L-thyroxine 100 Berlin-Chemie tablets 100 mcg No. 50

Instructions for L-thyroxine 100 Berlin-Chemie tablets 100 mcg No. 50

Composition

active ingredient: levothyroxine sodium;

1 tablet contains levothyroxine sodium 50 mcg or 100 mcg;

Excipients: cysteine hydrochloride, monohydrate (partly contained in tablets as cystine); microcrystalline cellulose; pregelatinized starch; corn starch; light magnesium oxide; talc.

Dosage form

Pills.

Main physicochemical properties

L-Thyroxine 50 Berlin-Chemie: round, slightly convex tablets from white to beige in color, with a dividing line on one side.

L-Thyroxine 100 Berlin-Chemie: round, slightly convex tablets from white to beige in color, with a dividing line on one side.

The tablet can be divided into equal doses.

Pharmacotherapeutic group

Thyroid therapy, thyroid hormones. ATC code H03A A01.

Pharmacological properties

Pharmacodynamics.

Mechanism of action.

Synthetic levothyroxine, which is contained in the preparations L-Thyroxine 50 Berlin-Chemie and L-Thyroxine 100 Berlin-Chemie, is identical in its action to the natural thyroid hormone, which is produced mainly by the thyroid gland. There are no differences between endogenously formed and exogenous levothyroxine for the body.

Pharmacodynamic effects.

After partial conversion to liothyronine (T3), mainly in the liver and kidneys, and transfer to the body's cells, the characteristic effects of thyroid hormones are observed on development, growth, and metabolism through activation of T3 receptors.

Clinical efficacy and safety.

Thyroid hormone replacement leads to normalization of metabolic processes. For example, taking levothyroxine leads to a significant reduction in elevated cholesterol levels caused by hypothyroidism.

Pharmacokinetics.

Absorption.

Absorption of orally administered levothyroxine occurs mainly in the upper small intestine, the degree of absorption of which depends mainly on the galenic form of the drug and can be up to 80% when taken on an empty stomach. If the drug is taken with food, its absorption is significantly reduced.

The maximum concentration in blood plasma is reached approximately 2-3 hours after administration.

The effect of the drug is observed 3-5 days after the start of oral therapy.

Distribution.

The volume of distribution is approximately 10-12 L. Levothyroxine is approximately 99.97% bound to specific plasma proteins. The protein-hormone binding is not covalent, so there is a constant and very rapid exchange between free and bound hormone.

Breeding.

The metabolic clearance of levothyroxine is approximately 1.2 liters of plasma per day. The main routes of metabolism are the liver, kidneys, brain, and muscles. Metabolites are excreted in the urine and feces. The half-life of the drug is approximately 7 days; this is shortened (to 3-4 days) in hyperthyroidism and prolonged (to approximately 9-10 days) in hypothyroidism.

Pregnancy and breastfeeding.

Levothyroxine crosses the placenta only in small amounts. When taking the drug in normal doses, levothyroxine is excreted in breast milk only in small amounts.

Kidney dysfunction.

Due to the high level of protein binding, neither hemodialysis nor hemoperfusion affects levothyroxine levels.

Indication

L-THYROXINE 50 BERLIN-CHEMI, L-THYROXINE 100 BERLIN-CHEMI:

• benign goiter with euthyroid thyroid function;
• prevention of goiter recurrence after goiter resection with euthyroid thyroid function;
• replacement therapy for hypothyroidism of various etiologies;
• an adjunct to thyrostatic therapy of hyperthyroidism after achieving a euthyroid functional state;
• suppressive and replacement therapy for thyroid cancer, mainly after thyroidectomy.

For L-THYROXINE 100 BERLIN-CHEMI:

• as a diagnostic tool when performing a thyroid suppression test.

Contraindication

Hypersensitivity to the active substance or to any of the excipients of the drug. Untreated hyperthyroidism of any origin. Untreated adrenal insufficiency. Untreated pituitary insufficiency (this leads to adrenal insufficiency requiring treatment). Acute myocardial infarction. Acute myocarditis. Acute pancarditis.

During pregnancy, the simultaneous use of levothyroxine and any thyreostatic agent is contraindicated (for more detailed information on use during pregnancy or breastfeeding, see the section “Use during pregnancy or breastfeeding”).

Interaction with other medicinal products and other types of interactions

Antidiabetic agents

Levothyroxine may reduce the blood sugar-lowering effect of antidiabetic drugs (e.g. metformin, glimepiride, glibenclamide and insulin). It is recommended to monitor blood glucose levels more frequently in diabetes mellitus, especially at the beginning and end of thyroid hormone treatment. If necessary, adjust the dose of the hypoglycemic drug.

Levothyroxine may enhance the effect of coumarin derivatives by displacing them from plasma protein binding sites. Therefore, in case of simultaneous use, it is necessary to regularly monitor coagulation parameters and, if necessary, adjust (reduce) the dose of anticoagulant drugs.

Ion exchange resins

Ion exchange resins such as cholestyramine, colestipol or calcium and sodium salts of polystyrene sulfonic acid inhibit the absorption of levothyroxine by binding thyroid hormones in the gastrointestinal tract; therefore, they should be used 4–5 hours after taking L-Thyroxin Berlin-Chemie.

Proton pump inhibitors (PPIs):

Concomitant use with PPIs may result in reduced absorption of thyroid hormones due to the increase in gastric pH caused by the PPI. Regular monitoring of thyroid function and clinical observation are recommended during concomitant treatment. An increase in the dose of thyroid hormones may be necessary. Caution should also be exercised when PPI treatment is discontinued.

Drugs that bind bile acids

Colesevelam binds levothyroxine and thus reduces the absorption of levothyroxine from the gastrointestinal tract. No interaction has been observed when levothyroxine is administered at least 4 hours before colesevelam. Therefore, L-Thyroxine Berlin-Chemie should be administered at least 4 hours before colesevelam.

Aluminum-containing antacids, as well as iron- and calcium-containing drugs

The absorption of levothyroxine may be reduced by concomitant use of aluminum-containing antacids (antacids, sucralfate), iron-containing and calcium-containing drugs. L-Thyroxine Berlin-Chemie should be taken at least 2 hours before taking these drugs.

Sevelamer and lanthanum carbonate

Sevelamer and lanthanum carbonate may reduce the bioavailability of levothyroxine (see also section "Special warnings and precautions for use").

Propylthiouracil, glucocorticoids, and beta-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 radiocontrast agents

Due to the high iodine content, amiodarone and iodinated radiopaque agents can cause both hyperthyroidism and hypothyroidism. Particular caution should be exercised in nodular goiter with possible undetermined autonomy. Amiodarone inhibits the conversion of T4 to T3, resulting in a decrease in T3 concentration and an increase in thyroid-stimulating hormone (TSH) levels in the blood plasma. Due to the effect of amiodarone on thyroid function, a dosage adjustment of L-Thyroxin Berlin-Chemie may be necessary.

Salicylates, dicumarol, furosemide, clofibrate

Salicylates (especially at doses above 2 g/day), dicumarol, high doses of furosemide (250 mg), clofibrate and other substances may displace levothyroxine from plasma protein binding sites. This may lead to an initial transient increase in free thyroid hormone levels, leading to a decrease in total thyroid hormone levels.

Estrogen-containing contraceptives, drugs 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. Increased binding of levothyroxine is possible, which may lead to errors in diagnosis and treatment.

Sertraline, chloroquine/proguanil

These substances reduce the effectiveness of levothyroxine and increase serum TSH levels.

Cytochrome P450 inducers

Enzyme-inducing drugs such as rifampicin, carbamazepine, phenytoin, barbiturates and 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 hormones if these drugs are administered concomitantly.

Protease inhibitors

There have been reports of loss of therapeutic effect of levothyroxine when co-administered with lopinavir/ritonavir. Therefore, patients receiving levothyroxine and protease inhibitors should be closely monitored for clinical symptoms and thyroid function. Patients receiving levothyroxine should have their TSH levels monitored for at least the first month after starting and/or stopping ritonavir treatment.

Tyrosine kinase inhibitors

Tyrosine kinase inhibitors (e.g. imatinib, sunitinib, sorafenib, motezanib) may reduce the efficacy of levothyroxine. Therefore, patients receiving levothyroxine and tyrosine kinase inhibitors concomitantly should be closely monitored for clinical symptoms and thyroid function. If necessary, the dose of levothyroxine should be adjusted.

Soy products may inhibit the intestinal absorption of levothyroxine. There have been reports of increased serum TSH levels in children on a soy diet who were treated with levothyroxine for congenital hypothyroidism. High doses of levothyroxine are recommended to achieve normal serum T4 and TSH levels. Serum T4 and TSH levels should be closely monitored during and after the soy diet; dose adjustment of levothyroxine may be necessary.

Orlistat

Hypothyroidism and/or decreased control of hypothyroidism may occur when levothyroxine and orlistat are used concomitantly. This may be due to reduced absorption of levothyroxine.

Impact on laboratory test results

Biotin may interfere with the results of immunoassays for thyroid function that are based on the biotin/streptavidin interaction, resulting in falsely low or falsely high test results (see section "Special warnings and precautions for use").

Application features

Before initiating thyroid hormone therapy or testing for thyroid suppression, the following diseases or conditions should be ruled out or treated:

• Coronary heart disease
• Angina pectoris
• Hypertension
• Pituitary insufficiency and/or adrenal insufficiency.

Thyroid autonomy should also be ruled out or treated before starting treatment with thyroid hormones.

In ischemic heart disease, heart failure, tachyarrhythmia, myocarditis outside the acute phase, chronic hypothyroidism or in patients who have suffered a myocardial infarction, pharmacologically induced hyperthyroidism, even in its mild degree, must be avoided. When conducting thyroid hormone therapy in these patients, more frequent monitoring of thyroid hormone levels should be carried out (see section "Method of administration and dosage").

In case of secondary hypothyroidism, it is necessary to check for concomitant adrenocortical insufficiency. If this disease is present, replacement therapy (hydrocortisone) should be carried out first. Without adequate corticosteroid supply, thyroid hormone therapy in patients with adrenocortical or pituitary insufficiency may cause an Addisonian crisis.

When initiating levothyroxine therapy, hemodynamic parameters should be monitored in premature infants with very low birth weight, as circulatory disorders may occur due to immaturity of adrenal function.

If autonomous thyroiditis is suspected, TSH levels should be determined or thyroid scintigraphy should be performed before starting treatment.

Postmenopausal women are at increased risk of osteoporosis; therefore, it is necessary to titrate the dose of levothyroxine sodium to the minimum effective dose and, in order to avoid an increase in the concentration of levothyroxine in the blood above the physiological level, these patients should have their thyroid function checked more frequently (see section 4.8).

Thyroid hormones should not be used for weight loss. Physiological doses do not result in weight loss in euthyroid patients. Higher doses may result in serious or even life-threatening adverse reactions, especially when combined with some weight loss agents.

Hypersensitivity reactions (including angioedema) have been reported, sometimes serious, with levothyroxine. If signs and symptoms of allergic reactions occur, levothyroxine therapy should be discontinued and appropriate symptomatic treatment should be initiated (see sections 4.3 and 4.8).

If a levothyroxine therapy regimen is established, switching to another drug containing thyroid hormones should only be done under the control of laboratory tests and clinical data.

In patients taking levothyroxine concomitantly with other medicinal products that may affect the thyroid gland (e.g. amiodarone, tyrosine kinase inhibitors, salicylates and high doses of furosemide), thyroid function should be monitored (see also section 4.5).

For patients with diabetes mellitus and patients receiving anticoagulants, see section “Interaction with other medicinal products and other types of interactions”.

Hypothyroidism has been reported in patients receiving sevelamer and levothyroxine concomitantly. Therefore, TSH levels should be closely monitored in such patients receiving both drugs (see also section 4.5).

Biotin may interfere with thyroid assays based on biotin/streptavidin interactions, 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 potential for biotin interactions should be considered, especially if there is a lack of agreement with the clinical picture. For patients taking biotin-containing products, laboratory personnel should be informed of the best time to perform thyroid function tests. 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 medicinal product contains less than 1 mmol (23 mg) sodium/tablet, i.e. essentially sodium-free.

Use during pregnancy or breastfeeding

Pregnancy.

Thyroid hormone treatment should be continued throughout pregnancy. It is important that thyroid hormone levels remain within normal limits to ensure optimal maternal and fetal health.

Despite its widespread use during pregnancy, there is no information on the presence of undesirable effects of levothyroxine on the course of pregnancy or on the health of the fetus/newborn.

Due to estrogen, the need for levothyroxine may increase during pregnancy. For this reason, thyroid function should be monitored during pregnancy and, if necessary, the dose of thyroid hormone should be adjusted.

During pregnancy, the use of levothyroxine as an adjunct to thyrostatic drugs in the treatment of hyperthyroidism is contraindicated. When levothyroxine is additionally taken, an increase in the dose of thyrostatic drugs may be required. Thyrostatic drugs, unlike levothyroxine, penetrate the placental barrier in significant doses. This can cause the development of fetal hypothyroidism. For this reason, in pregnant women with hyperthyroidism, thyrostatic drugs should always be used as monotherapy and in low doses.

It is forbidden to perform a test for thyroid suppression during pregnancy.

Breast-feeding.

Thyroid hormone treatment should be continued during breastfeeding. There is currently no information on the presence of undesirable effects of levothyroxine on the health of the newborn. The amount of thyroid hormone that penetrates into breast milk during breastfeeding, even with high-dose thyroid hormone therapy, is insufficient to cause hyperthyroidism or suppression of TSH secretion in infants.

Due to estrogen, the need for levothyroxine may increase during pregnancy. For this reason, thyroid function should be monitored after pregnancy and, if necessary, the dose of thyroid hormone should be adjusted.

It is forbidden to perform a test for thyroid suppression during breastfeeding.

Fertility

Hypothyroidism or hyperthyroidism is likely to affect fertility. Treatment of hypothyroidism with levothyroxine should be adjusted based on laboratory monitoring, as an insufficient dose will not have a positive effect and an overdose may lead to hyperthyroidism.

Ability to influence reaction speed when driving vehicles or other mechanisms

No relevant studies have been conducted to study the effect on the ability to drive or use other mechanisms.

Method of administration and doses

The dosage data should be considered as recommendations. The individual daily dose of the drug should be determined on the basis 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, serum TSH levels are more appropriate for monitoring treatment regimens.

Adult patients.

Treatment of benign goiter: 75-200 mcg/day.

Prevention of goiter recurrence: 75-200 mcg/day.

Replacement therapy for hypothyroidism: initial dose is 25-50 mcg/day, 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 performing a thyroid suppression test (only for L-Thyroxine 100 Berlin-Chemie): 200 mcg (equivalent to 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 1 m2 of body surface area per day.

For children with acquired hypothyroidism, the recommended starting dose is 12.5-50 mcg of levothyroxine per day, for which the drug should be used in the appropriate dosage. Based on clinical data on thyroid hormone, 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 3 years of age, the full daily dose should be administered at least 30 minutes before the first feeding of the day. The tablets can also be taken in the form of a suspension. The tablets should be dissolved in a small amount of water (10-15 ml) beforehand, and the resulting freshly prepared suspension should be given to the child, adding a small amount of water (5-10 ml).

Elderly patients.

In some cases, for elderly patients, for example, for patients with heart disease, a gradual reduction in the dose of levothyroxine sodium with constant determination of TSH levels should be preferred.

Experience shows that using the lowest dose is the optimal solution for low body weight and large nodular goiter.

The entire daily dose should be swallowed whole, without chewing the tablets, with a small amount of liquid, such as ½ glass of water. Take the drug 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 the dividing notch facing up and press on it with your finger from above in a perpendicular direction.

Duration of treatment.

The drug is usually used throughout life for hypothyroidism, after surgical interventions - strumectomy or thyroidectomy, as well as to prevent relapses after removal of euthyroid goiter. The duration of use of the drug as an auxiliary agent for the treatment of hyperthyroidism after achieving a euthyroid functional state corresponds to the duration of thyreostatic therapy. In mild forms of euthyroid goiter, the duration of treatment is from 6 months to 2 years. If the patient's condition does not improve after treatment, surgery or radioactive iodine therapy should be prescribed.

Thyroid suppression test.

When testing for thyroid suppression, take 150-200 mcg of levothyroxine sodium daily for 14 days.

Children.

The drug can be used in pediatric practice. Detailed information on the recommended doses and method of administration of the drug is provided in the section "Method of administration and dosage".

Overdose

In case of overdose, there is an accelerated pulse, rapid heartbeat, a feeling of anxiety, a feeling of heat, an increase in body temperature, increased sweating, arrhythmia, insomnia, tremor, an increase in the frequency of angina attacks, anxiety, weight loss, vomiting, diarrhea, headache, weakness and muscle cramps, menstrual disorders, pseudotumor cerebri. There have been reports of isolated cases of epileptic seizures in the relevant category of patients when the limit of the individual tolerated dose was exceeded.

It is recommended to stop taking the drug and conduct follow-up examinations.

Elevated T3 levels are a more reliable indicator of drug overdose than elevated T4 and fT4 levels.

In case of overdose and intoxication, symptoms characteristic of moderate or significant acceleration of metabolism occur (see section "Adverse reactions"). Depending on the degree of overdose, it is recommended to stop taking the drug and undergo a control examination.

In cases of intoxication in humans (suicide attempts), levothyroxine in doses up to 10 mg is tolerated without complications. The development of such serious complications as impaired vital functions (respiration and blood circulation) is unlikely, provided that there is no history of ischemic heart disease. Despite this, there are reports of the development of thyrotoxic crisis, seizures, heart failure and coma. There have been isolated reports of sudden death associated with cardiac dysfunction in patients who have used elevated doses of levothyroxine for a long time.

In cases of acute overdose, absorption from the gastrointestinal tract can be reduced by taking activated charcoal. Treatment is usually symptomatic and supportive. In the case of severe beta-sympathomimetic symptoms such as tachycardia, anxiety, agitation or hyperkinesia, they can be reduced by using beta-adrenergic blockers. Thyrostatic agents should not be used in this case, since thyroid function is already completely suppressed.

In extreme doses (suicide attempts), plasmaphoresis may help.

In case of overdose with levothyroxine, prolonged observation is necessary. Due to the gradual conversion of levothyroxine to liothyronine, the development of symptoms may be delayed by up to 6 days.

Adverse reactions

If the dose is not tolerated by the patient, which is very rare, or in the event of overdose, especially if the dose is increased too quickly at the beginning of treatment, typical symptoms of hyperthyroidism may occur.

In case of hypersensitivity to levothyroxine or any of the excipients of the drug, allergic reactions of the skin (e.g. angioedema, skin rash, urticaria) and respiratory tract are possible. There are isolated reports of the development of anaphylactic shock. In this case, the use of the drug should be discontinued.

Adverse reactions are classified by frequency of occurrence as follows:

On the part of the immune system

Not known: hypersensitivity

From the endocrine system:

Common: hyperthyroidism

From the heart

Very common: rapid heartbeat

Common: tachycardia

Not known: arrhythmia, angina pectoris

Skin and subcutaneous tissue disorders

Not known: angioedema, rash, urticaria, hyperhidrosis

Mental disorders

Very common: insomnia

Common: nervousness

Unknown: feeling of inner restlessness

Musculoskeletal and connective tissue disorders

Not known: muscle weakness, muscle cramps, osteoporosis with suppressive doses of levothyroxine, especially in postmenopausal women, mainly during long-term treatment

From the vascular side

Not known: feeling hot, collapse (acute vascular insufficiency) in premature infants with very low birth weight (see section "Special warnings and precautions for use")

Reproductive system and breast disorders

Not known: menstrual irregularities

Gastrointestinal tract

Not known: diarrhea, vomiting and nausea

Results of additional research methods

Not known: weight loss

From the nervous system

Very common: headache

Rare: pseudotumor cerebri (predominantly in children)

Not known: tremor

General disorders and administration site conditions

Not known: heat intolerance, fever

Reporting of suspected adverse reactions.

Reporting of adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should be informed of all cases of suspected adverse reactions and

lack of effectiveness of the medicinal product through the Automated Pharmacovigilance Information System at the link: https://aisf.dec.gov.ua.

Expiration date

2 years. Do not use the drug after the expiration date indicated on the package.

Storage conditions

Store at a temperature not exceeding 30 ° C. Keep the medicine out of the reach of children.

Packaging

Blister of 25 tablets; 1 or 2 or 4 blisters in a cardboard box.

Vacation category

According to the recipe.

Producer

BERLIN-CHEMI AG.

Location of the manufacturer and its business address.

Glienicker Weg 125, 12489 Berlin, Germany.