部份中文地拉罗司斯处方资料（仅供参考）

商品名：Exjade

英文名：deferasirox

中文名：地拉罗司

生产商：诺华公司

药品简介

开发与上市厂商

本品由诺华公司研发，2005年12月在美国首次上市，之后在瑞士上市。此外，本品还在加拿大、澳大利亚和新西兰获优先审批资格，在瑞士、加拿大、澳大利亚和欧盟获罕用药认定。

批准日期：2005年11月2日 公司：诺华

EXJADE（地拉罗司 deferasirox）片剂，用于口服混悬液

美国最初批准：2005年

警告：

肾功能衰竭，肝功能衰竭和胃肠道出血请参阅完整的处方信息以获取完整的盒装警告。

Exjade可能会导致：

急性肾损伤，包括需要透析的急性肾功能衰竭和包括Fanconi综合征在内的肾小管毒性。

肝毒性，包括失败：

消化道出血：

Exjade疗法需要密切监测患者，包括肾功能和肝功能的实验室检查。

最近的主要变化

盒装警告：5/2018

适应症和用法：5/2018

剂量和管理：5/2018

禁忌症：5/2018

警告和注意事项：5/2018

作用机制

Exjade（地拉罗司）是一种口服活性螯合剂，对铁有选择性（如Fe3 +）。 它是一种以2：1比率高亲和力结合铁的三齿配体。 尽管地拉罗司对锌和铜具有非常低的亲和力，但在给予地拉罗司后，这些痕量金属的血清浓度有不同的降低。 这些降低的临床意义是不确定的。

适应症和用法

Exjade是一种铁螯合剂，用于治疗因2岁及以上患者输血引起的慢性铁超负荷。

Exjade适用于治疗10岁及以上患者的慢性铁超负荷，非输血依赖性地中海贫血（NTDT）综合征，肝脏铁（Fe）浓度（LIC）至少为5 mg Fe / g干重和血清铁蛋白大于300 mcg / L.该指示基于LIC小于5mg Fe / g dw的实现。尚未确定存活率或疾病相关症状的改善。

使用限制：

尚未进行Exreade对骨髓增生异常综合征（MDS）和输血引起的慢性铁超负荷患者的对照临床试验。

当与其他铁螯合疗法一起使用时，Exjade的安全性和有效性尚未确定。

剂量和给药

在输血性铁超负荷的患者中，估计肾小球滤过率（eGFR）大于60 mL / min / 1.73 m2的患者的推荐初始日剂量为每天每公斤体重20 mg，作为口服混悬液。计算剂量到最近的整个片剂。

对于eGFR大于60mL/min/1.73 m2的NTDT综合征患者，推荐的初始日剂量为每日一次10 mg / kg体重，为口服混悬液。计算剂量到最近的整个片剂。

每月监测血清铁蛋白并相应调整剂量。 

每6个月监测一次LIC并相应调整剂量。

不要咀嚼或吞服整个片剂。

食物前至少30分钟空腹服用。通过在适量的水，橙汁或苹果汁中搅拌来分散片剂。

将中度（Child-Pugh B）肝功能损害患者的起始剂量降低50％。避免在患有严重（Child-Pugh C）肝功能损害的患者中使用Exjade。

肾功能损害患者的起始剂量降低50％eGFR 40-60 mL/min/1.73m2。对于eGFR在40到60 mL /分钟/ 1.73 m2之间的儿科患者，请务必谨慎。

剂量形式和强度

片剂用于口服混悬液：125mg，250mg，500mg。

禁忌症

估计GFR小于40mL/min/1.73 m2。

表现不佳的患者。

高风险MDS患者。

晚期恶性肿瘤患者。

血小板计数低于50x109/L的患者。

已知对地拉罗司或Exjade的任何成分过敏。

警告和注意事项

急性肾损伤：在开始治疗前一式两份测量血清肌酐。在Exjade疗法期间监测肾功能并减少剂量或中断治疗毒性。

肝毒性：监测肝功能。减少剂量或中断治疗毒性。

致死性和非致死性胃肠道出血，溃疡和刺激：将Exjade与已知具有溃疡性或出血潜力的药物联合使用的患者的风险可能更高。

骨髓抑制：中性粒细胞减少症，粒细胞缺乏症，恶化的贫血和血小板减少症，包括致命事件;在Exjade疗法期间监测血细胞计数。中毒治疗毒性。

与年龄相关的毒性风险：密切监测老年人和儿科患者的毒性。

超敏反应：停止对严重反应的Exjade并进行医疗干预。

严重皮肤反应包括史蒂文斯 - 约翰逊综合征（SJS），中毒性表皮坏死松解症（TEN）和嗜酸粒细胞增多症和系统症状的药物反应（DRESS）：停止Exjade。

不良反应

在输血性铁超负荷的患者中，最常发生（大于5％）的不良反应是腹泻，呕吐，恶心，腹痛，皮疹和血清肌酐增加。在Exjade治疗的NTDT综合征患者中，最常发生的（大于5％）不良反应是腹泻，皮疹和恶心。

要报告可疑的不良反应，请联系诺华制药公司1-888-669-6682或FDA 1-800-FDA-1088或www.fda.gov/medwatch。

药物相互作用

避免将Exjade与含铝抗酸制剂一起使用。

Exjade增加CYP2C8底物瑞格列奈的暴露。考虑瑞格列奈剂量减少和m

如何提供/存储和处理

Exjade是以125mg，250mg和500mg的口服悬浮液片剂形式提供的。

125毫克

灰白色圆形扁平平板，斜边，一面印有“J”和“125”字样，另一面印有“NVR”字样。

瓶装30片........................................................................ ..（NDC 0078-0468-15）

250毫克

带有斜边的灰白色圆形平板，一面印有“J”和“250”，另一面印有“NVR”。

瓶装30片........................................................................ ..（NDC 0078-0469-15）

500毫克

带有斜边的灰白色圆形平板，一面印有“J”和“500”，另一面印有“NVR”。

瓶装30粒..........................................................................................（NDC 0078-0470-15）

将Exjade片剂储存在25°C（77°F）;允许偏移为15°C-30°C（59°F-86°F）[见USP受控室温]。防潮。

完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3495a70c-870c-4968-940e-8baea152cf85

Exjade (deferasirox) - Notice of Compliance with Conditions - Qualifying Notice

[employee's name removed]

Senior Manager, Drug Regulatory Affairs

Novartis Pharmaceuticals Canada Inc.

385 Bouchard Boulevard

DORVAL, Quebec

H9S 1A9

NOTICE OF COMPLIANCE WITH CONDITIONS-QUALIFYING NOTICE

Dear [employee's name removed] :

This Notice of Compliance with Conditions-Qualifying Notice, issued in accordance with the Health Canada NOC/c policy, is to advise you that information submitted in support of the New Drug Submission for EXJADE (deferasirox), Control Number 099621, qualifies to be considered for approval, under the NOC/c policy. In keeping with the provisions outlined in the NOC/c policy, the following additional information is required to complete the assessment:

1.) A letter signed by the Chief Executive Officer, or designated signing authority of Novartis Pharmaceuticals Canada Inc., indicating that you agree to have this submission considered under the NOC/c policy.

2.) A draft Letter of Undertaking signed by the Chief Executive Officer or designated signing authority of Novartis Pharmaceuticals Canada Inc., having a form and content satisfactory to Health Canada , including commitments to supply the following:

Confirmatory studies

i.Complete and submit data from the extension studies 105E2, 106E1, 107E1, 108E1 and 109E1 for a total of 4 years after the core trial.

ii.Pursue assessment of safety and efficacy of Exjade in pediatric patients 2-<6 years of age at study entry through a registry involving approximately 200 children with a 5 year follow-up. Data collection should include at least monthly assessments of renal and hepatic functions, blood pressure measurements and growth and development assessments every 3 months.

iii.Study the PK of Exjade in patients with hepatic impairment [not included in the Letter of Undertaking] and at doses of 20 [not included in the Letter of Undertaking] mg/kg per day.

iv.In view of the fact that 20 mg/kg could maintain body iron burden, conduct clinical studies in adult and pediatric patients with congenital or acquired anemias and chronic iron overload and a LIC < 7 mg Fe/g dw liver treated with Exjade at doses of 20 or 30 mg/kg per day.

v.Complete study of long-term follow-up in 150 patients with myelodysplastic syndromes receiving Exjade, including patients with baseline serum creatinine values up to 2 x ULN, to better define cardiac, hepatic, endocrine and renal functions, and haematological and clinical benefit of Exjade for a duration of follow-up on Exjade of at least 3 years.

vi.eva luate cardiac iron and cardiac function as well as clinical outcomes to explore the relationship amongst iron body burden as measured by LIC, cardiac iron, serum ferritin, transfusion rates and clinical endpoints in patients treated with Exjade.

Post marketing safety monitoring studies

i.Conduct a renal mechanistic study [information removed].

ii.Conduct a hepatic study [information removed].

iii.Conduct an ophthalmologic study in at least 60 patients receiving Exjade with 2 years follow-up. Examinations should include distance visual acuity, lens photography and wide angle fundus photography of retina and optic nerve and done at baseline, prior to initiating Exjade, and at six month intervals.

iv.[commitment iv removed, as it was not included in the Letter of Undertaking].

v.Report of all serious ADRs that occurred in Canada and all serious unexpected ADRs that occurred outside of Canada should be forwarded within 15 days to the Marketed Health Products Directorate and the appropriate review bureau in Therapeutic Products Directorate in accordance with current regulations and guidelines.

vi.Periodic Safety Update Reports (PSUR-Cs), to be submitted semi-annually, until the conditions have been fulfilled and removed from the NOC/c by Health Canada. PSURs should be prepared in accordance with ICH Guidelines.

3.) A draft of the "Dear Health Care Professional Letter" detailing the conditional approval of EXJADE.

4.) A draft of the "Fact Sheet", outlining in lay language the risks and benefits and side effects of the new indication for EXJADE.

5.) A draft of the Product Monograph which is consistent with the requirements outlined in section 5.2.1 of the Notice of Compliance with Conditions Guidance. Please note that, if applicable, a boxed text must appear on the cover page, at the beginning of each major section of the Product Monograph (Parts I, II and III) and the first page and the start of the Consumer Information section.

I wish to advise you that this Qualifying Notice is being issued in accordance with Health Canada 's guidance and policy on the Management of Drug Submissions and Notice of Compliance with Conditions, respectively. Sponsors are instructed to submit a complete response (refer to "Guidance for Industry; Notice of Compliance with Conditions") to the outstanding information within 30 calendar days of the date of this letter.

In order to facilitate and to ensure proper processing, please include a revised Submission Certificate with your response, quote the product name and control number, and address all correspondence to Chief, Submission and Information Policy Division, Bureau of Operational Services, Therapeutic Products Directorate, Finance Building, Tunney's Pasture, Address Locator 0201A1, Ottawa, Ontario, K1A 0K9.

Yours sincerely,Original signed by,Barbara Rotter, Ph.D.