药品名称:
通用名称：甲巯咪唑片
英文名称：Thyrozol(Thiamazole Tablets)
成分:甲巯咪唑
适应症:● 甲状腺功能亢进症的药物治疗，尤其适用于不伴有或伴有轻度甲状腺增大（甲状腺肿）的患者及年轻患者。
● 用于各种类型的甲状腺功能亢进症的手术前准备。
● 甲状腺功能亢进症患者拟采用放射性碘治疗时的准备用药，以预防治疗后甲状腺毒性危象的发生。
● 放射碘治疗后间歇期的治疗。
● 在个别的情况下，因患者一般状况或个人原因不能采用常规的治疗措施，或因患者拒绝接受常规的治疗措施时，由于对甲巯咪唑片剂（在尽可能低的剂量）耐受性良好，可用于甲状腺功能亢进症的长期治疗。
 ● 对于必须使用碘照射（如使用含碘造影剂检查）的有甲状腺功能亢进病史的患者和功能自主性甲状腺瘤患者作为预防性用药。
用法用量:通常服用本品可在餐后用适量液体（如半杯水）整片送服。
● 甲状腺功能亢进症的药物治疗（保守治疗）：
治疗初期，根据疾病的严重程度，甲巯咪唑的服用剂量为每天20mg-40mg（以甲巯咪唑计）（初始治疗），每天1次或每天2次（每天总剂量相同）。如果在治疗后的第2周到第6周病情得到改善，医生可以按照需要逐步调整剂量。之后1到2年内的服药剂量为每天2.5mg-10mg（以甲巯咪唑计）；该剂量推荐每天1次在早餐后服用，如需要可与甲状腺激素同服。病情严重的患者，尤其是摄入碘引起甲状腺功能亢进症的患者，剂量可以适当增加。在甲状腺功能亢进症的保守治疗中，甲巯咪唑片剂通常疗程为6个月至2年（平均1年）。从统计学看，延长疗程可使缓解率增加。
 ● 用于各种类型的甲状腺功能亢进症的术前准备：
如上文所述，采用相同的治疗原则。
在手术前的最后10天，外科医生可能加用碘剂以使甲状腺组织固定。
当甲状腺功能亢进症患者进行外科手术的准备，使用本品治疗可在择期手术前3-4个星期开始（个别病例可能需更早），在手术前一天停药。
● 放射性碘治疗前的用药：
如上文所述，由医生决定本品的使用剂量和疗程。
● 在放射性碘治疗后，用于间歇期治疗：
由医生决定本品的使用剂量和疗程。
● 长期的抗甲状腺治疗，用于疾病不能缓解，而常规的治疗措施不能被采用或被患者拒绝时：
给予尽可能低剂量的甲巯咪唑，通常每天使用本品2.5-10mg（以甲巯咪唑计），同时合用或不合用少量的甲状腺激素。
● 对于必须使用含碘制剂进行诊断（如造影剂）的患者，为预防发生甲状腺功能亢进症时的用药：
使用含碘制剂前，按医嘱使用本品每天10-20mg（以甲巯咪唑计），和每天1g高氯酸盐，周期8-10天（如经肾排的造影剂）。
有功能自主性腺瘤或有潜在甲状腺功能亢进症的患者，如必须使用碘制剂时，需按照碘制剂在体内停留的时间决定本品的使用疗程。
另外，对于甲状腺显著肿大并且气管狭窄的患者，只能使用本品进行短期治疗，由于其长期治疗甲状腺会进一步肿大，
从而导致呼吸道更加狭窄。治疗过程中应全程监测，并且最好同时合用甲状腺素。
或遵医嘱。
禁忌:赛治严禁用于以下患者中：对甲巯咪唑、其它硫酰胺衍生物或任何赋形剂过敏：中到重度血细胞计数紊乱（中性粒细胞减少）；既存的并非由甲状腺功能亢进症导致的胆汁淤积；在接受甲巯咪唑或卡比马唑治疗后，曾出现骨髓损害。 <br/>在妊娠期间，禁忌应用甲巯咪唑与甲状腺激素联合治疗。
注意事项:赛治不应用于以下患者中：具有轻微超敏反应病史的患者（比如，过敏性皮疹、搔痒症）。
在以下患者中，甲巯咪唑仅能在严密监测下用作短期治疗
气管受压的大甲状腺肿患者，因为具有使甲状腺肿生长的危险。
据报告大约0.3%-0.6%的病例发生了粒细胞缺乏症，因此在开始治疗前，应提醒患者注意粒细胞缺乏症的症状（口腔炎、咽炎、发热）。这通常发生在治疗的最初几周，但也可能在治疗开始后数月以及再次治疗时出现。在治疗开始之前和之后，特别是在以前发生过轻度粒细胞减少的病例中，推荐对血细胞计数进行严密监测。如果观察到任何这些症状，特别是在治疗的最初几周，应该建议患者与其医生取得联系，立即进行血细胞计数。如果确诊为粒细胞缺乏症，那么必须停药。在推荐剂量下，其它骨髓毒性不良反应是罕见的。通常是在应用非常高剂量的甲巯咪唑（大约每日120mg）治疗中报告。
 这些剂量应该在特殊适应症中保留（严重的疾病、甲状腺危象）。在甲巯咪唑治疗期间，如果出现骨髓毒性，需要停止给药，如果有必要，应转换为使用其它类型的抗甲状腺药物。过量给药可以导致亚临床型或临床型甲状腺功能减退和甲状腺肿生长，这是由于TSH增高所致。因此，一旦获得甲状腺功能正常的代谢状态，就应该下调甲巯咪唑的剂量，必要时应添加左旋甲状腺素。完全停止甲巯咪唑以及仅继续接受左旋甲状腺素治疗是没用的。在甲巯咪唑治疗时，尽管TSH被抑制，但甲状腺肿仍然生长，这是基础疾病造成的，不能通过添加左旋甲状腺素治疗而预防。
 为了使内分泌眼病恶化的危险性最小化，获得正常TSH水平是关键的。但是，这一状态经常独立于甲状腺疾病的病程。这样的并发症并不是更改适当治疗方案的原因，也不被认为是正确实施的治疗产生的不良反应。在进行抗甲状腺治疗后，即使没有另外实施任何手术治疗措施，也有低比例的患者可能出现远期甲状腺功能减退。这很可能不是药物产生的不良反应，而认为是由基础疾病所致的甲状腺实质的炎症和破坏过程引起。在甲状腺功能亢进症患者应用甲巯咪唑治疗期间，病理性增高的能量消耗的下降可能导致（一般是期望得到的）体重增加。应该告知患者，临床症状的改善表明了他们能量消耗的正常化。赛治含有乳糖；因此，在罕见的遗传性疾病半乳糖不耐症、Lapp乳糖酶缺乏症或葡萄糖一半乳糖吸收不良症患者中，不推荐应用该药物。
特殊人群用药：
在肝功能受损患者中，甲巯咪唑的血浆清除率下降。因此，给药剂量应尽可能低，并应对患者进行严密监测。在肾功能受损患者中，由于缺乏甲巯咪唑药代动力学行为方面的数据，所以在该患者人群中，推荐在严密监测下小心地对剂量进行个体化调整，给药剂量应该尽可能低。
驾车及操作机器：
甲巯咪唑对驾驶和操作机械的能力没有任何影响。
不良反应:基于以下发生率定义，对不良反应进行评估：
非常常见 ≥1/10
常见 ≥1/100，＜1/10
不常见 ≥1/1000，＜1/100
罕见 ≥1/10000，＜1/1000
非常罕见 ＜ 1/10000
血液和淋巴系统异常
不常见：
粒细胞缺乏症出现在大约0.3%-0.6%的病例中。在治疗开始后数周或数月也可以出现粒细胞缺乏症，如果出现粒细胞缺乏症必须停药。大部分病例可自发恢复。
非常罕见：
血小板减少、全血细胞减少、泛发性淋巴结病。
内分泌异常
非常罕见：
胰岛素自身免疫综合征（伴有血糖水平的显著下降）。
神经系统异常
罕见：
罕有味觉紊乱（味觉障碍、味觉丧失）的发生；在停药后可以恢复。但是，恢复到正常可能需要数周时间。
非常罕见：
神经炎、多发性神经病。
胃肠道异常
非常罕见：
急性唾液腺肿胀。
肝胆异常
非常罕见：
已经有报道个别病例出现胆汁淤积性黄疸或中毒性肝炎。在停药后症状一般可以恢复。必须要注意鉴别治疗期间胆汁淤积所致的不显著的临床征象和由甲状腺功能亢进导致的改变，如GGT（Y-谷氨酰转肽酶）和碱性磷酸酶或其骨特异性同工酶的增高。
皮肤和皮下组织异常
非常常见：
不同程度的过敏性皮肤反应（搔痒症、皮疹、风疹）。这些皮肤反应大部分是轻微的，经常在继续治疗期间缓解。
非常罕见：
严重的过敏性皮肤反应，包括泛发性皮炎，脱发、药物诱导的红斑狼疮。
骨胳肌肉和结缔组织异常
常见：
关节痛可能逐渐出现，而且即使在数月的治疗后也会出现。
一般疾病和给药部位状态
罕见：
药物热。
相互作用:碘不足会增加，而过多的碘会降低甲状腺对甲巯咪唑片的反应性。目前尚没有发现与其他药物的直接相互作用。但是，应注意的是在甲状腺功能亢进的情况下，其他药物的分解和排泄可被加速，随着甲状腺功能逐渐恢复正常时，这些反应也可恢复正常。需要时，医生应调整其剂量。
生产厂家
默克（德国）。

Thyrozol
The Latin name of the drug tirozol ®
Thyrozol ® ATX
H03BB02 TiamazolFarmakologicheskaya group
• Thyroid hormones and their analogs and antagonists (including antithyroid drugs)
The nosological classification (ICD-10)
• D34 Benign neoplasm of thyroid gland
• E05 thyrotoxicosis [hyperthyroidism]
Dosage form and composition
Tablets, film-coated Table 1.
Active ingredient:
thiamazole 5 mg
Other ingredients: colloidal silicon dioxide, sodium carboxymethyl starch, magnesium stearate, hypromellose 2910/15, talc, powdered cellulose, corn starch, lactose monohydrate, dimethicone 100, titanium dioxide, iron oxide yellow, macrogol 400, hypromellose 2910/15
Tablets, film-coated Table 1.
Active ingredient:
thiamazole 10 mg
Other ingredients: colloidal silicon dioxide, sodium carboxymethyl starch, magnesium stearate, hypromellose 2910/15, talc, powdered cellulose, corn starch, lactose monohydrate, dimethicone 100, titanium dioxide, iron oxide yellow, iron oxide red, macrogol 400, hypromellose 2910/15
Description of the dosage form
Tirozol ®, 5mg: light yellow, round, biconvex, film-coated, with a mark on one side.
Tirozol ®, 10mg: gray-orange, round, biconvex, film-coated, with a mark on one side.
View on a break: white or almost white mass.
Mode of action
Mode of action - антитиреоидное.Фармакодинамика
Violates the synthesis of thyroid hormone by blocking the enzyme peroxidase, which participates in the iodization of thyronine in the thyroid gland to produce tri-and tetraiodothyronine. This property allows the symptomatic treatment of hyperthyroidism, with the exception of cases of hyperthyroidism due to the release of hormones after the destruction of the thyroid cells (after treatment with radioactive iodine or thyroiditis). Tirozol ® does not affect the release of synthesized thyronines of thyroid follicles. Hence the latent period of varying lengths, which may be preceded by normalization of T3 and T4 in blood plasma, i.e. improvement of the clinical picture.
Reduces basal metabolism, accelerates the removal of the thyroid iodide increases the reciprocal activation of the synthesis and release of thyroid-stimulating hormone by the pituitary gland, which may be accompanied by a hyperplasia of the thyroid gland.
The duration of action of a single dose of the dose is almost 24 hours
Pharmacokinetics
Tirozol ® when taken orally is rapidly and almost completely absorbed. Cmax in plasma is reached within 0.4-1.2 hours with plasma proteins practically does not bind. Tirozol ® accumulates in the thyroid gland, which is slowly metabolized. Small amounts Tiamazol found in breast milk. T1 / 2 - about 3-6 hours, hepatic failure, it increases. Not a dependence of the kinetics of the functional state of the thyroid gland. Drug metabolism tirozol ® is the kidney and liver, elimination of the drug is carried out by the kidneys and the bile. The kidneys remove 70% of tyrosol ® for 24 h, and 12.7% - unchanged.
Indications drug tirozol®
thyrotoxicosis;
preparation for surgical treatment of hyperthyroidism;
Preparations for the treatment of hyperthyroidism with radioactive iodine;
Therapy in the latent period of the radioactive iodine (held before the start of the radioactive iodine - for 4-6 months);
in exceptional cases - long-term maintenance therapy of hyperthyroidism, when in connection with the overall health or personal reasons can not perform radical treatment;
prevention of hyperthyroidism in the appointment of iodine preparations (including cases of iodine-containing contrast media), in the presence of latent hyperthyroidism, autonomous adenomas, or a history of hyperthyroidism.
Contraindications
Hypersensitivity to Tiamazol thiourea derivatives;
agranulocytosis during therapy previously held carbimazole or Tiamazol;
granulocytopenia (including history);
cholestasis before the start of treatment;
Tiamazol in combination therapy with levothyroxine during pregnancy.
Relative contraindication - previously observed allergic skin reaction to derivatives of thiourea.
Precautions: goiter is very large with a narrowing of the trachea (only short-term treatment in preparation for surgery), liver failure.
Pregnancy and breast-feeding
Untreated hyperthyroidism during pregnancy can lead to serious complications such as premature birth, fetal malformations. Tiamazol crosses the placental barrier and the blood of the fetus can reach the same concentration as that of the mother. Due to the fact that the effect on the fetus Tiamazol can not be completely excluded during pregnancy drug must be administered after a complete evaluation of the benefits and risks of its application in the minimum effective dose of levothyroxine without supplementation.
Tiamazol dose far in excess of the recommended can cause the formation of goiter and hypothyroidism in the fetus, as well as low birth weight.
During lactation the drug treatment of hyperthyroidism tirozol ® if necessary, can be continued. Since tiamazol passes into breast milk and may reach it a concentration corresponding to its level in the blood of the mother, the newborn may develop hypothyroidism. Therefore, the need to continue the treatment of hyperthyroidism during breast-feeding tirozol ® should be taken in low doses (10 mg / day) without receiving levothyroxine.
Side effects
Sometimes - allergic skin reactions (itching, redness, rash), vomiting, dizziness, and weakness.
An increase in temperature, change in taste are rare and are reversible.
Approximately 0.3-0.6% of cases may agranulocytosis. His symptoms (see "Special Instructions") can appear even after weeks and months after the start of treatment and cause a withdrawal of the drug.
In a few cases there were reports of arthralgia, developing, usually slowly and gradually, a few months after starting treatment. There were no clinical signs of arthritis.
Described isolated cases of cholestatic jaundice and toxic hepatitis.
In some cases, have been described: generalized lymphadenopathy, acute salivary gland enlargement, thrombocytopenia, pancytopenia, neuritis, neuropathy, lupus-like reactions, as well as autoimmune syndrome with hypoglycemia.
Increased body weight.
Clinical and subclinical hypothyroidism may occur when taking high doses of the drug. It may also begin enlargement of the thyroid gland, which is associated with an increase in TSH.
Interaction
In the appointment of the drug after using iodinated contrast media in high doses may weaken the effect of tyrosol ®.
Iodine deficiency increases the effect of tyrosol ®.
Patients taking tirozol ® about hyperthyroidism, after reaching a euthyroid state, ie, normalization of thyroid hormones in the blood serum, it may be necessary to reduce doses received cardiac glycosides (digoxin and digitoxin), aminophylline, and increase the received dose warfarin or other anticoagulants - coumarin derivatives and indandiona (pharmacodynamic interaction).
Lithium drugs, β-blockers, reserpine, enhance the effect of amiodarone Tiamazol (requires tuning the dose).
While the use of sulfonamides, Metamizole and myelotoxic drugs increase the risk of leucopenia.
Leucogen and folic acid, while the use Tiamazol reduce the risk of leucopenia.
Gentamicin enhances the effect of antithyroid Tiamazol.
Data on the effect of other drugs on the pharmacokinetics and pharmacodynamics of the drug is not present. However, it should be borne in mind that in thyrotoxicosis accelerates metabolism and elimination of substances. Therefore, in some cases it is necessary to adjust the dose of other medications.
Dosage and administration
Inside.
Take after a meal without chewing, with some liquid. The daily dose is administered in a single dose or divided into 2-3 single doses. At the beginning of treatment used in single doses for the day at a fixed time.
Maintenance dose should be taken at once after breakfast.
Hyperthyroidism: Depending on the severity of the disease - 20-40 mg / day tirozol ® for 3-6 weeks. After normalization of thyroid function (usually 3-8 weeks), move on to receive a maintenance dose of 5-20 mg / day. Since that time, we recommend supplementation of levothyroxine.
In preparation for the surgical treatment of hyperthyroidism: assigning 20-40 mg / day to achieve euthyroid state. Since that time, we recommend supplementation of levothyroxine.
In order to reduce the time needed to prepare for the operation, in addition prescribe beta-blockers and iodine.
In preparation for treatment with radioactive iodine: 20-40 mg / day until the euthyroid state. It should be remembered that tiamazol and thiourea derivatives may reduce the sensitivity of the thyroid gland to radiation therapy.
Therapy in the latent period of the radioactive iodine: Depending on the severity of the disease - by 5-20 mg before the action of radioactive iodine (4-6 months).
Long-term maintenance therapy tireostaticheskim: 1,25-2,5-10 mg / day with an additional intake of small doses of levothyroxine.
Prophylaxis with hyperthyroidism prescribing iodine (including cases of iodinated contrast media) in the presence of latent thyrotoxicosis or hyperthyroidism autonomous adenoma history 10-20 mg / tyrosol ® and 1 g of potassium perchlorate per day for 8-10 days prior to receiving iodinated means.
Children: initial dose - 0.3-0.5 mg / kg daily; maintenance dose - at 0.2-0.3 mg / kg, if necessary, appoint additional levothyroxine.
Pregnant designate the lowest possible doses: a single dose - 2.5 mg daily - 10 mg.
Hepatic failure prescribed minimum effective dose.
In the treatment of hyperthyroidism treatment duration of 1.5 to 2 years.
In preparation for surgery in patients with hyperthyroidism drug treatment is carried out until the euthyroid state - duration) and ends the day before. In all cases, the duration of treatment determined by the physician.
Overdose
Symptoms of chronic overdose leads to an increase of thyroid and hypothyroidism.
Reception very high doses thiamazole (about 120 mg per day) may result in the development myelotoxic effects.
Treatment: the drug is stopped. Levothyroxine replacement therapy is carried out in the event that it is warranted by the severity of hypothyroidism. As a rule, after the drug is observed spontaneous recovery of thyroid function.
When very high doses of the drug - removal of the drug, gastric lavage, activated charcoal, symptomatic therapy.
Cautions
Patients with a significant enlargement of the thyroid gland, narrowing a lumen of the trachea, tyrosol ® is administered in combination with a short-term levothyroxine because long-term use may increase the craw and even greater compression of the trachea. For a careful monitoring of patients (control of TSH, the lumen of the trachea).
During treatment should regularly monitor the pattern of peripheral blood.
If during treatment with suddenly appear a sore throat, difficulty swallowing, fever, stomatitis or signs of abrasions (possible symptoms of agranulocytosis), you should immediately stop taking the drug and seek medical advice.
When prompted during the treatment s / hemorrhage, or bleeding of unknown origin, generalized skin rash and itching, persistent nausea or vomiting, jaundice, severe epigastric pain and severe weakness of the drug should be discontinued.
In the event of early termination of treatment is possible recurrence of the disease.
The emergence or worsening of endocrine ophthalmopathy is not a side effect of treatment tirozol ®, conducted properly.
In rare cases, after the treatment may occur later hypothyroidism, which is not a side effect of the drug, and is associated with inflammatory and destructive processes in the thyroid, flowing in the main disease.
Form release
Tablets, film-coated, 5 mg and 10 mg: in blisters of PVC / aluminum foil of 10 or 25 units.; In cardboard pack 2, 4, 5 or 10 blisters.
Manufacturer
Merck KGaA (Germany).
Frankfurtershtrasse, 250, D-64293, Darmstadt, Germany.
Merck KGaA (Germany).
Frankfurterstrasse, 250, D-64293, Darmstadt, Germany.
Presented in Russia and the CIS
Nycomed Austria GmbH, Austria.
Customer complaints addressed
Ltd. Nycomed Distribyushn Sente.