近日，美国食品和药物管理局（FDA）批准Strensiq（asfotase alfa）用于治疗围产期患者， 婴儿和青少年发作性低磷酸盐血症（HPP）。 Strensiq是一种创新的酶替代疗法（ERT），是美国批准用于治疗HPP患者的第一种疗法，HPP是一种遗传性，慢性和进行性超罕见代谢性疾病，患者对多种系统产生破坏性影响。 身体，导致衰弱或危及生命。
批准日期： 2015年10月23日 公司：亚力兄制药
STRENSIQ™(asfotase α)注射液，为皮下使用
美国初次批准: Pending
作用机制
HPP由TNSALP酶活性缺乏引起，其导致几种TNSALP底物（包括无机焦磷酸盐（PPi））升高。 PPi阻滞羟基磷灰石晶体生长的细胞外水平升高，其抑制骨矿化并导致矿化骨基质的积聚，其表现为婴儿和儿童的佝偻病和骨变形以及一旦生长板闭合时骨软化（骨软化）以及肌肉无力。
在STRENSIQ处理后替换TNSALP酶降低了酶底物水平。
适应证和用途
STRENSIQ™是一种组织非特异性碱性磷酸酶适用为有围产期/婴儿-和青少年-发病低磷酸酯酶(HPP)患者的治疗。
剂量和给药方法
围产期/婴儿-发病HPP
⑴ 推荐剂量方案是2mg/kg皮下给药每周3次，或1mg/kg每周给药6次。注射部位反应可能限于每周6次方案的耐受度。
⑵ 对疗效不足剂量可被增加至每周三次3mg/kg。
青少年-发病HPP
⑶ 推荐剂量方案是2mg/kg皮下给药每周3次，或1mg/kg每周给药6次。注射部位反应可能限于每周6次方案耐受度。
制备和基于体重给药:
⑷ 谨慎: 在体重低于40kg儿童患者不要使用80mg/0.8mL小瓶因为用80mg/0.8mL小瓶(较高浓度)达到asfotase α的全身暴露是较低与用其他规格小瓶(较低浓度)实现暴露。对这个亚组患者一个较低暴露可能不适当。
⑸ 对按治疗方案基于体重给药表见完整处方资料。
给药:
⑹ 只为皮下注射.
⑺ 轮转注射部位。不要给药至发红，发炎或肿胀区域。
剂型和规格
注射液: 一次性使用小瓶18mg/0.45mL，28mg/0.7mL，40mg/mL，或80mg/0.8mL溶液。
禁忌证
无。
警告和注意事项
⑴ 超敏性反应: 监视和如发生严重反应，终止治疗和开始适当药物治疗。
⑵ 脂肪代谢障碍: 适当注射技术和轮转注射部位后治疗后几个月被报道局部反应。
⑶ 异位性钙化(眼和肾): 在基线时和治疗期间定期用眼科检查和肾超声监视。
不良反应
最常见不良反应(≥10%)是注射部位反应，脂肪代谢障碍，异位性钙化和超敏性反应。
包装供应/贮存和处置
STRENSIQ被供应为无菌，无热原，无防腐剂，清澈，略微乳白或乳白，无色至略微黄水性溶液；可能存在少许小半透明或白颗粒。可得到产品为一次用小瓶在1个或12个小瓶的纸盒以以下规格：
表10：STRENSIQ瓶演讲强度国家药品代码（NDC）在纸箱的2毫升小瓶数量
18毫克/0.45毫升NDC25682-010-011
NDC25682-010-1212
28毫克/0.7毫升NDC25682-013-011
NDC25682-013-1212
40毫克/毫升NDC-25682-016-011
NDC-25682-016-1212
对于小儿患者在40公斤，更大
80毫克/0.8毫升NDC25682-019-011
NDC25682-019-1212
STRENSIQ小瓶用前必须贮存在原始纸盒和避光保护在冰箱条件在2°C至8°C(36°F至46°F)。一旦从冰箱取出，STRENSIQ应在1小时内给药。不要使用超过纸盒标志失效期药物。不要冻结或摇晃。小瓶是只为一次性使用。遗弃任何未使用产品。
完整说明附件：https://alexion.com/Documents/Strensiq_USPI.aspx
STRENSIQ® is indicated for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP)
Important Safety Information
Hypersensitivity reactions, including anaphylaxis, have been reported in STRENSIQ-treated patients. Signs and symptoms consistent with anaphylaxis included difficulty breathing, choking sensation, nausea, periorbital edema, and dizziness. These reactions have occurred within minutes after subcutaneous administration of STRENSIQ and can occur in patients on treatment for more than one year. Other hypersensitivity reactions have also been reported in STRENSIQ-treated patients, including vomiting, fever, headache, flushing, irritability, chills, skin erythema, rash, pruritus and oral hypoesthesia. If a severe hypersensitivity reaction occurs, discontinue STRENSIQ treatment and initiate appropriate medical treatment. Consider the risks and benefits of re-administering STRENSIQ to individual patients following a severe reaction. If the decision is made to re-administer the product, monitor patients for a reoccurrence of signs and symptoms of a severe hypersensitivity reaction.
Localized lipodystrophy, including lipoatrophy and lipohypertrophy, has been reported at injection sites after several months in patients treated with STRENSIQ. Advise patients to follow proper injection technique and to rotate injection sites.
Patients with HPP are at increased risk for developing ectopic calcifications. In clinical trials, 14 cases (14%) of ectopic calcification of the eye including the cornea and conjunctiva, and the kidneys (nephrocalcinosis) were reported. There was insufficient information to determine whether or not the reported events were consistent with the disease or due to STRENSIQ. No visual changes or changes in renal function were reported. Ophthalmology examinations and renal ultrasounds are recommended at baseline and periodically during treatment with STRENSIQ to monitor for signs and symptoms of ophthalmic and renal ectopic calcifications and for changes in vision or renal function.
The most common adverse reactions (≥ 10%)are injection site reactions, lipodystrophy, ectopic calcifications and hypersensitivity reactions.