FDA批准甲氨蝶呤解毒新药
2012年1月17日，美国食品与药物管理局（FDA）批准Voraxaze（谷卡匹酶，glucarpidase）治疗因肾衰竭导致血中甲氨蝶呤达到中毒水平的患者。该药可帮助降低患者血甲氨蝶呤水平。
甲氨蝶呤常用于癌症患者的化疗，正常情况下由肾脏清除。然而，当患者接受大剂量甲氨蝶呤治疗后，可能会发生肾功能衰竭。
Voraxaze是一种快速降低甲氨蝶呤水平的酶，它可将该化疗药降解为可从体内清除的形式。
FDA药物评价与研究中心血液肿瘤学产品部办公室主任理查德·帕兹杜尔说：“长时间暴露于高水平的甲氨蝶呤，可导致肝肾损伤、严重的口腔溃疡、小肠黏膜损伤、皮疹，以及因血细胞计数降低而致死亡。Voraxaze为癌症患者提供了一种重要的治疗选择，旨在预防与持续高水平甲氨蝶呤相关的中毒事件。”
一项纳入22例患者的临床试验，评估了Voraxaze有效性。所有患者均接受Voraxaze治疗。该研究的治疗成功标准是，甲氨蝶呤水平在15分钟之内降至低于临界值并维持8天。结果显示，22例患者中有10人达到了上述标准。虽然不是所有患者都有此结果，但Voraxaze清除了所有患者体内95%的甲氨蝶呤。
另外一项临床试验在290例患者中评估了Voraxaze安全性，这些患者存在从血中清除甲氨蝶呤的问题。在多于1%的患者中观察到的该药最常见的不良反应包括低血压、头痛、恶心、呕吐、面色潮红和感觉异常。
Voraxaze（谷卡匹酶，glucarpidase）详情说明书
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Voraxaze(羧肽酶glucarpidase)批准日期：2012年1月17日；公司：BTG International Inc
美国初次批准：2012
Generic Name and Formulations:
Glucarpidase; 1,000 Units/vial; lyophilized pwd for IV inj after reconstitution; preservative-free.
Company:
BTG International
Indications for VORAXAZE:
Treatment of toxic plasma methotrexate (MTX) concentrations (>1 micromole per liter) in patients with delayed MTX clearance due to impaired renal function.
Adults and Children's Dose:
<1 month: not recommended. ≥1 month: Give as bolus IV inj over 5 minutes. 50Units/kg as a single injection. Continue leucovorin therapy until the MTX concentration is below the leucovorin treatment threshold for at least 3 days. Do not administer leucovorin within 2hrs before or after a dose of glucarpidase. First 48hrs after glucarpidase: administer same leucovorin dose as given prior to glucarpidase. Beyond 48hrs after glucarpidase: give leucovorin dose based on the measured MTX concentration.
Pharmacological Class:
Carboxypeptidase enzyme.
Warnings/Precautions:
Not indicated for use in patients who exhibit the expected clearance of MTX (plasma MTX concentrations within 2 standard deviations of the mean MTX excretion curve specific for the dose of MTX administered) or those with normal or mildly impaired renal function. Monitor MTX concentrations only by chromatographic methods within 48hrs following administration. Continue hydration and alkalinization of urine as indicated. Pregnancy (Cat. C). Nursing mothers.
Interactions:
See Adults and children. Other exogenous substrates including reduced folates and folate antimetabolites may cause interference.
Adverse Reactions:
Paresthesia, flushing, GI upset, hypotension, headache; rare: allergic reactions.
