简介：

Voraxaze经FDA批准用于减轻部分癌症患者由肾功能障碍导致的甲氨蝶呤毒性
2012年1月18日，BTG国际公司宣布，美国食品药品管理局(FDA)已批准Voraxaze(glucarpidase)用于甲氨蝶呤清除延迟的患者，以降低其体内毒性血浆甲氨蝶呤浓度，这种清除延迟可由患者肾功能损害导致。该药品已被FDA指定为孤儿药。Voraxaze作为一种酶，可将甲氨蝶呤降解为无活性代谢产物并通过肾外途径(主要通过肝脏)将其排出体外，从而快速降低其血浆水平。
大剂量的甲氨蝶呤化疗用于治疗骨肉瘤、白血病及淋巴瘤等某些类型的癌症或预防其复发。接受甲氨蝶呤治疗的部分患者可出现肾功能损害，导致甲氨蝶呤在血液中积聚达到毒性水平，增加患者的毒性风险。
FDA批准Vorazxaze是基于在2项单组、开放性、多中心试验中接受治疗的290例患者的数据。这些受试者的中位年龄为17岁(1个月龄~85岁)，男性占64%，32%患有骨源性肉瘤或肉瘤，63%患有白血病或淋巴瘤。支持该药审批的是该试验的药代动力学终点数据，此终点是指血浆甲氨蝶呤浓度快速、持续的降低且具有临床意义(RSCIR)(具体定义为“在给予glucarpidase后的15 min内血浆甲氨蝶呤浓度达到≤ 1 μmol/L的水平并维持长达8 d”)。
Voraxaze的疗效是通过对一个患者亚组进行的研究而得到证实的，涉及其中一项研究中22例可评估治疗的患者。入组该研究的患者存在继发于肾功能障碍的甲氨蝶呤清除延迟(标准列线图上显示超出平均值2个标准差以上)。疗效评估仅限于在治疗前后采集了血浆样本并按照正确操作规程进行处理、利用色谱法得出可靠的甲氨蝶呤测定值的患者。其中10例患者达到RSCIR(45%:95%置信区间，27%~65%)。所有可评估的患者的甲氨蝶呤浓度均较预处理时的基线水平降低95%以上，并在glucarpidase治疗后持续长达8 d。
研究中受试者报告最多的不良反应包括感觉异常、面部潮红、恶心和(或)呕吐、低血压以及头痛。
Voraxeze经静脉注射给药。在给予glucarpidase后48 h内只能利用色谱法方可测得可靠的甲氨蝶呤浓度值，而采用免疫分析法测量则会高估甲氨蝶呤浓度。
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, nausea, vomiting, hypotension, headache; rare: allergic reactions, antibody formation.

How Supplied:
Single-use vials—1

Voraxaze（谷卡匹酶，glucarpidase）详情说明书
[附件:/uploadfile/article/uploadfile/201201/20120118110313479.pdf]

简介：

Voraxaze经FDA批准用于减轻部分癌症患者由肾功能障碍导致的甲氨蝶呤毒性
2012年1月18日，BTG国际公司宣布，美国食品药品管理局(FDA)已批准Voraxaze(glucarpidase)用于甲氨蝶呤清除延迟的患者，以降低其体内毒性血浆甲氨蝶呤浓度，这种清除延迟可由患者肾功能损害导致。该药品已被FDA指定为孤儿药。Voraxaze作为一种酶，可将甲氨蝶呤降解为无活性代谢产物并通过肾外途径(主要通过肝脏)将其排出体外，从而快速降低其血浆水平。
大剂量的甲氨蝶呤化疗用于治疗骨肉瘤、白血病及淋巴瘤等某些类型的癌症或预防其复发。接受甲氨蝶呤治疗的部分患者可出现肾功能损害，导致甲氨蝶呤在血液中积聚达到毒性水平，增加患者的毒性风险。
FDA批准Vorazxaze是基于在2项单组、开放性、多中心试验中接受治疗的290例患者的数据。这些受试者的中位年龄为17岁(1个月龄~85岁)，男性占64%，32%患有骨源性肉瘤或肉瘤，63%患有白血病或淋巴瘤。支持该药审批的是该试验的药代动力学终点数据，此终点是指血浆甲氨蝶呤浓度快速、持续的降低且具有临床意义(RSCIR)(具体定义为“在给予glucarpidase后的15 min内血浆甲氨蝶呤浓度达到≤ 1 μmol/L的水平并维持长达8 d”)。
Voraxaze的疗效是通过对一个患者亚组进行的研究而得到证实的，涉及其中一项研究中22例可评估治疗的患者。入组该研究的患者存在继发于肾功能障碍的甲氨蝶呤清除延迟(标准列线图上显示超出平均值2个标准差以上)。疗效评估仅限于在治疗前后采集了血浆样本并按照正确操作规程进行处理、利用色谱法得出可靠的甲氨蝶呤测定值的患者。其中10例患者达到RSCIR(45%:95%置信区间，27%~65%)。所有可评估的患者的甲氨蝶呤浓度均较预处理时的基线水平降低95%以上，并在glucarpidase治疗后持续长达8 d。
研究中受试者报告最多的不良反应包括感觉异常、面部潮红、恶心和(或)呕吐、低血压以及头痛。
Voraxeze经静脉注射给药。在给予glucarpidase后48 h内只能利用色谱法方可测得可靠的甲氨蝶呤浓度值，而采用免疫分析法测量则会高估甲氨蝶呤浓度。
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, nausea, vomiting, hypotension, headache; rare: allergic reactions, antibody formation.

How Supplied:
Single-use vials—1

Voraxaze（谷卡匹酶，glucarpidase）详情说明书
[附件:/uploadfile/article/uploadfile/201201/20120118110313479.pdf]