Composition
active ingredient: levothyroxine sodium;
1 tablet contains levothyroxine sodium in terms of 100% substance 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, magnesium stearate.
Release form
Pills.
Main physicochemical properties: tablets from white to white with a yellowish tint, round in shape with a flat surface with beveled edges and a score.
Pharmacological properties
Pharmacodynamics. Synthetic levothyroxine, which is contained in the drug Sintorix, exhibits effects identical to those of the hormone secreted by the thyroid gland. It is converted to TZ (triiodothyronine) in peripheral organs, and as an endogenous hormone affects TZ 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
Sintorix 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.
Sintorix 25–100 mcg
– As an adjunct to antithyroid therapy for hyperthyroidism.
Sintorix 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”).
Application
Dosage.
To treat each individual patient, depending on their individual needs, Sintrex 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/m 2 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 | Sintrex 100 mcg | 2 tables. per day | 2 tables. per day | Sintrex 150 mcg | ½ table per day | ½ tablet. per day | 1 table per day | 1 table per day |
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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).
Sintrex 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.
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).
Overdose
An increase in the level of TZ (triiodothyronine) is a reliable indicator of drug overdose, more so than an increase in the levels of T4 and fT4 (free) in the blood serum.
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.
Interaction
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.
Cholestyramine, colestipol. Taking ion exchange resins such as cholestyramine and colestipol inhibits the absorption of levothyroxine sodium. Therefore, levothyroxine sodium should be taken 4-5 hours before taking these drugs.
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 the increase in intragastric pH caused by the PPI.
Regular monitoring of thyroid function and clinical monitoring with possible increase in thyroid hormone dose is recommended. Caution should also be exercised when PPI treatment is discontinued.
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 agents 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.
Effect of drugs that induce cytochrome P-450: Enzyme-inducing drugs such as barbiturates, carbamazepine, and St. John's wort (Hypericum perforatum L.) products may increase the hepatic clearance of levothyroxine, resulting in decreased serum thyroid hormone concentrations. Therefore, patients receiving thyroid replacement therapy may require an increase in the dose of thyroid hormones if these drugs are administered concomitantly.
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 Syntrex should be adjusted, especially at the beginning and after the end of taking soy-containing supplements.
Effect on laboratory test results Biotin may interfere with the results of 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").
Storage conditions
Does not require special storage conditions.
Keep out of reach of children.
