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【药品名称】

商品名称：依伴侬
通用名称：依托孕烯植入剂
英文名称：Etonogestrel Implants

【成份】

本品为皮下植入剂，含依托孕烯68mg。

化学名称：（17）13-乙基-17-羟基-11-亚甲基-18，19-二去甲孕甾烷-4-烯-20-炔-3-酮

化学结构式： 

 

分子量： 324.46

分子式：C22H28O2

【 适应症 】

避孕。

【用法用量】

每支植入剂含68mg依托孕烯：释放率在植入后5-6周内约为60-70μg/天，第一年末下降到约35-45μg/天，第2年末下降到约30-40μg/天，第3年末下降到约25-30μg/天。新给药器的设计使操作可单手完成只需一只手，并使得正确皮下植入本品更为便利。

在植入本品前应该先排除妊娠。

强烈建议医疗专业人员在实施本品植入或取出操作前参加有关操作的培训，以熟悉本品给药器的使用以及本品的植入和取出技术。建议在适当的情况下，在植入和取出本品时在有经验的医生指导下进行。

在植入和取出本品前应仔细阅读本说明书“如何植入本品”和“如何取出本品”中植入和取出的说明。

有关植入剂植入和取出的更多信息和详细指导可免费从本公司获取。

如何使用本品

本品是一种长效避孕药，皮下植入1支植入剂，提供长达三年的避孕效果。使用者可以在任何时候要求取出植入剂，但同一支植入剂不可持续埋植超过3年。对体重较重的妇女，临床医师可以考虑提早替换植入剂(见“注意事项”)。取出植入剂后，立即植入另一支植入剂以便继续得到避孕保护。如果不想继续使用本品，但还想继续避孕，应予以推荐其他的避孕方法。

按照说明书正确并认真地实施皮下植入，是确保正确植入和随后取出本品的前提。如果本品没有按照说明书要求的方法及正确的时间被植入(参见“如何植入本品”和“何时植入本品”)，可能导致意外怀孕。

本品植入剂应植入在上臂内侧皮下，以避开位于二头肌和三头肌肌肉之间结缔组织深层的大血管和神经。

植入剂的存在与否可以在植入后通过直接触摸来证实。如果未触到本品或不能确定是否有本品时，必须用其他方法证实其存在(参见“如何植入本品)。在证实本品存在前，应建议使用一种非激素避孕方法。

本品的包装内有一个给使用者的用户卡片，以记录植入剂的批号。要求医生在用户卡片记录植入的日期、植入侧上臂和预期取出的日期。包装中还含有显示批号的不干胶标签供医生记录。

如何植入本品

按照说明书正确认真地将植入剂皮下植入于非惯用手臂中，是正确植入和随后取出本品的前提。在植入后，医生和使用者均应可触摸到皮下的植入剂。

植入剂应仅在皮下浅表层被植入。如果植入太深，可能发生神经或血管损伤。太深或不正确的植入可能出现感觉异常(神经损伤)和植入剂移动(因植入到筋膜或肌肉层而造成)，罕见有插到血管内的植入错误。此外，植入太深也可使植入剂无法被触摸到，并使植入剂的定位和/或取出困难。

本品的植入必须在无菌条件下由熟悉操作过程的合格的医生进行。植入本品必须采用包装内含有的预填充无菌给药器。

建议医生在整个植入过程中保持坐位，以便可以从侧面清楚地看到植入位置和针的移动。

·使用者应平卧，非惯用手臂的肘部弯曲向外展，使腕部与耳朵平行或手与头靠近(图1)

 

 

·确定插入位置，应在非惯用上臂内侧内上髁以上8-250px处(图2)。应仅在皮下浅表层植入本品以避开皮下组织三头肌和二头肌沟之间的大血管和神经(见【注意事项】)

·用无菌标记笔做两个记号：第一个记号是插入点;第二个记号是距第一个点几厘米近身体近端的点(图2)。第二个点随后将被用作植入时的方向指引。

 

 

·用消毒剂清洁插入部位。

·对植入部位施行麻醉(如喷洒麻醉剂麻醉或沿着插入路径皮下注射2ml 1%的利多卡因)。

·从泡罩中取出含有本品的一次性无菌给药器。如可疑被污染，则不应使用。

·握住给药器的针头上方纹理处。将透明保护套按照箭头方向水平划出，拿掉针头(图 3)。如果保护套不易拿掉，则不应使用此给药器。通过针尖可以看到白色的植入剂。在没有完全将针头插入皮下前千万不要碰紫色滑块，否则它会使针头回缩并提前将植入剂从给药器中释放出来。

 

 

·用另一只手的拇指和食指在插入部位周围绷紧皮肤(图4)。

 

     

·与皮肤约成30度角略微插入针尖(图5)。

 

     

·放低给药器到水平位置，用针尖提起皮肤(图6)，轻轻将针全部扎入，会感觉到略微的阻力但阻力不会太大。

如果针头没有全部插入，植入剂将不会被正确植入。 如果是坐位从侧面(而不是上方)看给药器可以最清楚的看到针头的移动。在该位置，可以清楚的看到植入位置和针头在皮下的移动。

 

 

·保持给药器位置并确定针的整个长度全部插入。如果需要的话，可以在随后步骤中使用另一只手将给药器固定在一个位置。略微向下按紫色滑块将其解锁。将滑块移到最后直至停止(图7)。此时植入剂在其最终的皮下位置，同时针头被锁在给药器内。此时可以拿开给药器。如果给药器在操作过程中未保持位置或紫色滑块没有完全移到最后，植入剂将不能正确植入。

 

 

·植入后立即触摸受试者上臂以确认植入剂的存在。通过触摸到植入剂的端，可以确认 100px软杆的存在(图8)。

 

 

·同样也让妇女自己来触摸它。

如果未触到植入剂或怀疑其存在

·检查给药器。针应当完全收回，只能看到针内芯的紫色小尖。

·应用其他方法来确认本品的存在。适合的方法有：二维X射线，X射线电脑断层扫描(CT扫描)，带高频线阵探头(10MHz或更高)的超声波扫描(USS)或核磁共振成像(MRI)。在进行X-射线CT、USS或MRI确定植入剂位置前，建议咨询当地本产品的供应商以便得到指导。如果这些影像学方法失败，建议检测血液中依托孕烯的含量来确定植入剂的存在。这种情况下当地的供应商将会提供适当的操作指导。在确认本品被植入之前，必须采取一种非激素避孕法避孕。

·将一小块粘贴绷带贴于植入位置上。让妇女触摸植入剂。

·用无菌纱布加压包扎避免淤血。妇女可以在24小时内去除加压绷带，然后在第3-5天去除小块绷带。

·填写用户卡片，将其交给被植入者本人保存。另外，完整填写标签将其附在医疗记录后。

·给药器为一次性用品，用完后，必须适当销毁，按照当地的规定进行生物废弃处理。

何时植入本品

重要：植入本品前需排除妊娠。植入时间取决于妇女近期的避孕情况，如下：

上个月没有使用过激素类避孕药

本品也应在妇女自然月经的第1-5天(第1天为月经来潮的第1天)植入，即便仍在出血期。如按照说明书植入本品，则不需避孕措施。如植入时间与推荐时间有偏差，应建议妇女在植入7天内使用屏障避孕。如已同房，则应排除妊娠。

从其他避孕方法转为植入本品

1.从复方激素避孕药(复方口服避孕药(COCs)、阴道环或透皮贴剂) 转为植入本品

最好在服用原复方口服避孕药最后一片活性药片(最后一片含有活性成份的药片)的次日植入本品，但最晚不超过原复方口服避孕药最后一天停药期(或原复方口服避孕药最后一片非活性片)的次日。如果已经使用了阴道环或透皮贴剂，应当在阴道环或透皮贴剂被取出的当天植入本品，最晚不超过下一次应使用阴道环或透皮贴剂的当日。

如按照说明书植入本品，则不需采取避孕措施。如植入时间与推荐时间有偏差，应建议妇女应在植入后7天内使用屏障避孕。如已同房，则应排除妊娠。

2.从单纯孕激素避孕法(如仅含孕激素的药片、注射剂、植入剂或宫内节育器(IUS))转为植入本品。

由于有很多单纯孕激素的避孕法，本品的植入时间必须按照以下说明：

·从使用仅含孕激素的避孕药片的：可随时从仅含孕激素的避孕片转为植入本品，应在停用避孕片24小时内植入本品。

·从使用其他植入剂或宫内节育器(IUS)的：应在被取出当日转为植入本品。

·从使用避孕注射剂的：在下一次应使用注射剂的当日转为植入本品。 如按照说明书植入本品，则不需采取避孕措施。如植入时间与推荐时间有偏差，应建议妇女应在植入后7天内使用屏障避孕。如已同房，则应排除妊娠。

3.流产或人工流产后

·早孕期：本品可在早孕期流产或人流后5天内植入。

·中孕期：应在中孕期流产或人流后的第21至28天植入本品。

如按照说明书植入本品，则不需采取避孕措施。如植入时间与推荐时间有偏差，应建议妇女应在植入后7天内使用屏障避孕。如已同房，则应排除妊娠。

4.产后

·哺乳：应在第四个哺乳周后植入本品，参见“妊娠和哺乳期用法”。 应建议妇女应在植入7天内使用屏障避孕。如已同房，则应排除妊娠。

·非哺乳：应在产后第21-28天植入本品。如按照说明书植入本品，则不需采取避孕措施。如在产后第28天之后植入，应建议妇女应在植入后7天内使用屏障避孕。如已同房，则应排除妊娠。

如何取出本品

本品的取出只能在无菌条件下由有经验的医生操作。

取出操作开始前，医生应参考用户卡片上植入剂的位置。通过触摸来确定植入剂在上臂的准确位置。

如果未触摸到植入剂，可以进行二维X射线以确认其存在。未能触及的植入剂必须先定位再取出。合适的定位方法包括X射线电脑断层扫描(CT)、高频线阵探头(10 MHz或更高)的超声(USS)或选择核磁共振成像(MRI)。如果以上影像学方法失败，可以通过检测依托孕烯的血液水平来确证本品的存在。关于进一步的操作指导请联系当地供应商。

在对未能触及的植入剂定位后，应考虑在超声指导下进行取出操作。

偶有报道植入剂移动，通常在原位置小幅移动，除非插入的太深(见 “注意事项”)。这可能使通过触摸、超声和/或MRI方法进行定位变得复杂，导致取出需要更大的切口及更多的时间。

强烈反对在不了解植入确切位置的情况下进行探察性手术。

取出被深埋的植入剂时应该谨慎操作以防损伤上肢较深神经和血管结构。该操作应由熟悉上肢解剖学结构的医师进行。

如果植入剂不能取出，请联系当地供应商以获得指导。

·清洁将要切口的位置并用消毒剂消毒。通过触摸确定植入剂的位置，使用无菌记号笔标出植入剂远端(近肘部端) (图9)。

 

 

·手臂局部麻醉，如用0.5-1ml 1%的利多卡因对标记好的将要进行切口处进行局部麻醉 (图10)。确保在植入剂下方注射麻醉剂以使其紧贴皮肤表面。

 

 

·压住植入剂近端(图11)使之固定;这时皮肤表面可能会有一个鼓起，为植入剂的远端。 从植入剂远端开始，向肘部做一个2mm的纵向切口。

 

 

·向切口方向轻轻推动植入剂，直到看到尖端。用钳子(最好为“蚊式”止血钳)夹住植入剂取出(图12)。

 

 

·如果植入剂被包裹，对纤维组织做一个切口，然后用钳子夹出植入剂(图13和图14)。

 

 

 

 

·如果切口处仍然看不到植入剂的尖端，轻轻的将钳子探入切口内(图15)，夹住植入剂。 将钳子换至另一只手(图16)。用另一把钳子仔细分离植入剂周围的组织，夹住植入剂(图17)，然后将其取出。

 

 

通过测量长度是否是100px，确认已取出整根植入剂。如果取出的仅是部分植入剂(比100px 短)，应按照“如何取出本品”项下的说明取出剩余部分。

如果妇女想要继续使用本品, 新的植入剂可以在旧的被取出来后立即植入。(见“如何替换本品”)

·取出植入剂后，用免缝胶带闭合切口并加用一粘性绷带。

·用无菌纱布和加压绷带包扎以减少淤青。妇女可以在24小时内去除加压绷带，然后在第3-5天去除小绷带。

如何替换本品

取出旧的植入剂后，可立即替换新的植入剂，操作程序与 “如何植入本品” 中描述的植入程序相同。

新的植入剂可以在同一上肢并从旧的植入剂的同一切口处植入。如果采用同一切口植入新植入剂，使用麻醉剂(如2ml 1%的利多卡因)于皮肤切口处下沿着“埋植线”进行局部麻醉，接下的操作按植入说明操作。

【不良反应】

使用本品期间，妇女的月经出血情况很可能有所改变。这些可能包括出血情况不规律(无月经、月经稀发、更频繁或持续)，出血量(减少或增多)或出血时间延长，有约占1/5 的妇女出现闭经;另1/5妇女出血较为频繁和/或延长。偶尔报告严重出血。在临床试验中， 出血情况的改变是停止使用本品最常见的原因(约11%)。使用本品可能会改善痛经。前3个月的出血情况可以基本预测以后的出血情况。

临床试验中报告的可能相关的不良反应见下表。

 

 

在本品的一项临床研究中，研究者被要求检查植入位置，其中有8.6%的女性报道植入位置的反应。红斑是最常见的植入部位并发症，在植入期间和/或植入后不久，在3.3%的受试者中发生。此外，血肿(3.0%)，青紫(2.0%)，疼痛(1.0%)，肿胀(0.7%)也有报道。

上市后的监测中，观察到极少数人出现血压升高。有发生脂溢性皮炎的报告，可能发生过敏反应，荨麻疹和血管性水肿(加重)和/或遗传性血管水肿加重。植入或取出本品可能导致淤伤、轻微局部刺激感、疼痛或瘙痒。偶尔在植入部位会形成纤维化、疤痕或溃疡。可能会出现感觉异常或类似的情况。可能出现本品排出或移动(见“注意事项”)。在取出本品时，有时可能需要小型外科手术。

异位妊娠罕有报告(见 “注意事项”)。

已有报道的使用(复方口服)避孕药的妇女中发生的(严重)不良反应，包括静脉栓塞、动脉栓塞、激素依赖性肿瘤(如肝脏肿瘤、乳腺癌)和黄褐斑，其中一些在 “注意事项”中进行了详细描述。

【禁忌】

在以下情况存在时，不应使用单纯孕激素避孕。在使用本品期间，如第一次出现以下任何一种情况，应立刻停止使用。

·已知或可疑妊娠。

·活动性静脉血栓栓塞性疾病。

·现有或曾患有严重肝病，肝功能未恢复正常。

·已知或可疑的对性激素敏感的恶性肿瘤。

·现患肝肿瘤或有肝肿瘤病史(良性或恶性)

·不明原因阴道出血。

·对本品任一成份过敏。

【注意事项】

警告

如果有下列任何情况/危险因素，要个体化权衡使用孕激素的利弊，在决定使用本品前要与使用者讨论。一旦以下任何情况首次出现或情况加重、恶化，应与医生联系，由医生决定是否停止使用本品。

·随着年龄的增长，乳腺癌的患病率增加。在使用(复方)口服避孕药期间，乳腺癌的风险轻微增加。在停服口服避孕药10年之内这种风险会逐渐消失，且与使用年限无关，但与妇女服用口服避孕药时的年龄有关。

每10000名使用(复方)口服避孕药的妇女(停药超过10年)和同期从未服用过的妇女估计诊断出乳腺癌的数目在各个年龄组计算分别为：4.5/4(16-19岁)，17.5/16(20-24岁)，48.7/44(25-29岁)，110/100(30-34岁)，180/160(35-39岁)和260/230(40-44岁)。

在避孕方法使用的风险上，只含孕激素的风险与复方避孕药的风险相似。然而，对于这些避孕方法来说，没有确定性的结论。与一生中患乳腺癌的风险相比，口服避孕药相关的乳腺癌增加的风险是很低的。使用口服避孕药者诊断出的乳腺癌的临床级别比不用口服避孕药者低。所观察到的口服避孕药使用者乳腺癌风险增加可能与早期诊断、口服避孕药的生物学作用有关或者二者皆有。

·出现急性或慢性肝功能受损时，应该咨询专业医生进行。

·流行病学调查发现应用复方口服避孕药与血栓栓塞疾病发生增加有关(静脉血栓栓塞、深静脉血栓栓塞症和肺栓塞)。尽管依托孕烯(去氧孕烯的生物活性代谢物)没有雌激素成分，也并没有发现与静脉血栓有临床相关性，但是如果确诊血栓性疾病应将本品取出。因手术或疾病而长期制动也要考虑将本品取出。尽管本品仅含有孕激素，仍然推荐对已知增加静脉或动脉栓塞的风险因素进行评估。有血栓栓塞病史的妇女应告知使用本品可能导致复发。

·上市后，使用不含显影剂的植入剂的妇女中，已有严重动脉和静脉病例的报道，包括肺栓塞(一些致命)，深静脉栓塞，心肌梗死和卒中。如有栓塞应取出本品。

·如果在本品使用期间出现持续性高血压或血压明显增高且对抗高血压治疗无反应，应取出本品。

·尽管使用含孕激素的避孕药可能对周围组织胰岛素抵抗和糖耐量有影响，但没有证据提示对糖尿病患者在使用单纯孕激素避孕药时需要改变治疗方案。然而，患有糖尿病的妇女使用单纯孕激素避孕时要仔细观察。

·一直接受高血脂治疗的妇女如选择使用本品，应密切随访。一些孕激素可能会使LDL水平升高，并可能导致对高血脂的控制更困难。

·偶尔可能发生黄褐斑，尤其是那些曾有过妊娠黄褐斑史的妇女。有黄褐斑倾向的妇女在使用本品时，要避免暴露在阳光或紫外线下。

·本品的避孕效果与依托孕烯的血浆水平有关，与体重成反比，随植入时间延长而降低。对超重妇女使用本品第3年的临床经验有限。所以不能排除体重超重的妇女在第3年的避孕效果有可能较正常体重的妇女低。医生可考虑提前替换较重体重妇女体内的植入剂。

·同所有低剂量的激素避孕法一样，使用本品会发生卵泡生长，偶尔卵泡生长到超过正常周期所达到的大小。通常，这些大卵泡会自然消失。一般无症状，有时会伴随有轻微腹痛。一般不需要外科干预。

·使用传统单纯孕激素避孕药对异位妊娠的保护不如复方口服避孕药，这与使用这些避孕方法过程中频繁的发生排卵有关。尽管本品能持续抑制排卵，如使用者发生闭经或腹痛，在鉴别诊断中，需考虑异位妊娠。

·在妊娠和使用性激素期间，有报道下述情况，但并没有确定与使用孕激素有关：与胆汁郁积有关的黄疸和/或瘙痒;胆石形成;卟啉症;系统性红斑狼疮;溶血性尿毒症;Sydenham’s舞蹈病;妊娠疱疹;与耳硬化症相关的听力损失;遗传性血管水肿。

·如果未按照“如何植入本品”的方法正确植入则有可能脱落，或可能导致局部炎症。

·在极少数的情况下植入剂可能会从植入部位移位，且大部分与最初过深的埋植(见“如何植入本品”)或与外力作用相关(例如埋植操作或接触运动)。在这些情况中，对植入剂的定位可能更加困难，取出时可能需要更大的切口(见“如何植入本品”)。如果不能取出本品，避孕和孕激素相关的不良反应可能超出预期的时间。

体格检查/咨询

在开始或重新开始埋植本品时，要采集完整的病史(包括家族史)并且排除妊娠。要根据禁忌症和注意事项测量血压，进行体格检查。建议埋植本品3个月后再进行一次体检。在这次体检中，要测量血压并询问所有问题、主诉或不良反应的发生。根据临床判断为妇女制定个体化的进一步的周期性检查的频率和类型。

应告知妇女，本品不能预防HIV(爱滋病)和其它性传播疾病。

效果降低

当同时使用某些药物(见“相互作用”)时，本品的效果可能降低。

月经出血模式的变化

使用本品期间，妇女的月经出血情况很可能有所改变。这些可能包括出血情况不规律(无月经，月经稀发、更频繁或持续)，出血量(减少或增多)或出血时间延长，有约占1/5的妇女出现闭经;另1/5妇女出血较为频繁和/或延长。

前3个月的出血情况可以基本预测以后的出血情况。向妇女提供信息和相关咨询以及出血日志可能改善对出血模式改变的接受度。应设置对阴道出血的评估，可能包括排除妇科疾病和妊娠的检查。

对驾驶和操作机器能力的影响

未观察到有影响。

【药物相互作用】

注意：应咨询合并用药的药物处方信息来判定可能的药物相互作用。

1.其他药品对本品的影响

与激素避孕药及其他药物的相互作用可导致出血和/或避孕失败。本品未进行特定的相互作用研究。文献报道过的相互作用如下(主要是与复方避孕药的相互作用，有时也与单纯孕激素避孕药有相互作用)：

肝脏代谢：诱导肝酶尤其是细胞色素P450酶的药物可能与本品发生药物相互作用，导致性激素的清除率增加(如苯妥英、苯巴比妥、普里米酮、波生坦、卡马西平、利福平，以及也有可能的奥卡西平、托吡酯、非尔氨酯、灰黄霉素及草药圣约翰草)。

HIV蛋白酶(例如，利托那韦，奈非那韦)，非核苷类逆转录酶抑制剂(例如，奈韦拉平，依法韦仑)，以及它们的组合，已报告可能会影响肝脏代谢。

服用上述任何一种药物的妇女应在使用本品之外采用非激素避孕方式。使用肝酶诱导药物，应同时采取其它非激素避孕方法持续到停药后28天。

对于长期服用肝酶诱导药物的妇女，建议取出本品，采用其它非激素避孕法。

共同服用会增加血浆激素的药物：抑制肝酶(如CYP3A4)的药物(如酮康唑)，可能会增加血浆激素水平。

2.本品对其他药物的影响

激素避孕可影响其它药物的代谢，相应的药物的血浆及组织浓度可能升高(如环孢霉素)或降低(如拉莫三嗪)。

注：应参考共同服药的处方信息以鉴定潜在的相互作用。

3.对实验室检查结果的影响

由复方口服避孕药所得的数据表明避孕类固醇可能影响某些实验室检查结果，包括肝、甲状腺、肾上腺和肾功能的生化参数，血清蛋白(载体)水平如皮质甾体结合球蛋白和脂质/脂蛋白片断，碳水化合物新陈代谢参数和凝血参数以及纤维蛋白溶解参数。这些参数的变化通常在正常值的范围之内。此影响在使用单纯孕激素避孕时情况未知。

【贮藏】

请置于原包装中2－30°C下保存。

【批准文号】

H20130884

【生产企业】

企业名称：N.V.Organon

企业简称：N.V.Organon

生产地址：Kloosterstraat 6， 5349 AB Oss 

 

Nexplanon

Generic Name: etonogestrel
Dosage Form: implant

Medically reviewed on May 1, 2017

 

 

 

Indications and Usage for Nexplanon

Nexplanon® is indicated for use by women to prevent pregnancy.

Nexplanon Dosage and Administration

The efficacy of Nexplanon does not depend on daily, weekly or monthly administration.

All healthcare providers should receive instruction and training prior to performing insertion and/or removal of Nexplanon.

A single Nexplanon implant is inserted subdermally in the upper arm. To reduce the risk of neural or vascular injury, the implant should be inserted at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus. The implant should be inserted subdermally just under the skin, avoiding the sulcus (groove) between the biceps and triceps muscles and the large blood vessels and nerves that lie there in the neurovascular bundle deeper in the subcutaneous tissues. An implant inserted more deeply than subdermally (deep insertion) may not be palpable and the localization and/or removal can be difficult or impossible [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. Nexplanon must be inserted by the expiration date stated on the packaging. Nexplanon is a long-acting (up to 3 years), reversible, hormonal contraceptive method. The implant must be removed by the end of the third year and may be replaced by a new implant at the time of removal, if continued contraceptive protection is desired.

 

 

 

 

Initiating Contraception with Nexplanon

IMPORTANT: Rule out pregnancy before inserting the implant.

Timing of insertion depends on the woman's recent contraceptive history, as follows:

• No preceding hormonal contraceptive use in the past month

Nexplanon should be inserted between Day 1 (first day of menstrual bleeding) and Day 5 of the menstrual cycle, even if the woman is still bleeding.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

• Switching contraceptive method to Nexplanon

Combination hormonal contraceptives:

Nexplanon should preferably be inserted on the day after the last active tablet of the previous combined oral contraceptive or on the day of removal of the vaginal ring or transdermal patch. At the latest, Nexplanon should be inserted on the day following the usual tablet-free, ring-free, patch-free or placebo tablet interval of the previous combined hormonal contraceptive.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Progestin-only contraceptives:

There are several types of progestin-only methods. Nexplanon should be inserted as follows:

· Injectable Contraceptives: Insert Nexplanon on the day the next injection is due.

· Minipill: A woman may switch to Nexplanon on any day of the month. Nexplanon should be inserted within 24 hours after taking the last tablet.

· Contraceptive implant or intrauterine system (IUS): Insert Nexplanon on the same day the previous contraceptive implant or IUS is removed.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

• Following abortion or miscarriage

· First Trimester: Nexplanon should be inserted within 5 days following a first trimester abortion or miscarriage.

· Second Trimester: Insert Nexplanon between 21 to 28 days following second trimester abortion or miscarriage.

If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

• Postpartum

· Not Breastfeeding: Nexplanon should be inserted between 21 to 28 days postpartum. If inserted as recommended, back-up contraception is not necessary. If deviating from the recommended timing of insertion, the woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

· Breastfeeding: Nexplanon should not be inserted until after the fourth postpartum week. The woman should be advised to use a barrier method until 7 days after insertion. If intercourse has already occurred, pregnancy should be excluded.

Insertion of Nexplanon

The basis for successful use and subsequent removal of Nexplanon is a correct and carefully performed subdermal insertion of the single, rod-shaped implant in accordance with the instructions. Both the healthcare provider and the woman should be able to feel the implant under the skin after placement.

All healthcare providers performing insertions and/or removals of Nexplanon should receive instructions and training prior to inserting or removing the implant. Information concerning the insertion and removal of Nexplanon will be sent upon request free of charge [1-877-467-5266].

Preparation

Prior to inserting Nexplanon carefully read the instructions for insertion as well as the full prescribing information.

Before insertion of Nexplanon, the healthcare provider should confirm that:

· The woman is not pregnant nor has any other contraindication for the use of Nexplanon [see Contraindications (4)].

· The woman has had a medical history and physical examination, including a gynecologic examination, performed.

· The woman understands the benefits and risks of Nexplanon.

· The woman has received a copy of the Patient Labeling included in packaging.

· The woman has reviewed and completed a consent form to be maintained with the woman's chart.

· The woman does not have allergies to the antiseptic and anesthetic to be used during insertion.

Insert Nexplanon under aseptic conditions.

The following equipment is needed for the implant insertion:

· An examination table for the woman to lie on

· Sterile surgical drapes, sterile gloves, antiseptic solution, sterile marker (optional)

· Local anesthetic, needles, and syringe

· Sterile gauze, adhesive bandage, pressure bandage

Insertion Procedure

Step 1. Have the woman lie on her back on the examination table with her non-dominant arm flexed at the elbow and externally rotated so that her wrist is parallel to her ear or her hand is positioned next to her head (Figure 1).

 

Figure 1

Step 2. Identify the insertion site, which is at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus, avoiding the sulcus (groove) between the biceps and triceps muscles and the large blood vessels and nerves that lie there in the neurovascular bundle deeper in the subcutaneous tissue (Figure 2). The implant should be inserted subdermally just under the skin [see Warnings and Precautions (5.1)].

Step 3. Make two marks with a sterile marker: first, mark the spot where the etonogestrel implant will be inserted, and second, mark a spot a few centimeters proximal to the first mark (Figure 2). This second mark will later serve as a direction guide during insertion.

 

Figure 2

Step 4. Clean the insertion site with an antiseptic solution.

Step 5. Anesthetize the insertion area (for example, with anesthetic spray or by injecting 2 mL of 1% lidocaine just under the skin along the planned insertion tunnel).

Step 6. Remove the sterile preloaded disposable Nexplanon applicator carrying the implant from its blister. The applicator should not be used if sterility is in question.

Step 7. Hold the applicator just above the needle at the textured surface area. Remove the transparent protection cap by sliding it horizontally in the direction of the arrow away from the needle (Figure 3). If the cap does not come off easily, the applicator should not be used. You can see the white colored implant by looking into the tip of the needle. Do not touch the purple slider until you have fully inserted the needle subdermally, as it will retract the needle and prematurely release the implant from the applicator.

 

Figure 3

Step 8. With your free hand, stretch the skin around the insertion site with thumb and index finger (Figure 4).

 

Figure 4

Step 9. Puncture the skin with the tip of the needle slightly angled less than 30° (Figure 5).

 

Figure 5

Step 10. Lower the applicator to a horizontal position. While lifting the skin with the tip of the needle (Figure 6), slide the needle to its full length. You may feel slight resistance but do not exert excessive force. If the needle is not inserted to its full length, the implant will not be inserted properly.

You can best see movement of the needle, and that it is inserted just under the skin, if you are seated and are looking at the applicator from the side and NOT from above. In this position, you can clearly see the insertion site and the movement of the needle just under the skin.

 

Figure 6

Step 11. Keep the applicator in the same position with the needle inserted to its full length. If needed, you may use your free hand to keep the applicator in the same position during the following procedure. Unlock the purple slider by pushing it slightly down. Move the slider fully back until it stops (Figure 7). The implant is now in its final subdermal position, and the needle is locked inside the body of the applicator. The applicator can now be removed. If the applicator is not kept in the same position during this procedure or if the purple slider is not completely moved to the back, the implant will not be inserted properly.

 

Figure 7

Step 12. Always verify the presence of the implant in the woman's arm immediately after insertion by palpation. By palpating both ends of the implant, you should be able to confirm the presence of the 4 cm rod (Figure 8). See "If the rod is not palpable" below.

 

Figure 8

Step 13. Place a small adhesive bandage over the insertion site. Request that the woman palpate the implant.

Step 14. Apply a pressure bandage with sterile gauze to minimize bruising. The woman may remove the pressure bandage in 24 hours and the small bandage over the insertion site after 3 to 5 days.

Step 15. Complete the USER CARD and give it to the woman to keep. Also, complete the PATIENT CHART LABEL and affix it to the woman's medical record.

Step 16. The applicator is for single use only and should be disposed in accordance with the Center for Disease Control and Prevention guidelines for handling of hazardous waste.

If the rod is not palpable:

If you cannot feel the implant or are in doubt of its presence, the implant may not have been inserted or it may have been inserted deeply:

· Check the applicator. The needle should be fully retracted and only the purple tip of the obturator should be visible.

· Use other methods to confirm the presence of the implant. Given the radiopaque nature of the implant, suitable methods for localization are two-dimensional X-ray and X-ray computerized tomography (CT scan). Ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHz or greater) or magnetic resonance imaging (MRI) may be used. If these methods fail, call 1-877-467-5266 for information on the procedure for measuring etonogestrel blood levels.

Until the presence of the implant has been verified, the woman should be advised to use a non-hormonal contraceptive method, such as condoms.

Once the non-palpable implant has been located, removal is recommended [see Warnings and Precautions (5.1)].

Removal of Nexplanon

Preparation

Before initiating the removal procedure, the healthcare provider should carefully read the instructions for removal and consult the USER CARD and/or the PATIENT CHART LABEL for the location of the implant. The exact location of the implant in the arm should be verified by palpation. [See Dosage and Administration (2.3) and Localization and Removal of a Non-Palpable Implant.]

Procedure for Removal of an Implant that is Palpable

Before removal of the implant, the healthcare provider should confirm that:

· The woman does not have allergies to the antiseptic or anesthetic to be used.

Remove the implant under aseptic conditions.

The following equipment is needed for removal of the implant:

· An examination table for the woman to lie on

· Sterile surgical drapes, sterile gloves, antiseptic solution, sterile marker (optional)

· Local anesthetic, needles, and syringe

· Sterile scalpel, forceps (straight and curved mosquito)

· Skin closure, sterile gauze, adhesive bandage and pressure bandages

Removal Procedure

Step 1. Clean the site where the incision will be made and apply an antiseptic. Locate the implant by palpation and mark the distal end (end closest to the elbow), for example, with a sterile marker (Figure 9).

 

Figure 9

Step 2. Anesthetize the arm, for example, with 0.5 to 1 mL 1% lidocaine at the marked site where the incision will be made (Figure 10). Be sure to inject the local anesthetic under the implant to keep it close to the skin surface.

 

Figure 10

Step 3. Push down the proximal end of the implant (Figure 11) to stabilize it; a bulge may appear indicating the distal end of the implant. Starting at the distal tip of the implant, make a longitudinal incision of 2 mm towards the elbow.

 

Figure 11

Step 4. Gently push the implant towards the incision until the tip is visible. Grasp the implant with forceps (preferably curved mosquito forceps) and gently remove the implant (Figure 12).

 

Figure 12

Step 5. If the implant is encapsulated, make an incision into the tissue sheath and then remove the implant with the forceps (Figures 13 and 14).

Figure 13	Figure 14

Step 6. If the tip of the implant does not become visible in the incision, gently insert a forceps into the incision (Figure 15). Flip the forceps over into your other hand (Figure 16).

Figure 15	Figure 16

Step 7. With a second pair of forceps carefully dissect the tissue around the implant and grasp the implant (Figure 17). The implant can then be removed.

 

Figure 17

Step 8. Confirm that the entire implant, which is 4 cm long, has been removed by measuring its length. There have been reports of broken implants while in the patient's arm. In some cases, difficult removal of the broken implant has been reported. If a partial implant (less than 4 cm) is removed, the remaining piece should be removed by following the instructions in section 2.3. [See Dosage and Administration (2.3).] If the woman would like to continue using Nexplanon, a new implant may be inserted immediately after the old implant is removed using the same incision [see Dosage and Administration (2.4)].

Step 9. After removing the implant, close the incision with a steri-strip and apply an adhesive bandage.

Step 10. Apply a pressure bandage with sterile gauze to minimize bruising. The woman may remove the pressure bandage in 24 hours and the small bandage in 3 to 5 days.

Localization and Removal of a Non-Palpable Implant

There have been reports of migration of the implant; usually this involves minor movement relative to the original position [see Warnings and Precautions (5.1)], but may lead to the implant not being palpable at the location in which it was placed. An implant that has been deeply inserted or has migrated may not be palpable and therefore imaging procedures, as described below, may be required for localization.

A non-palpable implant should always be located prior to attempting removal. Given the radiopaque nature of the implant, suitable methods for localization include two-dimensional X-ray and X-ray computer tomography (CT). Ultrasound scanning (USS) with a high-frequency linear array transducer (10 MHz or greater) or magnetic resonance imaging (MRI) may be used. Once the implant has been localized in the arm, the implant should be removed according to the instructions in Dosage and Administration (2.3), Procedure for Removal of an Implant that is Palpable, and the use of ultrasound guidance during the removal should be considered.

If the implant cannot be found in the arm after comprehensive localization attempts, consider applying imaging techniques to the chest as events of migration to the pulmonary vasculature have been reported. If the implant is located in the chest, surgical or endovascular procedures may be needed for removal; healthcare providers familiar with the anatomy of the chest should be consulted.

If at any time these imaging methods fail to locate the implant, etonogestrel blood level determination can be used for verification of the presence of the implant. For details on etonogestrel blood level determination, call 1-877-467-5266 for further instructions.

If the implant migrates within the arm, removal may require a minor surgical procedure with a larger incision or a surgical procedure in an operating room. Removal of deeply inserted implants should be conducted with caution in order to prevent injury to deeper neural or vascular structures in the arm and be performed by healthcare providers familiar with the anatomy of the arm.

Exploratory surgery without knowledge of the exact location of the implant is strongly discouraged.

Replacing Nexplanon

Immediate replacement can be done after removal of the previous implant and is similar to the insertion procedure described in section 2.2 Insertion of Nexplanon.

The new implant may be inserted in the same arm, and through the same incision from which the previous implant was removed. If the same incision is being used to insert a new implant, anesthetize the insertion site [for example, 2 mL lidocaine (1%)] applying it just under the skin along the 'insertion canal.'

Follow the subsequent steps in the insertion instructions [see Dosage and Administration (2.2)].

Dosage Forms and Strengths

Single, white/off-white, soft, radiopaque, flexible, ethylene vinyl acetate (EVA) copolymer implant, 4 cm in length and 2 mm in diameter containing 68 mg etonogestrel and 15 mg of barium sulfate.

Single, white/off-white, soft, radiopaque, flexible, ethylene vinyl acetate (EVA) copolymer implant, 4 cm in length and 2 mm in diameter containing 68 mg etonogestrel, 15 mg of barium sulfate and 0.1 mg of magnesium stearate.

Contraindications

Nexplanon should not be used in women who have

· Known or suspected pregnancy

· Current or past history of thrombosis or thromboembolic disorders

· Liver tumors, benign or malignant, or active liver disease

· Undiagnosed abnormal genital bleeding

· Known or suspected breast cancer, personal history of breast cancer, or other progestin-sensitive cancer, now or in the past

· Allergic reaction to any of the components of Nexplanon [see Adverse Reactions (6)]

Warnings and Precautions

The following information is based on experience with the etonogestrel implants (IMPLANON and/or Nexplanon), other progestin-only contraceptives, or experience with combination (estrogen plus progestin) oral contraceptives.

Complications of Insertion and Removal

Nexplanon should be inserted subdermally so that it will be palpable after insertion, and this should be confirmed by palpation immediately after insertion. Failure to insert Nexplanon properly may go unnoticed unless it is palpated immediately after insertion. Undetected failure to insert the implant may lead to an unintended pregnancy. Complications related to insertion and removal procedures, such as pain, paresthesias, bleeding, hematoma, scarring or infection, may occur.

If Nexplanon is inserted deeply (intramuscular or in the fascia), neural or vascular injury may occur. To reduce the risk of neural or vascular injury, Nexplanon should be inserted at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus. Nexplanon should be inserted subdermally just under the skin avoiding the sulcus (groove) between the biceps and triceps muscles and the large blood vessels and nerves that lie there in the neurovascular bundle deeper in the subcutaneous tissues. Deep insertions of Nexplanon have been associated with paraesthesia (due to neural injury), migration of the implant (due to intramuscular or fascial insertion), and intravascular insertion. If infection develops at the insertion site, start suitable treatment. If the infection persists, the implant should be removed. Incomplete insertions or infections may lead to expulsion.

Implant removal may be difficult or impossible if the implant is not inserted correctly, is inserted too deeply, not palpable, encased in fibrous tissue, or has migrated.

There have been reports of migration of the implant within the arm from the insertion site, which may be related to deep insertion. There also have been postmarketing reports of implants located within the vessels of the arm and the pulmonary artery, which may be related to deep insertions or intravascular insertion. In cases where the implant has migrated to the pulmonary artery, endovascular or surgical procedures may be needed for removal.

If at any time the implant cannot be palpated, it should be localized and removal is recommended.

Exploratory surgery without knowledge of the exact location of the implant is strongly discouraged. Removal of deeply inserted implants should be conducted with caution in order to prevent injury to deeper neural or vascular structures in the arm and be performed by healthcare providers familiar with the anatomy of the arm. If the implant is located in the chest, healthcare providers familiar with the anatomy of the chest should be consulted. Failure to remove the implant may result in continued effects of etonogestrel, such as compromised fertility, ectopic pregnancy, or persistence or occurrence of a drug-related adverse event.

Changes in Menstrual Bleeding Patterns

After starting Nexplanon, women are likely to have a change from their normal menstrual bleeding pattern. These may include changes in bleeding frequency (absent, less, more frequent or continuous), intensity (reduced or increased) or duration. In clinical trials of the non-radiopaque etonogestrel implant (IMPLANON), bleeding patterns ranged from amenorrhea (1 in 5 women) to frequent and/or prolonged bleeding (1 in 5 women). The bleeding pattern experienced during the first three months of Nexplanon use is broadly predictive of the future bleeding pattern for many women. Women should be counseled regarding the bleeding pattern changes they may experience so that they know what to expect. Abnormal bleeding should be evaluated as needed to exclude pathologic conditions or pregnancy.

In clinical studies of the non-radiopaque etonogestrel implant, reports of changes in bleeding pattern were the most common reason for stopping treatment (11.1%). Irregular bleeding (10.8%) was the single most common reason women stopped treatment, while amenorrhea (0.3%) was cited less frequently. In these studies, women had an average of 17.7 days of bleeding or spotting every 90 days (based on 3,315 intervals of 90 days recorded by 780 patients). The percentages of patients having 0, 1-7, 8-21, or >21 days of spotting or bleeding over a 90-day interval while using the non-radiopaque etonogestrel implant are shown in Table 1.

Table 1: Percentages of Patients With 0, 1-7, 8-21, or >21 Days of Spotting or Bleeding Over a 90-Day Interval While Using the Non-Radiopaque Etonogestrel Implant (IMPLANON)
Total Days of Spotting or Bleeding	Percentage of Patients
	Treatment Days 91-180 (N = 745)	Treatment Days 271-360 (N = 657)	Treatment Days 631-720 (N = 547)
0 Days	19%	24%	17%
1-7 Days	15%	13%	12%
8-21 Days	30%	30%	37%
>21 Days	35%	33%	35%

Bleeding patterns observed with use of the non-radiopaque etonogestrel implant for up to 2 years, and the proportion of 90-day intervals with these bleeding patterns, are summarized in Table 2.

Table 2: Bleeding Patterns Using the Non-Radiopaque Etonogestrel Implant (IMPLANON) During the First 2 Years of Use*
BLEEDING PATTERNS	DEFINITIONS	%†
* Based on 3315 recording periods of 90 days duration in 780 women, excluding the first 90 days after implant insertion † % = Percentage of 90-day intervals with this pattern
Infrequent	Less than three bleeding and/or spotting episodes in 90 days (excluding amenorrhea)	33.6
Amenorrhea	No bleeding and/or spotting in 90 days	22.2
Prolonged	Any bleeding and/or spotting episode lasting more than 14 days in 90 days	17.7
Frequent	More than 5 bleeding and/or spotting episodes in 90 days	6.7

In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy.

Ectopic Pregnancies

As with all progestin-only contraceptive products, be alert to the possibility of an ectopic pregnancy among women using Nexplanon who become pregnant or complain of lower abdominal pain. Although ectopic pregnancies are uncommon among women using Nexplanon, a pregnancy that occurs in a woman using Nexplanon may be more likely to be ectopic than a pregnancy occurring in a woman using no contraception.

Thrombotic and Other Vascular Events

The use of combination hormonal contraceptives (progestin plus estrogen) increases the risk of vascular events, including arterial events (strokes and myocardial infarctions) or deep venous thrombotic events (venous thromboembolism, deep venous thrombosis, retinal vein thrombosis, and pulmonary embolism). Nexplanon is a progestin-only contraceptive. It is unknown whether this increased risk is applicable to etonogestrel alone. It is recommended, however, that women with risk factors known to increase the risk of venous and arterial thromboembolism be carefully assessed.

There have been postmarketing reports of serious arterial thrombotic and venous thromboembolic events, including cases of pulmonary emboli (some fatal), deep vein thrombosis, myocardial infarction, and strokes, in women using etonogestrel implants. Nexplanon should be removed in the event of a thrombosis.

Due to the risk of thromboembolism associated with pregnancy and immediately following delivery, Nexplanon should not be used prior to 21 days postpartum. Women with a history of thromboembolic disorders should be made aware of the possibility of a recurrence.

Evaluate for retinal vein thrombosis immediately if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions.

Consider removal of the Nexplanon implant in case of long-term immobilization due to surgery or illness.

Ovarian Cysts

If follicular development occurs, atresia of the follicle is sometimes delayed, and the follicle may continue to grow beyond the size it would attain in a normal cycle. Generally, these enlarged follicles disappear spontaneously. On rare occasion, surgery may be required.

Carcinoma of the Breast and Reproductive Organs

Women who currently have or have had breast cancer should not use hormonal contraception because breast cancer may be hormonally sensitive [see Contraindications (4)]. Some studies suggest that the use of combination hormonal contraceptives might increase the incidence of breast cancer; however, other studies have not confirmed such findings.

Some studies suggest that the use of combination hormonal contraceptives is associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which these findings are due to differences in sexual behavior and other factors.

Women with a family history of breast cancer or who develop breast nodules should be carefully monitored.

Liver Disease

Disturbances of liver function may necessitate the discontinuation of hormonal contraceptive use until markers of liver function return to normal. Remove Nexplanon if jaundice develops.

Hepatic adenomas are associated with combination hormonal contraceptives use. An estimate of the attributable risk is 3.3 cases per 100,000 for combination hormonal contraceptives users. It is not known whether a similar risk exists with progestin-only methods like Nexplanon.

The progestin in Nexplanon may be poorly metabolized in women with liver impairment. Use of Nexplanon in women with active liver disease or liver cancer is contraindicated [see Contraindications (4)].

Weight Gain

In clinical studies, mean weight gain in U.S. non-radiopaque etonogestrel implant (IMPLANON) users was 2.8 pounds after one year and 3.7 pounds after two years. How much of the weight gain was related to the non-radiopaque etonogestrel implant is unknown. In studies, 2.3% of the users reported weight gain as the reason for having the non-radiopaque etonogestrel implant removed.

Elevated Blood Pressure

Women with a history of hypertension-related diseases or renal disease should be discouraged from using hormonal contraception. For women with well-controlled hypertension, use of Nexplanon can be considered. Women with hypertension using Nexplanon should be closely monitored. If sustained hypertension develops during the use of Nexplanon, or if a significant increase in blood pressure does not respond adequately to antihypertensive therapy, Nexplanon should be removed.

Gallbladder Disease

Studies suggest a small increased relative risk of developing gallbladder disease among combination hormonal contraceptive users. It is not known whether a similar risk exists with progestin-only methods like Nexplanon.

Carbohydrate and Lipid Metabolic Effects

Use of Nexplanon may induce mild insulin resistance and small changes in glucose concentrations of unknown clinical significance. Carefully monitor prediabetic and diabetic women using Nexplanon.

Women who are being treated for hyperlipidemia should be followed closely if they elect to use Nexplanon. Some progestins may elevate LDL levels and may render the control of hyperlipidemia more difficult.

Depressed Mood

Women with a history of depressed mood should be carefully observed. Consideration should be given to removing Nexplanon in patients who become significantly depressed.

Return to Ovulation

In clinical trials with the non-radiopaque etonogestrel implant (IMPLANON), the etonogestrel levels in blood decreased below sensitivity of the assay by one week after removal of the implant. In addition, pregnancies were observed to occur as early as 7 to 14 days after removal. Therefore, a woman should re-start contraception immediately after removal of the implant if continued contraceptive protection is desired.

Fluid Retention

Hormonal contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. It is unknown if Nexplanon causes fluid retention.

Contact Lenses

Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist.

In Situ Broken or Bent Implant

There have been reports of broken or bent implants while in the patient's arm. Based on in vitro data, when an implant is broken or bent, the release rate of etonogestrel may be slightly increased.

When an implant is removed, it is important to remove it in its entirety [see Dosage and Administration (2.3)].

Monitoring

A woman who is using Nexplanon should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated health care.

Drug-Laboratory Test Interactions

Sex hormone-binding globulin concentrations may be decreased for the first six months after Nexplanon insertion followed by gradual recovery. Thyroxine concentrations may initially be slightly decreased followed by gradual recovery to baseline.

Adverse Reactions

The following adverse reactions reported with the use of hormonal contraception are discussed elsewhere in the labeling:

· Changes in Menstrual Bleeding Patterns [see Warnings and Precautions (5.2)]

· Ectopic Pregnancies [see Warnings and Precautions (5.3)]

· Thrombotic and Other Vascular Events [see Warnings and Precautions (5.4)]

· Liver Disease [see Warnings and Precautions (5.7)]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical trials involving 942 women who were evaluated for safety, change in menstrual bleeding patterns (irregular menses) was the most common adverse reaction causing discontinuation of use of the non-radiopaque etonogestrel implant (IMPLANON) (11.1% of women).

Adverse reactions that resulted in a rate of discontinuation of ≥1% are shown in Table 3.

Table 3: Adverse Reactions Leading to Discontinuation of Treatment in 1% or More of Subjects in Clinical Trials of the Non-Radiopaque Etonogestrel Implant (IMPLANON)
Adverse Reactions	All Studies N = 942
* Includes "frequent", "heavy", "prolonged", "spotting", and other patterns of bleeding irregularity. † Among US subjects (N=330), 6.1% experienced emotional lability that led to discontinuation. ‡ Among US subjects (N=330), 2.4% experienced depression that led to discontinuation.
Bleeding Irregularities*	11.1%
Emotional Lability†	2.3%
Weight Increase	2.3%
Headache	1.6%
Acne	1.3%
Depression‡	1.0%

Other adverse reactions that were reported by at least 5% of subjects in the non-radiopaque etonogestrel implant clinical trials are listed in Table 4.

Table 4: Common Adverse Reactions Reported by ≥5% of Subjects in Clinical Trials With the Non-Radiopaque Etonogestrel Implant (IMPLANON)
Adverse Reactions	All Studies N = 942
Headache	24.9%
Vaginitis	14.5%
Weight increase	13.7%
Acne	13.5%
Breast pain	12.8%
Abdominal pain	10.9%
Pharyngitis	10.5%
Leukorrhea	9.6%
Influenza-like symptoms	7.6%
Dizziness	7.2%
Dysmenorrhea	7.2%
Back pain	6.8%
Emotional lability	6.5%
Nausea	6.4%
Pain	5.6%
Nervousness	5.6%
Depression	5.5%
Hypersensitivity	5.4%
Insertion site pain	5.2%

In a clinical trial of Nexplanon, in which investigators were asked to examine the implant site after insertion, implant site reactions were reported in 8.6% of women. Erythema was the most frequent implant site complication, reported during and/or shortly after insertion, occurring in 3.3% of subjects. Additionally, hematoma (3.0%), bruising (2.0%), pain (1.0%), and swelling (0.7%) were reported.

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of IMPLANON and Nexplanon. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal disorders: constipation, diarrhea, flatulence, vomiting.

General disorders and administration site conditions: edema, fatigue, implant site reaction, pyrexia.

Immune system disorders: anaphylactic reactions.

Infections and infestations: rhinitis, urinary tract infection.

Investigations: clinically relevant rise in blood pressure, weight decreased.

Metabolism and nutrition disorders: increased appetite.

Musculoskeletal and connective tissue disorders: arthralgia, musculoskeletal pain, myalgia.

Nervous system disorders: convulsions, migraine, somnolence.

Pregnancy, puerperium and perinatal conditions: ectopic pregnancy.

Psychiatric disorders: anxiety, insomnia, libido decreased.

Renal and urinary disorders: dysuria.

Reproductive system and breast disorders: breast discharge, breast enlargement, ovarian cyst, pruritus genital, vulvovaginal discomfort.

Skin and subcutaneous tissue disorders: angioedema, aggravation of angioedema and/or aggravation of hereditary angioedema, alopecia, chloasma, hypertrichosis, pruritus, rash, seborrhea, urticaria.

Vascular disorders: hot flush.

Complications related to insertion or removal of the etonogestrel implants reported include: bruising, slight local irritation, pain or itching, fibrosis at the implant site, paresthesia or paresthesia-like events, scarring and abscess. Expulsion or migration of the implant has been reported, including to the chest wall. In some cases, implants have been found within the vasculature, including the pulmonary artery. Some cases of implants found within the pulmonary artery reported chest pain and/or dyspnea; others have been reported as asymptomatic [see Warnings and Precautions (5.1)]. Surgical intervention might be necessary when removing the implant.

Drug Interactions

Consult the labeling of concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

Effects of Other Drugs on Hormonal Contraceptives

Substances decreasing the plasma concentrations of hormonal contraceptives (HCs) and potentially diminishing the efficacy of HCs:

Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of HCs and potentially diminish the effectiveness of HCs or increase breakthrough bleeding.

Some drugs or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between HCs and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are used with HCs, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances increasing the plasma concentrations of HCs:

Co-administration of certain HCs and strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase the serum concentrations of progestins, including etonogestrel.

Human Immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) protease inhibitors and non-nucleoside reverse transcriptase inhibitors:

Significant changes (increase or decrease) in the plasma concentrations of progestin have been noted in cases of co-administration with HIV protease inhibitors (decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., boceprevir and telaprevir]) or with non-nucleoside reverse transcriptase inhibitors (decrease [e.g., nevirapine, efavirenz] or increase [e.g., etravirene]). These changes may be clinically relevant in some cases.

Consult the prescribing information of anti-viral and anti-retroviral concomitant medications to identify potential interactions.

Effects of Hormonal Contraceptives on Other Drugs

Hormonal contraceptives may affect the metabolism of other drugs. Consequently, plasma concentrations may either increase (for example, cyclosporine) or decrease (for example, lamotrigine). Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations.

USE IN SPECIFIC POPULATIONSPregnancy

Risk Summary

Nexplanon is contraindicated during pregnancy because there is no need for pregnancy prevention in a woman who is already pregnant [see Contraindications (4)]. Epidemiologic studies and meta-analyses have not shown an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following maternal exposure to low dose CHCs prior to conception or during early pregnancy. No adverse development outcomes were observed in pregnant rats and rabbits with the administration of etonogestrel during organogenesis at doses of 315 or 781 times the anticipated human dose (60 µg/day) (see Data).

Nexplanon should be removed if maintaining a pregnancy.

Data

Animal Data

Teratology studies have been performed in rats and rabbits using oral administration up to 315 and 781 times the human etonogestrel dose (based upon body surface) and revealed no evidence of fetal harm due to etonogestrel exposure.

Lactation

Risk Summary

Small amounts of contraceptive steroids and/or metabolites, including etonogestrel are present in human milk. No significant adverse effects have been observed in the production or quality of breast milk, or on the physical and psychomotor development of breastfed infants (see Data).

Hormonal contraceptives, including etonogestrel, can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. When possible, advise the nursing mother about both hormonal and non-hormonal contraceptive options, as steroids may not be the initial choice for these patients. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Nexplanon and any potential adverse effects on the breastfed child from Nexplanon or from the underlying maternal condition.

Data

The amount of etonogestrel contained within breast milk was measured in 38 lactating women who began using IMPLANON during the fourth to eighth week postpartum. The study evaluated Implanon versus another contraceptive, was not randomized and data were considered observational and exploratory; therefore, comparisons could not be made. Based on the findings of this study, during the first months after insertion of IMPLANON, when maternal blood levels of etonogestrel are highest, about 100 ng of etonogestrel may be ingested by the child per day based on an average daily milk ingestion of 658 mL. Based on daily milk ingestion of 150 mL/kg, the mean daily infant etonogestrel dose one month after insertion of IMPLANON is about 2.2% of the weight-adjusted maternal daily dose, or about 0.2% of the estimated absolute maternal daily dose. Adverse reactions were not observed in breastfed infants exposed to etonogestrel through breast milk. No adverse effects on the production or quality of breast milk were detected.

Pediatric Use

Safety and efficacy of Nexplanon have been established in women of reproductive age. Safety and efficacy of Nexplanon are expected to be the same for postpubertal adolescents. However, no clinical studies have been conducted in women less than 18 years of age. Use of this product before menarche is not indicated.

Geriatric Use

This product has not been studied in women over 65 years of age and is not indicated in this population.

Hepatic Impairment

No studies were conducted to evaluate the effect of hepatic disease on the disposition of Nexplanon. The use of Nexplanon in women with active liver disease is contraindicated [see Contraindications (4)].

Overweight Women

The effectiveness of the etonogestrel implant in women who weighed more than 130% of their ideal body weight has not been defined because such women were not studied in clinical trials. Serum concentrations of etonogestrel are inversely related to body weight and decrease with time after implant insertion. It is therefore possible that Nexplanon may be less effective in overweight women, especially in the presence of other factors that decrease serum etonogestrel concentrations such as concomitant use of hepatic enzyme inducers.

Overdosage

Overdosage may result if more than one implant is inserted. In case of suspected overdose, the implant should be removed.

Nexplanon Description

Nexplanon is a radiopaque, progestin-only, soft, flexible implant preloaded in a sterile, disposable applicator for subdermal use. The implant is white/off-white, non-biodegradable and 4 cm in length with a diameter of 2 mm (see Figure 18). Each implant consists of an ethylene vinyl acetate (EVA) copolymer core, containing 68 mg of the synthetic progestin etonogestrel, barium sulfate (radiopaque ingredient), and may also contain magnesium stearate, surrounded by an EVA copolymer skin. Once inserted subdermally, the release rate is 60-70 mcg/day in week 5-6 and decreases to approximately 35-45 mcg/day at the end of the first year, to approximately 30-40 mcg/day at the end of the second year, and then to approximately 25-30 mcg/day at the end of the third year. Nexplanon is a progestin-only contraceptive and does not contain estrogen. Nexplanon does not contain latex.

 

Figure 18 (Not to scale)

Etonogestrel [13-Ethyl-17-hydroxy-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3-one], structurally derived from 19-nortestosterone, is the synthetic biologically active metabolite of the synthetic progestin desogestrel. It has a molecular weight of 324.46 and the following structural formula (Figure 19).

 

Figure 19

Nexplanon - Clinical PharmacologyMechanism of Action

The contraceptive effect of Nexplanon is achieved by suppression of ovulation, increased viscosity of the cervical mucus, and alterations in the endometrium.

Pharmacodynamics

Exposure-response relationships of Nexplanon are unknown.

Pharmacokinetics

Absorption

After subdermal insertion of the etonogestrel implant, etonogestrel is released into the circulation and is approximately 100% bioavailable.

In a three year clinical trial, Nexplanon and the non-radiopaque etonogestrel implant (IMPLANON) yielded comparable systemic exposure to etonogestrel. For Nexplanon, the mean (± SD) maximum serum etonogestrel concentrations were 1200 (± 604) pg/mL and were reached within the first two weeks after insertion (n=50). The mean (± SD) serum etonogestrel concentration decreased gradually over time, declining to 202 (± 55) pg/mL at 12 months (n=41), 164 (± 58) pg/mL at 24 months (n=37), and 138 (± 43) pg/mL at 36 months (n=32). For the non-radiopaque etonogestrel implant (IMPLANON), the mean (± SD) maximum serum etonogestrel concentrations were 1145 (± 577) pg/mL and were reached within the first two weeks after insertion (n=53). The mean (± SD) serum etonogestrel concentration decreased gradually over time, declining to 223 (± 73) pg/mL at 12 months (n=40), 172 (± 77) pg/mL at 24 months (n=32), and 153 (± 52) pg/mL at 36 months (n=30).

The pharmacokinetic profile of Nexplanon is shown in Figure 20.

Figure 20: Mean (± SD) Serum Concentration-Time Profile of Etonogestrel After Insertion of Nexplanon During 3 Years of Use

Distribution

The apparent volume of distribution averages about 201 L. Etonogestrel is approximately 32% bound to sex hormone binding globulin (SHBG) and 66% bound to albumin in blood.

Metabolism

In vitro data shows that etonogestrel is metabolized in liver microsomes by the cytochrome P450 3A4 isoenzyme. The biological activity of etonogestrel metabolites is unknown.

Excretion

The elimination half-life of etonogestrel is approximately 25 hours. Excretion of etonogestrel and its metabolites, either as free steroid or as conjugates, is mainly in urine and to a lesser extent in feces. After removal of the implant, etonogestrel concentrations decreased below sensitivity of the assay by one week.

Nonclinical ToxicologyCarcinogenesis, Mutagenesis, Impairment of Fertility

In a 24-month carcinogenicity study in rats with subdermal implants releasing 10 and 20 mcg etonogestrel per day (equal to approximately 1.8-3.6 times the systemic steady state exposure in women using Nexplanon), no drug-related carcinogenic potential was observed. Etonogestrel was not genotoxic in the in vitro Ames/Salmonella reverse mutation assay, the chromosomal aberration assay in Chinese hamster ovary cells or in the in vivo mouse micronucleus test. Fertility in rats returned after withdrawal from treatment.

Clinical StudiesPregnancy

In clinical trials of up to 3 years duration that involved 923 subjects, 18-40 years of age at entry, and 1756 women-years of use with the non-radiopaque etonogestrel implant (IMPLANON), the total exposures expressed as 28-day cycle equivalents by study year were:

Year 1: 10,866 cycles

Year 2: 8,581 cycles

Year 3: 3,442 cycles

The clinical trials excluded women who:

· Weighed more than 130% of their ideal body weight

· Were chronically taking medications that induce liver enzymes

In the subgroup of women, 18-35 years of age at entry, 6 pregnancies during 20,648 cycles of use were reported. Two pregnancies occurred in each of Years 1, 2, and 3. Each conception was likely to have occurred shortly before or within 2 weeks after removal of the non-radiopaque etonogestrel implant. With these 6 pregnancies, the cumulative Pearl Index was 0.38 pregnancies per 100 women-years of use.

Return to Ovulation

In clinical trials with the non-radiopaque etonogestrel implant (IMPLANON), the etonogestrel levels in blood decreased below sensitivity of the assay by one week after removal of the implant. In addition, pregnancies were observed to occur as early as 7 to 14 days after removal. Therefore, a woman should re-start contraception immediately after removal of the implant if continued contraceptive protection is desired.

Implant Insertion and Removal Characteristics

Out of 301 insertions of the Nexplanon implant in a clinical trial, the mean insertion time (from the removal of the protection cap of the applicator until retraction of the needle from the arm) was 27.9 ± 29.3 seconds. After insertion, 300 out of 301 (99.7%) Nexplanon implants were palpable. The single, non-palpable implant was not inserted according to the instructions.

For 112 out of 114 (98.2%) subjects in 2 clinical trials for whom insertion and removal data were available, Nexplanon implants were clearly visible with use of two-dimensional x-ray after insertion. The two implants that were not clearly visible after insertion were clearly visible with two-dimensional x-ray before removal.

How Supplied/Storage and HandlingHow Supplied

Nexplanon is supplied as follows:

NDC 0052-0274-01

One Nexplanon package consists of a single implant containing 68 mg etonogestrel and 15 mg of barium sulfate that is 4 cm in length and 2 mm in diameter, which is pre-loaded in the needle of a disposable applicator. The sterile applicator containing the implant is packed in a blister pack.

NDC 0052-4330-01

One Nexplanon package consists of a single implant containing 68 mg etonogestrel, 15 mg of barium sulfate and 0.1 mg of magnesium stearate that is 4 cm in length and 2 mm in diameter, which is pre-loaded in the needle of a disposable applicator. The sterile applicator containing the implant is packed in a blister pack.

Storage and Handling

Store Nexplanon (etonogestrel implant) Radiopaque at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF) [see USP Controlled Room Temperature]. Avoid storing Nexplanon at temperatures above 30ºC (86ºF).

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

· Counsel women about the insertion and removal procedure of the Nexplanon implant. Provide the woman with a copy of the Patient Labeling and ensure that she understands the information in the Patient Labeling before insertion and removal. A USER CARD and consent form are included in the packaging. Have the woman complete a consent form and retain it in your records. The USER CARD should be filled out and given to the woman after insertion of the Nexplanon implant so that she will have a record of the location of the implant in the upper arm and when it should be removed.

· Counsel women to contact their healthcare provider immediately if, at any time, they are unable to palpate the implant.

· Counsel women that Nexplanon does not protect against HIV infection (AIDS) or other sexually transmitted diseases.

· Counsel women that the use of Nexplanon may be associated with changes in their normal menstrual bleeding patterns so that they know what to expect.

Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: N.V. Organon, Oss, The Netherlands, a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

For patent information: www.merck.com/product/patent/home.html

Copyright © 2011-2017 Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc.
All rights reserved.

uspi-mk8415-iptx-1705r019

FDA-Approved Patient Labeling

Nexplanon® (etonogestrel implant)
Radiopaque
Subdermal Use Only

Nexplanon® does not protect against HIV infection (the virus that causes AIDS) or other sexually transmitted diseases.

Read this Patient Information leaflet carefully before you decide if Nexplanon is right for you. This information does not take the place of talking with your healthcare provider. If you have any questions about Nexplanon, ask your healthcare provider.

What is Nexplanon?

Nexplanon is a hormone-releasing birth control implant for use by women to prevent pregnancy for up to 3 years. The implant is a flexible plastic rod about the size of a matchstick that contains a progestin hormone called etonogestrel. It contains a small amount of barium sulfate so that the implant can be seen by X-ray, and may also contain magnesium stearate. Your healthcare provider will insert the implant just under the skin of the inner side of your upper arm. You can use a single Nexplanon implant for up to 3 years. Nexplanon does not contain estrogen.

 

What if I need birth control for more than 3 years?

The Nexplanon implant must be removed after 3 years. Your healthcare provider can insert a new implant under your skin after taking out the old one if you choose to continue using Nexplanon for birth control.

What if I change my mind about birth control and want to stop using Nexplanon before 3 years?

Your healthcare provider can remove the implant at any time. You may become pregnant as early as the first week after removal of the implant. If you do not want to get pregnant after your healthcare provider removes the Nexplanon implant, you should start another birth control method right away.

How does Nexplanon work?

Nexplanon prevents pregnancy in several ways. The most important way is by stopping the release of an egg from your ovary. Nexplanon also thickens the mucus in your cervix and this change may keep sperm from reaching the egg. Nexplanon also changes the lining of your uterus.

How well does Nexplanon work?

When the Nexplanon implant is placed correctly, your chance of getting pregnant is very low (less than 1 pregnancy per 100 women who use Nexplanon for 1 year). It is not known if Nexplanon is as effective in very overweight women because studies did not include many overweight women.

The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

 

Who should not use Nexplanon?

Do not use Nexplanon if you:

· Are pregnant or think you may be pregnant

· Have, or have had blood clots, such as blood clots in your legs (deep venous thrombosis), lungs (pulmonary embolism), eyes (total or partial blindness), heart (heart attack), or brain (stroke)

· Have liver disease or a liver tumor

· Have unexplained vaginal bleeding

· Have breast cancer or any other cancer that is sensitive to progestin (a female hormone), now or in the past

· Are allergic to anything in Nexplanon

Tell your healthcare provider if you have or have had any of the conditions listed above. Your healthcare provider can suggest a different method of birth control.

In addition, talk to your healthcare provider about using Nexplanon if you:

· Have diabetes

· Have high cholesterol or triglycerides

· Have headaches

· Have gallbladder or kidney problems

· Have a history of depressed mood

· Have high blood pressure

· Have an allergy to numbing medicines (anesthetics) or medicines used to clean your skin (antiseptics). These medicines will be used when the implant is placed into or removed from your arm.

Interaction with Other Medicines

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Certain medicines may make Nexplanon less effective, including:

· aprepitant

· barbiturates

· bosentan

· carbamazepine

· felbamate

· griseofulvin

· oxcarbazepine

· phenytoin

· rifampin

· St. John's wort

· topiramate

· HIV medicines

· Hepatitis C Virus medicines

Ask your healthcare provider if you are not sure if your medicine is one listed above.

If you are taking medicines or herbal products that might make Nexplanon less effective, you and your doctor may decide to leave Nexplanon in place; in that case, an additional non-hormonal contraceptive should be used. Because the effect of another medicine on Nexplanon may last up to 28 days after stopping the medicine, it is necessary to use the additional non-hormonal contraceptive for that long.

When you are using Nexplanon, tell all of your healthcare providers that you have Nexplanon in place in your arm.

How is the Nexplanon implant placed and removed?

Your healthcare provider will place and remove the Nexplanon implant in a minor surgical procedure in his or her office. The implant is placed just under the skin on the inner side of your upper arm.

The timing of insertion is important. Your healthcare provider may:

· Perform a pregnancy test before inserting Nexplanon

· Schedule the insertion at a specific time of your menstrual cycle (for example, within the first days of your regular menstrual bleeding)

Your healthcare provider will cover the site where Nexplanon was placed with 2 bandages. Leave the top bandage on for 24 hours. Keep the smaller bandage clean, dry, and in place for 3 to 5 days.

Immediately after the Nexplanon implant has been placed, you and your healthcare provider should check that the implant is in your arm by feeling for it.

If you cannot feel the implant immediately after insertion, the implant may not have been inserted, or it may have been inserted deeply. A deep insertion may cause problems with locating and removing the implant. Once the healthcare professional has located the implant, removal may be recommended.

If at any time you cannot feel the Nexplanon implant, contact your healthcare provider immediately and use a non-hormonal birth control method (such as condoms) until your healthcare provider confirms that the implant is in place. You may need special tests to check that the implant is in place or to help find the implant when it is time to take it out. If the implant cannot be found in the arm after a thorough search, your healthcare professional may use x-rays or other imaging methods on your chest.

Depending on the exact position of the implant, removal may be difficult and may require surgery.

You will be asked to review and sign a consent form prior to inserting the Nexplanon implant. You will also get a USER CARD to keep at home with your health records. Your healthcare provider will fill out the USER CARD with the date the implant was inserted and the date the implant is to be removed. Keep track of the date the implant is to be removed. Schedule an appointment with your healthcare provider to remove the implant on or before the removal date.

Be sure to have checkups as advised by your healthcare provider.

What are the most common side effects I can expect while using Nexplanon?

• Changes in Menstrual Bleeding Patterns (menstrual periods)

The most common side effect of Nexplanon is a change in your normal menstrual bleeding pattern. In studies, one out of ten women stopped using the implant because of an unfavorable change in their bleeding pattern. You may experience longer or shorter bleeding during your periods or have no bleeding at all. The time between periods may vary, and in between periods you may also have spotting.

Tell your healthcare provider right away if:

· You think you may be pregnant

· Your menstrual bleeding is heavy and prolonged

Besides changes in menstrual bleeding patterns, other frequent side effects that caused women to stop using the implant include:

· Mood swings

· Weight gain

· Headache

· Acne

· Depressed mood

Other common side effects include:

· Headache

· Vaginitis (inflammation of the vagina)

· Weight gain

· Acne

· Breast pain

· Viral infections such as sore throats or flu-like symptoms

· Stomach pain

· Painful periods

· Mood swings, nervousness, or depressed mood

· Back pain

· Nausea

· Dizziness

· Pain

· Pain at the site of insertion

Implants have been reported to be found in a blood vessel, including a blood vessel in the lung.

This is not a complete list of possible side effects. For more information, ask your healthcare provider for advice about any side effects that concern you. You may report side effects to the FDA at 1-800-FDA-1088.

What are the possible risks of using Nexplanon?

• Problems with Insertion and Removal

The implant may not be placed in your arm at all due to a failed insertion. If this happens, you may become pregnant. Immediately after insertion, and with help from your healthcare provider, you should be able to feel the implant under your skin. If you can't feel the implant, tell your healthcare provider.

Location and removal of the implant may be difficult or impossible because the implant is not where it should be. Special procedures, including surgery in the hospital, may be needed to remove the implant. If the implant is not removed, then the effects of Nexplanon will continue for a longer period of time.

Implants have been found in the pulmonary artery (a blood vessel in the lung). If the implant cannot be found in the arm, your healthcare professional may use x-rays or other imaging methods on the chest. If the implant is located in the chest, surgery may be needed.

Other problems related to insertion and removal are:

· Pain, irritation, swelling, or bruising at the insertion site

· Scarring, including a thick scar called a keloid around the insertion site

· Infection

· Scar tissue may form around the implant making it difficult to remove

· The implant may come out by itself. You may become pregnant if the implant comes out by itself. Use a back-up birth control method and call your healthcare provider right away if the implant comes out.

· The need for surgery in the hospital to remove the implant

· Injury to nerves or blood vessels in your arm

· The implant breaks making removal difficult

• Ectopic Pregnancy

If you become pregnant while using Nexplanon, you have a slightly higher chance that the pregnancy will be ectopic (occurring outside the womb) than do women who do not use birth control. Unusual vaginal bleeding or lower stomach (abdominal) pain may be a sign of ectopic pregnancy. Ectopic pregnancy is a medical emergency that often requires surgery. Ectopic pregnancies can cause serious internal bleeding, infertility, and even death. Call your healthcare provider right away if you think you are pregnant or have unexplained lower stomach (abdominal) pain.

• Ovarian Cysts

Cysts may develop on the ovaries and usually go away without treatment but sometimes surgery is needed to remove them.

• Breast Cancer

It is not known whether Nexplanon use changes a woman's risk for breast cancer. If you have breast cancer now, or have had it in the past, do not use Nexplanon because some breast cancers are sensitive to hormones.

• Serious Blood Clots

Nexplanon may increase your chance of serious blood clots, especially if you have other risk factors such as smoking. It is possible to die from a problem caused by a blood clot, such as a heart attack or a stroke.

Some examples of serious blood clots are blood clots in the:

· Legs (deep vein thrombosis)

· Lungs (pulmonary embolism)

· Brain (stroke)

· Heart (heart attack)

· Eyes (total or partial blindness)

The risk of serious blood clots is increased in women who smoke. If you smoke and want to use Nexplanon, you should quit. Your healthcare provider may be able to help.

Tell your healthcare provider at least 4 weeks before if you are going to have surgery or will need to be on bed rest. You have an increased chance of getting blood clots during surgery or bed rest.

• Other Risks

A few women who use birth control that contains hormones may get:

· High blood pressure

· Gallbladder problems

· Rare cancerous or noncancerous liver tumors

· Broken or Bent Implant
If you feel that the implant may have broken or bent while in your arm, contact your healthcare provider.

When should I call my healthcare provider?

Call your healthcare provider right away if you have:

· Pain in your lower leg that does not go away

· Severe chest pain or heaviness in the chest

· Sudden shortness of breath, sharp chest pain, or coughing blood

· Symptoms of a severe allergic reaction, such as swollen face, tongue or throat; trouble breathing or swallowing

· Sudden severe headache unlike your usual headaches

· Weakness or numbness in your arm, leg, or trouble speaking

· Sudden partial or complete blindness

· Yellowing of your skin or whites of your eyes, especially with fever, tiredness, loss of appetite, dark colored urine, or light colored bowel movements

· Severe pain, swelling, or tenderness in the lower stomach (abdomen)

· Lump in your breast

· Problems sleeping, lack of energy, tiredness, or you feel very sad

· Heavy menstrual bleeding

What if I become pregnant while using Nexplanon?

You should see your healthcare provider right away if you think that you may be pregnant. It is important to remove the implant and make sure that the pregnancy is not ectopic (occurring outside the womb). Based on experience with other hormonal contraceptives, Nexplanon is not likely to cause birth defects.

Can I use Nexplanon when I am breastfeeding?

If you are breastfeeding your child, you may use Nexplanon if 4 weeks have passed since you had your baby. A small amount of the hormone contained in Nexplanon passes into your breast milk. The health of breast-fed children whose mothers were using the implant has been studied up to 3 years of age in a small number of children. No effects on the growth and development of the children were seen. If you are breastfeeding and want to use Nexplanon, talk with your healthcare provider for more information.

Additional Information

This Patient Information leaflet contains important information about Nexplanon. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider for information about Nexplanon that is written for healthcare professionals. You may also call 1-877-467-5266 or visit www.Nexplanon-USA.com.

Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA

Manufactured by: N.V. Organon, Oss, The Netherlands, a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ 08889, USA

For patent information: www.merck.com/product/patent/home.html

Copyright © 2011-2017 Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc.
All rights reserved.

Revised: 05/2017

usppi-mk8415-iptx-1705r018

PRINCIPAL DISPLAY PANEL - 68 mg Carton

NDC 0052-0274-01
1 applicator containing 1 subdermal implant

Nexplanon®
(etonogestrel implant) 68 mg
Radiopaque
Subdermal Use Only

This product is intended to prevent pregnancy. It does not protect
against HIV infection (AIDS) and other sexually transmitted diseases.
Rx only

 

PRINCIPAL DISPLAY PANEL - 68 mg Implant Blister Pack Carton

NDC 0052-4330-01
1 applicator containing 1 subdermal implant

Nexplanon®
(etonogestrel implant) 68 mg
Radiopaque
Subdermal Use Only

This product is intended to prevent pregnancy. It does not protect
against HIV infection (AIDS) and other sexually transmitted diseases.
Rx only

 

Nexplanon etonogestrel implant

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0052-0274 Route of Administration SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength etonogestrel (etonogestrel) etonogestrel 68 mg

Inactive Ingredients Ingredient Name Strength barium sulfate 15 mg ethylene-vinyl acetate copolymer (15% vinyl acetate)   ethylene-vinyl acetate copolymer (28% vinyl acetate)

Product Characteristics Color WHITE (white/off-white) Score      Shape   Size   Flavor   Imprint Code   Contains

Packaging # Item Code Package Description   1 NDC:0052-0274-01 1 BLISTER PACK in 1 CARTON   1   1 IMPLANT in 1 BLISTER PACK   2 NDC:0052-0274-80 1 BLISTER PACK in 1 CARTON   2   1 IMPLANT in 1 BLISTER PACK

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021529 07/17/2006

Nexplanon etonogestrel implant

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0052-4330 Route of Administration SUBCUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength etonogestrel (etonogestrel) etonogestrel 68 mg

Inactive Ingredients Ingredient Name Strength barium sulfate 15 mg magnesium stearate 0.1 mg ethylene-vinyl acetate copolymer (15% vinyl acetate)   ethylene-vinyl acetate copolymer (28% vinyl acetate)

Product Characteristics Color WHITE (white/off-white) Score      Shape   Size   Flavor   Imprint Code   Contains

Packaging # Item Code Package Description   1 NDC:0052-4330-01 1 BLISTER PACK in 1 CARTON   1   1 IMPLANT in 1 BLISTER PACK

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA021529 09/27/2013

Labeler - Organon USA Inc. (078796541)

 

Organon USA Inc.