Levoleucovorin注射剂。该药用于使用高剂量甲氨蝶呤治疗之后的骨肉瘤患者的药物治疗，可以减少高剂量甲氨蝶呤和过量叶酸拮抗剂类药物的毒性，增强这些药物的疗效。该药是唯一获FDA批准销售的含甲酰四氢叶酸异构体[Levoleucovorin或（6S）-leucovorin]药品，

FUSILEV

指示（S）：

在骨肉瘤，以减少高剂量甲氨蝶呤（MTX）治疗的毒性。为了减少毒性和制止受损MTX消除无意的过量叶酸拮抗剂的影响。

药理学：

Levoleucovorin是消旋药物D，L -亚叶酸钙，叶酸acid.It衍生的药理活性的异构体可以抵消的疗效和毒副作用，如MTX的叶酸拮抗剂抑制活性酶二氢reductase.Levoleucovorin在消旋体亚叶酸钙的常用剂量的1 / 2剂量。

临床试验：

levoleucovorin救援的安全性和疗效，大剂量MTX 16例6岁21年骨肉瘤治疗的58门课程的学习。大剂量MTX被用作跨越几个试验评估几种不同的联合化疗方案的一个组成部分。 13例患者共收到超过4小时levoleucovorin 7.5mg每6小时，60小时或更长的时间开始24小时后完成的MTX MTX 12g/m2四。三名患者接受超过6小时MTX 12.5g/m2四，然后levoleucovorin 7.5mg每3小时18剂量MTX治疗完成后开始的12个小时。不良反应的配置文件是基于levoleucovorin疗效。 6例患者（37.5％），报口腔炎，一个3级或更高（6.3％）。 6例患者（37.5％），呕吐，恶心3例（18.8％）发生。等不良反应，如呼吸困难，神经病变，和皮炎的患者人数曾报道为一体。在治疗的58门课程，共为口腔炎，14 10个事件为恶心呕吐，3，肾功能异常3。

法律分类：

RX

成年人和儿童：

<6年：见文献。 ≥6年：给静脉注射;最大速率160mg/min。大剂量MTX救援：开始24小时后开始的呤输液（MTX的12g/m2的剂量超过4小时）。正常甲氨蝶呤消除：给levoleucovorin 7.5mg（约5mg/m2），每6小时10剂量。延迟甲氨蝶呤消除后期：继续levoleucovorin 7.5mg每6小时，直到甲氨蝶呤<0.05micromolar;早期MTX的延迟消除和/或急性肾损伤的证据：levoleucovorin 75毫克每3个小时，直到甲氨蝶呤<1micromolar，然后7.5mg每3个小时，直到甲氨蝶呤<0.05micromolar。另一种可能继续在显着的临床毒性情况下后续课程24小时。无心甲氨蝶呤过量：尽快启动尽可能在24小时内如果延迟甲氨喋呤的排泄。 Levoleucovorin 7.5mg每6小时，直到甲氨蝶呤<0.05micromolar。参见文献。

警告/注意事项：

不适用于治疗恶性贫血和巨幼细胞性anemia.Monitor血肌酐和MTX水平每24hrs.Delayed早期甲氨蝶呤消除可能导致可逆的肾功能衰竭;提供水化，alkalinize尿液与碳酸氢钠，密切监视，直到血清MTX的液体和电解质< 0.05微摩尔和肾功能衰竭resolves.Pregnancy（Cat.C）。哺乳的母亲。

相互作用（S）：

Potentiates，5 - 氟尿嘧啶toxicity.Antagonizes川芎嗪/ SMZ.Antagonizes抗惊厥药（如苯巴比妥，扑米酮，苯妥英），可能由药物影响甲氨蝶呤消除影响。。

不良反应（S）：

口腔炎，呕吐，恶心。

如何提供：单用小瓶- 1

最后更新：1/14/2009

INDICATIONS AND USAGE

• FUSILEV is a folate analog.
• FUSILEV rescue is indicated after high-dose methotrexate therapy in osteosarcoma.
• FUSILEV is also indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of
inadvertent overdosage of folic acid antagonists.

LIMITATIONS OF USE

FUSILEV is not approved for pernicious anemia and megaloblastic anemias. Improper use may cause a hematologic remission while neurologic manifestations continue to progress.
IMPORTANT SAFETY INFORMATION

Contraindications
• FUSILEV is contraindicated for patients who have had previous allergic reactions attributed to folic acid or folinic acid.

Warnings and Precautions
• Due to Ca++ content, no more than 16 mL (160 mg) of levoleucovorin solution should be injected intravenously per minute
• FUSILEV enhances the toxicity of fluorouracil.
• Concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in HIV patientswas associated with increased rates of treatment failure in a placebo-controlled study.

Adverse Reactions
Allergic reactions were reported in patients receiving FUSILEV.
Vomiting (38%), stomatitis (38%) and nausea (19%) were reported in patients receiving FUSILEV as rescue after high dose methotrexate therapy.

Drug Interactions
FUSILEV may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible patients.

Reporting of Suspected Adverse Reactions
You are encouraged to report side effects of prescription drugs to the FDA.

向美国FDA提交新药上市申请(NDA)补件，以注射剂FUSILEV合并5-FU containing regimens，治疗恶性直肠大肠癌病患。
FDA已批准其Levoleucovorin注射剂。骨肉瘤患者用高剂量甲氨蝶呤之后进而用这种药物进行治疗，可以减少高剂量甲氨蝶呤和过量叶酸拮抗剂类药物的毒性，增强这些药物的疗效。Levoleucovorin是Spectrum制药公司近日宣布，FDA已批准其Levoleucovorin注射剂。骨肉瘤患者用高剂量甲氨蝶呤之后进而用这种药物进行治疗，可以减少高剂量甲氨蝶呤和过量叶酸拮抗剂类药物的毒性，增强这些药物的疗效。Levoleucovorin是唯一获准销售的含甲酰四氢叶酸异构体（Levoleucovorin或(6S)-leucovorin）药品，它有望于今年6月份上市。
        
Spectrum公司负责人称，Levoleucovorin是2008年通过FDA批准的第一种癌症治疗药。这给患者带来了一种全新的选择，有了这种药物，正在接受化疗的患者无需再使用非活性右旋异构体药物进行治疗。前临床实验结果显示，若同时使用非活性异构体药物和活性异构体药物，则两者在进入细胞过程中会互相竞争。
        
Levoleucovorin 关键词：骨肉瘤治疗药物
           
Spectrum制药公司近日宣布，美国FDA批准了该公司的Levoleucovorin注射剂上市销售。该药用于使用高剂量甲氨蝶呤治疗之后的骨肉瘤患者的药物治疗，可以减少高剂量甲氨蝶呤和过量叶酸拮抗剂类药物的毒性，增强这些药物的疗效。该药是唯一获FDA批准销售的含甲酰四氢叶酸异构体[Levoleucovorin或(6S)-leucovorin]药品，该公司希望可以在今年6月份完成该药的上市工作。

Levoleucovorin不能用于之前有对叶酸或者甲酰四氢叶酸过敏经历的患者。由于该药含钙，因此在静脉注射时，每分钟不能超过16
mL（160 mg）。该药会增加氟脲嘧啶的毒性。在安慰剂对照试验中发现，甲酰四氢叶酸和甲氧苄氨嘧啶-磺胺甲异噁唑同时用于HIV患者中卡氏肺囊虫肺炎的治疗时，可能会增加治疗的失败率。在接受该药注射的患者中有过敏反应发生。在高剂量甲氨蝶呤治疗之后注射该药的患者报告有呕吐（38%）、口腔炎（38%）和恶心（19%）发生。注射该药可能会抵消镇静安眠剂、苯妥英和扑米酮的抗癫痫作用，有癫痫史或存在癫痫风险的患者需要注意。

【原产地英文商品名】FUSILEV I.V. 50mg/10ml/vial
【原产地英文药品名】LEVOLEUCOVORIN CALCIUM
【中文参考商品译名】FUSILEV I.V. 50毫克/10毫升/瓶
【中文参考药品译名】左旋亚叶酸钙
【生产厂家中文参考译名】SPECTRUM PHARMS
【生产厂家英文名】SPECTRUM PHARMS

FUSILEV

Indication(s):

In osteosarcoma, to reduce toxicity of high-dose methotrexate (MTX) therapy. To reduce toxicity and counteract effects of impaired MTX elimination and of inadvertent overdose of folic acid antagonists.

Pharmacology:

Levoleucovorin is the pharmacologically active isomer of the racemic drug d,l-leucovorin, a derivative of folic acid.It can counteract the therapeutic and toxic effects of folic acid antagonists such as MTX which inhibit the activity of the enzyme dihydrofolate reductase.Levoleucovorin is dosed at 1/2 the usual dose for racemic leucovorin.

Clinical Trials:

The safety and efficacy of levoleucovorin rescue following high-dose MTX was studied in 16 patients 6–21years of age who received 58 courses of therapy for osteogenic sarcoma. High-dose MTX was used as one component of several different combination chemotherapy regimens evaluated across several trials. Thirteen patients received MTX 12g/m² IV over 4 hours and levoleucovorin 7.5mg every 6 hours for 60 hours or longer beginning 24 hours after the completion of MTX. Three patients received MTX 12.5g/m² IV over 6 hours, then levoleucovorin 7.5mg every 3 hours for 18 doses starting 12 hours after completion of MTX therapy. The efficacy of levoleucovorin was based on the adverse reaction profile. Six patients (37.5%) reported stomatitis, with one (6.3%) having grade 3 or higher. Six patients (37.5%) reported vomiting while nausea occurred in 3 patients (18.8%). The number of patients who had other adverse reactions such as dyspnea, neuropathy, and dermatitis was reported as one. In the 58 courses of therapy, there was a total of 10 occurrences for stomatitis, 14 for vomiting, 3 for nausea, and 3 for abnormal renal function.

Legal Classification:

Rx

Adults & Children:

<6years: see literature. ≥6years: Give by IV inj; max rate 160mg/min. High-dose MTX rescue: Start 24hrs after the beginning of MTX infusion (based on MTX dose of 12g/m² over 4hrs). Normal MTX elimination: give levoleucovorin 7.5mg (approximately 5mg/m²) every 6hrs for 10 doses. Delayed late MTX elimination: continue levoleucovorin 7.5mg every 6hrs until MTX <0.05micromolar; delayed early MTX elimination and/or evidence of acute renal injury: levoleucovorin 75mg every 3hrs until MTX <1micromolar, then 7.5mg every 3hrs until MTX <0.05micromolar. May continue another 24hrs for subsequent courses in cases of significant clinical toxicity. Inadvertent MTX overdose: Start as soon as possible or within 24hrs if delayed MTX excretion. Levoleucovorin 7.5mg every 6hrs until MTX <0.05micromolar. See literature.

Warnings/Precautions:

Not for treating pernicious anemia and megaloblastic anemia.Monitor serum creatinine and MTX levels every 24hrs.Delayed early MTX elimination may cause reversible renal failure; provide hydration, alkalinize urine with sodium bicarbonate, closely monitor fluid and electrolytes until serum MTX <0.05 micromolar and renal failure resolves.Pregnancy (Cat.C).Nursing mothers.

Interaction(s):

Potentiates 5-fluorouracil toxicity.Antagonizes TMP/SMZ.Antagonizes anticonvulsants (eg, phenobarbital, primidone, phenytoin).May be affected by drugs that affect MTX elimination.

Adverse Reaction(s):

Stomatitis, vomiting, nausea.

How Supplied:

Single-use vial—1

Last Updated:

1/14/2009