2007—10—12批准GlaxoSmithKline生产的0．25和1mg剂量盐酸托泊替康胶囊（topotecan HCl，商品名：Hycamtin）用于对一线化疗产生应答或部分应答的复发性小细胞肺癌患者，推荐给药剂量为2.3mg／m^2，qd，连续5d给药，每21d重复1次。据该公司透露，这是获得批准用于治疗复发陛小细胞肺癌的唯一可单独使用的口服化疗药物。 药物说明 盐酸拓扑替康是一种半合成的喜树碱衍生物，是反与拓扑的I -抑制活性肿瘤的药物。 对盐酸拓扑替康化学名称为（ 拧 ）-10 - [（二甲氨基）甲基] - N -乙基-4,9 -二羟基氢 -吡喃[3'，4'：6,7] indolizino [1,2 - b]喹啉- 3，14 - （4小时，12小时）二酮盐酸盐。它的分子式C 23 0 5•盐酸和457.9分子量ħ 23 ñ 3。 It is soluble in water and melts with decomposition at 213° to 218°C.它溶于水和分解熔点213 °至218 ° C的 和美新胶囊含有盐酸拓扑替康，其内容是免费的基础拓扑替康表示。 主要辅料是氢化植物油，硬脂酸甘油酯，明胶，和二氧化钛。 该胶囊是印有食用黑色墨水。在1毫克胶囊还含有红色氧化铁。 适应症 和美新胶囊批准用于复发性小细胞肺癌患者的治疗与事先完全或部分缓解，谁是至少45个，从第一线化疗结束天。 剂量和用法 推荐计量 和美新胶囊的推荐剂量为2.3毫克/平方米/天，连续5天，每日一次，每21天重复。 环球每日口服剂量计算到最近的0.25毫克，并规定了1毫克和0.25毫克胶囊的最低人数。 在相同数量的胶囊，应订明的5天，每次剂量。 和美新胶囊可采取或没有食物。 胶囊必须整个吞没，不能咀嚼，粉碎，或分歧。 如果在走和美新剂量的病人呕吐，患者不应采取替代剂量。 剂量调整的特殊人群 肾功能损害：没有和美新胶囊剂量调整似乎治疗轻度肾功能不全患者的需要（CLcr = 50-80毫升/分钟）。和美新胶囊的调整剂量为1.8毫克/立方米/天，预计调整曲线下面积（AUC）的病人正常范围内中度肾功能不全的地区（CLcr = 30-49毫升/分钟）。 I资料不充分，治疗重度肾功能不全（CLcr“30毫升/分），以提供一个和美新胶囊剂量的建议[见在特定人群的使用 ]。 调整剂量指南 患者不应该被随后与和美新课程，直到中性粒细胞恢复到“1000个/毫米3，血小板恢复到”十万个/毫米3， 血红蛋白水平恢复到≥9.0克/分升（与输血如有必要）。 对于病人谁遇到严重的中性粒细胞 （中性粒细胞“500细胞/毫米3 发烧或感染或7天或更持久的联系）或中性粒细胞减少（中性粒细胞500至1000个/毫米3天以后的治疗过程持续21）中，和美新胶囊剂量应减少0.4毫克/平方米/天以后的课程。 D.同样剂量应减少，如果血小板计数低于25000个/毫米3瀑布。 谁的经验，为病人3或4级腹泻 ，在和美新胶囊剂量应减少0.4毫克/平方米/天以后的课程[见警告和注意事项 ]。与2级腹泻患者可能需要遵循相同的剂量调整的指导方针。   剂型和优势 和美新胶囊含有盐酸拓扑替康为基础，表达自由拓扑替康。在0.25毫克胶囊是不透明的白色或微黄色，白色和和美新印和0.25毫克。 在1毫克胶囊是不透明的粉红色和和美新印和1毫克。 在和美新胶囊0.25毫克是不透明的白色或微黄色，白色，和美新印和0.25毫克 在和美新胶囊1毫克是不透明的粉红色印有和美新和1毫克 商店冷藏2 º至8℃（36 º至46 º F）之间。存储瓶避光原外箱。 1-4为妥善处理和处置程序抗癌药物应使用。此问题已出版了若干准则。1-4 和美新胶囊不应当打开或粉碎。 D对皮肤或粘膜膜的胶囊内容直接接触，应避免。.如果发生这种接触，洗净用肥皂和水清洗眼睛，或立即轻轻地流了至少15分钟的水。 在咨询皮肤反应的情况下，如果医疗服务提供者或药物在眼睛里。 临床试验经验 和美新胶囊的安全性进行了评估，在682名癌症患者胸部（3复发性小细胞肺癌[小细胞肺癌] 1经常研究和非小细胞肺癌[肺癌]研究）谁获得至少一个和美新胶囊剂。由于临床试验正在广泛地不同的条件下进行，不良反应发生率在药物的临床试验中观察到，不能直接比较率的另一种药物的临床试验，可能没有反映在实践中发现率。 表1描述了血液和非经常性小细胞肺癌与和美新胶囊加最佳支持治疗（BSC）和整体人口胸部癌症患者接受治疗的病人血液不良反应。 腹泻：不良反应是谁的70例和美新胶囊加BSC，发病率与毒品有关的腹泻收到14％，4％和1级3％，四级。 在682名病人谁和美新的4胸胶囊癌症研究收到的发病率与药物有关的腹泻为22％，4％，三级和0.4％，四级。 药物的总发生率有关的腹泻比较常见患者≥65岁（28％，ñ = 225）的10％，1级，2级9％，7％，3级，1级4％，相对于“65岁（19％，ñ = 457 7％）1级，2级9％，3％，三级和0％，四级。 在3级或4近因腹泻的发病率（在5天），3或4级的和美新胶囊治疗组中性粒细胞的活动是5％。 中位时间为2级腹泻发病或者更糟的是9天和美新胶囊组。 发生的死亡后30天内的最后一剂药物的研究：在682名病人谁和美新的4胸部癌症研究胶囊收到39人死亡之后发生的研究药物的渐进性疾病的原因比其他的最后剂量;在30天内13这些死亡是由于血液毒性，五是由于非血液毒性，21个是由于其他原因。 其中一名病人死亡（68岁）是由于治疗相关的腹泻，1人死亡（68岁）归入供款时，这两名患者接受和美新胶囊腹泻。   上市后经验 没有与和美新胶囊上市后的经验。 下列不良反应后期间已经确定的用途批准和美新注射。 由于这些反应，报告从人口规模不确定的自愿，并非总是能够可靠地估计自己的频率，或设立一个因果关系对药物的风险。 血液和淋巴系统疾病：严重出血（与血小板协会）。 免疫系统疾病：过敏性表现，过敏性反应。  胃肠道疾病：腹部疼痛可能与中性粒细胞结肠炎相关（见警告和注意事项 ）。 皮肤及皮下组织： 血管性水肿 ，严重皮炎 ，严重瘙痒 。 DRUG DESCRIPTION Topotecan hydrochloride is a semi-synthetic derivative of camptothecin and is an anti-tumor drug with topoisomerase I-inhibitory activity. The chemical name for topotecan hydrochloride is (S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7] indolizino [1,2-b]quinoline-3,14-(4H,12H)-dione monohydrochloride. It has the molecular formula C23H23N3O5•HCl and a molecular weight of 457.9. It is soluble in water and melts with decomposition at 213° to 218°C. HYCAMTIN capsules contain topotecan hydrochloride, the content of which is expressed as topotecan free base. The major excipients are hydrogenated vegetable oil, glyceryl monostearate, gelatin, and titanium dioxide. The capsules are imprinted with edible black ink. The 1 mg capsules also contain red iron oxide. INDICATIONS HYCAMTIN capsules are indicated for the treatment of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy. DOSAGE AND ADMINISTRATION Recommended Dosing The recommended dose of HYCAMTIN capsules is 2.3 mg/m2/day once daily for 5 consecutive days repeated every 21 days. Round the calculated oral daily dose to the nearest 0.25 mg, and prescribe the minimum number of 1 mg and 0.25 mg capsules. The same number of capsules should be prescribed for each of the 5 dosing days. HYCAMTIN capsules may be taken with or without food. The capsules must be swallowed whole and must not be chewed, crushed, or divided. If your patient vomits after taking the dose of HYCAMTIN, the patient should not take a replacement dose. Adjustment of Dose in Special Populations Renal Function Impairment: No dosage adjustment of HYCAMTIN capsules appears to be required for treating patients with mild renal impairment (CLcr = 50-80 mL/min). A dose adjustment of HYCAMTIN capsules to 1.8 mg/m2/day is predicted to adjust the area under the curve (AUC) to the normal range for patients with moderate renal impairment (CLcr = 30-49 mL/min). Insufficient data are available in patients with severe renal impairment (CLcr < 30 mL/min) to provide a dosage recommendation for HYCAMTIN capsules [see Use in Specific Populations]. Dose Modification Guidelines Patients should not be treated with subsequent courses of HYCAMTIN until neutrophils recover to > 1,000 cells/mm3, platelets recover to > 100,000 cells/mm3, and hemoglobin levels recover to ≥ 9.0 g/dL (with transfusion if necessary). For patients who experience severe neutropenia (neutrophils < 500 cells/mm3 associated with fever or infection or lasting for 7 days or more) or neutropenia (neutrophils 500 to 1,000 cells/mm3 lasting beyond day 21 of the treatment course), the HYCAMTIN capsules dose should be reduced by 0.4 mg/m2/day for subsequent courses. Doses should be similarly reduced if the platelet count falls below 25,000 cells/mm3. For patients who experience Grade 3 or 4 diarrhea, the HYCAMTIN capsules dose should be reduced by 0.4 mg/m2/day for subsequent courses [see WARNINGS AND PRECAUTIONS]. Patients with Grade 2 diarrhea may need to follow the same dose modification guidelines. HOW SUPPLIED Dosage Forms And Strengths HYCAMTIN capsules contain topotecan hydrochloride expressed as topotecan free base. The 0.25 mg capsules are opaque white to yellowish-white and imprinted with HYCAMTIN and 0.25 mg. The 1 mg capsules are opaque pink and imprinted with HYCAMTIN and 1 mg. The 0.25 mg HYCAMTIN capsules are opaque white to yellowish-white imprinted with HYCAMTIN and 0.25 mg and are available in bottles of 10: NDC 0007-4205-11. The 1 mg HYCAMTIN capsules are opaque pink imprinted with HYCAMTIN and 1 mg and are available in bottles of 10: NDC 0007-4207-11. Store refrigerated 2º to 8ºC (36º to 46ºF). Store the bottles protected from light in the original outer cartons. Procedures for proper handling and disposal of anticancer drugs should be used. Several guidelines on this subject have been published.1-4 HYCAMTIN capsules should not be opened or crushed. Direct contact of the capsule contents with the skin or mucous membranes should be avoided. If such contacts occur, wash thoroughly with soap and water or wash the eyes immediately with gently flowing water for at least 15 minutes. Consult the healthcare provider in case of a skin reaction or if the drug gets in the eyes. Clinical Trials Experience The safety of HYCAMTIN capsules has been evaluated in 682 patients with thoracic cancer (3 recurrent small cell lung cancer [SCLC] studies and 1 recurrent non-small cell lung cancer [NSCLC] study) who received at least one dose of HYCAMTIN capsules. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 1 describes the hematologic and non-hematologic adverse reactions in recurrent SCLC patients treated with HYCAMTIN capsules plus best supportive care (BSC) and in the overall thoracic cancer patient population. Diarrhea Adverse Reactions: Of the 70 patients who received HYCAMTIN capsules plus BSC, the incidence of drug-related diarrhea was 14%, with 4% Grade 3 and 1% Grade 4. In the 682 patients who received HYCAMTIN capsules in the 4 thoracic cancer studies, the incidence of drug-related diarrhea was 22%, with 4% Grade 3 and 0.4% Grade 4. The overall incidence of drug-related diarrhea was more frequent in patients ≥ 65 years of age (28%, n = 225) with 10% Grade 1, 9% Grade 2, 7% Grade 3, and 1% Grade 4 compared to those < 65 years of age (19%, n = 457) with 7% Grade 1, 9% Grade 2, 3% Grade 3, and 0% Grade 4. The incidence of Grade 3 or 4 diarrhea proximate (within 5 days) to Grade 3 or 4 neutropenia events in the HYCAMTIN capsules treatment group was 5%. The median time to onset of Grade 2 or worse diarrhea was 9 days in the HYCAMTIN capsules group. Deaths Occurring Within 30 Days Following the Last Dose of Study Medication: In the 682 patients who received HYCAMTIN capsules in the 4 thoracic cancer studies, 39 deaths occurred within 30 days after the last dose of study medication for a reason other than progressive disease; 13 of these deaths were attributed to hematologic toxicity, 5 were attributed to non-hematologic toxicity, and 21 were attributed to other causes. One patient death (68 years of age) was attributed to treatment-related diarrhea and one death (68 years of age) attributed diarrhea as a contributory event; both patients received HYCAMTIN capsules. In addition to the adverse reactions listed previously, the following adverse reactions have been reported with HYCAMTIN for Injection: •Incidence > 10%: Febrile neutropenia, abdominal pain, stomatitis, constipation. •Incidence 1 to 10%: Sepsis, hypersensitivity (including rash), hyperbilirubinemia, malaise. Postmarketing Experience There is no postmarketing experience with HYCAMTIN capsules. The following adverse reactions have been identified during post-approval use of HYCAMTIN for Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders: Severe bleeding (in association with thrombocytopenia). Immune system disorders: Allergic manifestations, anaphylactoid reactions. Gastrointestinal disorders:Abdominal pain potentially associated with neutropenic colitis (see WARNINGS AND PRECAUTIONS). Skin and subcutaneous tissue disorders: Angioedema, severe dermatitis, severe pruritus