Berlin-Chemie #Non_sex_hormones #Thyroid #HEALTH_CARE
Pharmacological properties
Pharmacodynamics
Mechanism of action. Synthetic levothyroxine, which is contained in the preparation L-Tyroxin 50, 75, 100, 125 and 150 Berlin-Chemie, is identical in biological activity to the natural thyroid hormone. There is no difference between endogenously formed and exogenous levothyroxine for the body.
Pharmacodynamic effects. After partial conversion to liothyronine (T3), mainly in the liver and kidneys, and the transition to the cells of the body, the characteristic effects of thyroid hormones are observed on the development, growth and metabolism.
Clinical efficacy and safety. Substitution of thyroid hormones leads to the normalization of metabolic processes. For example, taking levothyroxine leads to a significant decrease in elevated cholesterol levels associated with hypothyroidism.
Pharmacokinetics
Suction. The absorption of orally taken levothyroxine occurs mainly in the upper part of the small intestine, the degree of absorption of which mainly depends on the galenic form of the preparation and can be up to 80% when taken on an empty stomach. If the preparation is taken with food, its absorption is significantly reduced. Cmax in blood plasma is reached approximately 2-3 hours after application. The therapeutic effect is noted on the 3-5th day after the start of oral administration.
Distribution. The volume of distribution is about 10-12 liters. Levothyroxine binds to specific blood plasma proteins by approximately 99.97%. The binding of proteins to hormones is not covalent, thus there is a constant and very rapid exchange between free and bound hormone.
Excretion. The metabolic clearance of levothyroxine is about 1.2 liters of blood plasma per day. Cleavage occurs mainly in the liver, kidneys, brain, and muscles. Metabolites are excreted in urine and feces. T½ of the preparation is about 7 days. With thyrotoxicosis, this period is reduced to 3-4 days, and with hyperthyroidism, it is extended to 9-10 days.
During pregnancy and breastfeeding. Levothyroxine crosses the placenta only in small amounts. In the case of taking the preparation in usual doses, levothyroxine passes into breast milk only in small amounts.
Impaired renal function. Due to the high level of protein binding, neither hemodialysis nor hemoperfusion affects the level of levothyroxine.
Indications
L-thyroxine 50 berlin-chemi, l-thyroxine 100 berlin-chemi:
- benign goiter with euthyroid state of thyroid function;
- prevention of recurrence of goiter after resection of goiter with euthyroid state of thyroid function;
- replacement therapy for hypothyroidism of various etiologies;
- adjuvant for thyreostatic therapy of hyperthyroidism after reaching the euthyroid functional state;
- suppressive and replacement therapy for thyroid cancer, mainly after thyroidectomy.
Additional indication for L-Thyroxin 100 Berlin-Chemie and L-Thyroxin 150 Berlin-Chemie:
- as a diagnostic tool when performing a thyroid suppression test.
L-Thyroxin 75 Berlin-Chemie, L-Thyroxin 125 Berlin-Chemie, L-Thyroxin 150 Berlin-Chemie:
- replacement therapy for hypothyroidism of various etiologies;
- prevention of recurrence of goiter after resection of goiter with euthyroid state of thyroid function;
- benign goiter with euthyroid state of thyroid function;
- suppressive and replacement therapy for malignant tumors of the thyroid gland, mainly after thyroidectomy.
Additional indication for L-Thyroxin 75 Berlin-Chemie:
- adjuvant for thyreostatic therapy of hyperthyroidism after reaching the euthyroid functional state.
Application
L-thyroxine 50 berlin-chemi, l-thyroxine 100 berlin-chemi. dosing data should be considered as recommendations. the individual daily dose is determined based on the results of laboratory tests and clinical examination. thyroid hormone therapy should be started at a low dose and gradually increased (every 2–4 weeks) to the required therapeutic dose.
Because T4 or free thyroxine (fT4) levels may be elevated in some patients, plasma TSH is better suited for monitoring treatment regimen.
Adult patients. Benign goiter treatment: 75-200 mcg / day.
Prevention of recurrent goiter: 75-200 mcg / day.
Substitution therapy for hypothyroidism: the initial dose is 25-50 mcg / day, the maintenance dose is 100-200 mcg / day.
Concomitant therapy in the treatment of hyperthyroidism with thyreostatic agents: 50–100 mcg / day.
Suppressive and replacement therapy for thyroid cancer: 150–300 mcg / day.
When conducting a thyroid suppression test (for L-thyroxin 100 Berlin-Chemie): 200 μg (2 tablets) / day (14 days before the test).
Children with congenital and acquired hypothyroidism. The maintenance dose is usually 100–150 mcg of levothyroxine per m2 of body surface area per day.
For infants and children with congenital hypothyroidism, for whom immediate replacement therapy with levothyroxine is indicated, the recommended initial dose of levothyroxine in the first 3 months is 10-15 mcg / kg / day. In the future, the dose is adjusted on an individual basis according to the results of clinical studies, taking into account the indicators of the level of the thyroid hormone, as well as the level of TSH.
For children with acquired hypothyroidism, the initial dose of levothyroxine is 12.5–50 mcg / day, for which the preparation should be used in an appropriate dose. Based on clinical evidence regarding thyroid hormone levels as well as TSH levels, the dose should be increased gradually at intervals of 2–4 weeks until the full dose required for replacement therapy is reached. For infants and children under the age of 3 years, the full daily dose is added at least 30 minutes before the first feeding on that day. The tablets are preliminarily dissolved in a small amount of water (10-15 ml), and the resulting freshly prepared suspension is given to the child by adding a small amount of water (5-10 ml) to it.
Elderly patients. In some cases, in the elderly, for example, in patients with heart disease, preference should be given to a gradual decrease in the dose of levothyroxine sodium with a constant determination of the TSH level.
Experience shows that the use of the minimum dose is the optimal solution for low body weight and large nodular goiter.
The entire daily dose should be swallowed without chewing the tablets, washed down with a small amount of liquid, for example ½ glass of water. Take the preparation on an empty stomach, at least 30 minutes before breakfast.
Due to the special shape of the tablet, it can be divided as follows: place the tablet on a hard surface with a notch for dividing upwards and press it with your finger from above in a perpendicular direction.
Duration of treatment. The preparation is used throughout life with hypothyroidism, after surgical interventions - strumectomy or thyroidectomy, as well as to prevent relapses after removal of euthyroid goiter. The duration of use of the preparation as an adjuvant for the treatment of hyperthyroidism after reaching the euthyroid functional state corresponds to the period of thyreostatic therapy. With a mild form of euthyroid goiter, the duration of treatment is from 6 months to 2 years. If the patient's condition does not improve after treatment, then surgery or radioactive iodine therapy is prescribed.
Thyroid suppression test. When performing a thyroid suppression test, take 150-200 mcg of levothyroxine sodium daily for 14 days.
L-Thyroxin 75 Berlin-Chemie, L-Thyroxin 125 Berlin-Chemie, L-Thyroxin 150 Berlin-Chemie. Dosing data should be considered as recommendations. The individual daily dose is determined based on the results of laboratory tests and clinical examination. If the thyroid gland remains at a minimum, the minimum effective dose should be used.
In elderly patients, patients with coronary artery disease and with severe or chronic hypothyroidism, treatment with thyroid hormones should be started with extreme caution, for example, it is recommended to start treatment with a low dose and increase it slowly, at long intervals, often controlling the level of thyroid hormones. Considering the experience of using both in patients with low body weight and in patients with large nodular goiter, lower doses of the preparation are sufficient.
Since the level of T4 or free thyroxine (fT4) may be elevated in some patients, the determination of the serum TSH concentration is better for monitoring the treatment regimen.
Adult patients
Hypothyroidism The initial dose is 25-50 mcg / day, the maintenance dose is 100-200 mcg / day (the dose is increased by 25-50 mcg at intervals of 2-4 weeks).
Prevention of goiter recurrence - 75-200 mcg / day.
Benign goiter with euthyroid state of function - 75-200 mcg / day.
Concomitant therapy in the treatment of hyperthyroidism with thyreostatics - 50-100 mcg / day.
After thyroidectomy for a malignant tumor - 150–300 mcg / day.
When conducting a thyroid suppression test (for L-thyroxin 150 Berlin-Chemie): 150 μg (1 tablet) / day (14 days before the test).
If dose adjustment for this preparation is not possible, there are preparations at a different dosage. You should consult your doctor for a recommendation.
Children with congenital and acquired hypothyroidism. The maintenance dose is usually 100–150 mcg of levothyroxine per m2 of body surface area per day.
For infants and children with congenital hypothyroidism, for whom immediate replacement therapy with levothyroxine is indicated, the recommended initial dose of levothyroxine in the first 3 months is 10-15 mcg / kg / day. In the future, the dose is adjusted on an individual basis according to the results of clinical studies, taking into account the indicators of the level of the thyroid hormone, as well as the level of TSH.
For children with acquired hypothyroidism, the initial dose of levothyroxine is 12.5–50 mcg / day, for which the preparation should be used in an appropriate dose. Based on clinical evidence regarding thyroid hormone levels as well as TSH levels, the dose should be increased gradually at intervals of 2–4 weeks until the full dose required for replacement therapy is reached. For children, take the full daily dose at least 30 minutes before the first feeding on that day. The tablets can also be taken in suspension form. The tablets are preliminarily dissolved in a small amount of water (10-15 ml), and the resulting freshly prepared suspension is given to the child by adding a small amount of water (5-10 ml) to it.
Elderly patients. In some cases, in elderly patients, for example, in patients with heart disease, preference should be given to a gradual decrease in the dose of levothyroxine sodium with a constant determination of the TSH level.
The entire daily dose should be swallowed without chewing the tablets, washed down with a small amount of liquid. Take the preparation on an empty stomach, at least 30 minutes before breakfast.
Due to the special shape of the tablet, it can be divided as follows: place the tablet on a hard surface with a notch for dividing upwards and press it with your finger from above in a perpendicular direction.
Duration of treatment
The preparation is usually used throughout life for hypothyroidism and after thyroidectomy due to a malignant tumor of the thyroid gland; with euthyroid goiter and for the prevention of recurrence of goiter - from several months or years to use throughout life, as an adjunct in the treatment of hyperthyroidism - depending on the duration of thyrostatic therapy.
The duration of treatment for euthyroid goiter should be from 6 months to 2 years. If the patient's condition does not improve after treatment with L-thyroxine 75 Berlin-Chemie or L-thyroxine 125 Berlin-Chemie or L-thyroxine 150 Berlin-Chemie, other therapeutic approaches should be considered.
Thyroid suppression test. When performing a thyroid suppression test, take 150-200 mcg of levothyroxine sodium daily for 14 days.
Contraindications
Hypersensitivity to the active substance or any of the components of the preparation; untreated hyperthyroidism of any etiology; untreated adrenal cortex insufficiency; untreated pituitary insufficiency; acute myocardial infarction; acute myocarditis; acute pancarditis.
During pregnancy, the simultaneous use of levothyroxine and any thyrostatic agent is contraindicated. (For more information on use during pregnancy and lactation, see section Use during pregnancy and lactation).
Side effects
If the patient is intolerant of the dose of the preparation, which is very rare, or in case of an overdose, especially if the dose is increased too quickly at the beginning of treatment, typical symptoms of hyperthyroidism may occur.
In these cases, it is recommended to reduce the daily dose or stop using the preparation for several days. When the side effects disappear, the treatment is resumed, carefully selecting the dose of the preparation.
In case of hypersensitivity to levothyroxine or any of the excipients of the preparation, allergic reactions from the skin (for example, skin rash, urticaria) and the respiratory tract may occur. There are isolated reports of the development of anaphylactic shock. In this case, the use of the preparation should be discontinued.
Adverse reactions are classified by frequency of occurrence as follows: very often (≥1 / 10); often (from? 1/100 to 1/10); sometimes (from ≥1 / 1000 to 1/100); rarely (from ≥1 / 10,000 to 1/1000); very rare (1/10 000); the frequency is unknown (cannot be estimated from the available data).
From the immune system: frequency unknown - hypersensitivity.
From the side of the heart: very often - palpitations; often - tachycardia; unknown - arrhythmia, angina pectoris.
On the part of the skin and subcutaneous tissue: the frequency is unknown - rash, urticaria, hyperhidrosis.
Mental disorders: very often - insomnia; often - nervousness; frequency unknown - feeling of inner anxiety.
On the part of the musculoskeletal system and connective tissue: the frequency is unknown - muscle weakness, muscle cramps, osteoporosis against the background of the use of depressing doses of levothyroxine, especially in postmenopausal women, mainly during long-term treatment.
From the side of the vessels: the frequency is unknown - a feeling of heat, collapse (acute vascular insufficiency) in premature infants with very low birth weight (see SPECIAL INSTRUCTIONS).
Reproductive system and breast disorders: frequency unknown - menstrual irregularities.
From the gastrointestinal tract: the frequency is unknown - diarrhea, vomiting.
The results of additional research methods: frequency is unknown - weight loss.
From the side of the nervous system: very often - headache; rarely - pseudotumor of the brain (mainly in children); frequency unknown - tremor.
General disorders and reactions at the injection site: frequency unknown - heat intolerance, fever.
Reporting suspected adverse reactions. It is extremely important to report suspected adverse reactions after a medicinal product is registered. This makes it possible to continuously monitor the benefit / risk ratio of the medicinal product. Health professionals are asked to be sure to report any suspected adverse reactions through the national reporting system.
Special instructions
Before starting therapy with thyroid hormones or thyroid suppression tests, it is necessary to exclude the presence or treat the following diseases or conditions: coronary heart disease, angina pectoris, arterial hypertension, pituitary insufficiency and / or adrenal cortex insufficiency.
The functional autonomy of the thyroid gland should also be excluded or cured before starting treatment with thyroid hormones.
In the case of coronary artery disease, heart failure, tachyarrhythmias, myocarditis in remission, chronic hypothyroidism, or in patients who have had myocardial infarction, it is imperative to avoid pharmacologically induced hyperthyroidism, even mild ones.
When carrying out therapy with thyroid hormones in these patients, frequent monitoring of thyroid hormone parameters should be carried out (see APPLICATION).
In the case of secondary hypothyroidism, it is necessary to check for the presence of concomitant adrenal insufficiency. If this disease is detected, first of all, replacement therapy (hydrocortisone) should be carried out. Without adequate supply of corticosteroids, thyroid hormone therapy in patients with adrenal or pituitary insufficiency can lead to an Addison crisis.
Due to the immaturity of adrenal function and possible collapse (acute vascular insufficiency) (see SIDE EFFECTS), special care should be taken when initiating levothyroxine therapy in premature infants with very low birth weight.
If autonomic thyroiditis is suspected, TSH levels should be determined or thyroscintigraphy performed prior to treatment.
In postmenopausal women, there is an increased risk of osteoporosis, therefore it is necessary to select (titrate) the dose of levothyroxine until the minimum effective dose is reached, and also, in order to avoid an increase in the concentration of levothyroxine in the blood above the physiological level, the function of the thyroid gland should be checked more often in these patients (see . SIDE EFFECTS).
Thyroid hormones should not be used to reduce body weight. The appointment of physiological doses does not lead to a decrease in body weight in patients with an euthyroid state. Higher doses can lead to serious or even life-threatening adverse reactions, especially when combined with certain weight loss preparations.
If a regime of therapy with levothyroxine is established, the transition to another preparation containing thyroid hormones should be carried out only under the supervision of laboratory tests and clinical data.
In patients concurrently taking levothyroxine and other preparations that can affect the thyroid gland (amiodarone, tyrosine kinase inhibitors, salicylates and high doses of furosemide), thyroid function should be monitored (see INTERACTIONS).
For patients with diabetes mellitus and patients receiving anticoagulants, see INTERACTIONS.
Cases of hypothyroidism have been reported in patients simultaneously receiving sevelamer and levothyroxine. Therefore, in such patients who receive both preparations, it is necessary to carefully monitor the level of TTG (also see INTERACTIONS).
Use during pregnancy and lactation
Pregnancy. Treatment with thyroid hormones must be carried out consistently during pregnancy.
For optimal maternal and fetal health, it is important that thyroid hormone levels remain within the normal range.
Despite its widespread use during pregnancy, there is no evidence of side effects of levothyroxine on the course of pregnancy or on the health of the fetus / newborn.
Due to estrogens, the need for levothyroxine during pregnancy may increase. For this reason, during pregnancy, the function of the thyroid gland should be monitored, and, if necessary, the dose of thyroid hormone should be adjusted.
During pregnancy, the use of levothyroxine sodium is contraindicated as an adjuvant in the treatment of hyperthyroidism with thyreostatic preparations. Additional administration of levothyroxine may require an increase in the dose of thyreostatics. Thyrostatic preparations, unlike levothyroxine, penetrate the placental barrier in significant doses. This can lead to the development of fetal hypothyroidism. For this reason, in pregnant women with hyperthyroidism, thyrostatics should always be used as monotherapy and in low doses.
It is forbidden to perform a thyroid suppression test during pregnancy.
Lactation. Treatment with thyroid hormones must be carried out consistently during lactation. Currently, there is no information on the presence of side effects of levothyroxine on the health of the newborn. The amount of thyroid hormones that pass into breast milk during breastfeeding, even in the case of high-dose thyroid hormone therapy, is insufficient for the development of hyperthyroidism in infants or suppression of TSH secretion.
Due to estrogen, the need for levothyroxine may increase during pregnancy. Therefore, after pregnancy, the function of the thyroid gland should be monitored, and, if necessary, the dose of thyroid hormone should be adjusted.
It is forbidden to perform the thyroid suppression test during breastfeeding.
Children. The preparation is used in pediatric practice. Detailed information on the recommended doses and methods of application of the preparation is given in the APPLICATION section.
The ability to influence the reaction rate when driving or operating other mechanisms. No relevant studies have been carried out.
Interactions
Antidiabetic preparations. levothyroxine can reduce the severity of the blood-lowering effect of antidiabetic preparations (eg metformin, glimepiride, glibenclamide and insulin). it is recommended to carry out frequent monitoring of blood glucose levels in diabetes mellitus, especially at the beginning and end of treatment with thyroid hormones, and, if necessary, adjust the dose of a hypoglycemic preparation.
Coumarin derivatives Levothyroxine can enhance the effect of coumarin derivatives by displacing them from the sites of binding to blood plasma proteins. Therefore, in the case of simultaneous use, it is necessary to regularly monitor the coagulation parameters, and, if necessary, adjust (reduce) the dose of anticoagulants.
Ion exchange resins. Ion exchange resins such as cholestyramine, colestipol, or the calcium and sodium salts of polystyrene sulfonic acid inhibit the absorption of levothyroxine by binding thyroid hormones in the gastrointestinal tract; therefore, they should not be used earlier than 4–5 hours after taking L-Thyroxin Berlin Chemie.
Bile acid binders. Kolesevelam binds levothyroxine and thus reduces the absorption of levothyroxine in the gastrointestinal tract. No interaction was observed in the case of using levothyroxine at least 4 hours before taking colesevelam. Therefore, L-Tyroxin Berlin-Chemie should be used at least 4 hours before taking the wheelchair.
Aluminum-containing antacids, as well as iron-containing and calcium-containing preparations. The absorption of levothyroxine may decrease in the case of the simultaneous use of aluminum-containing antacids (antacids, sucralfate), iron-containing preparations and calcium-containing preparations. Therefore, L-Tyroxin Berlin-Chemie should be taken at least 2 hours before taking these funds.
Sevelamer and lanthanum carbonate. Sevelamer and lanthanum carbonate may reduce the bioavailability of levothyroxine (see also SPECIAL INSTRUCTIONS).
Propylthiouracil, GCS and β-adrenergic receptor blockers (especially propranolol). These substances inhibit the conversion of thyroxine (T4) to T3 and can lead to a decrease in the concentration of T3 in the blood plasma.
Amiodarone and iodinated X-ray contrast agents. Due to their high iodine content, amiodarone and iodinated X-ray contrast agents can cause both hyper- and hypothyroidism. Special care should be taken for nodular goiter with possible undefined autonomy. Amiodarone inhibits the conversion of T4 to T3, resulting in a decrease in the concentration of T3 and an increase in the level of TSH in the blood plasma. Due to the effect of amiodarone on the function of the thyroid gland, it may be necessary to adjust the dose of the preparation L-Tyroxin Berlin-Chemie.
Salicylates, dicumarol, furosemide, clofibrate. Salicylates (especially at a dose of 2 g / day), dicumarol, high doses of furosemide (250 mg), clofibrate and other substances can displace levothyroxine from the sites of binding to blood plasma proteins. This can lead to an initial transient increase in free thyroid hormone levels, which leads to a decrease in total thyroid hormone levels.
Estrogen-containing contraceptives, preparations for hormone replacement therapy in the postmenopausal period. The need for levothyroxine may increase with the use of estrogen-containing contraceptives or hormone replacement therapy in the postmenopausal period. An increase in the binding of levothyroxine is possible, which can lead to errors in diagnosis and treatment.
Sertraline, chloroquine / proguanil These substances reduce the effectiveness of levothyroxine and increase serum TSH levels.
Enzyme-inducing preparations. Barbiturates, rifampicin, carbamazepine, phenytoin and other preparations that can activate liver enzymes can increase hepatic clearance of levothyroxine and lead to a decrease in its level in blood plasma.
Protease inhibitors (eg ritonavir, indinavir, lopinavir). There are reports of a loss of the therapeutic effect of levothyroxine when combined with lopinavir / ritonavir. Thus, in patients concomitantly taking levothyroxine and protease inhibitors, careful monitoring of clinical symptoms and thyroid function is necessary. The dose of levothyroxine should be adjusted if necessary.
Tyrosine kinase inhibitors. Tyrosine kinase inhibitors (eg imatinib, sunitinib, sorafenib, motesanib) can reduce the effectiveness of levothyroxine. Therefore, in patients taking levothyroxine and tyrosine kinase inhibitors at the same time, careful monitoring of clinical symptoms and indicators of thyroid function is necessary. The dose of levothyroxine should be adjusted if necessary.
Preparations containing soy. Preparations containing soy can inhibit the absorption of levothyroxine in the intestine.
Increased serum TSH levels have been reported in children on a soy diet and treated with levothyroxine due to congenital hypothyroidism. To achieve normal serum T4 and TSH levels, high doses of levothyroxine are recommended. Serum T4 and TSH levels should be carefully monitored during and after completion of the soy diet, and levothyroxine dose adjustment may be necessary.
Overdose
In case of an overdose, there is a rapid pulse, increased heartbeat, anxiety, fever, fever, increased sweating, arrhythmia, insomnia, tremors, increased frequency of angina attacks, anxiety, weight loss, vomiting, diarrhea, headache, weakness and muscle cramps , violation of the menstrual cycle, pseudotumor of the brain. there have been reports of isolated cases of epileptic seizures in the corresponding category of patients when the individual tolerated dose limit was exceeded. it is recommended to stop taking the preparation and conduct a follow-up examination.
An increase in T3 levels is a reliable indicator of preparation overdose than an increase in T4 and fT4 levels.
In case of overdose and intoxication, symptoms occur that are characteristic of a moderate or significant acceleration of metabolism (see SIDE EFFECTS). Depending on the degree of overdose, it is recommended to stop taking the preparation and conduct a follow-up examination.
In cases of human intoxication (attempted suicide), levothyroxine at a dose of up to 10 mg is tolerated without complications. The development of such serious complications as a violation of vital functions (breathing and circulation) is unlikely, provided that there is no history of coronary heart disease. Despite this, the development of thyrotoxic crisis, seizures, heart failure and coma were reported. There have been isolated reports of cases of sudden death associated with cardiac dysfunction in patients who have been taking high doses of levothyroxine for a long time.
In cases of acute overdose, absorption of the preparation in the gastrointestinal tract can be reduced by taking activated carbon. Treatment is usually symptomatic and supportive. Severe beta-sympathomimetic symptoms, such as tachycardia, anxiety, agitation, or hyperkinesia, can be alleviated by the use of beta-adrenergic receptor blockers. The use of thyrostatics is not indicated, since the function of the thyroid gland is already completely suppressed.
In the case of taking the preparation in extremely high doses (suicide attempt), it is advisable to carry out plasmapheresis.
In case of an overdose of levothyroxine, long-term observation is necessary. Due to the gradual conversion of levothyroxine to liothyronine, the development of symptoms may be delayed up to 6 days.
Storage conditions
At a temperature not exceeding 25 ° c.
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