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PREVNAR 13(肺炎球菌13-价组合疫苗[白喉CRM197蛋白])使用说明书2011年12月版

PREVNAR 13(肺炎球菌13-价组合疫苗[白喉CRM197蛋白])使用说明书2011年12月版
批准日期2011年12月30日；公司：Wyeth药业
FDA的生物制品评价和研究主任Karen Midthun, M.D.说“按照美国最近信息，估计约300,000的50岁和以上成年每年因为肺炎球菌肺炎住院”，“肺炎球菌疾病是疾病和死亡的实质原因。今天的批准提供另一种疫苗为在这个年龄组预防肺炎球菌肺炎和侵入性疾病。”

在监督管理局加速批准途径下批准Prevnar 13的新用途，允许早期批准严重和危及生命疾病。 通路允许用合理预测临床获益的免疫标志物显示疫苗有效性。

加速批准是授予该疫苗批准上市后期间条件下进行一项临床试验证实期望的临床获益。一项另外试验在既往没有接受Pneumovax 23史的85,000年龄65岁和以上人， 正在进行证实Prevnar 13预防肺炎球菌肺炎的临床获益。

Prevnar 13为50岁和以上成年的批准支持美国卫生和人类服务部的2020目标
http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM201669.pdf

处方资料重点
这些重点不包括安全和有效使用PREVNAR 13所需所有资料。请参阅PREVNAR 13的完整处方资料

为肌肉注射悬液
美国初始批准: 2010

最近重要修改------------------------- 红色表示修改部分
适应证和用途(1) 01/2012
剂量和给药方法，免疫接种时间表为50岁和以上成年 (2.6) 01/2012

适应证和用途
在6周至5岁儿童中(第6次生日前)，Prevnar 13是一种疫苗适用于：
（1）主动免疫预防链球菌肺炎血清型1，3，4，5，6A，6B，7F，9V，14，18C，19A，19F和23F所致侵入性疾病。
（2）主动免疫为预防链球菌肺炎血清型4，6B，9V，14，18C，19F，和23F所致中耳炎。对血清型1，3，5，6A，7F，和19A未能得到中耳炎疗效资料。 (1.1)

在50岁和以上成年中，Prevnar 13是一种疫苗适用于：
（1）为预防链球菌肺炎血清型1，3，4，5，6A，6B，7F，9V，14，18C，19A，19F和23F所致肺炎和侵入性疾病主动免疫。该适应证是根据用Prevnar 13引发免疫反应。在成年中没有对照试验证实用 Prevnar 13免疫接种后肺炎球菌肺炎或侵入性疾病减低。(1.2)
使用限制
（1）Prevnar 13将不保护未包括在疫苗中链球菌肺炎血清型所致疾病。 (1.3)
（2）不知道 肺炎球菌多糖疫苗Prevnar 13接种后小于5年有效性。 (1.3)

剂量和给药方法
6周至5岁儿童：四-剂量系列免疫接种由在2，4，6，和12-15月龄0.5 mL肌肉注射接种组成。 (2.3)
50岁和以上成年：单剂量。(2.6)

剂型和规格
0.5 mL肌肉注射悬液，在单-剂量预装注射器内提供。 (3)

禁忌证
对Prevnar 13任何组分或含任何白喉类毒素疫苗严重过敏反应(如，过敏反应)。(4)

警告和注意事项
在一些早产婴儿中肌肉内免疫接种后曾观察到无呼吸。关于当给予肌肉疫苗时决策，包括Prevnar 13，至早产婴儿应根据个体婴儿医学状态，和潜在获益和免疫接种的可能风险考虑。(5.3)

不良反应
在2，4，6，和12-15月龄婴儿和幼儿中接种美国的临床试验中，最常报道诱发不良反应是过敏性(>70%)，注射部位压痛(>50%)，食欲减低(>40%), 睡眠减少(>40%), 睡眠增加(>40%), 发热(>20%), 注射部位发红(>20%)，和注射部位肿胀(>20%)。 (6.1)
在50岁和以上成年中最常报道诱发不良反应是注射部位疼痛(>50%)，疲乏(>30%)，头痛(>20%)，肌肉痛(>20%)，关节痛(>10%)，食欲减低(>10%)，注射部位发红(>10%)，注射部位肿胀(>10%)，手臂运动受限(>10%)，畏寒(>5%)或皮疹(>5%)。 (6.2)

药物相互作用
成年中，对Prevnar 13的抗体反应消失当给予灭活流感病毒疫苗。(14.3)

特殊人群中使用
妊娠: 尚未确定Prevnar 13在妊娠妇女中的安全性和有效性。(8.1)
儿童使用：尚未确定Prevnar 13在小于6周龄或第6生日后儿童中安全性和有效性。 (8.4)
老年人使用：在>65岁人中对Prevnar 13的抗体反应比50至59 岁人对的抗体反应较低。 (8.5)

完整处方资料
1 适应证和用途
1.1 6周至5岁龄儿童
在6周至5岁龄儿童(第6次生日前)，Prevnar 13是适用于：
（1）主动免疫预防链球菌肺炎血清型1，3，4，5，6A，6B，7F，9V，14，18C，19A，19F和23F所致侵入性疾病。
（2）主动免疫为预防链球菌肺炎血清型4，6B，9V，14，18C，19F，和23F所致中耳炎。对血清型1，3，5， 6A，7F，和19A中耳炎疗效无可供利用资料。

1.2 50岁和以上成年
50岁和以上成年中，Prevnar 13是适用于：
（1）主动免疫为预防肺炎和侵入性疾病所致链球菌肺炎血清型1，3，4，5，6A，6B，7F，9V，14，18C，19A，19F和23F。这个适应证是给予被Prevnar 13引发的免疫反应。在成年中没有对照试验证实免疫接种Prevnar 13后侵入性肺炎球菌疾病或肺炎球菌肺炎减低。.

1.3  Prevnar 13 使用的局限性和有效性
Prevnar 13将不保护疫苗中不含链球菌肺炎血清型所致的疾病。

不知道给予Pneumovax 23®(肺炎球菌疫苗多价, PPSV23)后小于5年给Prevnar 13的有效性[见临床试验14.3]。

2 剂量和给药方法
2.1 为给药制备
因为本产品是含赋形剂的悬液，在得到疫苗容器内均匀，白色悬液后，用前立即剧烈摇动。如不能重新悬浮不要使用疫苗。非肠道药品在给予前应肉眼观测有无颗粒物质和变色[见一般描述(11)]。如发现颗粒物质和变色不应使用产品。
不要在相同注射器内混合Prevnar 13与其它疫苗/产品。

2.2 给药信息
仅为肌肉注射。不要静脉，皮内，或皮下注射。.
用无菌针头附着在供应的预装注射器肌肉注射每0.5 mL剂量。婴儿中最好的注射部位是大腿前外侧而幼儿，青少年和成年是上臂三角肌。不应将疫苗注入臀区或可能是主要神经干和/或血管的区域。

2.3 为婴儿和幼儿免疫接种时间表
Prevnar 13将以四剂系列在2，4，6，和12-15月龄给予。
2.4 对 ≥ 7月龄未接种儿童免疫接种时间表
对超出常规婴儿时间表年龄范围儿童和没有接受Prevnar®或Prevnar 13，应用下列追赶时间表。
这个追赶时间表诱发的免疫反应对某些血清型可能导致抗体浓度比4剂Prevnar 13(在2，4，6，和12至15个月给予)后抗体浓度较低。在24个月至5岁儿童中，追赶时间表对某些血清型可能导致抗体浓度比三剂Prevnar 13(在2，4，和6个月给予)后抗体浓较低。

2.5 对既往接种疫苗用Prevnar 肺炎球菌7-价组合疫苗(白喉CRM197蛋白)儿童免疫接种时间表
曾接受一剂或更多剂Prevnar儿童可能完成用Prevnar 13免疫接种系列。15个月至5岁儿童被认为完全免疫可能接受一剂对6种附加血清型用Prevnar 13引发免疫反应。这种追赶(补充)剂量Prevnar 13应在最后剂量Prevnar后至少间隔8周给予。这个Prevnar 13时间表诱发免疫反应可能对6种另外血清型(类型1，3，5，6A，7F，和19A)，导致抗体浓度比4剂Prevnar 13后(在2，4，6，和12至15 个月给予)抗体浓度较低。

2.6 为50岁和以上成年免疫接种时间表
Prevnar 13作为单剂量给予。

7 药物相互作用
7.1 同时免疫接种
在用婴儿和幼儿临床试验中，Prevnar 13同时给予以下美国许可的疫苗：Pediarix[白喉和破伤风类毒素和非细胞百日咳吸附，乙型肝炎(重组)和灭活脊髓灰质炎病毒疫苗组合](DTaP-HBV-IPV)和ActHIB [嗜血杆菌b 结合疫苗(破伤风类毒素(结合)](PRP-T)对头三剂和用PedvaxHIB[嗜血杆菌b结合疫苗(脑膜炎双球菌蛋白结合)](PRP-OMP)，M-M-R II[麻疹，流行性腮腺炎，风疹病毒疫苗活](MMR)和Varivax[水痘病毒疫苗活]，或ProQuad[麻疹，流行性腮腺炎，风疹病毒疫苗活](MMRV)和VAQTA[甲肝疫苗，灭活](HepA)对4剂[见临床试验(14.2)]。

在成年中，Prevnar 13与对2007/2008对流感季节美国许可Fluarix(TIV)同时给予时[见临床试验(14.3)]。没有Prevnar 13与含白喉类毒素疫苗和对在50岁和以上成年许可使用许可其它疫苗同时给药的资料。

当与Prevnar 13给予相同时间给予另一个可注射疫苗(s)时，应总是用不同注射器和在不同注射部位给予。

不要在相同注射器中将Prevnar 13与其它疫苗/产品混合。

以下各节省略
3 剂型和规格
4 禁忌证
5 警告和注意事项
5.1 过敏反应的处理
5.2 免疫活性改变
5.3 早产婴儿中无呼吸
6 不良反应
6.1 在婴儿和幼儿中用Prevnar 13临床试验经验
6.2 在成年中年龄 ≥50岁用 Prevnar 13临床试验经验
6.3 在婴儿和幼儿中用Prevnar临床试验经验
6.4 在婴儿和幼儿中用Prevnar上市后经验
7  药物相互作用经验
7.1 同时免疫
7.2 免疫抑制治疗
8 特殊人群中使用
8.1 妊娠
8.3 哺乳母亲
8.4 儿童使用
8.5 老年人使用
11 一般描述
12 临床药理学
12.1 作用机制
14 临床研究
14.1 Prevnar疗效资料
14.2 在婴儿和幼儿中Prevnar 13有效性的评价
省略以上各节

14.3 Prevnar 13在成年中免疫原性临床试验
在美国和欧洲在不同成年年龄组中，在曾或未曾既往接种PPSV23疫苗(未接种PPSV23)或曾接受一剂PPSV23(既往接种PPSV23疫苗)个体中进行五项3期临床试验评价Prevnar 13的免疫原性。

每项研究包括健康成年和有稳定的患病情况免疫功能受损成年包括慢性心血管病，慢性肺部疾病，肾病，糖尿病，慢性肝病，和医学风险情况和行为(如酗酒和吸烟)已知增加严重肺炎球菌肺炎和侵入性肺炎球菌疾病的风险。稳定医学情况被定义为研究疫苗接受者在12周前治疗不需要明显改变的医学情况(即，由于疾病恶化改变为新治疗)或疾病恶化住院。

用一种mcOPA分析(注：用细菌微集落计数活细菌细胞数，OPA antibody，为调理吞噬抗体，opsonophagocytic antibody，血清中一种抗体或补体产物的激活引起细菌或其它外来细胞对吞噬细胞的作用更易感=一种调理素，用流式细胞仪分析)测量Prevnar 13和PPSV23引发的免疫反应为Prevnar 13中所含的13种肺炎球菌血清型。每种疫苗接种后1个月计算测量的血清型-特异性OPA滴度的几何均数(GMTs)。对两种疫苗共有的12种血清型，如GMT比值的2-侧95%可信区间(CI)的低限(Prevnar 13/PPSV23)大于0.5则符合疫苗间非劣效性。

另外对血清型6A的反应，在Prevnar 13中含有但PPSV23中不含有，以上免疫接种前水平，评估抗-6A OPA滴度显示增加4-倍。被确定对Prevnar 13统计上显著较大反应，成年的百分率的差异(Prevnar 13减去PPSV23) 抗-6A OPA滴度达到增加4-倍，因95% CI 2-侧的低限大于零。对OPA GMTs的比较，对血清型6A统计上较大反应被定义为GMT比值(Prevnar 13/PPSV23)的95% CI 2-侧低限大于2。

在五项3期临床试验中，进行2项非劣效性试验其中对Prevnar 13免疫反应与对PPSV23免疫反应比较；一项在未接种PPSV23年龄50至64岁成年(研究1)，和一项在年龄 ≥ 70岁成年PPSV23疫苗接种前(研究2)。第三项研究在纳入时PPSV23未接种年龄60至64岁成年中比较Prevnar 13单剂量免疫反应与对Prevnar 13给予一年后一剂量PPSV23反应(研究3)。研究还比较单剂量PPSV23的免疫反应与对PPSV23给予一年后一个剂量Prevnar 13的反应比较。两项研究在美国(研究5)和欧洲(研究6)评估同时给予Prevnar 13与季节性灭活流感疫苗Fluarix(TIV)。

在未接种PPSV23成年中进行临床试验

在一项在美国Prevnar 13的阳性对照修饰双盲临床试验(研究1)，未接种PPSV23年龄60至64岁成年被随机赋予(1:1)接受Prevnar 13或PPSV23。此外，纳入年龄50至59岁成年和接受一剂Prevnar 13(开放试验)。

在年龄60至64岁成年中，对两种疫苗均常见12种血清型，Prevnar 13引发OPA抗体GMTs是不劣于于被PPSV23引发的OPA抗体GMTs(见表19)。此外，对8种常见血清型，对OPA GMT比值(Prevnar 13/PPSV23)的95%可信区间的低限是大于1。

在PPSV23-未接种疫苗年龄60至64岁成年中，对Prevnar 13独特的血清型6A，在Prevnar 13后有增加4-倍受试者的比例(88.5%)是统计上显著大于PPSV23后(39.2%)。Prevnar 13后与PPSV23后比较对血清型6A的OPA GMTs是统计上显著较大(见表19)。
年龄50至59岁成年中Prevnar 13引发OPA抗体GMTs是不劣于年龄60至64岁成年中对所有13种血清型对Prevnar 13引发相应OPA抗体GMTs(见表19).
 
a 修饰的双盲意味著地点工作人员非盲态发放和给予疫苗，但所有其它研究人员包括主要研究者和受试者均为盲态。

既往接种疫苗PPSV23成年中进行临床试验
在美国和瑞典Prevnar 13的一项3期阳性对照，修饰双盲临床试验(研究2)，PPSV23疫苗接种前年龄 ≥ 70岁成年曾接受一剂PPSV23 ≥ 5 年前被随机赋予(1:1)接受或Prevnar 13或PPSV23。

对12中常见血清型Prevnar 13引发OPA抗体GMTs是不劣于被PPSV23引发OPA抗体GMTs，当既往剂量PPSV23后最少5年时给予Prevnar 13或PPSV23。此外，对10种常见血清型对OPA GMT比值(Prevnar 13/PPSV23)95%可信区间的低限是大于1。

在PPSV23-前疫苗接种年龄 ≥ 70岁成年中，Prevnar 13后对Prevnar独特的血清型6A的OPA滴度增加4-倍的受试者比例(71.1%)，是统计上显著大于PPSV23后(27.3%). Prevnar 13后与PPSV23后比较，对血清型6A的OPA GMTs是统计上显著较大。

这个临床试验证实在年龄 ≥ 70岁成年和≥ 5年以前前接种疫苗PPSV23，用Prevnar 13疫苗接种当与再次-疫苗接种PPSV23比较引发不劣于免疫反应(见表20)。

在未接种PPSV23成年中顺序疫苗接种Prevnar 13和PPSV23的临床试验
在未接种-PPSV23疫苗60至64岁成年进行一项随机化临床试验(研究3)，223人接受PPSV23接着一年后Prevnar 13(PPSV23/Prevnar 13)，和478人只接受Prevnar 13。表21中显示Prevnar 13疫苗接种用后一个月测定的OPA抗体滴度。Prevnar 13一年后接受PPSV23当与单独接受Prevnar 13比较，OPA GMTs抗体滴度减弱 。相似地，在研究2中≥ 70岁成年PPSV23-前-接种疫苗的开拓分析，Prevnar 13一年后接受PPSV23当与单独接受Prevnar 13比较观察到OPA GMTs减弱。

给药间隔大于1年没有可供利用资料。既往未接种人对Prevnar 13给予一年后PPSV23反应无可供利用资料。

还在研究3中，266人接受Prevnar 13接着一年后PPSV23(Prevnar 13/PPSV23)。Prevnar 13后一年给予PPSV23 (Prevnar 13/PPSV23)OPA抗体GMTs是不劣于单剂量PPSV23后(N=237)，对12种常见血清型[对GMT比值95% CI的低限[Prevnar 13/PPSV23相对于PPSV23]是 > 0.5](见表22)。在研究1中，第一天PPSV23-未接种疫苗60至64岁成年进行，108人PCV13后3.5至4年接受PPSV23(Prevnar 13/PPSV23)和414人接受单剂量PPSV23。在研究3中[(Prevnar 13/PPSV23)/PPSV23]与一年给药间隔比较一般观察到较高血清型-特异性OPA GMT比值。

在未接种PPSV23成年中评估Prevnar 13与季节性三价灭活流感疫苗(TIV)给予临床试验
两项在未接种PPSV23成年中年龄50至59岁(研究5，在美国进行)和in成年≥ 65岁(研究6,在欧洲进行)随机化，双盲临床试验与灭活TIV(秋季2007/春季2008 Fluarix, A/H1N1，A/H3N2，和B株)给予评价Prevnar 13的免疫原性。
 
在各个临床试验中一组同时接受Prevnar 13和TIV，接着约一个月后安慰剂。其它组同时接受TIV和安慰剂，接着约一个月后Prevnar 13。

TIV疫苗接种后一个月，用红细胞凝集抑制分析(HAI)测定TIV引发抗体反应。疫苗接种后一个月评价对每个TIV株在HAI滴度增加达到≥4-倍(有反应者)的受试者比例。对每个TIV疫苗抗原如有反应者的比例两组间(同时减去(TIV+Placebo))95% CI的低限的差别是大于-10%是证实非劣效性。
在50至59岁受试者中，在Prevnar 13后给予3株TIV株各株与TIV同时给予与单独给TIV比较显示非劣效性。

在≥65岁受试者中，显示对A/H1N1和B-株非劣效性，但不是对A/H3N2，对95% CI低限-10.4%。
当Prevnar 13被与TIV同时给予与单独给予Prevnar 13比较时，研究还评估Prevnar 13的抗体反应。Prevnar 13疫苗接种后一个月，在一子组受试者中，用ELISA IgG测量抗多糖结合抗体反应(IgG)。如2-侧，95% CI对IgG GMC比值(Prevnar 13+ TIV相对于单独Prevnar 13)的低限是 > 0.5证实非劣效性。在一项事后分析中，用相同标准评价OPA抗体反应(调理吞噬抗体，opsonophagocytic antibody，注：血清中一种抗体或补体产物的激活引起细菌或其它外来细胞对吞噬细胞的作用更易感=一种调理素)。

在50至59岁受试者中，当用ELISA测量，Prevnar 13 IgG抗体反应， Prevnar 13被与TIV同时给予后与单独给予Prevnar 13比较对全部13血清型符合非劣效性，而观察到对8/13血清型OPA GMT比值的非劣效性。

在≥65岁受试者中，当用ELISA测量，Prevnar 13 IgG抗体反应, Prevnar 13被与TIV同时给予后与单独给予Prevnar 13比较对12/13中血清型符合非劣效性，和观察到对10/13血清型OPA GMT比值的非劣效性。

 

 

 

 

 

 

 

 

What is Prevnar 13?

Prevnar 13 vaccine is used to prevent infection caused by pneumococcal bacteria. Prevnar 13 contains 13 different types of pneumococcal bacteria.

Pneumococcal disease is a serious infection caused by a bacteria. Pneumococcal bacteria can infect the sinuses and inner ear. It can also infect the lungs, blood, and brain, and these conditions can be fatal.

Prevnar 13 works by exposing you to a small amount of the bacteria or a protein from the bacteria, which causes the body to develop immunity to the disease. Prevnar 13 will not treat an active infection that has already developed in the body.

Prevnar 13 is for use in children from 6 weeks to 5 years old, and in adults who are 50 and older.

Update: Pfizer Receives FDA Approval for Prevnar 13 in Adults Age 18 Through 49 July 12, 2016

Becoming infected with pneumococcal disease (such as pneumonia or meningitis) is much more dangerous to your health than receiving Prevnar 13. However, like any medicine, Prevnar 13 can cause side effects but the risk of serious side effects is extremely low.

Like any vaccine, Prevnar 13 may not provide protection from disease in every person.

Important information

For children, Prevnar 13 vaccine is given in a series of shots. The first shot is usually given when the child is 2 months old. The booster shots are then given at 4 months, 6 months, and 12 to 15 months of age. Adults usually receive only one dose of the vaccine.

In a child older than 6 months who has not yet received Prevnar 13, the first dose can be given any time from the age of 7 months through 5 years (before the 6th birthday).

If the child is less than 1 year old at the time of the first Prevnar 13 shot, he or she will need 2 booster doses. If the child is 12 to 23 months old at the time of the first shot, he or she will need 1 booster dose. A child who is 2 years or older at the time of the first shot may need only the one shot and no booster doses.

 

The timing of a vaccination with Prevnar 13 is very important for it to be effective. Your child's individual booster schedule may be different from these guidelines. Follow your doctor's instructions or the schedule recommended by the health department of the state you live in. Keep track of any and all side effects your child has after receiving Prevnar 13. When the child receives a booster dose, you will need to tell the doctor if the previous shot caused any side effects.

You can still receive a vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving Prevnar 13.

Becoming infected with pneumococcal disease (such as pneumonia or meningitis) is much more dangerous to your health than receiving Prevnar 13. However, like any medicine, this vaccine can cause side effects but the risk of serious side effects is extremely low.

Be sure to keep your child on a regular schedule for other immunizations against diseases such as diphtheria, tetanus, pertussis (whooping cough), measles, mumps, hepatitis, or varicella (chicken pox). Your doctor or state health department can provide you with a recommended immunization schedule.

Before receiving Prevnar 13

Keep track of any and all side effects your child has after receiving Prevnar 13. When the child receives a booster dose, you will need to tell the doctor if the previous shot caused any side effects. You should not receive Prevnar 13 if you ever had a severe allergic reaction to a pneumococcal or diphtheria vaccine.

Before your child receives Prevnar 13, tell your doctor if the child was born prematurely.

To make sure you or your child can safely receive Prevnar 13, tell your doctor if you or your child have any of these other conditions:

· a bleeding or blood clotting disorder such as hemophilia or easy bruising; or

· a weak immune system caused by disease, bone marrow transplant, or by using certain medicines or receiving cancer treatments.

You can still receive a vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving Prevnar 13.

How is Prevnar 13 given?

Prevnar 13 is injected into a muscle. You will receive this injection in a doctor's office or clinic setting.

For children, Prevnar 13 vaccine is given in a series of shots. The first shot is usually given when the child is 2 months old. The booster shots are then given at 4 months, 6 months, and 12 to 15 months of age. Adults usually receive only one dose of the vaccine.

The first injection should be given no earlier than 6 weeks of age. Allow at least 2 months to pass between injections.

If your child is older than 6 months, he or she can still receive Prevnar 13 on the following schedule:

· Age 7-11 months: two Prevnar 13 injections at least 4 weeks apart, followed by a third injection after the child turns 1 year (at least 2 months after the second injection);

· Age 12-23 months: two Prevnar 13 injections at least 2 months apart;

· Age 24 months to 5 years (before the 6th birthday): one Prevnar 13 injection.

The timing of a vaccination with Prevnar 13 is very important for it to be effective. Your child's individual booster schedule may be different from these guidelines. Follow your doctor's instructions or the schedule recommended by the health department of the state you live in.

Your doctor may recommend treating fever and pain with an aspirin-free pain reliever such as acetaminophen (Tylenol) or ibuprofen (Motrin, Advil, and others) when the shot is given and for the next 24 hours. Follow the label directions or your doctor's instructions about how much of this medicine to give your child.

It is especially important to prevent fever from occurring in a child who has a seizure disorder such as epilepsy.

Be sure to keep your child on a regular schedule for other immunizations such as diphtheria, tetanus, pertussis (whooping cough), hepatitis, and varicella (chicken pox). Your doctor or state health department can provide you with a recommended immunization schedule.

What happens if I miss a dose?

Contact your doctor if your child will miss a booster dose or gets behind schedule. The next dose should be given as soon as possible. There is no need to start over.

Be sure your child receives all recommended doses of Prevnar 13. If your child does not receive the full series of vaccines, he or she may not be fully protected against the disease.

What happens if I overdose?

An overdose of Prevnar 13 is unlikely to occur.

What should I avoid?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Prevnar 13 side effects

Your child should not receive a booster vaccine if he or she had a life-threatening allergic reaction after the first Prevnar 13 shot. Keep track of any and all side effects your child has after receiving Prevnar 13. When the child receives a booster dose, you will need to tell the doctor if the previous shot caused any side effects. Get emergency medical help if your child has any of these signs of an allergic reaction to Prevnar 13: hives; difficulty breathing; swelling of the face, lips, tongue, or throat.

Call your doctor at once if you or your child has a serious side effect such as:

· high fever (103 degrees or higher);

· seizure (convulsions);

· wheezing, trouble breathing;

· severe stomach pain, severe vomiting or diarrhea;

· easy bruising or bleeding; or

· severe pain, itching, irritation, or skin changes where the shot was given.

Less serious Prevnar 13 side effects include

· crying, fussiness;

· headache, tired feeling;

· muscle or joint pain;

· drowsiness, sleeping more or less than usual;

· mild redness, swelling, tenderness, or a hard lump where the shot was given;

· loss of appetite, mild vomiting or diarrhea;

· low fever (102 degrees or less), chills; or

· mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report vaccine side effects to the US Department of Health and Human Services at 1-800-822-7967.

What other drugs will affect Prevnar 13?

Before receiving Prevnar 13, tell the doctor about all other vaccines you or your child have recently received.

Also tell the doctor if you or your child have recently received drugs or treatments that can weaken the immune system, including:

· an oral, nasal, inhaled, or injectable steroid medicine;

· chemotherapy or radiation;

· medications to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders, such as azathioprine (Imuran), etanercept (Enbrel), leflunomide (Arava), and others; or

· medicines to treat or prevent organ transplant rejection, such as basiliximab (Simulect), cyclosporine (Sandimmune, Neoral, Gengraf), muromonab CD3 (Orthoclone), mycophenolate mofetil (CellCept), sirolimus (Rapamune), or tacrolimus (Prograf).

If you are using any of these medications, you may not be able to receive the vaccine, or may need to wait until the other treatments are finished.

There may be other drugs that can interact with Prevnar 13. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.  

 

 

Prevnar 13

Generic Name: pneumococcal 13-valent conjugate vaccine
Dosage Form: injection, suspension

Medically reviewed on Apr 2, 2018

 

 

 

Indications and Usage for Prevnar 13

Prevnar 13™ is a vaccine approved for use in children 6 weeks through 5 years of age (prior to the 6th birthday).

Prevnar 13 is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F.

 

Prevnar 13 is also indicated for the prevention of otitis media caused by Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. No otitis media efficacy data are available for serotypes 1, 3, 5, 6A, 7F, and 19A.

 

 

 

Prevnar 13 Dosage and Administration

For intramuscular injection only.

Preparation for Administration

Since this product is a suspension containing an adjuvant, shake vigorously immediately prior to use to obtain a homogenous, white suspension in the vaccine container. Do not use the vaccine, if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration [see Description (11)]. This product should not be used if particulate matter or discoloration is found.

Do not mix Prevnar 13 with other vaccines/products in the same syringe.

Administration Information

Do not inject intravenously, intradermally, or subcutaneously.

Each 0.5 mL dose is to be injected intramuscularly. The preferred sites for injection are the anterolateral aspect of the thigh in infants or the deltoid muscle of the upper arm in toddlers and young children. The vaccine should not be injected in the gluteal area or areas where there may be a major nerve trunk and/or blood vessel.

 

 

 

 

Vaccine Schedule for Infants and Toddlers

Prevnar 13 is to be administered as a four-dose series at 2, 4, 6, and 12-15 months of age.

Table 1: Vaccination Schedule for Infants and Toddlers
Dose	Dose 1*†	Dose 2†	Dose 3†	Dose 4‡
* Dose 1 may be given as early as 6 weeks of age. † The recommended dosing interval is 4 to 8 weeks. ‡ The fourth dose should be administered at approximately 12-15 months of age, and at least 2 months after the third dose.
Age at Dose	2 months	4 months	6 months	12-15 months

Vaccine Schedule for Unvaccinated Children ≥7 Months of Age

For children who are beyond the age of the routine infant schedule and have not received Prevnar or Prevnar 13, the following catch-up schedule applies:

Table 2: Vaccine Schedule for Unvaccinated Children ≥7 Months of Age
* The first 2 doses at least 4 weeks apart; third dose after the one-year birthday, separated from the second dose by at least 2 months. † Two doses at least 2 months apart.
Age at First Dose	Total Number of 0.5 mL Doses
7-11 months of age	3*
12-23 months of age	2†
24 months through 5 years of age (prior to the 6th birthday)	1

The immune responses induced by this catch-up schedule may result in lower antibody concentrations for some serotypes, compared to antibody concentrations following 4 doses of Prevnar 13 (given at 2, 4, 6, and 12 to 15 months). In children 24 months through 5 years of age, the catch-up schedule may result in lower antibody concentrations for some serotypes, compared to antibody concentrations following 3 doses of Prevnar 13 (given at 2, 4, and 6 months). The clinical relevance of these lower antibody responses is not known.

Prevnar 13 Vaccine Schedule for Children Previously Vaccinated With Prevnar (Streptococcus pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F)

Children who have received one or more doses of Prevnar may complete the 4-dose immunization series with Prevnar 13. Children 15 months through 5 years of age who have received 4 doses of Prevnar may receive one dose of Prevnar 13 to elicit immune responses to the six additional serotypes. This catch-up dose of Prevnar 13 should be administered with an interval of at least 8 weeks after the fourth dose of Prevnar. The immune responses induced by this Prevnar 13 transition schedule may result in lower antibody concentrations for the 6 additional serotypes (types 1, 3, 5, 6A, 7F, and 19A), compared to antibody concentrations following 4 doses of Prevnar 13 (given at 2, 4, 6, and 12 to 15 months). The clinical relevance of these lower antibody responses is not known.

Dosage Forms and Strengths

Prevnar 13 is a suspension for intramuscular injection available in 0.5 mL single-dose pre-filled syringes.

Contraindications

Severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13, Prevnar or any diphtheria toxoid-containing vaccine.

Warnings and PrecautionsManagement of Allergic Reactions or Other Adverse Reactions

Before administration of any dose, all precautions should be taken to prevent allergic or any other adverse reactions. This includes a review of the patient’s immunization history for possible sensitivity to the vaccine or similar vaccines and for previous vaccination-related adverse reactions in order to determine the existence of any contraindication to immunization with Prevnar 13 and to allow an assessment of risks and benefits. Epinephrine and other appropriate agents used for the control of immediate allergic reactions must be immediately available should an acute anaphylactic reaction occur following the administration of the vaccine.

Limitations of Vaccine Effectiveness

Prevnar 13 may not protect all individuals receiving the vaccine. Prevnar 13 will not protect against Streptococcus pneumoniae serotypes that are not in the vaccine or serotypes unrelated to those in the vaccine. It will also not protect against other microorganisms. This vaccine does not treat active infection.

Protection against otitis media is expected to be substantially lower than protection against invasive disease. In addition, because otitis media is caused by many organisms other than the 7 serotypes of Streptococcus pneumoniae included in the indication, protection against all causes of otitis media is expected to be lower than for pneumococcal otitis media caused by these 7 vaccine serotypes [see Clinical Studies (14.2)].

The duration of protection from immunization is not known.

Altered Immunocompetence

Data on the safety and effectiveness of Prevnar 13 when administered to children in specific groups at higher risk for invasive pneumococcal disease (e.g., children with congenital or acquired splenic dysfunction, HIV infection, malignancy, nephrotic syndrome) are not available.

Children in these groups may have reduced antibody response to active immunization due to impaired immune responsiveness. Vaccination in high-risk groups should be considered on an individual basis [see Drug Interactions (7.2)].

The use of pneumococcal conjugate vaccine does not replace the use of 23-valent pneumococcal polysaccharide vaccine (PPV23) in children ≥24 months of age with sickle cell disease, asplenia, HIV infection, chronic illness or who are otherwise immunocompromised.

Premature Infants

Apnea following intramuscular vaccination has been observed in some infants born prematurely. Decisions about when to administer an intramuscular vaccine, including Prevnar 13, to infants born prematurely should be based on consideration of the individual infant’s medical status, and the potential benefits and possible risks of vaccination.

Adverse Reactions

Because clinical trials are conducted under widely varying conditions, adverse-reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. As with any vaccine, there is the possibility that broad use of Prevnar 13 could reveal adverse reactions not observed in clinical trials.

Clinical Trials Experience With Prevnar 13

The safety of Prevnar 13 was evaluated in 13 clinical trials in which 4,729 infants and toddlers received at least one dose of Prevnar 13 and 2,760 infants and toddlers received at least one dose of Prevnar active control. Safety data for the first three doses are available for all 13 infant studies; dose 4 data are available for 10 studies; and data for the 6-month follow-up are available for 7 studies. The vaccination schedule and concomitant vaccinations used in these infant trials were consistent with country-specific recommendations and local clinical practice. There were no substantive differences in demographic characteristics between the vaccine groups. By race, 84.0% of subjects were White, 6.0% were Black or African-American, 5.8% were Asian and 3.8% were of ‘Other’ race (most of these being biracial). Overall, 52.3% of subjects were male infants.

Three studies in the U.S. evaluated the safety of Prevnar 13 when administered concomitantly with routine U.S. pediatric vaccinations at 2, 4, 6, and 12-15 months of age. Solicited local and systemic adverse events were recorded daily by parents/guardians using an electronic diary for 7 consecutive days following each vaccination. For unsolicited adverse events, study subjects were monitored from administration of the first dose until one month after the infant series, and for one month after the administration of the toddler dose. Information regarding unsolicited and serious adverse events, newly diagnosed chronic medical conditions, and hospitalizations since the last visit were collected during the clinic visit for the fourth-study dose and during a scripted telephone interview 6 months after the fourth-study dose. Serious adverse events were also collected throughout the study period. Overall, the safety data show a similar proportion of Prevnar 13 and Prevnar subjects reporting serious adverse events. Among U.S. study subjects, a similar proportion of Prevnar 13 and Prevnar recipients reported solicited local and systemic adverse reactions as well as unsolicited adverse events.

Serious Adverse Events in All Infant and Toddler Clinical Studies

Serious adverse events were collected throughout the study period for all 13 clinical trials. This reporting period is longer than the 30-day post-vaccination period used in some vaccine trials. The longer reporting may have resulted in serious adverse events being reported in a higher percentage of subjects than for other vaccines. Serious adverse events reported following vaccination in infants and toddlers occurred in 8.2% among Prevnar 13 recipients and 7.2% among Prevnar recipients. Serious adverse events observed during different study periods for Prevnar 13 and Prevnar respectively were: 1) 3.7% and 3.5% from dose 1 to the bleed after the infant series; 2) 3.6% and 2.7% from the bleed after the infant series to the toddler dose; 3) 0.9% and 0.8% from the toddler dose to the bleed after the toddler dose and 4) 2.5% and 2.8% during the 6 month follow up period after the last dose.

The most commonly reported serious adverse events were in the ‘Infections and infestations’ system organ class including bronchiolitis (0.9%, 1.1%), gastroenteritis, (0.9%, 0.9%), and pneumonia (0.9%, 0.5%) for Prevnar 13 and Prevnar respectively.

There were 3 (0.063%) deaths among Prevnar 13 recipients, and 1 (0.036%) death in Prevnar recipients, all as a result of sudden infant death syndrome (SIDS). These SIDS rates are consistent with published age specific background rates of SIDS from the year 2000.

There was 1 hypotonic-hyporesponsive episode adverse reaction reported (0.015%).

Solicited Adverse Reactions in the Three U.S. Infant and Toddler Studies

A total of 1,907 subjects received at least 1 dose of Prevnar 13 and 701 subjects received at least 1 dose of Prevnar in the three U.S. studies. Most subjects were White (77.3%), 14.2% were Black or African-American, and 1.7% were Asian; 79.1% of subjects were non-Hispanic and non-Latino and 14.6% were Hispanic or Latino. Overall, 53.6% of subjects were male infants.

The incidence and severity of solicited adverse reactions that occurred within 7 days following each dose of Prevnar 13 or Prevnar administered to U.S. infants and toddlers are shown in Tables 3 and 4.

Table 3: Percentage of U.S. Infant and Toddler Subjects Reporting Solicited Local Reactions at the Prevnar 13 or Prevnar Injection Sites Within 7 Days After Each Vaccination at 2, 4, 6, and 12-15 Months of Agea
		Dose 1				Dose 2				Dose 3				Dose 4
* Statistically significant difference p < 0.05 a Data are from three primary U.S. safety studies (the U.S. phase II infant study, the pivotal U.S. non-inferiority study, and the U.S. consistency study). All infants received concomitant routine infant immunizations. Concomitant vaccines and pneumococcal conjugate vaccines were administered in different limbs. b Number of subjects reporting Yes for at least 1 day or No for all days. c Diameters were measured in caliper units of whole numbers from 1 to 14 or 14+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of induration and erythema were then characterized as Mild (0.5-2.0 cm), Moderate (2.57.0 cm), or Severe (>7.0 cm).
Graded Local Reaction		Prevnar 13 (Nb=1375-1612)		Prevnar (Nb=516-606)		Prevnar 13 (Nb=1069-1331)		Prevnar (Nb=405-510)		Prevnar 13 (Nb=998-1206)		Prevnar (Nb=348-446)		Prevnar 13 (Nb=874-1060)		Prevnar (Nb=283-379)
Rednessc
Any		24.3		26.0		33.3		29.7		37.1		36.6		42.3		45.5
Mild		23.1		25.2		31.9		28.7		35.3		35.3		39.5		42.7
Moderate		2.2		1.5		2.7		2.2		4.6		5.1		9.6		13.4*
Severe		0		0		0		0		0		0		0		0
Swellingc
Any		20.1		20.7		25.2		22.5		26.8		28.4		31.6		36.0*
Mild		17.2		18.7		23.8		20.5		25.2		27.5		29.4		33.8
Moderate		4.9		3.9		3.7		4.9		3.8		5.8		8.3		11.2*
Severe		0		0		0.1		0		0		0		0		0
Tenderness
Any		62.5		64.5		64.7		62.9		59.2		60.8		57.8		62.5
Interferes    with limb    movement		10.4		9.6		9.0		10.5		8.4		9.0		6.9		5.7
Table 4: Percentage of U.S. Infant and Toddler Subjects Reporting Solicited Systemic Adverse Reactions Within 7 Days After Each Vaccination at 2, 4, 6, and 12-15 Months of Agea,b
a Number of subjects reporting Yes for at least 1 day or No for all days. b Data are from three primary U.S. safety studies (the U.S. phase II infant study, the pivotal U.S. non-inferiority study, and the U.S. consistency study). All infants received concomitant routine infant immunizations. Concomitant vaccines and pneumococcal conjugate vaccines were administered in different limbs. c Fever gradings: Mild (≥38oC but ≤39oC), Moderate (>39oC but ≤40oC), and Severe (> 40oC). No other systemic event other than fever was graded. Parents reported the use of antipyretic medication to treat or prevent symptoms in 62 to 75% of subjects after any of the 4 doses. There were no statistical differences between the Prevnar 13 and Prevnar groups.
	Dose 1				Dose 2				Dose 3				Dose 4
Graded Systemic Events	Prevnar 13 (Na=1360-1707)		Prevnar (Na=497-640)		Prevnar 13 (Na=1084-1469)		Prevnar (Na=409-555)		Prevnar 13 (Na=997-1361)		Prevnar (Na=354-521)		Prevnar 13 (Na=850-1227)		Prevnar (Na=278-436)
Feverc
Any	24.3		22.1		36.5		32.8		30.3		31.6		31.9		30.6
Mild	23.6		21.7		34.9		31.6		29.1		30.2		30.3		30.0
Moderate	1.1		0.6		3.4		2.8		4.2		3.3		4.4		4.6
Severe	0.1		0.2		0.1		0.3		0.1		0.7		1.0		0
Decreased appetite	48.3		43.6		47.8		43.6		47.6		47.6		51.0		49.4
Irritability	85.6		83.6		84.8		80.4		79.8		80.8		80.4		77.8
Increased sleep	71.5		71.5		66.6		63.4		57.7		55.2		48.7		55.1
Decreased sleep	42.5		40.6		45.6		43.7		46.5		47.7		45.3		40.3

Unsolicited Adverse Reactions in the Three U.S. Infant and Toddler Safety Studies

The following were determined to be adverse drug reactions based on experience with Prevnar 13 in clinical trials:

Reactions occurring in greater than 1% of infants and toddlers: diarrhea, vomiting, and rash.

Reactions occurring in less than 1% of infants and toddlers: crying, hypersensitivity reaction (including face edema, dyspnea, and bronchospasm), seizures (including febrile seizures), and urticaria or urticaria-like rash.

Safety Assessments in the Catch-Up Studies

In a catch-up study conducted in Poland, 354 children (7 months through 5 years of age) receiving at least one dose of Prevnar 13 were also monitored for safety. All subjects in this study were White and non-Hispanic. Overall, 49.6% of subjects were male infants. The incidence and severity of solicited adverse reactions that occurred within 4 days following each dose of Prevnar 13 administered to pneumococcal-vaccine naïve children 7 months through 5 years of age are shown in Tables 5 and 6.

Table 5: Percentage of Subjects 7 Months Through 5 Years of Age Reporting Solicited Local Reactions Within 4 Days After Each Catch-Up Prevnar 13 Vaccinationa
	7 through 11 months					12 through 23 months			24 months through 5 years
a Study conducted in Poland. b Number of subjects reporting Yes for at least 1 day or No for all days. c Diameters were measured in caliper units of whole numbers from 1 to 14 or 14+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as Mild (0.5-2.0 cm), Moderate (2.5-7.0 cm), or Severe (>7.0 cm).
Graded Local Reaction	Dose 1 Nb=86 %	Dose 2 Nb=86-87 %		Dose 3 Nb=78-82 %		Dose 1 Nb=108-110 %	Dose 2 Nb=98-106 %		Dose 1 Nb=147-149 %
Rednessc
Any	48.8	46.0		37.8		70.0	54.7		50.0
Mild	41.9	40.2		31.3		55.5	44.7		37.4
Moderate	16.3	9.3		12.5		38.2	25.5		25.7
Severe	0.0	0.0		0.0		0.0	0.0		0.0
Swellingc
Any	36.0	32.2		25.0		44.5	41.0		36.9
Mild	32.6	28.7		20.5		36.7	36.2		28.2
Moderate	11.6	14.0		11.3		24.8	12.1		20.3
Severe	0.0	0.0		0.0		0.0	0.0		0.0
Tenderness
Any	15.1	15.1		15.2		33.3	43.7		42.3
Interferes    with limb    movement	1.2	3.5		6.4		0.0	4.1		4.1
Table 6: Percentage of Subjects 7 Months Through 5 Years of Age Reporting Solicited Systemic Adverse Reactions Within 4 Days After Each Catch-Up Prevnar 13 Vaccinationa
	7 through 11 months					12 through 23 months		24 months through 5 years
a Study conducted in Poland. b Number of subjects reporting Yes for at least 1 day or No for all days. c Fever gradings: Mild (≥38oC but ≤39oC), Moderate (>39oC but ≤40oC), and Severe (> 40oC). No other systemic event other than fever was graded.
Systemic Reaction	Dose 1 Nb=86-87 %		Dose 2 Nb=86-87 %		Dose 3 Nb=78-81 %	Dose 1 Nb=108 %	Dose 2 Nb=98-100 %	Dose 1 Nb=147-148 %
Feverc
Mild	3.4		8.1		5.1	3.7	5.1	0.7
Moderate	1.2		2.3		1.3	0.9	0.0	0.7
Severe	0.0		0.0		0.0	0.0	0.0	0.0
Decreased appetite	19.5		17.2		17.5	22.2	25.5	16.3
Irritability	24.1		34.5		24.7	30.6	34.0	14.3
Increased sleep	9.2		9.3		2.6	13.0	10.1	11.6
Decreased sleep	24.1		18.4		15.0	19.4	20.4	6.8

A U.S. study evaluated the use of Prevnar 13 in children previously immunized with Prevnar. In this open label trial, 284 healthy children 15 through 59 months of age previously vaccinated with at least 3 doses of Prevnar, received 1 or 2 doses of Prevnar 13. Children 15 months through 23 months of age (group 1) received 2 doses, and children 24 months through 59 months of age (group 2) received one dose. Most subjects were White (75.0%), 15.8% were Black or African-American, and 1.6% were Asian; 86.6% of subjects were non-Hispanic and non-Latino and 13.4% were Hispanic or Latino. Overall, 54.0% of subjects were male infants.

The incidence and severity of solicited adverse reactions that occurred within 7 days following one dose of Prevnar 13 administered to children 15 months through 59 months of age are shown in Tables 7 and 8.

Table 7: Percentage of Subjects 15 Months Through 59 Months of Age, Previously Vaccinated with 3 or 4 Prior Infant Doses of Prevnar, Reporting Solicited Local Reactions Within 7 Days After One Supplemental Prevnar 13 Vaccination
	15 months through 23 monthsa				24 months through 59 monthsb
a Dose 2 data not shown. b The data for this age group are only represented as a single result as 95% of children received 4 doses of Prevnar prior to enrollment. c Number of subjects reporting Yes for at least 1 day or No for all days. d Diameters were measured in caliper units of whole numbers from 1 to 14 or 14+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as Mild (0.52.0 cm), Moderate (2.5-7.0 cm), or Severe (>7.0 cm).
Graded Local Reaction	1 dose Prevnar 13 3 prior Prevnar doses Nc=28-32 %		1 dose Prevnar 13 4 prior Prevnar doses Nc=62-76 %		1 dose Prevnar 13 3 or 4 prior Prevnar doses Nc=138-155 %
Rednessd
Any	46.9		36.6		34.9
Mild	31.0		31.4		31.5
Moderate	22.6		7.9		9.9
Severe	0.0		0.0		0.0
Swellingd
Any	35.5		21.2		22.2
Mild	26.7		18.8		20.3
Moderate	13.8		7.7		5.7
Severe	0.0		0.0		0.0
Tenderness
Any	53.1		50.0		61.9
Interferes with    limb movement	10.3		6.3		10.6
Table 8: Percentage of U.S. Subjects 15 Months Through 59 Months of Age, Previously Vaccinated with 3 or 4 Prior Infant Prevnar Doses, Reporting Solicited Systemic Adverse Reactions Within 7 Days After One Supplemental Prevnar 13 Vaccination
	15 through 23 monthsa			24 months through 59 monthsb
a Dose 2 data not shown. b The data for this age group are only represented as a single result as 95 % of children received 4 doses of Prevnar prior to enrollment. c Number of subjects reporting Yes for at least 1 day or No for all days. d Fever gradings: Mild (≥38ºC but ≤39ºC), Moderate (>39ºC but ≤40ºC), and Severe (> 40ºC). No other systemic event other than fever was graded.
Systemic Reaction	1 dose Prevnar 13 3 prior Prevnar doses Nc=28-33 %	1 dose Prevnar 13 4 prior Prevnar doses Nc=62-75 %		1 dose Prevnar 13 3 or 4 prior Prevnar doses Nc=138-151 %
Feverd
Mild	10.7	18.8		5.1
Moderate	7.1	3.2		0.7
Severe	0.0	0.0		0.7
Decreased appetite	56.7	36.2		24.8
Irritability	66.7	57.3		39.7
Increased sleep	30.0	33.8		15.9
Decreased sleep	22.6	22.7		14.0

Clinical Trials Experience With Prevnar®

The safety experience with Prevnar is relevant to Prevnar 13 because the two vaccines share common components.

Generally, the adverse reactions reported in clinical trials with Prevnar 13 were also reported in clinical trials with Prevnar.

Overall, the safety of Prevnar was evaluated in a total of five clinical studies in the U.S. in which 18,168 infants and children received a total of 58,699 doses of vaccine at 2, 4, 6, and 1215 months of age.

Adverse events reported in clinical trials with Prevnar include:

Bronchiolitis, UTI, acute gastroenteritis, asthma, aspiration, breath holding, influenza, inguinal hernia repair, viral syndrome, URI, croup, thrush, wheezing, choking, conjunctivitis, pharyngitis, colic, colitis, congestive heart failure, roseola, sepsis.

Post-marketing Experience With Prevnar

The following adverse reactions have been reported through passive surveillance since market introduction of Prevnar and therefore, are considered adverse reactions for Prevnar 13 as well. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to the vaccine.

Administrative site conditions: Injection-site dermatitis, injection-site pruritus, injection-site urticaria

Blood and lymphatic system disorders: Lymphadenopathy localized to the region of the injection site

Immune system disorders: Anaphylactic/anaphylactoid reaction including shock

Skin and subcutaneous tissue disorders: Angioneurotic edema, erythema multiforme

Respiratory: Apnea

The safety of Prevnar given concomitantly with other vaccines as part of routine care was assessed in a three-year observational study performed at Northern California Kaiser Permanente in which 65,927 children received three doses of Prevnar in the first year of life. Primary safety outcomes analyses included an evaluation of pre-defined adverse events occurring in temporal relationship to immunization. Rates of adverse events occurring within various time periods post-vaccination (e.g., 0-2, 0-7, 0-14, and 0-30 days) were compared to the rates of those events occurring within a control time window (i.e., 31-60 days). Secondary safety outcomes analyses included comparisons to a historical control population of infants (1995-1996, N=40,223) prior to the introduction of Prevnar. In addition, the study included extended follow-up of subjects originally enrolled in the NCKP efficacy trial (N=37,866).

The primary safety outcomes analyses did not demonstrate a consistently elevated risk of healthcare utilization for croup, gastroenteritis, allergic reactions, seizures, wheezing diagnoses, or breath-holding across doses, healthcare settings, or multiple time windows. As in prelicensure trials, fever was associated with Prevnar administration. In analyses of secondary safety outcomes, the adjusted relative risk of hospitalization for reactive airways disease was 1.23 (95% CI: 1.11, 1.35). Potential confounders, such as differences in concomitantly administered vaccines, yearly variation in respiratory infections, or secular trends in reactive airways disease incidence, could not be controlled. Extended follow-up of subjects originally enrolled in the NCKP efficacy trial revealed no increased risk of reactive airways disease among Prevnar recipients. In general, the study results support the previously described safety profile of Prevnar.

Drug InteractionsConcomitant Immunizations

In clinical trials, Prevnar 13 was administered concomitantly with the following U.S. licensed vaccines: Pediarix [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined] (DTaP-HBV-IPV) and ActHIB [Haemophilus b Conjugate Vaccine (Tetanus Toxoid Conjugate)] (PRP-T) for the first three doses and with PedvaxHIB [Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate)] (PRP-OMP), M-M-R II [Measles, Mumps, Rubella Virus Vaccine Live] (MMR) and Varivax [Varicella Virus Vaccine Live], or ProQuad [Measles, Mumps, Rubella and Varicella Virus Vaccine Live] (MMRV) and VAQTA [Hepatitis A vaccine, Inactivated] (HepA) for dose 4 [see Clinical Studies (14.2)].

When Prevnar 13 is administered at the same time as another injectable vaccine(s), the vaccines should always be administered with different syringes and given at different injection sites.

Do not mix Prevnar 13 with other vaccines/products in the same syringe.

Immunosuppressive Therapies

Children with impaired immune responsiveness due to the use of immunosuppressive therapy (including irradiation, corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents) may not respond optimally to active immunization.

USE IN SPECIFIC POPULATIONSPregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with Prevnar 13. It is also not known whether Prevnar 13 can cause fetal harm when administered to a pregnant woman or whether it can affect reproductive capacity.

Pediatric Use

Safety and effectiveness of Prevnar 13 in children below the age of 6 weeks or on or after the 6th birthday have not been established. Prevnar 13 is not approved for use in children in these age groups [see Dosage and Administration (2)].

Immune responses elicited by Prevnar 13 among infants born prematurely have not been specifically studied.

Geriatric Use

The safety and effectiveness of Prevnar 13 in geriatric populations have not been established.

Prevnar 13 is not to be used as a substitute for 23-valent pneumococcal polysaccharide vaccine (PPV23) in geriatric populations.

Overdosage

Overdose with Prevnar 13 is unlikely due to its presentation as a pre-filled syringe. However, there have been reports of overdose with Prevnar 13 defined as subsequent doses administered closer than recommended to the previous dose. In general, adverse events reported with overdose are consistent with those which have been reported with doses given in the recommended schedules of Prevnar 13.

Prevnar 13 Description

Prevnar 13, Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM197 Protein) is a sterile suspension of saccharides of the capsular antigens of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F, individually linked to nontoxic diphtheria CRM197 protein. Each serotype is grown in soy peptone broth. The individual polysaccharides are purified through centrifugation, precipitation, ultrafiltration, and column chromatography. The polysaccharides are chemically activated to make saccharides, which are directly conjugated by reductive amination to the protein carrier CRM197, to form the glycoconjugate. CRM197 is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract-based medium. CRM197 is purified through ultrafiltration, ammonium sulfate precipitation, and ion-exchange chromatography. The individual glycoconjugates are purified by ultrafiltration and column chromatography and analyzed for saccharide to protein ratios, molecular size, free saccharide, and free protein.

The individual glycoconjugates are compounded to formulate Prevnar 13. Potency of the formulated vaccine is determined by quantification of each of the saccharide antigens and by the saccharide to protein ratios in the individual glycoconjugates. Each 0.5 mL dose of the vaccine is formulated to contain approximately 2.2 μg of each of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F saccharides, 4.4 μg of 6B saccharides, 34 μg CRM197 carrier protein, 100 μg polysorbate 80, 295 μg succinate buffer and 125 μg aluminum as aluminum phosphate adjuvant.

The tip cap and rubber plunger of the pre-filled syringe do not contain latex.

Prevnar 13 - Clinical Pharmacology

A serum anti-capsular polysaccharide antibody concentration of 0.35 µg/mL measured one month after the third dose as a single antibody reference concentration was used to estimate the effectiveness of Prevnar 13 against IPD. The assay used for this determination is a standardized ELISA involving pre-absorption of the test sera with pneumococcal Cpolysaccharide and serotype 22F polysaccharide to reduce non-specific background reactivity. The single antibody reference value was based on pooled efficacy estimates from three placebo-controlled IPD efficacy trials with either Prevnar or the investigational 9-valent CRM197 conjugate pneumococcal polysaccharide vaccine. This reference concentration is only applicable on a population basis and cannot be used to predict protection against IPD on an individual basis. Functional antibodies elicited by the vaccine (as measured by opsonophagocytic assay [OPA]) were also evaluated.

Mechanism of Action

B-cells produce antibodies in response to antigenic stimulation via Tdependent and Tindependent mechanisms. Prevnar 13, comprised of polysaccharides conjugated to a carrier protein, elicits a T-cell dependent immune response. Protein carrier-specific T-cells provide the signals needed for maturation of the B-cell response and generation of B-cell memory. This type of response induces immune memory and elicits booster responses on re-exposure in infants and young children to pneumococcal polysaccharides.

Nonclinical ToxicologyCarcinogenesis, Mutagenesis, Impairment of Fertility

Prevnar 13 has not been evaluated for any carcinogenic or mutagenic potential, or impairment of fertility.

Clinical StudiesPrevnar Efficacy Data

Invasive Pneumococcal Disease (IPD)

Prevnar was licensed in the U.S. in 2000, following a randomized, double-blind clinical trial in a multiethnic population at Northern California Kaiser Permanente (NCKP) from October 1995 through August 20, 1998, in which 37,816 infants were randomized to receive either Prevnar or a control vaccine (an investigational meningococcal group C conjugate vaccine [MnCC]) at 2, 4, 6, and 12-15 months of age. In this study, the efficacy of Prevnar against invasive disease due to S. pneumoniae in cases accrued during this period was 100% in both the per-protocol and intent-to-treat analyses (95% CI: 75.4%-100% and 81.7%-100%, respectively). Data accumulated through an extended follow-up period to April 20, 1999, resulted in similar efficacy estimates of 97.4% in the per-protocol analysis and 93.9% in the intent-to-treat analysis (95% CI: 82.7% - 99.9% and 79.6% - 98.5%, respectively).

Acute Otitis Media (AOM)

The efficacy of Prevnar against otitis media was assessed in two clinical trials: a trial in Finnish infants at the National Public Health Institute and the pivotal-efficacy trial in U.S. infants at Northern California Kaiser Permanente (NCKP).

The Finnish Otitis Media (FinOM) trial was a randomized, double-blind trial in which 1,662 infants were equally randomized to receive either Prevnar or a control vaccine Recombivax HB (Hepatitis B vaccine (Recombinant) [Hep B]) at 2, 4, 6, and 12-15 months of age. In this study, conducted between December 1995 and March 1999, parents of study participants were asked to bring their children to the study clinics if the child had respiratory infections or symptoms suggesting acute otitis media (AOM). If AOM was diagnosed, tympanocentesis was performed, and the middle-ear fluid was cultured. If S. pneumoniae was isolated, serotyping was performed; the primary endpoint was efficacy against AOM episodes caused by vaccine serotypes in the per-protocol population. In the NCKP trial, the efficacy of Prevnar against otitis media was assessed from the beginning of the trial in October 1995 through April 1998. The otitis media analysis included 34,146 infants randomized to receive either Prevnar (N=17,070), or the control vaccine (N=17,076), at 2, 4, 6, and 12-15 months of age. In this trial, no routine tympanocentesis was performed, and no standard definition of otitis media was used by study physicians. The primary otitis media endpoint was efficacy against all otitis media episodes in the perprotocol population.

The vaccine efficacy against AOM episodes due to vaccine serotypes assessed in the Finnish trial, was 57% (95% CI: 44%-67%) in the per-protocol population and 54% (95% CI: 41%64%) in the intent-to-treat population. The vaccine efficacy against AOM episodes due to vaccine-related serotypes (6A, 9N, 18B, 19A, 23A), also assessed in the Finnish trial, was 51% (95% CI: 27, 67) in the per-protocol population and 44% (95% CI: 20, 62) in the intent-totreat population. There was a nonsignificant increase in AOM episodes caused by serotypes unrelated to the vaccine in the per-protocol population, compared to children who received the control vaccine, suggesting that children who received Prevnar appeared to be at increased risk of otitis media due to pneumococcal serotypes not represented in the vaccine. However, vaccination with Prevnar reduced pneumococcal otitis media episodes overall. In the NCKP trial, in which the endpoint was all otitis media episodes regardless of etiology, vaccine efficacy was 7% (95% CI: 4%-10%) and 6% (95% CI: 4%-9%), respectively, in the per-protocol and intent-to-treat analyses. Several other otitis media endpoints were also assessed in the two trials.

Recurrent AOM, defined as 3 episodes in 6 months or 4 episodes in 12 months, was reduced by 9% in both the per-protocol and intent-to-treat populations (95% CI: 3%-15% in per-protocol and 95% CI: 4%-14% in intent-to-treat) in the NCKP trial; a similar trend was observed in the Finnish trial. The NCKP trial also demonstrated a 20% reduction (95% CI: 2, 35) in the placement of tympanostomy tubes in the per-protocol population and a 21% reduction (95% CI: 4, 34) in the intent-to-treat population. Data from the NCKP trial accumulated through an extended follow-up period to April 20, 1999, in which a total of 37,866 children were included (18,925 in Prevnar group and 18,941 in MnCC control group), resulted in similar otitis media efficacy estimates for all endpoints.

Evaluation of Prevnar 13 Effectiveness

Prevnar 13 effectiveness against invasive pneumococcal disease was inferred from comparative studies to a U.S. licensed 7-valent pneumococcal conjugate vaccine, Prevnar, in which Prevnar 13 elicited immune responses as measured by antipolysaccharide binding and functional OPA antibodies. These studies were designed to evaluate immunologic non-inferiority of Prevnar 13 to Prevnar.

Clinical trials have been conducted in the U.S. using a 2, 4, 6, and 12 to 15 month schedule.

The pivotal U.S. non-inferiority study was a randomized, double-blind, active-controlled trial in which 2 month-old infants were randomly assigned to receive either Prevnar 13 or Prevnar in a 1:1 ratio. The 2 vaccine groups were well balanced with respect to race, ethnicity, and age and weight at enrollment. Most subjects were White (69.1%), 19.6% were Black or AfricanAmerican, and 2.4% were Asian; 82.1% of subjects were non-Hispanic and non-Latino and 17.3% were Hispanic or Latino. Overall, 54.0% of subjects were male infants.

In the pivotal U.S. non-inferiority study, immune responses were compared in subjects receiving either Prevnar 13 or Prevnar using a set of non-inferiority criteria. Co-primary endpoints included the percentage of subjects with serum pneumococcal anti-capsular polysaccharide IgG ≥0.35 μg/mL measured one month after the third dose and serum pneumococcal anti-capsular polysaccharide IgG geometric mean concentrations (GMCs) one month after the fourth dose. The assay used for this determination was a standardized ELISA involving pre-absorption of the test sera with pneumococcal C-polysaccharide and serotype 22F polysaccharide to reduce non-specific background reactivity. Responses to the 7 common serotypes in Prevnar 13 and Prevnar recipients were compared directly. Responses to the 6 additional serotypes in Prevnar 13 recipients were each compared to the lowest response observed among the Prevnar serotypes in Prevnar recipients.

Pneumococcal Immune Responses Following Three Doses

In the pivotal U.S. non-inferiority study, the non-inferiority criterion for the proportion of subjects with pneumococcal anti-capsular polysaccharide IgG antibody concentrations ≥0.35 μg/mL one month after the third dose was met for 10 of the 13 serotypes. The exceptions were serotypes 6B, 9V, and 3. Although the response to serotypes 6B and 9V did not meet the pre-specified non-inferiority criterion, the differences were marginal. The clinical relevance of these differences, if any, is unknown.

The percentage of infants achieving pneumococcal anti-capsular polysaccharide IgG antibody concentrations ≥0.35 μg/mL one month after the third dose is shown below (Table 9).

Table 9: Percentage of Subjects With Anti-capsular Antibody Concentration ≥0.35 µg/mL One Month After Dose 3, U.S. Pivotal Noninferiority Study*†
Serotype	Prevnar 13 N=249-252 (95% CI)	Prevnar N=250-252 (95% CI)	Difference in % responders (95% CI)
* Non-inferiority was met when the lower bound of the 95% CI for the difference between groups (Prevnar 13 minus Prevnar) was greater than -10%. † Antibody measured by a standardized ELISA involving pre-absorption of the test sera with pneumococcal C-polysaccharide and serotype 22F polysaccharide to reduce non-specific background reactivity. †† Comparison for the 6 additional serotypes was to the lowest responder of the 7 common serotypes in Prevnar recipients, which for this analysis was serotype 6B (92.8%; 95% CI: 88.9, 95.7).
Prevnar Serotypes
4	94.4   (90.9, 96.9)	98.0   (95.4, 99.4)	-3.6     (-7.3, -0.1)
6B	87.3   (82.5, 91.1)	92.8   (88.9, 95.7)	-5.5   (-10.9, -0.1)
9V	90.5   (86.2, 93.8)	98.4   (96.0, 99.6)	-7.9   (-12.4, -4.0)
14	97.6   (94.9, 99.1)	97.2   (94.4, 98.9)	0.4     (-2.7, 3.5)
18C	96.8   (93.8, 98.6)	98.4   (96.0, 99.6)	-1.6      (-4.7, 1.2)
19F	98.0   (95.4, 99.4)	97.6   (99.4, 99.1)	0.4     (-2.4, 3.4)
23F	90.5   (86.2, 93.8)	94.0   (90.4, 96.6)	-3.6      (-8.5, 1.2)
Additional Serotypes††
1	95.6   (92.3, 97.8)	††	2.8     (-1.3, 7.2)
3	63.5   (57.1, 69.4)	††	-29.3   (-36.2, -22.4)
5	89.7   (85.2, 93.1)	††	-3.1      (-8.3, 1.9)
6A	96.0   (92.8, 98.1)	††	3.2     (-0.8, 7.6)
7F	98.4   (96.0, 99.6)	††	5.6      (1.9, 9.7)
19A	98.4   (96.0, 99.6)	††	5.6      (1.9, 9.7)

Functional OPA antibody responses were elicited for all 13 serotypes, as shown in Table 10.

Table 10: Pneumococcal OPA Geometric Mean Titers One Month After the Third Dose-Evaluable Immunogenicity Population, U.S. Pivotal Non-inferiority Study*
Serotype	Prevnar 13 N=91-94 (95% CI)	Prevnar N=89-94 (95% CI)
* The OPA (opsonophagocytic activity) assay measures the ability of immune sera, in conjunction with complement, to mediate the uptake and killing of S. pneumoniae by phagocytic cells.
Prevnar Serotypes
4	359     (276, 468)	536       (421, 681)
6B	1055     (817, 1361)	1514     (1207, 1899)
9V	4035   (2933, 5553)	3259     (2288, 4641)
14	1240     (935, 1646)	1481    (1133, 1934)
18C	276     (210, 361)	376       (292, 484)
19F	54       (40, 74)	45          (34, 60)
23F	791  (605, 1034)	924     (709, 1204)
Additional Serotypes
1	52           (39, 69)	4      (4, 5)
3	121          (92, 158)	7      (5, 9)
5	91        (67, 123)	4      (4, 4)
6A	980      (783, 1226)	100    (66, 152)
7F	9494   (7339, 12281)	128    (80, 206)
19A	152        (105, 220)	7      (5, 9)

Pneumococcal Immune Responses Following Four Doses

In the pivotal U.S. non-inferiority study, post-dose 4 antibody concentrations were higher for all 13 serotypes than those achieved after the third dose. The non-inferiority criterion for pneumococcal anti-capsular polysaccharide GMCs after 4 doses was met for 12 of the 13 pneumococcal serotypes. The non-inferiority criterion was not met for the response to serotype 3 (Table 11).

Table 11: Pneumococcal IgG GMCs (µg/mL) One Month After Dose 4, U.S. Pivotal Non-inferiority Study*†
Serotype	Prevnar 13 N=232-236 (95% CI)	Prevnar N=222-223 (95% CI)	GMC Ratio (95% CI)
* Non-inferiority was declared if the lower limit of the 2-sided 95% CI for Geometric Mean Ratio (Prevnar 13:Prevnar) was greater than 0.5. † Antibody measured by a standardized ELISA involving pre-absorption of the test sera with pneumococcal C-polysaccharide and serotype 22F polysaccharide to reduce non-specific background reactivity. †† Comparison for the 6 additional serotypes was to the lowest responder of the 7 common serotypes in Prevnar recipients, which for this analysis was serotype 9V (3.63; 95% CI 3.25, 4.05).
Prevnar Serotypes
4	3.73      (3.28, 4.24)	5.49     (4.91, 6.13)	0.68    (0.57, 0.80)
6B	11.53    (9.99, 13.30)	15.63  (13.80, 17.69)	0.74    (0.61, 0.89)
9V	2.62      (2.34, 2.94)	3.63     (3.25, 4.05)	0.72    (0.62, 0.85)
14	9.11   (7.95, 10.45)	12.72   (11.22, 14.41)	0.72    (0.60, 0.86)
18C	3.20     (2.82, 3.64)	4.70     (4.18, 5.28)	0.68   (0.57, 0.81)
19F	6.60     (5.85, 7.44)	5.60     (4.87, 6.43)	1.18   (0.98, 1.41)
23F	5.07     (4.41, 5.83)	7.84     (6.91, 8.90)	0.65   (0.54, 0.78)
Additional Serotypes††
1	5.06   (4.43, 5.80)	††	1.40   (1.17, 1.66)
3	0.94   (0.83, 1.05)	††	0.26   (0.22, 0.30)
5	3.72   (3.31, 4.18)	††	1.03   (0.87, 1.20)
6A	8.20   (7.30, 9.20)	††	2.26   (1.93, 2.65)
7F	5.67   (5.01, 6.42)	††	1.56   (1.32, 1.85)
19A	8.55   (7.64, 9.56)	††	2.36   (2.01, 2.76)

Following the 4th dose, the functional OPA response for each serotype was quantitatively greater than the response following the 3rd dose (see Table 12).

Table 12: Pneumococcal OPA Geometric Mean Titers One Month After the Fourth Dose-Evaluable Toddler Immunogenicity Population, U.S. Pivotal Non-inferiority Study*
Serotype	Prevnar 13 N=88-92 (95% CI)	Prevnar N=92-96 (95% CI)
* The OPA (opsonophagocytic activity) assay measures the ability of immune sera, in conjunction with complement, to mediate the uptake and killing of S. pneumoniae by phagocytic cells.
Prevnar Serotypes
4	1180     (847, 1643)	1492      (1114, 1999)
6B	3100   (2337, 4111)	4066      (3243, 5098)
9V	11856    (8810, 15955)	18032      (14125, 23021)
14	2002   (1453, 2760)	2366       (1871, 2992)
18C	993   (754, 1308)	1722       (1327, 2236)
19F	200     (144, 276)	167         (121, 230)
23F	2723   (1961, 3782)	4982       (3886, 6387)
Additional Serotypes
1	164      (114, 237)	5        (4, 6)
3	380      (300, 482)	12        (9, 16)
5	300      (229, 393)	5        (4, 6)
6A	2242   (1707, 2945)	539    (375, 774)
7F	11629    (9054, 14938)	268    (165, 436)
19A	1024     (774, 1355)	29      (19, 44)

Simultaneous Administration With Other Vaccines

The concomitant administration of routine U.S. infant vaccines [see Drug Interactions (7.1)] with Prevnar 13 was evaluated in two studies: the U.S. pivotal non-inferiority study [see Clinical Studies (14.2), Pneumococcal Immune Responses Following Three Doses] and the U.S. lot consistency study. In the lot consistency study, subjects were randomly assigned to receive one of 3 lots of Prevnar 13 or Prevnar in a 2:2:2:1 ratio. The total number of infants vaccinated was 663 (U.S. non-inferiority study) and 1699 (U.S. lot consistency study). Immune responses to concomitant vaccine antigens were compared in infants receiving Prevnar and Prevnar 13. Responses to diphtheria toxoid, tetanus toxoid, pertussis, polio types 1, 2, and 3, hepatitis B, PRP-T, PRP-OMP, measles, and varicella antigens in Prevnar 13 recipients were similar to those in Prevnar recipients. Based on limited data, responses to mumps and rubella antigens in Prevnar 13 recipients were similar to those in Prevnar recipients.

Previously Unvaccinated Older Infants and Children

In an open-label descriptive study of Prevnar 13 in Poland, children 7 through 11 months of age, 12 through 23 months of age and 24 months through 5 years of age (prior to the 6th birthday) who were naïve to pneumococcal conjugate vaccine, were given 3, 2 or 1 dose of Prevnar 13 respectively, according to the age-appropriate schedules in Table 1. Serum IgG concentrations were measured one month after the final dose in each age group and the data are shown in Table 13.

Table 13: Pneumococcal Anti-capsular Polysaccharide IgG Antibody Geometric Mean Concentrations (μg/mL) One Month After the Final Prevnar 13 Catch-Up Dose in Pneumococcal Vaccine Naïve Children 7 Months through 5 Years of Age by Age Group, Poland Catch-Up Study
Serotype	3 doses Prevnar 13 7 through 11 months N=83-84 (95% CI)	2 doses Prevnar 13 12 through 23 months N=104-110 (95% CI)	1 dose Prevnar 13 24 months through 5 years N=135-152 (95% CI)
1	2.88    (2.44, 3.39)	2.74    (2.37, 3.16)	1.78    (1.52, 2.08)
3	1.94    (1.68, 2.24)	1.86    (1.60, 2.15)	1.42    (1.23, 1.64)
4	3.63    (3.11, 4.23)	4.28    (3.78, 4.86)	3.37    (2.95, 3.85)
5	2.85    (2.34, 3.46)	2.16    (1.89, 2.47)	2.33    (2.05, 2.64)
6A	3.72    (3.12, 4.45)	2.62    (2.25, 3.06)	2.96    (2.52, 3.47)
6B	4.77    (3.90, 5.84)	3.38    (2.81, 4.06)	3.41    (2.80, 4.16)
7F	5.30    (4.54, 6.18)	5.99    (5.40, 6.65)	4.92    (4.26, 5.68)
9V	2.56    (2.21, 2.96)	3.08    (2.69, 3.53)	2.67    (2.32, 3.07)
14	8.04    (6.95, 9.30)	6.45    (5.48, 7.59)	2.24    (1.71, 2.93)
18C	2.77    (2.39, 3.23)	3.71    (3.29, 7.19)	2.56    (2.17, 3.03)
19A	4.77    (4.28, 5.33)	4.94    (4.31, 5.65)	6.03    (5.22, 6.97)
19F	2.88    (2.35, 3.54)	3.07    (2.68, 3.51)	2.53    (2.14, 2.99)
23F	2.16    (1.82, 2.55)	1.98    (1.64, 2.39)	1.55    (1.31, 1.85)

Children Previously Vaccinated with Prevnar

In an open-label descriptive study in the U.S., children previously vaccinated with 3 or 4 doses of Prevnar, received 2 doses of Prevnar 13 (children 15 through 23 months of age) or 1 dose of Prevnar 13 (children 24 months through 59 months of age). The data following one dose of Prevnar 13 in children 24 months through 59 months of age are shown in Table 14.

Table 14: Pneumococcal Anti-capsular Polysaccharide IgG Antibody Geometric Mean Concentrations (μg/mL) One Month After One Prevnar 13 Catch-Up Dose in Children 24 through 59 Months of Age With 3 or 4 Prior Doses of Prevnar, U.S. Catch-Up Study
Serotype	1 dose Prevnar 13 24 months through 59 months N=173-175 (95% CI)
1	2.43     (2.15, 2.75)
3	1.38     (1.17, 1.61)
5	2.13     (1.89, 2.41)
6A	12.96  (11.04, 15.21)
7F	4.22     (3.74, 4.77)
19A	14.18   (12.37, 16.25)

How Supplied/Storage and Handling

Pre-filled Syringe, 1 Dose (10 per package) – NDC 0005-1971-02.

Store refrigerated at +2ºC to +8ºC (36ºF to 46ºF).

The tip cap and rubber plunger of the pre-filled syringe do not contain latex.

Do not freeze. Discard if the vaccine has been frozen.

Patient Counseling InformationPotential Benefits and Risks

Prior to administration of this vaccine, the healthcare professional should inform the parent, guardian, or other responsible adult of the potential benefits and risks to the patient [see Warnings and Precautions (5) and Adverse Reactions (6)], and the importance of completing the immunization series unless contraindicated.

Adverse Reactions

Instruct parents, guardians, or other responsible adults to report any suspected adverse reactions to their healthcare professional.

Wyeth®

Wyeth Pharmaceuticals Inc.

Philadelphia, PA 19101

U.S. Govt. License No. 3

W10543C003

ET01

Rev 04/10

CPT Code 90670

United States Patent Number: 5,614,382.

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – One-Dose (0.5 mL) - LABEL

NDC 0005-1971-01

Pneumococcal 13-valent Conjugate Vaccine

(Diphtheria CRM197 Protein)

Prevnar 13™

One Dose (0.5 mL)

FOR IM USE ONLY

Refrigerate

Do not Freeze

Shake Well

Rx only

 

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 10 One-Dose (0.5 mL) Disposable Syringes Carton

NDC 0005-1971-02

Pneumococcal 13-valent Conjugate Vaccine

(Diphtheria CRM197 Protein)

Prevnar 13™

For use in children 6 weeks through 5 years of age

10 One-Dose (0.5 mL)

Disposable Syringes

FOR INTRAMUSCULAR USE ONLY

No Latex

Rx only

Wyeth®

 

Prevnar 13 pneumococcal 13-valent conjugate vaccine injection, suspension

Product Information Product Type VACCINE Item Code (Source) NDC:0005-1971 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength STREPTOCOCCUS PNEUMONIAE TYPE 1 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 1 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 1 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 3 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 3 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 3 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 4 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 4 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 4 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 5 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 5 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 5 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 6A CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 6A CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 6A CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 6B CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 6B CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 6B CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 4.4 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 7F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 7F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 7F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 9V CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 9V CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 9V CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 14 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 14 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 14 CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 18C CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN (STREPTOCOCCUS PNEUMONIAE TYPE 18C CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 18C CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 19A CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN (STREPTOCOCCUS PNEUMONIAE TYPE 19A CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 19A CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 19F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 19F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 19F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL STREPTOCOCCUS PNEUMONIAE TYPE 23F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN(STREPTOCOCCUS PNEUMONIAE TYPE 23F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN) STREPTOCOCCUS PNEUMONIAE TYPE 23F CAPSULAR POLYSACCHARIDE DIPHTHERIA CRM197 PROTEIN CONJUGATE ANTIGEN 2.2 ug  in 0.5 mL

Inactive Ingredients Ingredient Name Strength POLYSORBATE 80 100 ug  in 0.5 mL ALUMINUM PHOSPHATE 125 ug  in 0.5 mL

Packaging # Item Code Package Description   1 NDC:0005-1971-02 10 SYRINGE (SYRINGE) in 1 CARTON   1 NDC:0005-1971-01 0.5 mL in 1 SYRINGE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA125324 03/12/2010

Labeler - Wyeth Pharmaceutical Division of Wyeth Holdings Corporation (054065909)

Establishment
Name	Address	ID/FEI		Operations
Wyeth BioPharma		174350868		ANALYSIS, API MANUFACTURE
Establishment
Name		Address	ID/FEI		Operations
Wyeth Pharmaceutical Division of Wyeth Holdings Corporation			054065909		MANUFACTURE, ANALYSIS, API MANUFACTURE

 

Wyeth Pharmaceutical Division of Wyeth Holdings Corporation