Levoleucovorin：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16mL（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。

FUSILEV

Company:

Spectrum

Pharmacologic class:
Folate analogue

Active ingredient:
Levoleucovorin (as calcium pentahydrate) 50mg/vial; pwd for IV inj after reconstitution; contains mannitol 50mg/vial.

Indications:
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?1years 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.

Adults and 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.

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.

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

Adverse reactions:
Stomatitis, vomiting, nausea.

How supplied:
Single-use vial?

Last Updated:

FDA批准Fusilev用于晚期结直肠癌患者

2011年4月29日，Spectrum Pharmaceuticals公司宣布，美国食品药品管理局(FDA)已批准了Fusilev(左旋亚叶酸)的一项新适应证。该药现已获准与5-氟尿嘧啶联用，作为晚期转移性结直肠癌患者的姑息治疗。Fusilev是一种叶酸类似物，已获准的剂型包括即用的175 mg和250 mg两种瓶装注射液以及一种50 mg瓶装冻干粉剂。
除了结直肠癌外，Fusilev还可用作骨肉瘤患者行高剂量甲氨蝶呤治疗后的补救治疗药。此外，Fusilev的适应证还包括减轻化疗药物的毒性，对抗甲氨蝶呤消除受损和叶酸拮抗剂意外过量所产生的不良影响。
据Spectrum Pharmaceuticals公司的发言人称，美国国家综合癌症网(NCCN)结直肠癌治疗指南已经推荐将左旋亚叶酸用于治疗结直肠癌。
晚期结直肠癌患者在采用Fusilev联合5-氟尿嘧啶治疗方案后最常发生的不良反应为腹泻、恶心和胃炎。Fusilev可以与抗癫痫药发生相互作用，其中包括苯巴比妥、苯妥英以及普里米酮，并可增加疑似患者的癫痫发作频率。
Fusilev禁用于既往曾发生叶酸或亚叶酸过敏反应的患者。由于其含有钙，故每分钟静脉输注的左旋亚叶酸注射液量不得超过16 ml(160 mg)。