Pharmacological properties
Pharmacodynamics
The active component of L-Thyroxine is levothyroxine sodium - a synthetic levorotatory isomer of thyroxine, which in the kidneys and liver is partially converted into triiodothyronine, then passes into the body's cells and affects metabolism, development and tissue growth.
In small doses, the drug has an anabolic effect on fat and protein metabolism. In medium doses, it increases the oxygen demand of tissues, improves the functional activity of the central nervous system and cardiovascular system, stimulates growth and development by improving the metabolism of fats, carbohydrates and proteins. In high doses, levothyroxine sodium inhibits the production of thyroid-stimulating hormone from the pituitary gland and thyrotropin-releasing hormone from the hypothalamus.
The therapeutic effect develops within 7–12 days of taking the drug. The effect remains valid for the same number of days after its cancellation. For hypothyroidism, the clinical effect appears after 3–5 days. Diffuse goiter decreases or completely disappears within 3–6 months.
Pharmacokinetics
After entering the gastrointestinal tract, levothyroxine sodium is absorbed almost exclusively in the upper part of the small intestine. Absorption of the drug is about 80% of the dose taken. When eating at the same time, the absorption of the substance decreases.
The maximum concentration in the blood is reached approximately 5–6 hours after taking the tablet. Levothyroxine sodium is characterized by a very high (at least 99%) association with serum proteins - albumin, TSPA (thyroxine-binding prealbumin) and TSH (thyroxine-binding globulin). In various tissues, about 80% of the active substance of the drug is monodeiodinated with the formation of triiodothyronine (T3) and inactive products. Metabolism of thyroid hormones occurs primarily in the kidneys, liver, muscles and brain. A small amount of the drug undergoes decarboxylation and deamination, as well as conjugation with sulfuric and glucuronic acids (in the liver).
The route of elimination of metabolites is through the intestines and kidneys. The half-life is 6–7 days, in patients with thyrotoxicosis – 3–4 days, in patients with hypothyroidism – 9–10 days.
Contraindications
Absolute:
- Acute myocardial infarction, acute myocarditis;
- Untreated thyrotoxicosis;
- Untreated adrenal insufficiency;
- Hereditary lactase deficiency or lactose intolerance (impaired absorption of glucose and galactose);
- Hypersensitivity to levothyroxine.
Relative (L-thyroxine tablets must be taken with caution):
- Diseases of the cardiovascular system: arterial hypertension, arrhythmias, coronary heart disease (history of myocardial infarction, atherosclerosis, angina pectoris);
- Diabetes;
- Severe (long-term) hypothyroidism;
- Malabsorption syndrome (dose adjustment may be required).
Instructions for use of L-thyroxine: method and dosage
L-thyroxine tablets are taken orally in the morning on an empty stomach, at least 1/2 hour before meals, without chewing and with a small amount (1/2 glass) of water.
The daily dose of L-thyroxine is determined by the attending physician individually and depends on the indications.
For replacement therapy of hypothyroidism in patients under 55 years of age, in the absence of cardiovascular diseases, the recommended daily dose of L-thyroxine is 1.6-1.8 mcg/kg body weight. For patients over 55 years of age or with cardiovascular disease, the dose is determined at the rate of 0.9 mcg/kg body weight. Patients with severe obesity (BMI - body mass index ≥ 30 kg/m2) are calculated at the “ideal weight”.
At the initial stage of replacement therapy for hypothyroidism, the recommended dose of levothyroxine is:
- Patients without cardiovascular diseases under the age of 55 years: men – 100-150 mcg/day, women – 75-100 mcg/day;
- Patients over 55 years of age and/or with cardiovascular diseases: regardless of gender – 25 mcg/day with a gradual increase in dose (25 mcg at intervals of 2 months) until the level of thyroid-stimulating hormone (TSH) in the blood is normalized.
If symptoms from the cardiovascular system appear or worsen, the course of treatment for cardiovascular diseases should be adjusted.
Recommended daily doses of L-thyroxine for the treatment of congenital hypothyroidism, depending on the age of the child (dose of levothyroxine/dose of levothyroxine per body weight):
- From birth to 1/2 year – 25-50 mcg/10-15 mcg/kg;
- From 1/2 to 1 year – 50-75 mcg/6-8 mcg/kg;
- From 1 year to 5 years – 75-100 mcg/5-6 mcg/kg;
- From 6 to 12 years – 100-150 mcg/4-5 mcg/kg;
- Over 12 years old – 100-200 mcg/2-3 mcg/kg.
Recommended daily doses of L-thyroxine depending on the condition/disease:
- Therapy of euthyroid goiter – 75-200 mcg;
- Prevention of relapses after surgical treatment of euthyroid goiter – 75-200 mcg;
- Thyrotoxicosis (as part of complex therapy) – 50-100 mcg;
- Thyroid cancer (for suppressive therapy) – 150-300 mcg;
- Carrying out a thyroid suppression test - 3-4 weeks before the test - 75 mcg, 1-2 weeks before the test - 150-200 mcg.
For children from birth to 3 years of age, the daily dose of levothyroxine is given 1/2 hour before the first feeding (in one dose). Immediately before use, the tablet must be dissolved in water until a thin suspension is formed.
In case of hypothyroidism, L-thyroxine is usually taken throughout life. For the treatment of thyrotoxicosis, the drug is used in combination with antithyroid drugs after achieving a euthyroid state. The duration of levothyroxine therapy for any condition/disease is determined by the attending physician.
Indications for use
L-Thyroxine is used for maintenance HRT for hypothyroid conditions of various origins , including primary and secondary hypothyroidism that developed after thyroid surgery, as well as conditions provoked by therapy using radioactive iodine preparations .
It is also considered appropriate to prescribe the drug:
- with hypothyroidism (both congenital and in the case where the pathology is a consequence of lesions of the hypothalamic-pituitary system );
- for obesity and/or cretinism , which are accompanied by manifestations of hypothyroidism ;
- for cerebral-pituitary diseases ;
- as a prophylactic for recurrent nodular goiter after resection of the thyroid gland (if its function is not changed);
- for the treatment of diffuse euthyroid goiter (L-Thyroxine is used as an independent remedy);
- for the treatment of euthyroid hyperplasia of the thyroid gland , as well as Graves' disease after achieving compensation for intoxication with thyroid hormones using thyreostatic agents (as part of complex therapy);
- for Graves' disease and Hashimoto's disease (in complex treatment);
- for the treatment of patients with hormone-dependent well-differentiated malignant neoplasms in the thyroid gland (including papillary or follicular carcinoma );
- for suppressive therapy and HRT in patients with malignant neoplasms in the thyroid gland (including after surgery for thyroid cancer ); as a diagnostic tool when performing thyroid suppression .
In addition, thyroxine is often used in bodybuilding as a means of losing weight.
Overdose
In case of overdose, symptoms characteristic of thyrotoxicosis occur: increased sweating, heart pain, heart rhythm disturbances, rapid heartbeat, tremor, increased appetite, diarrhea, sleep disturbances, anxiety, weight loss.
Depending on the severity of overdose symptoms, the doctor may recommend a reduction in the daily dose of L-Thyroxine, a short (several days) break in taking it and/or the use of beta-blockers. After normalization of the condition, the drug should be started with caution, with a minimum dose.
Side effects of the drug L-thyroxine Berlin-Chemie
When using the drug, tachycardia, increased heart rate, arrhythmia, angina pectoris, tremor, a feeling of internal restlessness, insomnia, hyperhidrosis, a feeling of heat, increased body temperature, weight loss, vomiting, diarrhea, headache, weakness and muscle spasms, menstrual irregularities may occur. . If these symptoms appear, it is recommended to reduce the daily dose or interrupt the drug for several days. As soon as the side effects disappear, you can return to treatment again, carefully increasing the dosage of the drug. Allergic reactions may occur in the form of urticaria, bronchospasm and laryngeal edema, and in some cases, anaphylactic shock.
special instructions
In the case of hypothyroidism caused by damage to the pituitary gland, a diagnosis should be made and find out whether there is simultaneous insufficiency of the adrenal cortex. If the result is positive, it is necessary to begin replacement therapy with GCS (glucocorticosteroids) before taking thyroid hormones for the treatment of hypothyroidism in order to avoid the development of acute adrenal insufficiency.
The concentration of TSH in the blood should be periodically monitored; an increase in this indicator indicates an insufficient dose of L-thyroxine.
Levothyroxine does not affect the concentration of attention and the speed of psychomotor reactions necessary to control complex mechanisms and vehicles.
Combination with alcohol
A single intake of a small dose of alcohol that is not too strong, as a rule, does not provoke any negative consequences for the body, therefore the instructions for the drug do not categorically prohibit such a combination.
However, it is permissible only for patients with healthy heart and blood vessels.
Drinking alcohol during treatment with L-Thyroxine often provokes a number of undesirable reactions from the central nervous system and liver, which in turn can affect the effectiveness of treatment.
Use during pregnancy and lactation
Therapy for hypothyroidism during pregnancy and lactation must be continued. During pregnancy, the level of TSH increases, so an increase in the dose of L-Thyroxine is required.
The use of sodium levothyroxine during pregnancy is contraindicated in combination with antithyroid drugs, since their dose may need to be increased while taking L-Thyroxine. In addition, unlike levothyroxine sodium, antithyroid drugs can penetrate the placenta, which may result in the development of hypothyroidism in the fetus.
The amount of thyroid hormone that is excreted in breast milk (even when taking the drug in high doses) is small, so it is not capable of causing any problems in the child. However, breastfeeding women should undergo treatment under the supervision of a doctor, strictly adhering to the recommendations.
Overdose of the drug L-thyroxine Berlin-Chemie
In case of overdose, an accelerated pulse, increased heartbeat, sweating, arrhythmia, insomnia, tremor, increased frequency of angina attacks, and worsening of diabetes mellitus are noted. It is recommended to stop taking the pills and conduct follow-up examinations. If severe tachycardia develops, it can be weakened with the help of β-adrenergic receptor blockers; thyreostatic agents are not used. When taking levothyroxine in a very high dose (suicide attempt), plasmaphoresis is used.
Drug interactions
Mutual influence of the following substances/drugs and levothyroxine when used simultaneously:
- Insulin and oral hypoglycemic drugs - their dose may need to be increased (when starting therapy with levothyroxine sodium, as in the case of changing the dosage regimen, blood glucose concentrations should be checked more frequently);
- Indirect anticoagulants, tricyclic antidepressants – their effect is enhanced (dose reduction may be required);
- Colestipol, cholestyramine, aluminum hydroxide - reduce the concentration of levothyroxine sodium in the blood plasma due to a decrease in the rate of its absorption in the intestine;
- Anabolic steroids, asparaginase, tamoxifen - there is a possibility of pharmacokinetic interaction at the level of protein binding;
- Cardiac glycosides – their effectiveness decreases;
- Salicylates, clofibrate, furosemide (in high doses), phenytoin - increase the levels of sodium levothyroxine not bound to proteins and free thyroxine (T4) in the blood plasma; phenytoin reduces the volume of levothyroxine bound to proteins by 15%, T4 concentration by 25%;
- Estrogen-containing drugs – increase the amount of thyroxine-binding globulin, which may increase the need for levothyroxine in some patients;
- Somatotropin – possible acceleration of closure of epiphyseal growth zones;
- Phenobarbital, carbamazepine and rifampicin - may increase the clearance of levothyroxine sodium, which may result in an increase in its dose;
- Aminoglutethimide, amiodarone, para-aminosalicylic acid (PAS), antithyroid drugs, β-blockers, ethionamide, carbamazepine, chloral hydrate, levodopa, diazepam, dopamine, metoclopramide, somatostatin, lovastatin - affect the metabolism and distribution of L-thyroxine.
Interaction
The use of levothyroxine reduces the effectiveness of antidiabetic agents . At the beginning of treatment with the drug, as well as each time the dose is changed, you should monitor your blood glucose levels .
Levothyroxine potentiates the effects of anticoagulants (in particular, coumarins), thereby increasing the risk of cerebral hemorrhages (spinal or head), as well as gastrointestinal bleeding (especially in the elderly).
Therefore, if it is necessary to take these drugs in combination, it is recommended to regularly conduct blood clotting tests and, if appropriate, reduce the dose of anticoagulants.
The effect of levothyroxine may be impaired when taken concomitantly with protease inhibitors. In this regard, it is necessary to constantly monitor the concentration of thyroid hormones. In some situations, it may be necessary to review the dose of L-Thyroxine.
Cholestyramine and colestipol slow down the absorption of levothyroxine, so L-Thyroxine must be taken at least 4-5 hours before taking these medications.
Drugs that contain aluminum, calcium carbonate or iron may reduce the severity of the effects of levothyroxine, so take L-Thyroxine at least 2 hours before taking them.
The absorption of levothyroxine is reduced when taken in combination with lanthanum carbonate or sevelamer , so it should be taken one hour before or three hours after using these drugs.
When taking drugs in combination, monitoring the level of thyroid hormones is necessary at the initial and final stages of their simultaneous use. The dose of levothyroxine may need to be adjusted.
The effectiveness of the drug decreases when taken simultaneously with tyrosine kinase inhibitors, and therefore changes in thyroid function should be monitored during the initial and final stages of simultaneous use of these drugs.
Proguanil/chloroquine and sertraline reduce the effectiveness of the drug and provoke an increase in plasma concentrations of thyrotropin .
Drug-induced enzymes (for example, carbamazepine or barbiturates ) may increase the plasma concentration of levothyroxine.
Women taking hormonal contraceptives that contain an estrogen component , as well as postmenopausal women taking hormone replacement drugs , may require an increase in the dose of levothyroxine.
Thyroxine and L-Thyroxine
Furosemide in increased dosages, salicylates, clofibrate and a number of other substances help displace levothyroxine from plasma proteins, which in turn provokes an increase in the fT4 ( free thyroxine ) fraction.
Iodine-containing drugs , corticosteroids, amiodarone , propylthiouracil , sympatholytics inhibit the peripheral conversion of thyroxine to triiodothyronine . Due to the high concentration of iodine, amiodarone can cause the patient to develop both hypo- and hyperthyroid states.
Amiodarone is used with extreme caution in combination with L-Thyroxine for the treatment of patients with nodular goiter of unspecified etiology.
Phenytoin promotes the displacement of levothyroxine from blood plasma proteins . of free thyroxine and free triiodothyronine fractions increases .
In addition, phenytoin stimulates the metabolic transformations of levothyroxine in the liver, so patients taking levothyroxine in combination with phenytoin are recommended to constantly monitor the concentration of thyroid hormones .
Reviews about L-Thyroxine
Reviews about L-Thyroxine are mostly good. Patients indicate that the drug normalizes the balance of thyroid hormones, and this has a positive effect on overall well-being. Some negative messages contain complaints about the development of side effects.
Despite the fact that L-Thyroxine is intended for the treatment of endocrinological diseases, its anabolic effect is often used for weight loss purposes. Patients claim that the product helps to correct body weight, especially if it is supplemented with a low-carbohydrate diet. Doctors emphasize that levothyroxine sodium can only be used in cases of reduced thyroid function. Excess weight is often one of the signs of dysfunction of this organ, so a decrease in fat deposits can be considered a kind of side effect of the drug. Taking L-Thyroxine exclusively for weight loss is strictly contraindicated, as this can lead to various health problems. In this regard, the drug should be prescribed only by a doctor after establishing an accurate diagnosis.
Analogs
Level 4 ATC code matches:
Thyroidin
Levothyroxine
Thyrotome
Tyreocomb
Euthyrox
Structural analogues of L-Thyroxine are L-Thyroxine Berlin-Chemie (in particular, L-Thyroxine 50 Berlin-Chemie and L-Thyroxine 100 Berlin-Chemie), L-Thyroxine produced by pharmaceutical and Farmak, Bagotirox , Levothyroxine , Eutirox .
Which is better: Eutirox or L-Thyroxine?
The drugs are generics, that is, they have the same indications for use, the same range of contraindications and are dosed similarly.
The difference between Eutirox and L-Thyroxine is that in Eutirox sodium levothyroxine is present in slightly different concentrations than in L-Thyroxine.
