Novothyrox

Novothyrox说明

Novothyrox（左甲状腺素钠片，USP）含有合成的晶体L-3、3'，5,5'-四碘甲甲状腺素钠盐[左甲状腺素（T 4 ）钠]。合成的T 4与人类甲状腺产生的T 4相同。左甲状腺素（T 4 ）钠的化学式为C 15 H 10 I 4 NNaO 4 •H 2 O，分子量为798.86 g / mol（无水），结构式如下所示：

非活性成分

Novothyrox（左甲状腺素钠片，USP）含有以下非活性成分：玉米淀粉，交联羧甲基纤维素钠，明胶，乳糖一水合物和硬脂酸镁。 Novothyrox片剂的所有优势均针对对染料敏感的患者配制，不含任何颜色添加剂。

Novothyrox-临床药理学

甲状腺激素的合成和分泌受下丘脑-垂体-甲状腺轴的调节。下丘脑释放的促甲状腺激素释放激素（TRH）刺激垂体前叶分泌促甲状腺激素刺激激素TSH。 TSH，反过来，是用于合成和甲状腺激素，L-甲状腺素（T 4）和L碘甲状腺原氨酸（T 3）的分泌，由甲状腺的生理刺激。循环中的血清T 3和T 4水平对TRH和TSH分泌都有反馈作用。当血清T 3和T 4水平升高时，TRH和TSH分泌减少。当甲状腺激素水平降低时，TRH和TSH分泌增加。

甲状腺激素发挥其生理作用的机制尚不完全清楚，但据认为其主要作用是通过控制DNA转录和蛋白质合成发挥的。 T 3和T 4扩散到细胞核中并与附着在DNA上的甲状腺受体蛋白结合。这种激素核受体复合物激活基因转录和信使RNA和细胞质蛋白的合成。

甲状腺激素调节多种代谢过程，并在正常的生长和发育以及中枢神经系统和骨骼的正常成熟中起重要作用。甲状腺激素的代谢作用包括增强细胞呼吸作用和生热作用，以及蛋白质，碳水化合物和脂质的代谢。甲状腺激素的蛋白质合成代谢作用对于正常生长和发育至关重要。

甲状腺激素的生理作用主要由T 3产生，其中大部分（约80％）是由T 4通过在周围组织中脱碘而产生的。

左甲状腺素按患者反应的个体化剂量有效地替代或补充任何病因的甲状腺功能减退症，但亚急性甲状腺炎恢复期的短暂性甲状腺功能减退症除外。

左甲状腺素还可以有效地抑制垂体TSH分泌，从而治疗或预防各种类型的甲状腺甲状腺肿，包括甲状腺结节，桥本甲状腺炎，多结节性甲状腺肿，并作为辅助疗法治疗依赖于促甲状腺激素的高分化甲状腺癌（请参阅适应症和用法，注意事项以及剂量和管理）。

药代动力学

吸收性

胃肠道（GI）口服T 4的吸收范围为40％至80％。左旋甲状腺素的大部分剂量是从空肠和回肠吸收的。与相等剂量的口服左甲状腺素钠溶液相比，Novothyrox片的相对生物利用度约为99％。禁食可增加T 4的吸收，吸收不良综合征和某些食品（例如大豆婴儿配方食品）可降低T 4吸收。膳食纤维会降低T 4的生物利用度。吸收也可能随着年龄而减少。另外，许多药物和食物也会影响T 4的吸收（请参阅注意事项，药物相互作用和药物-食物相互作用）。

分配

循环甲状腺激素与血浆蛋白（包括甲状腺素结合球蛋白（TBG），甲状腺素结合前白蛋白（TBPA）和白蛋白（TBA））结合的血浆蛋白大于99％，它们的容量和亲和力随每种激素而变化。 TBG和TBPA对T 4的亲和力更高，部分说明了与T 3相比，T 4的血清水平更高，代谢清除率更低，半衰期更长。结合蛋白质的甲状腺激素与少量的游离激素反向平衡存在。仅未结合的激素具有代谢活性。许多药物和生理条件会影响甲状腺激素与血清蛋白的结合（请参阅预防措施，药物相互作用和药物实验室测试相互作用）。甲状腺激素不易穿过胎盘屏障（请参阅预防措施，怀孕）。

代谢

T 4被缓慢消除（见表1 ）。甲状腺激素代谢的主要途径是通过顺序碘化作用。循环的T 3的大约百分之八十是通过单碘化作用从外周T 4衍生而来的。肝脏是T 4和T 3降解的主要部位，T 4碘化作用也发生在许多其他部位，包括肾脏和其他组织。每天将约80％的T 4脱碘，以产生等量的T 3和反向T 3 （rT 3 ）。 T 3和rT 3进一步被去碘化为二碘甲甲状腺素。甲状腺激素也可通过与葡萄糖醛酸苷和硫酸盐结合而代谢，并直接排入胆汁和肠道，并在那里进行肠肝循环。

消除

甲状腺激素主要由肾脏消除。一部分结合激素未改变地到达结肠，并在粪便中被清除。粪便中消除了大约20％的T 4 。 T 4的尿排泄随着年龄的增长而减少。

Novothyrox的适应症和用法

左甲状腺素钠用于以下适应症：

甲状腺功能减退

作为先天性或获得性甲状腺功能减退症的任何病因的替代或补充治疗，但亚急性甲状腺炎恢复期的短暂性甲状腺功能减退除外。具体适应症包括：原发性（甲状腺），继发性（垂体）和三级（下丘脑）甲状腺功能减退和亚临床甲状腺功能减退。原发性甲状腺功能减退症可能是由于甲状腺功能低下，原发性萎缩，部分或全部先天性甲状腺功能不全或手术，放疗或药物的影响（有或没有甲状腺肿）引起的。

垂体促甲状腺激素抑制

在治疗或预防各种类型的甲状腺甲状腺肿（请参阅“警告和注意事项” ），包括甲状腺结节（请参阅“警告和注意事项” ），亚急性或慢性淋巴细胞性甲状腺炎（桥本甲状腺炎），多结节性甲状腺肿（请参阅“警告和注意事项” ）以及在甲状腺素依赖性高分化甲状腺癌的治疗中辅以手术和放射碘治疗。

禁忌症

在任何病因下未治疗的亚临床患者（血清TSH水平降低，T 3和T 4水平正常）或明显的甲状腺毒症和急性心肌梗死患者均禁用左甲状腺素。肾上腺皮质功能不全的患者禁用左甲状腺素，因为甲状腺激素可通过增加糖皮质激素的代谢清除率而引发急性肾上腺危机（请参阅注意事项）。 Novothyrox对Novothyrox片剂中的任何非活性成分过敏的患者禁用。 （请参阅说明，非活性成分。 ）

警告事项

左甲状腺素钠不应用于治疗男性或女性不育症，除非这种情况与甲状腺功能减退有关。

患者无毒的弥漫性甲状腺肿或结节性甲状腺疾病，尤其是老年人或患有心血管疾病底层，治疗左甲状腺素钠如果血清TSH水平已经抑制由于沉淀明显甲状腺毒症（见禁忌）的风险禁忌的。如果血清TSH水平没有被抑制，则应谨慎使用Novothyrox，同时仔细监测甲状腺功能以发现甲亢，并临床监测潜在的不良心血管症状和甲亢症状。

预防措施

一般

左甲状腺素具有狭窄的治疗指数。无论使用何种指示，都必须小心地进行剂量滴定，以免过度或治疗不足的后果。这些后果包括对生长和发育，心血管功能，骨骼代谢，生殖功能，认知功能，情绪状态，胃肠功能以及对葡萄糖和脂质代谢的影响。许多药物与左甲状腺素钠相互作用，因此必须调整剂量以维持治疗反应（请参阅药物相互作用）。

对骨矿物质密度的影响

在女性中，长期使用左甲状腺素钠治疗与骨吸收增加有关，从而降低了骨矿物质密度，尤其是在绝经后妇女使用大于补充剂量的妇女或正在接受抑制剂量的左甲状腺素钠的妇女。骨吸收增加可能与血清水平升高和尿中钙和磷排泄，骨碱性磷酸酶升高和血清甲状旁腺激素水平降低有关。因此，建议接受左甲状腺素钠的患者获得达到所需临床和生化反应所需的最小剂量。

基础心血管疾病患者

向患有心血管疾病的患者和患有隐匿性心脏病的风险增加的老年人服用左甲状腺素时要格外小心。在这些患者中，左甲状腺素治疗应以较低的剂量比年轻个体或患者无心脏病建议启动（见警告，注意事项，老年用药和剂量和用法）。如果心脏症状出现或恶化，应降低或停用左甲状腺素剂量一周，然后谨慎地以较低剂量重新开始。过度使用左甲状腺素钠可能会对心血管产生不良影响，例如心率，心脏壁厚和心脏收缩力增加，并可能导致心绞痛或心律不齐。接受左甲状腺素治疗的冠心病患者应在手术过程中密切监测，因为使用左甲状腺素治疗的患者发生心律不齐的可能性更大。对冠心病患者并用左甲状腺素和拟交感神经药可能会加重冠状动脉供血不足。

无毒弥漫性甲状腺肿或结节性甲状腺疾病的患者

对无毒性弥漫性甲状腺肿或结节性甲状腺疾病的患者服用左甲状腺素时，要小心，以防止甲状腺中毒的沉淀（请参阅警告）。如果血清TSH已被抑制，则不应服用左甲状腺素钠（请参阅禁忌症）。

相关内分泌疾病

下丘脑/垂体激素缺乏症

在继发性或三级甲状腺功能减退症的患者中，应考虑其他下丘脑/垂体激素缺乏症，如果确诊，应予以治疗（有关肾上腺功能不全的预防措施，自体免疫性腺体综合征）。

自主多腺综合征

有时，慢性自身免疫性甲状腺炎可能与其他自身免疫性疾病（如肾上腺功能不全，恶性贫血和胰岛素依赖型糖尿病）有关。伴有肾上腺功能不全的患者应在开始用左甲状腺素钠治疗之前用替代糖皮质激素治疗。否则，开始甲状腺激素治疗可能会导致急性肾上腺危机，因为甲状腺激素会增加糖皮质激素的代谢清除率。糖尿病患者使用左甲状腺素治疗时可能需要向上调整其抗糖尿病治疗方案（请参阅注意事项，药物相互作用）。

其他相关医疗状况

先天性甲状腺功能减退的婴儿患其他先天性异常的风险似乎增加，最常见的关联是心血管异常（肺部狭窄，房间隔缺损和室间隔缺损）。

给患者的信息

应告知患者以下信息，以帮助安全有效地使用诺维昔洛：

1.如果您对任何食物或药物过敏，怀孕或打算怀孕，正在哺乳或正在服用其他药物（包括处方药和非处方药），请通知医生。

2.通知医生您可能会遇到的任何其他疾病，特别是心脏病，糖尿病，凝血障碍以及肾上腺或垂体疾病。服用Novothyrox时可能需要调整用于控制其他疾病的药物剂量。如果您患有糖尿病，请按照医生的指示监测血液和/或尿液中的葡萄糖水平，并立即向医生报告任何变化。如果您服用抗凝剂（血液稀释剂），则应经常检查凝血状态。

3.仅按照医生的指示使用诺维昔罗。请勿中断或更改服用量或服用频率，除非您的医生指示这样做。

4. Novothyrox中的左甲状腺素旨在替代甲状腺中通常产生的激素。一般而言，除非短暂性甲状腺功能低下通常与甲状腺炎（甲状腺炎）有关，否则应终身接受替代疗法。

5.早餐前半小时至一小时，以单剂量Novothyrox服用，最好空腹服用。空腹时左甲状腺素吸收增加。

6.您可能需要数周的时间才能发现症状改善。

7.如果您遇到以下任何症状，请通知医生：快速或不规则的心跳，胸痛，呼吸急促，腿抽筋，头痛，神经质，烦躁，失眠，震颤，食欲变化，体重增加或减轻，呕吐，腹泻，出汗过多，不耐高温，发烧，经期变化，荨麻疹或皮疹或任何其他不寻常的医疗事件。

8.如果您在服用Novothyrox时怀孕，请通知您的医生。在您怀孕期间，可能需要增加Novothyrox的剂量。

9.在进行任何手术之前，请通知您的医生或牙医您正在服用Novothyrox。

10.在Novothyrox治疗的最初几个月中，很少会出现部分脱发，但这通常是暂时的。

11. Novothyrox不应在体重控制程序中用作主要或辅助治疗。

12. Novothyrox放在儿童接触不到的地方。将Novothyrox存放在远离热，湿气和光线的地方。

13.铁和钙补充剂和抗酸剂等药物可降低左甲状腺素片的吸收。因此，左旋甲状腺素钠片不应在这些药物的4小时内服用。

14.致电您的医生，寻求有关副作用的医疗建议。您可以通过1-800-FDA-1088向FDA报告副作用。

实验室测试

一般

甲状腺功能减退症的诊断通过使用敏感性测定（第二代测定灵敏度≤0.1 mIU / L或第三代测定灵敏度≤0.01 mIU / L）和游离T 4的测定来测定TSH水平来证实。

治疗的适当性通过定期评估适当的实验室检查和临床评估来确定。实验室检查的选择取决于多种因素，包括潜在的甲状腺疾病的病因，伴随的医疗状况（包括怀孕）的存在以及是否使用伴随的药物（请参阅“预防措施” ，“药物相互作用”和“药物-实验室试验相互作用” ）。尽管有足够的补充剂量的诺维罗司，但仍存在持续的甲状腺功能减退的临床和实验室证据，可能是药物吸收不足，依从性差，药物相互作用或药物T 4效力降低的证据。

成年人

在患有原发性（甲状腺）甲状腺功能减退症的成年患者中，仅血清TSH水平（使用敏感测定法）可用于监测治疗。乙酰甲状腺素剂量滴定期间监测TSH的频率取决于临床情况，但通常建议间隔6-8周直至恢复正常。对于刚开始使用左甲状腺素治疗且血清TSH已恢复正常的患者，或已改变左甲状腺素剂量的患者，应在8-12周后测量血清TSH浓度。当达到最佳替代剂量时，可根据临床情况以及每当患者状况发生变化时，每6-12个月进行一次临床（体格检查）和生化监测。建议接受Novothyrox的患者至少每年进行一次体格检查和血清TSH测定（请参阅“警告，注意事项以及剂量和给药方法”）。

儿科

对于先天性甲状腺功能减退的患者，应通过测量血清TSH（使用敏感测定）和总T或游离T 4来评估替代疗法的适当性。在生命的头三年中，血清总T或游离T 4应始终保持在正常范围的上半部分。尽管治疗的目的还在于使血清TSH水平正常化，但在少数患者中，尤其是在治疗的最初几个月中，这并不总是可能的。由于子宫内甲状腺功能减退症导致垂体-甲状腺反馈阈值的重新设置，TSH可能无法正常化。在开始诺维昔罗治疗后2周内血清T 4未能增加至正常范围的上半部和/或在4周内血清TSH未能降至20 mU / L以下应提醒医师注意以下可能性：孩子没有得到足够的治疗。然后应在增加Novothyrox剂量之前仔细询问依从性，给药剂量以及给药方法。

推荐的监测儿童TSH和总T-或游离T 4的频率如下：开始治疗后2周和4周；人生第一年每1-2个月一次； 1-3岁之间每2-3个月一次；之后每3到12个月，直到增长完成。如果怀疑合规性差或获得异常值，则可能需要更频繁的监视间隔。建议在Novothyrox剂量发生任何变化后2周进行TSH和T 4水平，并进行体格检查（如果指示）。应当定期进行常规临床检查，包括评估精神和身体的生长和发育以及骨骼的成熟度（请参见预防措施，儿科使用以及剂量和管理）。

中学（垂体）和高等教育（下丘脑）甲状腺功能减退症

应通过测量血清游离T 4水平来评估治疗的适当性，这些患者的血清游离T 4水平应保持在正常范围的上半部分。

药物相互作用

许多药物会影响甲状腺激素的药代动力学和新陈代谢（例如吸收，合成，分泌，分解代谢，蛋白质结合和靶组织反应），并可能改变对Novothyrox的治疗反应。此外，甲状腺激素和甲状腺状态对其他药物的药代动力学和作用也有不同的影响。表2列出了药物-甲状腺轴相互作用。

由于引入了与甲状腺轴相互作用的新药物或发现了以前未知的相互作用，表2中的药物-甲状腺轴相互作用列表可能并不完整。如果怀疑与左甲状腺素发生药物相互作用，则开药者应了解这一事实，并应咨询适当的参考资料（例如，新批准药物的包装插页，医学文献）以获取更多信息。

口服抗肿瘤药

左甲状腺素增加对口服抗凝治疗的反应。因此，可以通过纠正甲状腺功能减退状态或增加Novothyrox剂量来降低抗凝剂的剂量。应密切监测凝血酶原时间，以允许适当及时地调整剂量（见表2 ）。

DIGITALIS糖苷

左甲状腺素可能会降低洋地黄苷的治疗作用。当甲状腺机能减退的患者变得甲状腺功能正常时，血清洋地黄苷的水平可能会降低，因此有必要增加洋地黄苷的剂量（见表2 ）。

药物-食物相互作用

食用某些食物可能会影响左甲状腺素的吸收，因此需要调整剂量。大豆粉（婴儿配方食品），棉籽粉，核桃和膳食纤维可能会束缚并减少胃肠道中左甲状腺素钠的吸收。

药物实验室测试的相互作用

解释T 4和T 3值时，必须考虑TBG浓度的变化，这需要测量和评估未结合（游离）激素和/或确定游离T 4指数（FT 4 I）。怀孕，传染性肝炎，雌激素，含雌激素的口服避孕药和急性间歇性卟啉症可增加TBG浓度。在肾病，严重的低蛋白血症，严重的肝病，肢端肥大症以及雄激素或皮质类固醇治疗后，TBG浓度降低（参见表2 ）。已经描述了家族性高甲状腺素或低甲状腺素结合球蛋白血症，TBG缺乏症的发生率约为9000分之一。

致癌，诱变和生育能力受损

Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of levothyroxine. The synthetic T 4 in Novothyrox is identical to that produced naturally by the human thyroid gland. Although there has been a reported association between prolonged thyroid hormone therapy and breast cancer, this has not been confirmed. Patients receiving Novothyrox for appropriate clinical indications should be titrated to the lowest effective replacement dose.

Pregnancy-Category A

Studies in women taking levothyroxine sodium during pregnancy have not shown an increased risk of congenital abnormalities. Therefore, the possibility of fetal harm appears remote. Novothyrox should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.

Hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, pre-eclampsia, stillbirth and premature delivery. Maternal hypothyroidism may have an adverse effect on fetal and childhood growth and development. During pregnancy, serum T 4 levels may decrease and serum TSH levels increase to values outside the normal range. Since elevations in serum TSH may occur as early as 4 weeks gestation, pregnant women taking Novothyrox should have their TSH measured during each trimester. An elevated serum TSH level should be corrected by an increase in the dose of Novothyrox. Since postpartum TSH levels are similar to preconception values, the Novothyrox dosage should return to the pre-pregnancy dose immediately after delivery. A serum TSH level should be obtained 6-8 weeks postpartum.

Thyroid hormones cross the placental barrier to some extent as evidenced by levels in cord blood of athyreotic fetuses being approximately one-third maternal levels. Transfer of thyroid hormone from the mother to the fetus, however, may not be adequate to prevent in utero hypothyroidism.

护理母亲

Although thyroid hormones are excreted only minimally in human milk, caution should be exercised when Novothyrox is administered to a nursing woman. However, adequate replacement doses of levothyroxine are generally needed to maintain normal lactation.

儿科用

GENERAL

The goal of treatment in pediatric patients with hypothyroidism is to achieve and maintain normal intellectual and physical growth and development.

The initial dose of levothyroxine varies with age and body weight (see DOSAGE AND ADMINISTRATION , Table 3 ). Dosing adjustments are based on an assessment of the individual patient's clinical and laboratory parameters (see PRECAUTIONS , Laboratory Tests) .

In children in whom a diagnosis of permanent hypothyroidism has not been established, it is recommended that levothyroxine administration be discontinued for a 30-day trial period, but only after the child is at least 3 years of age. Serum T 4 and TSH levels should then be obtained. If the T 4 is low and the TSH high, the diagnosis of permanent hypothyroidism is established, and levothyroxine therapy should be reinstituted. If the T 4 and TSH levels are normal, euthyroidism may be assumed and, therefore, the hypothyroidism can be considered to have been transient. In this instance, however, the physician should carefully monitor the child and repeat the thyroid function tests if any signs or symptoms of hypothyroidism develop. In this setting, the clinician should have a high index of suspicion of relapse. If the results of the levothyroxine withdrawal test are inconclusive, careful follow-up and subsequent testing will be necessary.

Since some more severely affected children may become clinically hypothyroid when treatment is discontinued for 30 days, an alternate approach is to reduce the replacement dose of levothyroxine by half during the 30-day trial period. If, after 30 days, the serum TSH is elevated above 20 mU/L, the diagnosis of permanent hypothyroidism is confirmed, and full replacement therapy should be resumed. However, if the serum TSH has not risen to greater than 20 mU/L, levothyroxine treatment should be discontinued for another 30-day trial period followed by repeat serum T 4 and TSH testing.

The presence of concomitant medical conditions should be considered in certain clinical circumstances and, if present, appropriately treated (see PRECAUTIONS ).

CONGENITAL HYPOTHYROIDISM (see PRECAUTIONS , Laboratory Tests and DOSAGE AND ADMINISTRATION )

Rapid restoration of normal serum T 4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism on intellectual development as well as on overall physical growth and maturation. Therefore, Novothyrox therapy should be initiated immediately upon diagnosis and is generally continued for life.

During the first 2 weeks of Novothyrox therapy, infants should be closely monitored for cardiac overload, arrhythmias, and aspiration from avid suckling.

The patient should be monitored closely to avoid undertreatment or overtreatment. Undertreatment may have deleterious effects on intellectual development and linear growth. Overtreatment has been associated with craniosynostosis in infants, and may adversely affect the tempo of brain maturation and accelerate the bone age, with resultant premature closure of the epiphyses and compromised adult stature.

ACQUIRED HYPOTHYROIDISM IN PEDIATRIC PATIENTS

The patient should be monitored closely to avoid undertreatment and overtreatment. Undertreatment may result in poor school performance due to impaired concentration and slowed mentation and in reduced adult height. Overtreatment may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature.

Treated children may manifest a period of catch-up growth, which may be adequate in some cases to normalize adult height. In children with severe or prolonged hypothyroidism, catch-up growth may not be adequate to normalize adult height.

老人用

Because of the increased prevalence of cardiovascular disease among the elderly, levothyroxine therapy should not be initiated at the full replacement dose (see WARNINGS, PRECAUTIONS , and DOSAGE AND ADMINISTRATION ).

不良反应

Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage (see PRECAUTIONS and OVERDOSAGE ). They include the following:

General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating;

Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia;

Musculoskeletal: tremors, muscle weakness;

Cardiovascular: palpitations, tachycardia, arrythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest;

Respiratory: dyspnea;

Gastrointestinal: diarrhea, vomiting, abdominal cramps and elevations in liver function tests;

Dermatologic: hair loss, flushing;

Endocrine: decreased bone mineral density;

Reproductive: menstrual irregularities, impaired fertility.

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in children with resultant compromised adult height.

Seizures have been reported rarely with the institution of levothyroxine therapy.

Inadequate levothyroxine dosage will produce or fail to ameliorate the signs and symptoms of hypothyroidism.

Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

过量

The signs and symptoms of overdosage are those of hyperthyroidism (see PRECAUTIONS and ADVERSE REACTIONS ). In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures have occurred in a child ingesting approximately 18 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.

药物过量的治疗

Levothyroxine sodium should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur.

Acute Massive Overdosage

This may be a life-threatening emergency, therefore, symptomatic and supportive therapy should be instituted immediately. If not contraindicated (eg, by seizures, coma, or loss of the gag reflex), the stomach should be emptied by emesis or gastric lavage to decrease gastrointestinal absorption. Activated charcoal or cholestyramine may also be used to decrease absorption. Central and peripheral increased sympathetic activity may be treated by administering β-receptor antagonists, eg, propranolol, provided that there are no medical contraindications to their use. Provide respiratory support as needed; control congestive heart failure and arrhythmia; control fever, hypoglycemia, and fluid loss as necessary. Large doses of antithyroid drugs (eg, methimazole or propylthiouracil) followed in one to two hours by large doses of iodine may be given to inhibit synthesis and release of thyroid hormones. Glucocorticoids may be given to inhibit the conversion of T 4 to T 3 . Plasmapheresis, charcoal hemoperfusion and exchange transfusion have been reserved for cases in which continued clinical deterioration occurs despite conventional therapy. Because T 4 is highly protein bound, very little drug will be removed by dialysis.

Novothyrox Dosage and Administration

General Principles

The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of Novothyrox that is adequate to achieve these goals depends on a variety of factors including the patient's age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated (see WARNINGS and PRECAUTIONS ). Hence, the following recommendations serve only as dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters (see PRECAUTIONS , Laboratory Tests ).

Novothyrox is administered as a single daily dose, preferably one-half to one hour before breakfast. Novothyrox should be taken at least 4 hours apart from drugs that are known to interfere with its absorption (see PRECAUTIONS , Drug Interactions ).

Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not be attained for 4-6 weeks.

Caution should be exercised when administering Novothyrox to patients with underlying cardiovascular disease, to the elderly, and to those with concomitant adrenal insufficiency (see PRECAUTIONS ).

特定患者人群

HYPOTHYROIDISM IN ADULTS AND IN CHILDREN IN WHOM GROWTH AND PUBERTY ARE COMPLETE (see WARNINGS and PRECAUTIONS, Laboratory Tests )

Therapy may begin at full replacement doses in otherwise healthy individuals less than 50 years old and in those older than 50 years who have been recently treated for hyperthyroidism or who have been hypothyroid for only a short time (such as a few months). The average full replacement dose of levothyroxine sodium is approximately 1.7 mcg/kg/day (eg, 100-125 mcg/day for a 70 kg adult). Older patients may require less than 1 mcg/kg/day. Levothyroxine doses greater than 200 mcg/day are seldom required. An inadequate response to daily doses ≥ 300 mcg/day is rare and may indicate poor compliance, malabsorption, and/or drug interactions.

For most patients older than 50 years or for patients under 50 years of age with underlying cardiac disease, an initial starting dose of 25-50 mcg/day of levothyroxine sodium is recommended, with gradual increments in dose at 6-8 week intervals, as needed. The recommended starting dose of levothyroxine sodium in elderly patients with cardiac disease is 12.5-25 mcg/day , with gradual dose increments at 4-6 week intervals. The levothyroxine sodium dose is generally adjusted in 12.5-25 mcg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized.

In patients with severe hypothyroidism, the recommended initial levothyroxine sodium dose is 12.5-25 mcg/day with increases of 25 mcg/day every 2-4 weeks, accompanied by clinical and laboratory assessment, until the TSH level is normalized.

In patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism, the levothyroxine sodium dose should be titrated until the patient is clinically euthyroid and the serum free-T 4 level is restored to the upper half of the normal range.

PEDIATRIC DOSAGE – CONGENITAL OR ACQUIRED HYPOTHYROIDISM (see PRECAUTIONS , Laboratory Tests )

General Principles

In general, levothyroxine therapy should be instituted at full replacement doses as soon as possible. Delays in diagnosis and institution of therapy may have deleterious effects on the child's intellectual and physical growth and development.

Undertreatment and overtreatment should be avoided (see PRECAUTIONS , Pediatric Use ).

Novothyrox may be administered to infants and children who cannot swallow intact tablets by crushing the tablet and suspending the freshly crushed tablet in a small amount (5-10 mL or 1-2 teaspoons) of water. This suspension can be administered by spoon or dropper. DO NOT STORE THE SUSPENSION . Foods that decrease absorption of levothyroxine, such as soybean infant formula, should not be used for administering levothyroxine sodium tablets (see PRECAUTIONS , Drug-Food Interactions ).

Newborns

The recommended starting dose of levothyroxine sodium in newborn infants is 10-15 mcg/kg/day . A lower starting dose (eg, 25 mcg/day) should be considered in infants at risk for cardiac failure, and the dose should be increased in 4-6 weeks as needed based on clinical and laboratory response to treatment. In infants with very low (< 5 mcg/dL) or undetectable serum T 4 concentrations, the recommended initial starting dose is 50 mcg/day of levothyroxine sodium.

Infants and Children

Levothyroxine therapy is usually initiated at full replacement doses, with the recommended dose per body weight decreasing with age (see Table 3 ). However, in children with chronic or severe hypothyroidism, an initial dose of 25 mcg/day of levothyroxine sodium is recommended with increments of 25 mcg every 2-4 weeks until the desired effect is achieved.

Hyperactivity in an older child can be minimized if the starting dose is one-fourth of the recommended full replacement dose, and the dose is then increased on a weekly basis by an amount equal to one-fourth the full-recommended replacement dose until the full recommended replacement dose is reached.

注意：本文档包含有关左甲状腺素的副作用信息。此页面上列出的某些剂型可能不适用于品牌名称Novothyrox。

对于消费者

适用于左甲状腺素：口服胶囊填充液，口服液，口服片剂

其他剂型：

• 溶液注射粉

需要立即就医的副作用

除了需要的作用外，左甲状腺素（Novothyrox中所含的活性成分）可能会引起一些不良作用。尽管并非所有这些副作用都可能发生，但如果确实发生了，则可能需要医疗护理。

服用左甲状腺素时，如果有下列任何副作用，请立即与医生联系：

不常见

• 胸痛或不适
• 尿量减少
• 呼吸困难或劳累
• 吞咽困难
• 颈静脉扩张
• 极度疲劳
• 晕倒
• 快，慢，不规则，剧烈或心跳或脉搏加快
• 发热
• 不耐高温
• 荨麻疹或伤口，皮肤瘙痒，皮疹或发红
• 不规则的呼吸
• 易怒
• 月经变化
• 恶心
• 手臂，下颌，背部或颈部疼痛或不适
• 出汗
• 眼睛，脸，嘴唇，喉咙或舌头肿胀
• 胸闷
• 震颤

罕见

• 视力模糊或复视
• 头晕
• 眼痛
• 儿童缺乏或发育缓慢
• one脚或走路有利于一条腿
• 臀部或膝盖疼痛
• 癫痫发作
• 严重头痛

如果在服用左甲状腺素时出现以下任何过量症状，请立即寻求紧急帮助：

服用过量的症状

• 意识改变
• 寒冷，湿滑的皮肤
• 混乱
• 迷失方向
• 快或弱脉冲
• 头昏眼花
• 意识丧失
• 突然头痛
• 突然失去协调
• 突然的口齿不清

不需要立即就医的副作用

左甲状腺素的一些副作用可能会发生，通常不需要医疗。随着身体对药物的适应，这些副作用可能会在治疗期间消失。另外，您的医疗保健专业人员可能会告诉您一些预防或减少这些副作用的方法。

请咨询您的医疗保健专业人员，是否持续存在以下不良反应或令人讨厌，或者是否对这些副作用有任何疑问：

不常见

• 腹部或腹部绞痛
• 食欲变化
• 哭了
• 腹泻
• 错误或异常的幸福感
• 恐惧或紧张
• 感觉不舒服或不开心
• 不适感
• 温暖的感觉
• 感觉事情不真实
• 怀疑和不信任的感觉
• 脱发
• 头痛
• 食欲增加
• 精神抑郁
• 肌肉无力
• 情绪上反应迅速或反应过度
• 快速变化的心情
• 脸部，脖子，手臂发红，偶尔上胸部发红
• 躁动
• 怀孕有麻烦
• 坐着不动
• 异常疲倦或虚弱
• 呕吐
• 体重增加或减少

对于医疗保健专业人员

适用于左甲状腺素：复方散，注射用散剂，注射用静脉散剂，静脉内溶液剂，口服胶囊剂，口服溶液剂，口服片剂

一般

较常见的不良反应包括由于治疗过量而导致的甲亢，包括心律不齐，心肌梗塞，呼吸困难，肌肉痉挛，头痛，神经质，烦躁，失眠，震颤，肌肉无力，食欲增加，体重减轻，腹泻，不耐热，月经不调和皮疹。

心血管的

在20名年龄和性别相符的对照组中，评估了20例因甲状腺肿大或甲状腺切除术后需要TSH抑制的患者的心脏功能，并对甲状腺癌进行了放射性碘治疗。 TSH抑制与室性早搏发生率增加，左心室质量指数增加和左心室收缩功能增强有关。这些变化的临床意义尚待确定。

用这种药物过度治疗可能会导致心率，心脏壁厚度和心脏收缩力增加，并可能导致心绞痛或心律不齐，特别是在患有心血管疾病的患者和老年患者中。 ^[参考]

未报告频率：心Pal，心动过速，高血压，心律不齐，脉搏和血压升高，心力衰竭，心绞痛，心肌梗塞，心脏骤停^[参考]

内分泌

未报告频率：糖尿病和肾上腺皮质功能不全的症状表现改变^[参考]

神经系统

未报告的频率：头痛，活动过度，失眠，癫痫发作，假性脑瘤（儿童） ^[参考]

皮肤科

未报告频率：脱发，潮红，荨麻疹，瘙痒，皮疹，血管性水肿，出汗过多^[参考]

肌肉骨骼

未报告的频率：震颤，肌肉无力，肌肉抽筋，骨质疏松症的风险增加，股骨骨epi滑倒（儿童） ^[参考]

一项研究评估了长期甲状腺激素治疗对196名女性（平均年龄，74.4岁）与795名女性（平均年龄，72.1岁）的对照组骨密度的影响。每日平均甲状腺素剂量为1.99 mcg / kg（范围0.3至6.6 mcg / kg），平均治疗时间为20.4年（范围小于1至68年）。与对照组相比，每日服用1.6 mcg / kg或更多剂量的妇女在超dist，中轴radius，臀部和腰椎的骨矿物质密度水平明显降低。但是，使用雌激素似乎可以消除甲状腺激素对骨矿物质密度的不利影响。

从英国普通实践研究数据库对23183名患者进行了处方甲状腺激素的病例对照分析后，发现长期接受长期甲状腺激素治疗的男性（p = 0.008）的股骨骨折发生率高于对照组。

过度治疗可能会导致婴儿颅骨融合症，并导致儿童骨phy过早闭合，从而导致成人身高受损。 ^[参考]

胃肠道

未报告频率：腹泻，呕吐，腹部绞痛^[参考]

泌尿生殖

未报告频率：月经不调，生育能力受损^[参考]

过敏症

未报告频率：血清病，对非活性成分过敏^[参考]

发生超敏反应；然而，这归因于无活性成分。这些反应包括荨麻疹，瘙痒，皮疹，潮红，血管性水肿，各种胃肠道症状（腹痛，恶心，呕吐和腹泻），发烧，关节痛，血清病和喘息。尚不清楚对左甲状腺素本身过敏。 ^[参考]

新陈代谢

未报告频率：食欲增加，体重减轻^[参考]

免疫学的

未报告频率：自身免疫性疾病（例如慢性自身免疫性甲状腺炎） ^[参考]

其他

未报告频率：疲劳，不耐高温，发烧^[参考]

精神科

未报告的频率：神经质，焦虑，烦躁，情绪不稳^[参考]

某些副作用可能没有报道。您可以将其报告给FDA。