L-THIROXINE 100 BERLIN-CHEMIE, Berlin-Chemie AG

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Pharmacological properties

pharmacodynamics. Synthetic levothyroxine, which is contained in the preparation L-Thyroxine 50 and 100 Berlin-Chemie, is identical in biological activity to the natural thyroid hormone. After partial conversion to liothyronine (T 3 ), usually in the liver and kidneys, and passing into the cells of the body, it affects the development, growth and metabolism.
Pharmacokinetics. Absorption of oral levothyroxine usually occurs in the small intestine and is largely dependent on the galenic form of the drug – up to a maximum of 80% when taken before meals. Cmax _in blood plasma is reached approximately 6 hours after application. The therapeutic result is noted on the 3-5th day after the start of oral administration. The volume of distribution in the body is determined at the rate of 0.5 l/kg of body weight. Levothyroxine binds to plasma proteins by more than 99%. The bond with blood proteins is not considered to be covalent, thus the bound hormone, which is in the blood plasma, is capable of constant and rapid exchange with fractions of the free hormone. Due to the high level of protein binding, levothyroxine is not amenable to either hemodialysis or hemoperfusion. T ½ of the drug – 7 days. With thyrotoxicosis, this period is reduced to 3-4 days, and with hypothyroidism it is extended to 9-10 days. About 1/3 accumulates in the liverthe total amount of levothyroxine administered, which quickly interacts with levothyroxine in the blood plasma. Metabolic clearance is about 1.2 liters of blood plasma per day, splitting occurs mainly in the liver, brain tissue and muscles. Metabolites are excreted in urine and feces.

Composition and form of release

L-???????? 50 ??????-????

tab. 50 mcg, #25, #50, #100

 Levothyroxine sodium 50 mcg

Other ingredients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, dextrin, sodium starch glycolate (type A), long chain partial glycerides.

No. UA/8133/01/02 from 04/08/2013 to 04/08/2018

L-???????? 75 ??????-????

tab. 75 mcg blister, No. 25, No. 50, No. 100

 Levothyroxine sodium 75 mcg

No. UA/8133/01/03 from 04/09/2013 to 04/09/2018

L-???????? 100 ??????-????

tab. 100 mcg, #25, #50, #100

 Levothyroxine sodium 100 mcg

Other ingredients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, dextrin, sodium starch glycolate (type A), long chain partial glycerides.

No. UA/8133/01/01 from 04/08/2013 to 04/08/2018

L-???????? 125 ??????-????

tab. 125 mcg blister, No. 25, No. 50, No. 100

 Levothyroxine sodium 125 mcg

No. UA/8133/01/04 from 04/09/2013 to 04/09/2018

L-???????? 150 ??????-????

tab. 150 mcg blister, No. 25, No. 50, No. 100

 Levothyroxine sodium 150 mcg

No. UA/8133/01/05 from 04/09/2013 to 04/09/2018

Indications

L -Thyroxine 50 Berlin-Chemie, L -Thyroxine 100 Berlin-Chemie:

  • treatment of benign thyroid diseases;
  • prevention of goiter recurrence after goiter resection with euthyroid thyroid function;
  • replacement therapy for hypothyroidism;
  • an adjuvant for thyrostatic therapy of hyperthyroidism after reaching a euthyroid functional state.

Additional indications for L -thyroxine 100 Berlin-Chemie :

  • suppressive and replacement therapy for thyroid cancer, mainly after thyroidectomy;
  • as a diagnostic tool in the thyroid suppression test.

L -Thyroxine 75 Berlin-Chemie,

  • hypothyroidism;
  • prevention of recurrence of goiter after resection of the thyroid gland with a euthyroid state of thyroid function;
  • euthyroid goiter;
  • an adjuvant for thyrostatic therapy in hyperthyroidism after reaching a euthyroid functional state;
  • thyreostatic and replacement therapy for malignant tumors of the thyroid gland, mainly after thyroidectomy.

L -Thyroxine 125 Berlin-Chemie, L -Thyroxine 150 Berlin-Chemie:

  • hypothyroidism;
  • prevention of recurrence of goiter after resection of the thyroid gland with a euthyroid state of thyroid function;
  • euthyroid goiter;
  • thyreostatic and replacement therapy for malignant tumors of the thyroid gland, mainly after thyroidectomy.

 

Application

L -Thyroxin 50 Berlin-Chemie, L -Thyroxin 100 Berlin-Chemie . Dosing data should be considered as recommendations. For the treatment of each individual patient, depending on his individual needs, the drug is available in the form of tablets containing 50 and 100 micrograms of levothyroxine sodium. Tablets can be divided into two equal parts. The individual dose of the drug is determined based on the results of laboratory tests and clinical examination. Thyroid hormone therapy should be started at a low dosage and gradually increased (every 2-4 weeks) to an effective therapeutic dose. In case of preservation of the minimum function of the thyroid gland, the minimum replacement dose should be used.
adult patients.Treatment of benign thyroid diseases: 75-200 mcg / day.
Prevention of goiter recurrence: 75-200 mcg / day.
Replacement therapy for hypothyroidism: the initial dosage is 25-50 mcg / day, maintenance – 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: 200 mcg / day (14 days before the test).
Children with congenital and acquired hypothyroidism.For infants and children with congenital hypothyroidism who are indicated for immediate replacement therapy with levothyroxine, the recommended initial dosage of levothyroxine for the first 3 months is 10–15 mcg/kg/day. In the future, dosage adjustment is carried out on an individual basis according to the results of clinical studies, taking into account the indicators of the level of thyroid hormone, as well as the level of TSH. For children with acquired hypothyroidism, the initial dosage of levothyroxine is 12.5-50 mcg / day, for which the drug should be used at the appropriate dose. Based on clinical data regarding the level of thyroid hormone, as well as the level of TSH, the dose should be increased gradually at intervals of 2-4 weeks until the full dosage 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 initially dissolved in a small amount of water (10–15 ml), and the resulting freshly prepared suspension is given to the child, adding a small amount of water (5–10 ml) to it. The maintenance dosage is often 100-150 micrograms of levothyroxine per m2 body surface areas per day.
Patients of advanced age.Special care must be taken at the beginning of treatment with thyroid hormones in patients of advanced age, with coronary artery disease, severe hypothyroidism, or in the case when a decrease in thyroid function is noted for a long time. In these cases, treatment is started with extreme caution, using a minimum dose of 12.5 mcg / day, using the drug with the appropriate dosage for this. It is necessary to increase the dose to the maintenance level gradually, over a long time, adding 12.5 mcg of the drug per day every 2 weeks. In addition, it is necessary to increase the frequency of monitoring the level of TSH. It should be taken into account that the administration of a dosage below the optimal one, which provides complete replacement therapy, does not lead to a complete correction of TSH. Experience shows
duration of treatment. The drug is used throughout life with hypothyroidism, after surgical interventions – strumectomy or thyroidectomy, as well as for the prevention of relapses after removal of euthyroid goiter. The duration of the use of the drug as an adjuvant for the treatment of hyperthyroidism after reaching the euthyroid functional state corresponds to the duration 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 surgical intervention or radioactive iodine therapy is prescribed.
L -thyroxine 75 Berlin-Chemie.Dosing data should be considered as recommendations. Individual daily dosage should be determined based on the results of laboratory tests and clinical examination. If minimal thyroid function is maintained, the lowest effective dose should be used.
Adult patients
Hypothyroidism. The initial dosage is 25-50 mcg / day, for which the drug is used in accordance with the lower content of the active substance, the maintenance dose is 100-200 mcg / day (dosage increases by 25-50 mcg are carried out at intervals of 2-4 weeks).
Prevention of goiter recurrence  – 75-200 mcg / day.
Benign goiter with a 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.
Children over the age of 3 years. For children over the age of 3 years with acquired hypothyroidism, the initial dosage is 12.5-50 mcg / day, for this use the drug with the appropriate dosage. The dose should also be increased gradually, every 2-4 weeks, according to the results of the clinical examination, as well as taking into account the levels of thyroid hormone and TSH in the blood, until a dosage is reached that fully provides a replacement result.
Patients of advanced age.Special care must be taken at the beginning of treatment with thyroid hormones in people of advanced age, with coronary artery disease, severe hypothyroidism, or in the case when a decrease in thyroid function is noted for a long time. In these cases, treatment is started with extreme caution, using a minimum dose of 12.5 mcg / day, using the drug with the appropriate dosage for this. It is necessary to increase the dose to the maintenance level gradually, over a long time, adding 12.5 mcg of the drug per day every 2 weeks. In addition, it is necessary to increase the frequency of monitoring the level of TSH. Experience shows that the use of a minimum dosage is considered the best solution for underweight and large nodular goiter.
Duration of treatment:

  • with hypothyroidism: often throughout life;
  • in the prevention of recurrence of goiter: from several months or years or throughout life;
  • with euthyroid goiter: from several months or years or throughout life, for the treatment of euthyroid goiter, the necessary period is from 6 months to 2 years, but if treatment has not brought the desired result in this time, other therapeutic approaches should be considered;
  • as an adjuvant for the treatment of hyperthyroidism: according to the duration of use of the thyreostatic agent;
  • after thyroidectomy due to a malignant tumor of the thyroid gland – often throughout life.

The entire daily dose of the tablet should be swallowed without chewing, with a small amount of liquid, in particular ½ glass of water. Take the drug before meals at least 30 minutes before breakfast. Due to the special shape of the tablet, it is possible to divide it as follows: put the tablet on a hard surface with the notch for division upwards, press it with your finger from above in a perpendicular direction.
L -Thyroxine 125 Berlin-Chemie, L -Thyroxine 150 Berlin-Chemie . Dosing data should be considered as recommendations. Individual daily dosage should be determined based on the results of laboratory tests and clinical examination. If minimal thyroid function is maintained, the lowest effective dose should be used.
Adult patients
Hypothyroidism. The initial dosage is 25-50 mcg / day, for which the drug is used in accordance with the lower content of the active substance, the maintenance dose is 100-200 mcg / day (dosage increases by 25-50 mcg are carried out at intervals of 2-4 weeks).
Prevention of goiter recurrence  – 75-200 mcg / day.
Benign goiter with a euthyroid state of function  – 75-200 mcg / day.
After thyroidectomy for a malignant tumor  – 150-300 mcg / day.
Children over the age of 3 years.For children over the age of 3 years with acquired hypothyroidism, the initial dosage is 12.5-50 mcg / day, for this use the drug with the appropriate dosage. It is also necessary to increase the dose gradually, every 2-4 weeks, according to the results of a clinical examination, as well as taking into account the levels of thyroid hormone and TSH in the blood, until a dosage is reached that fully provides a replacement result.
Patients of advanced age.Special care must be taken at the beginning of treatment with thyroid hormones in patients of advanced age, with coronary artery disease, severe hypothyroidism, or in the case when a decrease in thyroid function is noted for a long time. In these cases, treatment is started with extreme caution, using a minimum dose of 12.5 mcg / day, using the drug with the appropriate dosage for this. It is necessary to increase the dose to the maintenance level gradually, over a long time, adding 12.5 mcg of the drug per day every 2 weeks. In addition, it is necessary to increase the frequency of monitoring the level of TSH. Experience shows that the use of a minimum dosage is considered the optimal solution for low body weight and large nodular goiter.
Duration of treatment:

  • with hypothyroidism: often throughout life;
  • in the prevention of recurrence of goiter: from several months or years or throughout life;
  • with euthyroid goiter: from several months or years or throughout life, for the treatment of euthyroid goiter, the necessary period is from 6 months to 2 years, however, if treatment has not brought the desired result in this time, other therapeutic approaches should be considered;
  • after a thyroidectomy due to a malignant thyroid tumor, often throughout life.

The entire daily dose of the tablet should be swallowed without chewing, with a small amount of liquid, in particular ½ glass of water. Take the drug before meals, at least 30 minutes before breakfast. Due to the special shape of the tablet, it is possible to divide it as follows: put the tablet on a hard surface with the notch for division upwards and press it with your finger from above in a perpendicular direction.

Contraindications

hypersensitivity to the active substance or any of the components of the drug; decompensated hyperthyroidism of any etiology; decompensated insufficiency of the adrenal cortex; untreated pituitary insufficiency; acute myocardial infarction; acute myocarditis; acute pancarditis.
During pregnancy, the simultaneous use of levothyroxine and any thyreostatic agent is contraindicated.

Side effects

if the dosage is not tolerated by the patient, which happens very rarely, or in case of overdose, especially if the dosage is increased too quickly at the beginning of treatment, the following symptoms are likely to occur.
From the nervous system: tremor, pseudotumor of the brain, anxiety, insomnia, headache.
From the side of the heart: tachycardia, palpitations, arrhythmia, the development of angina pectoris, atrial fibrillation, extrasystole.
From the gastrointestinal tract: vomiting, diarrhea.
From the skin and subcutaneous tissue: skin rash, itching, angioedema.
From the reproductive system: violation of the menstrual cycle.
General violations:hyperhidrosis, feeling hot, fever, weight loss, muscle weakness and cramps.
When these symptoms appear, it is recommended to reduce the daily dose or stop using the drug for several days. Cases of sudden death caused by cardiac disorders have been reported in patients who have been using high doses of levothyroxine for a long time. With the disappearance of side effects, treatment is resumed, carefully selecting the dosage of the drug. Probably the appearance of allergic reactions, including urticaria, bronchospasm and swelling of the larynx, in some cases – anaphylactic shock. In this case, the use of the medicine should be discontinued.

special instructions

thyroid hormones do not contribute to weight loss. Appointment in physiological doses does not lead to a decrease in body weight in patients with a well-functioning thyroid gland (euthyroid state). If the recommended doses are exceeded, adverse reactions are likely (see OVERDOSE). Before starting therapy with thyroid hormones, the following diseases should be excluded: IHD (angina pectoris), hypertension, pituitary insufficiency, adrenal insufficiency, functional autonomy of the thyroid gland, or normalize the patient’s condition. The development of even the smallest states of drug-induced hyperthyroidism should be avoided in coronary artery disease, heart failure, or tachyarrhythmias. In such cases, it is necessary to determine the level of thyroid hormone more often. In secondary hypothyroidism, you need to find out whether there is insufficiency of the adrenal cortex. If this pathology is confirmed, substitution therapy (hydrocortisone) must first be prescribed. When using levothyroxine for the treatment of hypothyroidism in menopausal women who may have an increased risk of developing osteoporosis, frequent monitoring of thyroid function should be carried out to prevent an increase in the level of levothyroxine in the blood above the physiological level. Hypothyroidism has been reported in patients taking sevelamer and levothyroxine at the same time, so TSH levels should be constantly monitored in such patients. Compliance with the dosage and frequency of taking the drug should be monitored in the elderly. If autoimmune thyroiditis is suspected, TSH levels should be measured or thyroid scintigraphy should be performed prior to treatment. If the recommended doses are exceeded, side effects are likely to occur (see OVERDOSE). After the start of the use of levothyroxine or when changing the drug, it is proposed to adjust the dose of the drug in accordance with the patient’s individual response to this drug and laboratory data. The drug should be used with caution in diabetic patients (see INTERACTIONS).
Use during pregnancy and lactation.Treatment with thyroid hormones should be carried out consistently, especially during pregnancy and lactation. Despite the widespread use of the drug during pregnancy, the fact that there is a danger to the fetus is still unknown. The amount of thyroid hormone excreted into milk during breastfeeding, even with high doses of thyroid hormone, is considered insufficient to cause hyperthyroidism or suppression of TSH secretion in infants. During pregnancy, in patients with hypothyroidism, the need for levothyroxine may increase, which is due to estrogen, so thyroid function should be monitored both during pregnancy and after, and, if necessary, the dosage of replacement therapy should be adjusted.
During pregnancy, the use of levothyroxine for concomitant therapy of hyperthyroidism with thyreostatic drugs is contraindicated, since this requires a higher dosage of thyreostatic drugs. Thyrostatic drugs, unlike levothyroxine, penetrate the placental barrier in significant doses, which can cause the development of fetal hypothyroidism. In this regard, in the presence of hyperthyroidism during pregnancy, monotherapy with thyreostatic drugs in low doses is recommended. During pregnancy, thyroid tests with suppression should be avoided.
Children. L -Thyroxine 50 Berlin-Chemie, L -Thyroxine 100 Berlin-Chemie.The drug is used in pediatric practice.
L -Thyroxin 75 Berlin-Chemie, L -Thyroxin 125 Berlin-Chemie, L -Thyroxin 150 Berlin-Chemie. These drugs are used in children over the age of 3 years.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms . Unknown.

Interactions

antidiabetic drugs. Levothyroxine may reduce the effect of antidiabetic drugs. More frequent monitoring of blood glucose levels is suggested at the beginning of treatment with levothyroxine, as well as when changing the dosage of the drug.
Coumarin derivatives: levothyroxine enhances the effects of anticoagulants, increases the risk of hemorrhage in the spinal cord and brain or gastrointestinal bleeding, especially in elderly patients. Therefore, it is necessary to carry out laboratory monitoring of coagulation parameters and, if necessary, reduce the dose of anticoagulants.
Protease inhibitors(ritonavir, indinavir, lopinavir) may interfere with the effects of levothyroxine. It is necessary to conduct constant monitoring of thyroid hormones. If necessary, the dose of levothyroxine should be adjusted.
Phenytoin can influence the effect of levothyroxine by displacing it from plasma proteins, resulting in an increase in the level of free thyroxine (fT 4 ) and free triiodothyronine (fT 3 ) fractions. On the other hand, phenytoin increases the hepatic metabolism of levothyroxine. Continuous monitoring of thyroid hormone levels is suggested.
Colestyramine, colestipol inhibit the absorption of levothyroxine. Therefore, levothyroxine sodium should be taken 4-5 hours before taking such drugs.
Preparations containing aluminum (antacids, sucralfate), iron and calcium carbonate may reduce the effect of levothyroxine. Therefore, drugs containing levothyroxine should be taken at least 2 hours before taking drugs containing aluminum, iron or calcium carbonate.
Salicylates, high doses of furosemide (250 mg), clofibrate and other substances can displace levothyroxine sodium from plasma proteins, which leads to an increase in the fT 4 fraction .
Sevelamer lanthanum carbonatemay reduce the absorption of levothyroxine. L-Thyroxine Berlin-Chemie should be used 1 hour before or 3 hours after their application. In this regard, it is proposed to monitor changes in thyroid function at the beginning and end of the period of simultaneous use. If necessary, the dose of levothyroxine is adjusted.
Tyrosine kinase inhibitors (imatinib, sunitinib) may reduce the effectiveness of levothyroxine. In this regard, it is proposed to monitor changes in thyroid function at the beginning and at the end of the period of simultaneous use. If necessary, the dose of levothyroxine is adjusted.
Propylthiouracil, glucocorticoids, sympatholytics, amiodarone and preparations containing iodine suppress the peripheral conversion of T 4 to T 3 .
Due to the high iodine content, amiodarone can contribute to the development of both hyper- and hypothyroidism. With extreme caution should be prescribed to patients with nodular goiter of unknown etiology.
Sertraline, chloroquine/proguanil reduce the effectiveness of levothyroxine and increase plasma TSH levels.
Drug-induced enzymes (barbiturates, carbamazepine) may increase hepatic clearance of levothyroxine.
Estrogens. Women taking hormonal contraceptives containing estrogens, as well as post-menopausal women taking hormone replacement drugs, may require higher doses of levothyroxine.
Preparations containing soymay inhibit intestinal absorption of levothyroxine. At first and especially at the end of the soy diet, the dosage of the drug may need to be adjusted.

Overdose

in case of overdose, rapid pulse, palpitations, anxiety, feeling of heat, fever, increased sweating, arrhythmia, insomnia, tremor, increased frequency of angina attacks, anxiety, weight loss, vomiting, diarrhea, headache, muscle weakness and cramps are noted , menstrual disorders, brain pseudotumor. It is proposed to stop taking the medication and conduct control examinations. In the case of the development of severe tachycardia, its severity can be reduced with the help of β-adrenergic blockers. Thyrostatic agents are not used in this case, since the function of the thyroid gland is already completely suppressed. When taken in extreme doses (suicide attempts), plasmapheresis is useful. Sudden death associated with impaired cardiac function has been reported in patients