近日，美国FDA批准Lucentis(ranibizumab-兰尼单抗)注射剂（PFS）作为一种新给药剂型用于所有糖尿病视网膜病的治疗。
Lucentis PFS由硼硅酸盐玻璃制成，包装在一个单一的无菌密封托盘中。该制剂允许医生在配制和给药过程中减少几个操作步骤，包括消毒小瓶，固定过滤针，用针头从小瓶中提取药物，从注射器中取出滤针并用注射针将其替换。使用Lucentis PFS，医生们可以将注射器帽摘下来，将注射针连接到注射器上，并在给药前调整剂量。
准日期：2015年2月6日 公司：基因泰克
LUCENTIS（雷珠单抗[ranibizumab]）注射液，用于玻璃体内注射
用于玻璃体内注射
美国初期审批：2006年
最近的主要变化
适应症和用法，糖尿病视网膜病变：2017年4月
适应症和用法，近视脉络膜新血管形成：01/2017
剂量和管理：2017年4月
剂型和优势：04/2017
作用机制
雷珠单抗结合VEGF-A活性形式的受体结合位点，包括该分子的生物活性切割形式VEGF110。 已显示VEGF-A在眼血管发生和血管阻塞模型中引起新血管形成和渗漏，并且被认为促成RVO后新生血管性AMD，mCNV，DR，DME和黄斑水肿的病理生理学。 雷珠单抗与VEGF-A的结合防止了VEGF-A与其在内皮细胞表面上的受体（VEGFR1和VEGFR2）的相互作用，减少内皮细胞增殖，血管渗漏和新血管形成。
适应症和用法
LUCENTIS是一种血管内皮生长因子（VEGF）抑制剂，用于治疗以下患者：
新生血管（湿）年龄相关性黄斑变性（AMD）
视网膜静脉阻塞（RVO）后黄斑水肿
糖尿病性黄斑水肿（DME）
糖尿病视网膜病变（DR）
近视脉络膜新血管形成（mCNV）
用法和管理
仅用于眼科玻璃体内注射。
新生血管性（湿）年龄相关性黄斑变性（AMD）：
推荐每月一次（大约28天）通过玻璃体内注射给药0.5mg（0.05mL）的LUCENTIS。
虽然效果不佳，但可以通过定期评估以较低的剂量给予患者治疗。
尽管效果不佳，但患者可能在每月4次剂量后每3个月接受一次剂量治疗。应定期评估患者。
视网膜静脉阻塞（RVO）后的黄斑水肿：
推荐每月一次（约28天）通过玻璃体内注射施用0.5mg（0.05mL）的鲁西尼菌。
糖尿病性黄斑水肿（DME）和糖尿病性视网膜病（DR）：
推荐每月一次（约28天）玻璃体内注射0.3mg（0.05mL）琉璃苣醇。
近视脉络膜新血管形成（mCNV）：
建议每月一次（约28天）一次玻璃体内注射0.5mg（0.05mL）萤光素，长达三个月。如果需要，患者可能会退缩。
剂型和强度
设计用于提供0.05mL玻璃体内注射的一次性预充式注射器：
-10mg/mL溶液（LUCENTIS 0.5mg）
设计用于提供0.05mL玻璃体内注射的一次性玻璃小瓶：
-10mg/mL溶液（LUCENTIS 0.5mg）
-6mg/mL溶液（LUCENTIS 0.3mg）
禁忌症
眼或眼周感染
过敏症
警告和注意事项
玻璃体内注射后可能会发生眼内炎和视网膜脱离。注射后应监测患者。
已经注意到玻璃体内注射前后的眼内压（IOP）增加。
玻璃体内使用VEGF抑制剂后存在动脉血栓栓塞事件的潜在风险。
基线时DME和DR患者发生致命事件的频率更高，与对照组相比，每月接受LUCENTIS治疗。
不良反应
最常见的不良反应（LUCENTIS治疗组比对照组报道更频繁）是结膜出血，眼痛，玻璃体飞蚊症和眼压升高。
包装提供/储存和处理
每个LUCENTIS 0.5mg纸板箱（NDC 50242-080-03）包含一次性预充式注射器，用于输送0.05mL 10 mg/mL ranibizumab溶液。预充式注射器有一个不可伸缩的柱塞塞和一个注射器盖。预充式注射器有一个柱塞杆和一个CLEAR手指夹。 预充式注射器是无菌的，并装在密封的托盘中。
每个LUCENTIS 0.5mg纸板箱（NDC 50242-080-02）包含一个一次性使用2mL玻璃瓶和一个BLUE CAP，设计用于提供0.05mL 10mg/mL ranibizumab溶液。
每个LUCENTIS 0.3mg纸板盒（NDC 50242-082-02）包含一个一次性使用2mL玻璃瓶和一个设计用于递送0.05mL 6mg/mL兰尼单抗溶液的WHITE CAP的玻璃瓶。
每个纸盒仅供单眼使用。
LUCENTIS应该在2°-8°C（36°-46°F）冷藏。不要冻结。不要使用标签上的日期。保护LUCENTIS预充式注射器和小瓶不受光线影响，并保存在原包装箱中，直到使用时间。在使用前，请勿打开LUCENTIS预充式注射器密封托盘。
完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de4e66cc-ca05-4dc9-8262-e00e9b41c36d 

LUCENTIS Was Designed for Rapid Systemic Clearance Through the Removal
of the Fc Region to Minimize Systemic Exposure1-4
LUCENTIS is an antigen-binding fragment (Fab) that was designed without an Fc region
Removal of the Fc region means LUCENTIS is not subject to FcRn recycling, resulting in rapid systemic clearance to minimize systemic exposure
Maximum serum concentrations have been observed approximately 1 day after intravitreal administration and were approximately 0.3 ng/mL to 2.36 ng/mL*
Removal of the Fc region means LUCENTIS may also have reduced potential to initiate immune-mediated inflammation
Important Select Safety Information
Although there was a low rate of ATEs observed in the LUCENTIS clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).
The clinical significance of the molecular design of LUCENTIS is not known.
ATE, arterial thromboembolic event; VEGF, vascular endothelial growth factor.
*This Cmax is based on a 0.5 mg dose.

INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
LUCENTIS® (ranibizumab injection) is indicated for the treatment of patients with:
Neovascular (wet) age-related macular degeneration (wAMD)
Macular edema following retinal vein occlusion (RVO)
Diabetic macular edema (DME)
IMPORTANT SAFETY INFORMATION
LUCENTIS is contraindicated in patients with ocular or periocular infections or hypersensitivity to ranibizumab or any of the excipients in LUCENTIS.
WARNINGS AND PRECAUTIONS
Intravitreal injections, including those with LUCENTIS, have been associated with endophthalmitis and retinal detachment. Proper aseptic injection technique should always be utilized when administering LUCENTIS. Patients should be monitored during the week following the injection to permit early treatment, should an infection occur.
Increases in intraocular pressure (IOP) have been noted both pre-injection and post-injection (at 60 minutes) with LUCENTIS. IOP and perfusion of the optic nerve head should be monitored and managed appropriately.
Although there was a low rate of arterial thromboembolic events (ATEs) observed in the LUCENTIS clinical trials, there is a potential risk of ATEs following intravitreal use of VEGF inhibitors. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause).
Neovascular (wet) age-related macular degeneration
The ATE rate in the 3 controlled neovascular AMD studies during the first year was 1.9% in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 1.1% in patients from the control arms. In the second year of Studies AMD-1 and AMD-2, the ATE rate was 2.6% in the combined group of LUCENTIS-treated patients compared with 2.9% in patients from the control arms. In Study AMD-4, the ATE rates observed in the study during the first year were similar to rates observed in Studies AMD-1, AMD-2, and AMD-3.
In a pooled analysis of 2-year controlled studies (AMD-1, AMD-2, and a study of LUCENTIS used adjunctively with verteporfin photodynamic therapy), the stroke rate (including both ischemic and hemorrhagic stroke) was 2.7% in patients treated with 0.5 mg LUCENTIS compared to 1.1% in patients in the control arms (odds ratio 2.2 [95% confidence interval (0.8-7.1)]).
Macular edema following retinal vein occlusion
The ATE rate in the 2 controlled RVO studies during the first 6 months was 0.8% in both the LUCENTIS and control arms of the studies (4 of 525 in the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS and 2 of 260 in the control arms). The stroke rate was 0.2% in the combined group of LUCENTIS-treated patients compared to 0.4% in the control arms.
Diabetic macular edema
In a pooled analysis of Studies DME-1 and DME-2, the ATE rate at 2 years was 7.2% with 0.5 mg LUCENTIS, 5.6% with 0.3 mg LUCENTIS, and 5.2% with control. The stroke rate at 2 years was 3.2% with 0.5 mg LUCENTIS, 1.2% with 0.3 mg LUCENTIS, and 1.6% with control. At 3 years, the ATE rate was 10.4% with 0.5 mg LUCENTIS and 10.8% with 0.3 mg LUCENTIS; the stroke rate was 4.8% with 0.5 mg LUCENTIS and 2.0% with 0.3 mg LUCENTIS.
A pooled analysis of Studies DME-1 and DME-2 showed that fatalities in the first 2 years occurred in 4.4% of patients treated with 0.5 mg LUCENTIS, in 2.8% of patients treated with 0.3 mg LUCENTIS, and in 1.2% of control patients. Over 3 years, fatalities occurred in 6.4% of patients treated with 0.5 mg LUCENTIS and in 4.4% of patients treated with 0.3 mg LUCENTIS. Although the rate of fatal events was low and included causes of death typical of patients with advanced diabetic complications, a potential relationship between these events and intravitreal use of VEGF inhibitors cannot be excluded.
ADVERSE EVENTS
Serious adverse events related to the injection procedure that occurred in <0.1% of intravitreal injections included endophthalmitis, rhegmatogenous retinal detachment, and iatrogenic traumatic cataract.
In clinical trials in neovascular (wet) age-related macular degeneration, the most common ocular side effects included conjunctival hemorrhage, eye pain, vitreous floaters, increased IOP, vitreous detachment, and intraocular inflammation. The most common non-ocular side effects included nasopharyngitis, headache, arthralgia, and bronchitis.
In clinical trials in macular edema following retinal vein occlusion, the most common ocular side effects included conjunctival hemorrhage, eye pain, and maculopathy. The most common non-ocular side effects included nasopharyngitis, headache, influenza, and sinusitis.
In clinical trials in diabetic macular edema, the most common ocular side effects included conjunctival hemorrhage, cataract, increased IOP, and vitreous detachment. The most common non-ocular side effects included nasopharyngitis, anemia, and nausea.
As with all therapeutic proteins, there is the potential for an immune response in patients treated with LUCENTIS. The clinical significance of immunoreactivity to LUCENTIS is unclear at this time.
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附件:
201121317262127.pdf