Instructions Euthyrox tablets 100 mcg blister No. 100
Composition
active ingredient: levothyroxine sodium;
1 tablet contains levothyroxine sodium 25 mcg, or 50 mcg, or 75 mcg, or 100 mcg, or 125 mcg, or 150 mcg;
excipients: mannitol (E 421); corn starch; gelatin; croscarmellose sodium; anhydrous citric acid, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: almost white round, flat on both sides, with beveled edges tablets, with a score line on both sides, engraved on one side with the symbols "EM + dosage".
Pharmacotherapeutic group
Hormone preparations for systemic use (except sex hormones and insulin). Preparations for the treatment of thyroid diseases. Thyroid preparations. Levothyroxine sodium. ATX code H03A A01.
Pharmacological properties
Pharmacodynamics
Synthetic levothyroxine, which is contained in the drug Euthyrox, has effects identical to those of the hormone secreted by the thyroid gland. It is converted to T3 (triiodothyronine) in peripheral organs, and as an endogenous hormone affects T3 receptors. There is no difference between the functions of the endogenous hormone and exogenous levothyroxine.
Pharmacokinetics
After oral administration, levothyroxine is almost completely absorbed in the upper small intestine. Depending on the galenic form of the drug, up to 80% of the dose is absorbed. The maximum concentration (Tmax) is reached after approximately 5-6 hours.
The clinical effect of the drug is manifested 3-5 days after oral administration. Levothyroxine quickly binds to specific transport proteins in the blood (up to 99.97%). The connection with proteins is not covalent, so the bound hormone in the plasma is able to constantly and quickly exchange with fractions of the free hormone.
Due to its high level of protein binding, levothyroxine is not amenable to either hemodialysis or hemoperfusion.
The half-life of the drug is 7 days. In hyperthyroidism, this period is reduced to 3-4 days, and in hypothyroidism it is extended to 9-10 days. The volume of distribution is 10-12 l. About 1/3 of the total amount of levothyroxine administered accumulates in the liver, which quickly interacts with levothyroxine in the blood serum. Thyroid hormones are metabolized mainly in the liver, kidneys, brain and muscles. Metabolites are excreted in urine and feces. The total metabolic clearance of levothyroxine is approximately 1.2 l of plasma/day.
Indication
Euthyrox 25–200 mcg
– Treatment of benign euthyroid goiter.
– Prevention of relapses after surgical treatment of euthyroid goiter, depending on the hormone level in the postoperative period.
– As replacement therapy for hypothyroidism.
– Suppressive therapy for thyroid cancer.
Euthyrox 25–100 mcg
– As an adjunct to antithyroid therapy for hyperthyroidism.
Euthyrox 100/150/200 mcg
– As a diagnostic tool when performing a thyroid suppression test.
Contraindication
– Increased individual sensitivity to any component of the drug.
– Adrenal insufficiency, pituitary insufficiency, thyrotoxicosis, which were not treated.
– Acute myocardial infarction, acute myocarditis, acute pancarditis.
– Combination therapy with levothyroxine and antithyroid drugs is not recommended during pregnancy (see section “Use during pregnancy or breastfeeding”).
Interaction with other medicinal products and other types of interactions
Hypoglycemic agents. Levothyroxine may reduce the effect of hypoglycemic agents. It is recommended to monitor blood glucose levels frequently at the beginning of thyroid hormone treatment and, if necessary, adjust the dose of hypoglycemic agents.
Coumarin derivatives. Levothyroxine enhances the effect of anticoagulant drugs, displacing them from plasma protein binding, which increases the risk of bleeding, for example, spinal and cerebral hemorrhage or gastrointestinal bleeding, especially in the elderly. Therefore, regular laboratory monitoring of coagulation parameters should be carried out at the beginning and during concomitant therapy and, if necessary, the daily dose of anticoagulant drugs should be adjusted.
Protease inhibitors (e.g. ritonavir, indinavir, lopinavir) may interfere with the action of levothyroxine. Close monitoring of thyroid hormone levels is required. If necessary, the dose of levothyroxine should be adjusted.
Phenytoin may interfere with the action of levothyroxine by displacing it from plasma protein binding, resulting in increased levels of free thyroxine (fT4) and free triiodothyronine (fT3). On the other hand, phenytoin increases the hepatic metabolism of levothyroxine. Close monitoring of thyroid hormone levels is recommended.
Preparations containing aluminum, iron and calcium salts. According to the data provided in the relevant literature, preparations containing aluminum (antacids, sucralfate) can potentially reduce the effect of levothyroxine. Therefore, levothyroxine should be taken at least 2 hours before the use of preparations containing aluminum. This also applies to medicines containing iron and calcium salts.
Salicylates, dicumarol, furosemide in high doses (250 mg), clofibrate and other substances can displace levothyroxine sodium from its binding to plasma proteins, leading to an increase in the fT4 fraction.
Proton pump inhibitors (PPIs). Concomitant use with PPIs may result in reduced absorption of thyroid hormones due to increased intragastric pH caused by the PPI. Regular monitoring of thyroid function and clinical monitoring is recommended during concomitant treatment, with a possible increase in the dose of thyroid hormones.
Caution should also be exercised when PPI treatment ends.
Orlistat: Concomitant use of orlistat and levothyroxine may lead to the development of hypothyroidism and/or worsening of hypothyroidism control. This may be due to reduced absorption of iodine salts and/or levothyroxine.
Sevelamer may reduce the absorption of levothyroxine. In this regard, it is recommended to monitor changes in thyroid function tests at the beginning and end of concomitant treatment. If necessary, the dose of levothyroxine should be adjusted.
Tyrosine kinase inhibitors (e.g. imatinib, sunitinib) may reduce the efficacy of levothyroxine. Therefore, it is recommended to monitor changes in thyroid function tests at the beginning and end of concomitant treatment. If necessary, the dose of levothyroxine should be adjusted.
Propylthiouracil, glucocorticoids, beta-sympatholytics, amiodarone and iodinated contrast media inhibit peripheral conversion of T4 to T3. Due to its high iodine content, amiodarone can contribute to the development of both hyperthyroidism and hypothyroidism. The drug should be prescribed with particular caution to patients with nodular goiter of unknown etiology.
Sertraline, chloroquine/proguanil reduce the effectiveness of levothyroxine and increase the level of laboratory indicators of TSH in serum.
Enzymes induced by drugs such as barbiturates, carbamazepine, or products containing St. John's wort (Hypericum perforatum L.) may increase the hepatic clearance of levothyroxine, leading to decreased serum thyroid hormone concentrations.
Therefore, patients receiving thyroid replacement therapy may require an increase in the dose of thyroid hormone if these drugs are taken concurrently.
Estrogens: Women taking contraceptives containing estrogens, as well as postmenopausal women taking hormone replacement drugs, may require higher doses of levothyroxine.
Soy-containing products may inhibit the intestinal absorption of levothyroxine. Therefore, the dose of Euthyrox should be adjusted, especially at the beginning and after the end of taking soy-containing supplements.
Effects on laboratory tests: Biotin may interfere with immunoassays for thyroid gland based on biotin/streptavidin interaction, leading to falsely low or falsely high test results (see section "Special warnings and precautions for use").
Application features
Before starting thyroid hormone treatment or performing tests for thyroid suppression, the presence of diseases such as coronary insufficiency, angina pectoris, atherosclerosis, arterial hypertension, pituitary insufficiency should be excluded or previously treated. Functional autonomy of the thyroid gland should also be excluded or previously treated before starting thyroid hormone therapy.
In case of adrenocortical dysfunction, appropriate replacement therapy should be initiated before starting levothyroxine therapy to prevent acute adrenal insufficiency (see section "Contraindications").
Levothyroxine therapy in patients at risk of developing psychotic disorders should be initiated with low doses of the drug, gradually increasing the dosage at the beginning of therapy. It is recommended to monitor the patient's condition. In case of development of psychotic disorders, the possibility of adjusting the dose of levothyroxine should be considered.
The possibility of even minor manifestations of hyperthyroidism caused by the use of the drug should be avoided in patients with coronary insufficiency, heart failure, tachyarrhythmia. When treating such patients, it is necessary to regularly monitor the level of thyroid hormones.
In the case of secondary hypothyroidism, the cause should be identified before replacement therapy is prescribed. If necessary, a course of replacement therapy should be carried out to compensate for the insufficiency of the adrenal cortex.
If functional autonomy of the thyroid gland is suspected, TSH levels should be determined or thyroid scintigraphy should be performed before starting treatment with the drug.
In postmenopausal women with hypothyroidism, who are at increased risk of osteoporosis, very high serum levothyroxine levels above physiological levels should be avoided. Therefore, laboratory values of thyroid function should be carefully monitored.
Levothyroxine should not be prescribed to patients with hyperthyroidism who are receiving antithyroid drug therapy for hyperthyroidism.
Thyroid hormones should not be used for weight loss. Levothyroxine doses do not result in weight loss in euthyroid patients. Higher doses may result in serious or even life-threatening adverse reactions. Levothyroxine in high doses should not be used in combination with certain substances intended for weight loss (e.g. sympathomimetics) (see section 4.4).
If it is necessary to switch from one product to another containing levothyroxine, careful monitoring, including clinical and biological monitoring, is necessary during the transition period due to the potential risk of thyroid dysfunction. Some patients may require dose adjustment.
Concomitant use of orlistat and levothyroxine may lead to the development of hypothyroidism and/or worsening of hypothyroidism control (see section “Interaction with other medicinal products and other forms of interaction”). Patients taking levothyroxine should consult their doctor before starting, stopping or changing their treatment with orlistat, as orlistat and levothyroxine need to be taken at different times and the dose of levothyroxine needs to be adjusted. Monitoring of serum hormone levels in patients is recommended in the future.
Use the drug with caution in patients with diabetes mellitus and patients taking anticoagulant drugs (see section "Interaction with other medicinal products and other types of interactions").
Impact on laboratory tests
Biotin may interfere with immunoassays for thyroid function that rely on biotin/streptavidin interaction, resulting in falsely low or falsely high test results. The risk of interference increases with higher doses of biotin.
When interpreting laboratory test results, the possible interaction of biotin should be considered, especially if there is a lack of consistency with the clinical picture.
Patients taking biotin-containing products should inform laboratory personnel when thyroid function tests are required. Alternative tests that are not sensitive to biotin should be used, if available (see Interactions with other medicinal products and other forms of interaction).
This medicine contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
During pregnancy or breastfeeding, treatment with the drug prescribed for hypothyroidism should be continued. During pregnancy, the dose of the drug may need to be increased. Since an increase in serum TSH levels can occur as early as 4 weeks of pregnancy, pregnant women taking levothyroxine should have their TSH levels checked during each trimester. Serum TSH levels in pregnant women should be within the appropriate limits established for each trimester. The dose of levothyroxine should be increased to correct elevated serum TSH levels. Since postnatal TSH levels correspond to values present before conception, the dose of levothyroxine should be adjusted immediately after delivery to the pre-pregnancy dose. The required serum TSH level should be established 6-8 weeks after delivery.
Pregnancy
There is no evidence of teratogenicity and/or fetotoxicity when taking the drug at recommended therapeutic doses. Taking very high doses of levothyroxine during pregnancy may adversely affect the fetus and postnatal development of the child.
Combination therapy with levothyroxine and antithyroid drugs is not recommended for the treatment of hyperthyroidism during pregnancy because this combination requires higher doses of antithyroid drugs, which can cross the placenta and cause hypothyroidism in the infant. Thyroid suppression testing is not performed during pregnancy because the use of radioactive substances is contraindicated during pregnancy.
Breast-feeding
Levothyroxine passes into breast milk, however, when using the drug in recommended therapeutic doses, the concentration level of the drug in breast milk is insufficient to develop hyperthyroidism or suppress TSH secretion in the infant.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no data on the possible effect on the ability to drive or operate complex mechanisms. However, since levothyroxine is identical in action to the natural thyroid hormone, the effect of Euthyrox on the reaction speed when driving or operating other mechanisms is not expected.
Method of administration and doses
To treat each individual patient, depending on their individual needs, Euthyrox is available in tablets containing from 25 mcg to 150 mcg of levothyroxine sodium. Therefore, patients are usually prescribed only 1 tablet per day.
Dosage information is for guidance only.
The daily dose is determined individually, depending on laboratory parameters and the clinical picture of the disease.
Since a number of patients have experienced increases in T4 and fT4 concentrations during levothyroxine therapy, the basal serum concentration of thyroid-stimulating hormone is a more reliable indicator for subsequent dose adjustment.
Thyroid hormone therapy should be started at a low dose and gradually increased (every 2-4 weeks) to the required therapeutic dose.
In elderly patients, patients with coronary heart disease, patients with severe or long-term hypothyroidism, treatment should be started with special caution, with low doses (12.5 mcg per day), the dose should be increased to the maintenance dose at longer intervals (gradually by 12.5 mcg every 2 weeks), regularly monitoring the level of thyroid hormones. It should be noted that the appointment of doses less than the optimal one, which provides full replacement therapy, does not lead to complete correction of TSH levels.
Experience shows that lower doses are sufficient for patients with low body weight and for patients with large nodular goiter.
| Indication | Recommended doses (levothyroxine sodium, mcg/day) |
| Treatment of benign euthyroid goiter | 75–200 |
| Prevention of recurrence after surgical treatment of euthyroid goiter | 75–200 |
In replacement therapy for hypothyroidism in adults: - initial dose; - maintenance dose | 25–50 100–200 |
In replacement therapy for hypothyroidism in children: - initial dose; - maintenance dose | 12.5–50 100–150 μg/m2 body surface area |
| As an adjunct to antithyroid therapy for hyperthyroidism | 50–100 |
| Suppressive therapy for thyroid cancer | 150–300 |
| As a diagnostic tool when performing a thyroid suppression test | In 4 weeks before the test | In 3 weeks before the test | In 2 weeks before the test | In 1 week before the test | Euthyrox 100 mcg | 2 tables. per day | 2 tables. per day | Euthyrox 150 mcg | ½ table per day | ½ tablet. per day | 1 table per day | 1 table per day |
|
The daily dose can be taken in one dose.
The daily dose of the drug should be taken in the morning on an empty stomach, 30 minutes before meals, with a small amount of water (half a glass of water).
Euthyrox should be used throughout life as replacement therapy for hypothyroidism, after surgical interventions (strumectomy or thyroidectomy), and to prevent relapses after removal of a euthyroid goiter. Complex therapy with thyreostatics should be prescribed after achieving a euthyroid state.
In the case of benign euthyroid goiter, the duration of treatment is from 6 months to 2 years. If the condition does not improve after treatment, surgery or radioactive iodine therapy should be prescribed.
Children
For newborns and infants with congenital hypothyroidism, where rapid therapeutic response is essential, the recommended initial dose is 10 to 15 mcg/kg body weight per day for the first 3 months. Thereafter, the dose is adjusted individually, depending on clinical response and thyroid-stimulating hormone (TSH) levels.
Infants should be given the daily dose of the drug in one dose 30 minutes before the first feeding. Dissolve the tablet in water to obtain a suspension, which should be prepared immediately before taking the drug and used after adding a small amount of liquid.
Overdose
Elevated T3 (triiodothyronine) levels are a more reliable indicator of drug overdose than elevated serum T4 and fT4 (free).
Overdose may result in symptoms characteristic of increased metabolism (see section "Adverse reactions").
In case of overdose, the drug should be discontinued and laboratory tests should be performed.
Beta-blockers are prescribed for symptoms that manifest as pronounced beta-sympathomimetic effects, such as tachycardia, anxiety, nervous excitability, hyperkinesia. In case of significant overdose, plasmapheresis is recommended.
In some cases, patients prone to seizures may develop seizures when the individual permissible dose of the drug has been exceeded.
Overdose with levothyroxine can cause symptoms of hyperthyroidism and lead to acute psychosis, especially in patients at risk of developing psychotic disorders.
There are several reports of sudden coronary death in patients who have abused (exceeded the recommended dosage) levothyroxine for many years.
Adverse reactions
Clinical symptoms of hyperthyroidism may occur in case of overdose, in case of exceeding the individual tolerance of levothyroxine, if the dose is increased rapidly at the beginning of treatment. Symptoms: from the cardiovascular system: cardiac arrhythmias (atrial fibrillation, extrasystole), tachycardia, angina pectoris, palpitations, hot flashes; from the nervous system: headache, insomnia, anxiety, pseudotumor cerebri, tremor; from the digestive tract: vomiting, diarrhea, weight loss; from the skin and musculoskeletal system: increased sweating, muscle weakness and cramps; general disorders: increased body temperature, menstrual disorders.
In such cases, the daily dose of the drug should be reduced or treatment should be interrupted for several days. After the disappearance of adverse reactions, treatment can be continued.
In case of hypersensitivity to the components of the drug, allergic reactions on the skin (rash, urticaria) and on the respiratory tract, including skin rashes, itching, urticaria, shortness of breath, may occur. There have been reports of cases of angioedema (Quincke's edema).
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging. Keep out of the reach of children!
Packaging
25 tablets in a blister. 2 or 4 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Merck Healthcare KGaA, Germany.
Location of the manufacturer and address of its place of business
Frankfurter Strasse 250, 64293 Darmstadt, Germany/Frankfurter Strasse 250, 64293 Darmstadt, Germany.
