L-thyroxine 125 Berlin-Chemie - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate 2-water 39.875 mg, microcrystalline cellulose 40.00 mg, carboxymethyl starch sodium salt, type A 30.00 mg, dextrin 17.00 mg, long chain partial glycerides 3.0 mg.

Description:Round, slightly biconvex tablets from white to slightly beige, with a risk for division on one side and embossing "125" on the other.

Pharmacotherapeutic group:Thyroid agent

ATX: & nbsp

H.03.A.A Thyroid hormones

H.03.A.A.01 Levothyroxine sodium

Pharmacodynamics:

The active substance of the drug L-Tyroxine 125 Berlin-Chemie - levothyroxine sodium is a synthetic levothyroxine levorotatory isomer, which is in its effect is identical to thyroxine, normally synthesized human thyroid. After partial conversion to triiodothyronine (T3) in the liver and kidney and enter the body's cells, levothyroxine influences the development and growth of tissue metabolism. In small doses, it has an anabolic effect on protein and fat metabolism. The mean daily doses stimulates growth and development, increases tissue oxygen demand, stimulate the metabolism of proteins, fats and carbohydrates, increases the functional activity of the cardiovascular system and central nervous system. In high doses inhibits the production of levothyroxine thyrotropin-releasing hormone and hypothalamic thyrotropin (TSH) pituitary.

Therapeutic effect is observed after 7-12 days from the beginning of application, during the same time the action of the drug remains after its cancellation.The significant clinical effect of levothyroxine sodium in hypothyroidism is manifested in 3-5 days. The manifestations of diffuse euthyroid goiter decrease or disappear within 3-6 months of application of the drug.

Pharmacokinetics:

Absorption

Ingestion levothyroxine sodium absorbed mainly in the upper part of the small intestine. Absorbed up to 80% of the dose of the drug. Simultaneous food intake reduces the absorption of levothyroxine sodium. Time to reach the maximum concentration (TC_m_Oh) in the blood plasma after ingestion of a single dose is approximately 5-6 hours.

Distribution

The estimated volume of distribution is 10-12 liters. More than 99% of levothyroxine sodium binds to blood plasma proteins (thyroxin-binding globulin, thyroxine-binding prealbumin and albumin).

Metabolism

The process of monodeiodination in various tissues undergoes approximately 80% of levothyroxine sodium with the formation of T3 and inactive products. Thyroid hormones are metabolized mainly in the liver, kidneys, brain and muscles. A small amount of the drug is subjected to deamination and decarboxylation, as well as conjugation with sulfuric and glucuronic acids (in the liver).Metabolic clearance is approximately 1.2 liters of blood plasma per day.

Excretion

Metabolites are excreted by the kidneys and through the intestines. The half-life of the drug is 6-7 days. With thyrotoxicosis, the half-life period is shortened to 3-4 days, and with hypothyroidism it lengthens to 9-10 days.

Indications:

- hypothyroidism;

- euthyroid goiter;

- as a replacement therapy and for the prevention of recurrence of goiter after surgical interventions on the thyroid gland;

- as a suppressive and replacement therapy for malignant tumors of the thyroid gland, mainly after surgical treatment;

- diffuse toxic goiter: after reaching the euthyroid state with the help of antithyroid drugs;

- as a diagnostic tool in the test of thyroid suppression.

Contraindications:

- increased individual sensitivity to levothyroxine sodium and / or other components of the drug;

- untreated hyperthyroidism;

- untreated adrenal insufficiency;

- untreated hypofunction of the anterior lobe of the pituitary gland;

- acute myocardial infarction;

- acute myocarditis, acute pancarditis;

- simultaneous use with antithyroid drugs during pregnancy.

Carefully:

-in diseases of the cardiovascular system: coronary heart disease (ischemic heart disease) (atherosclerosis, angina pectoris, acute myocardial infarction in the anamnesis), arterial hypertension, cardiac rhythm disturbances;

-in adrenal insufficiency, hypofunction of the anterior lobe of the pituitary gland;

-in diabetes mellitus;

- with severe long-term hypothyroidism;

- with malabsorption syndrome (dose adjustment may be required);

-Pers who are in postmenopause, who have hypothyroidism and an increased risk of osteoporosis;

- With functional autonomy of the thyroid gland.

Pregnancy and lactation:

During pregnancy and breastfeeding, drug therapy L- Thyroxine 125 Berlin-Chemie, appointed for hypothyroidism, should continue. During pregnancy, an increase in the dose of the drug may be required L-Tyroxine 125 Berlin-Chemie because of the increased concentration in the blood plasma of thyroxine-binding globulin. There are no data on the occurrence of teratogenic and fetotoxic effects when the drug is used in recommended therapeutic doses.Simultaneous use of levothyroxine sodium and antithyroid drugs during pregnancy is contraindicated, since this may require increasing doses of antithyroid drugs. Since antithyroid drugs, in contrast to levothyroxine sodium, penetrate the placenta, the fetus may develop hypothyroidism. During the period of breastfeeding, the drug L -Tyroxine 125 Berlin-Chemie should be taken strictly at recommended doses under the supervision of a doctor. When levothyroxine sodium is used in the recommended therapeutic doses, the concentration of thyroid hormones in breast milk does not reach the level that can cause hyperthyroidism and suppression of TSH secretion in a child.

Dosing and Administration:

The daily dose of levothyroxine sodium is determined in each case individually depending on the indications, given laboratory tests and the clinical state of the patient.

The daily dose of the drug L-Tyroxine 125 Berlin-Chemie is taken once inside the morning on an empty stomach, but at least 30 minutes before a meal, squeezing a pill with a small amount of liquid (for example, half a glass of water) without chewing.

Indications	Recommended daily doses (L- Thyroxine 125 Berlin-Chemie, μg / day)
Hypothyroidism
Adults: -patients younger than 55 years with no cardiovascular disease	1.6-1.8 μg / kg body weight
-patients older than 55 years and / or having cardiovascular disease	the initial daily dose of -25 mcg; the dose of the drug is increased by 25 μg every 2-4 weeks
Treatment of euthyroid goiter	75-200
As a substitute therapy and for the prevention of recurrence of goiter after surgery on the thyroid gland	75-200
In the complex therapy of thyrotoxicosis in diffuse toxic goiter after reaching the euthyroid state with antithyroid drugs	50-100
As a suppressive and substitutive therapy for malignant tumors of the thyroid gland, mainly the surgical treatment	150-300
Thyroid suppression test	The dose is determined in accordance with the selected protocol for performing suppressive scintigraphy

For accurate dosing of the drug, it is recommended to use the most suitable of the dosages of the drug L-theirokcuMr. Berlin-Chemie (50, 75, 100, 125 or 150 μg).

Application for hypothyroidism

When carrying out substitution therapy for hypothyroidism in patients younger than 55 years with no cardiovascular disease, levothyroxine sodium appoint a daily dose of 1.6-1.8 mcg / kg body weight; in patients older than 55 years and / or with the presence of cardiovascular diseases, the initial daily dose is 25 μg per day, then the dose is increased by 25 μg every 2-4 weeks under the control of the concentration of TSH and clinical symptoms.

With partially preserved thyroid function (subclinical hypothyroidism) usually a smaller daily dose of sodium levothyroxine, which is determined empirically (based on the concentration of TSH).

Use in children with hypothyroidism

For newborns and children with congenital hypothyroidism, it is very important to start substitution therapy as soon as possible. The recommended initial dose of levothyroxine sodium is 10-15 μg / kg of body weight per day for the first three months. Subsequently, the dose of the drug should be adjusted depending on the patient's condition, concentration of TSH and thyroid hormones in the blood plasma.

Recommended doses of thyroxine for the treatment of congenital hypothyroidism
Age	The dose of thyroxin in terms of body weight per day (mcg / kg / day)
0-3 months	10-15
3-6 months	10-15
6-12 months	6-8
15 years	5-6
6-12 years old	4-5
> 12 years	2-3

For children with acquired hypothyroidism, the recommended initial dose is 12.5 - 50 μg per day; then the dose is increased by 25 mcg every 2-4 weeks under the control of thyroid hormone concentrations, TSH and clinical symptoms.

The maintenance dose of levothyroxine sodium, as a rule, is 100-150 μg / m² body surface area per day.

Breast children and children under 3 years of age daily dose of levothyroxine sodium are given in one session 30 minutes before the first feeding. Tablet of the drug L-Tyroxine 125 Berlin-Chemie is dissolved in a small amount of water until a fine suspension, which is prepared immediately before taking the drug.

In patients with severe or long-term hypothyroidism, treatment should be started with extreme caution, from small doses - from 12.5 μg / day - 25 μg / day, the dose is increased to supportive at longer intervals - by 25 μg / day every 2- 4 weeks and more often determine the concentration of TSH in the blood.

In elderly patients, patients with IHD, treatment should be started with extreme caution, with small doses; The daily dose of levothyroxine sodium is increased to the maintenance dose at longer intervals, more often the concentration of TSH in the blood plasma is determined.

The use of lower doses of levothyroxine sodium is also indicated in patients with low body weight and in patients with large goiter.

With hypothyroidism levothyroxine sodium take, as a rule, throughout life. With diffuse toxic goiter levothyroxine sodium They are used in complex therapy with antithyroid drugs after reaching the euthyroid state. In the treatment of euthyroid goiter, the duration of therapy ranges from six months to two years. In case of insufficient effectiveness of therapy with the drug L-Tyroxine 125 Berlin-Chemie euthyroid goiter should consider other methods of treatment.

In all cases, the duration of treatment with the drug is determined by the doctor.

Side effects:

With the correct use of the drug L-Tyroxine 125 Berlin-Chemie under the control of clinical and laboratory indicators, side effects are not observed.

In case of overdose, or if the individual tolerance threshold of levothyroxine sodium is exceeded, or if the dose of the drug is increased too fast from the start of therapy, the patient may have symptoms typical of hyperthyroidism (see section Overdose). In this case, a reduction in the daily dose of the drug or a break in treatment for several days is recommended. After the disappearance of symptoms, the use of the drug should be resumed with caution, with a lower dose.

If hypersensitivity to the components of the drug may cause allergic reactions from the skin and respiratory organs; Single cases of anaphylactic shock development were reported. In case of occurrence of the specified signs application of a preparation L-Tyroxine 125 Berlin-Chemie should be discontinued immediately.

Overdose:

Clinical signs of hyperthyroidism may develop in case of an overdose if the individual threshold of tolerability of levothyroxine sodium is exceeded or if the daily dose of the drug is increased too quickly from the beginning of therapy. Symptoms typical of hyperthyroidism: palpitations, heart rhythm disturbances, pain in the heart, anxiety, tremors, sleep disorders, increased sweating, decreased appetite, weight loss, diarrhea, headache, muscle weakness and muscle twitching, fever, hyperemia (especially - persons), menstrual irregularity, fever, vomiting, idiopathic intracranial hypertension.

There were reported cases of sudden cardiac arrest in patients who were taking excessively high doses of levothyroxine sodium for many years. In patients with convulsive readiness, individual cases of seizures were noted when the individual threshold of tolerance was exceeded. Individual cases of thyrotoxic crises, heart failure and coma have been reported.

An increase in T3 concentration in the blood plasma is a more reliable laboratory indicator indicating a possible overdose of levothyroxine sodium than the concentrations of T4 and free T4.

In the case of acute overdose of the drug, its absorption from the gastrointestinal tract can be reduced by taking activated charcoal.

Depending on the severity of symptoms, a doctor may recommend a reduction in the daily dose of the drug, a break in treatment for several days, the appointment of beta-blockers. The use of beta-blockers can reduce manifestations of such β-sympathomimetic effects like tachycardia, anxiety, agitation or hyperkinesia. In the case of the application of extremely high doses of levothyroxine sodium, plasmapheresis is indicated.

Overdosage of levothyroxine sodium requires a long period of follow-up.Because of its gradual conversion to T3, symptoms may appear with a delay of up to 6 days.

After the disappearance of symptoms of an overdose, the use of levothyroxine sodium should be resumed with caution from a lower dose.

Interaction:

Levotiroksin sodium enhances the effect of indirect anticoagulants (coumarin derivatives), displacing them from the binding sites with plasma proteins. With simultaneous application, regular monitoring of blood coagulation parameters is necessary.

If necessary, the dose of anticoagulant should be adjusted.

Absorption of levothyroxine sodium may decrease in the case of simultaneous use with aluminum-containing antacid drugs, iron-containing drugs, calcium carbonate. Therefore, taking levothyroxine sodium is recommended at least 2 hours before use.

Seslamer and lanthanum carbonate can reduce the bioavailability of levothyroxine sodium, in this connection levothyroxine sodium should be taken at least two hours before their application. Very rare cases of development of hypothyroidism with their simultaneous application with levothyroxine sodium.In case of the need for simultaneous use, it is recommended to carefully monitor the concentration of TSH.

The simultaneous use of tricyclic antidepressants with levothyroxine sodium can lead to an increase in the effect of antidepressants.

Thyroid hormones can increase the need for insulin and oral hypoglycemic drugs. More frequent monitoring of the concentration of glucose in the blood plasma is recommended to be performed during the start of the use of levothyroxine sodium, as well as with a change in the daily dose of the drug.

Levotiroksin sodium reduces the action of cardiac glycosides.

Simultaneous application with ion-exchange resins (colestramine, colestipol), as well as calcium and sodium salts of polystyrene-sulfonic acid reduces the concentration of sodium levothyroxine in the blood plasma due to inhibition of its absorption in the intestine. Concerning levothyroxine sodium should be taken 4-5 hours before taking these drugs.

Inhibitors of tyrosine kinase (eg, imatinib, sunitinib) may decrease the efficacy of levothyroxine sodium.Therefore, at the beginning or at the end of the course of simultaneous application, it is recommended to monitor the function of the thyroid gland. If necessary, the dose of levothyroxine sodium is adjusted.

When used simultaneously with anabolic steroids, asparaginase, tamoxifen, pharmacokinetic interaction at the level of binding to plasma proteins is possible.

Salicylates, dicoumarol, furosemide in high doses (250 mg), clofibrate, phenytoin and other drugs are able to displace levothyroxine sodium from the connection with blood plasma proteins, which can lead to an increase in the concentration of the free T4 fraction.

Somatropin, when used concomitantly with levothyroxine sodium, can accelerate the closure of epiphyseal growth zones.

The simultaneous use of barbiturates and other drugs capable of inducing the activity of "hepatic" enzymes (carbamazepine and rifampicin), can lead to an increase in the clearance of levothyroxine sodium, which may require an increase in the daily dose of the drug.

In women who simultaneously use estrogen-containing contraceptives; in postmenopausal women undergoing hormone replacement therapy, the need for levothyroxine sodium may increase.

Propylthiouracil, glucocorticosteroids, beta-adrenoblockers with simultaneous application with levothyroxine sodium inhibit the conversion of T4 to T3.

Simultaneous use of amiodarone and iodine-containing contrast agents, due to high iodine content, may be accompanied by the development of both hyperthyroidism and hypothyroidism.

Particular attention should be paid to patients with nodular goiter with possible development of unrecognized functional autonomy of the thyroid gland. It may be necessary to adjust the dose of levothyroxine sodium.

Sertralin, chloroquine / proguanil reduce the effectiveness of levothyroxine sodium and increase the concentration of TSH in the blood plasma.

Protease inhibitors (eg, ritonavir, lopinavir) can lead to a decrease in the efficacy of levothyroxine sodium. With the simultaneous use of regular monitoring of the concentration of thyroid hormones in the blood plasma is recommended.

With the use of levothyroxine sodium in children with congenital hypothyroidism and the simultaneous consumption of foods containing soy, there was an increase in the concentration of TSH in the blood plasma. In this case, higher doses of levothyroxine sodium may be required to achieve normal concentrations of TSH and T4.Therefore, when used in food products containing soy, and after termination of their use requires regular monitoring of the concentration of TSH and T4 in blood plasma, for possible correction of the daily dose.

Special instructions:

Before the beginning of therapy with thyroid hormones, the presence of functional autonomy of the thyroid gland or its treatment should be excluded.

It is necessary to exclude the possibility of even a minor drug-caused hyperthyroidism in patients with coronary artery disease, heart failure, tachyarrhythmias, myocarditis (outside the acute phase), long-term hypothyroidism in patients with previous myocardial infarction. In this group of patients, thyroid hormone therapy requires more frequent laboratory monitoring of thyroid hormone and TSH concentrations.

With secondary hypothyroidism, it is necessary to exclude the presence of insufficiency of the adrenal cortex. If necessary, start glucocorticosteroid replacement therapy to compensate for adrenal insufficiency.

In postmenopausal women with hypothyroidism and an increased risk of developing osteoporosis,a careful selection of the daily dose of the drug and a more frequent monitoring of laboratory parameters to prevent an overdose of levothyroxine sodium.

Thyroid hormones should not be used to reduce body weight. Therapeutic doses of levothyroxine sodium do not cause weight loss in patients who are in a state of euthyroidism. The use of higher doses can cause serious, up to life-threatening side effects, especially with simultaneous use with some drugs used to reduce body weight.

In case of transfer of a patient from one drug of levothyroxine sodium to another, it is recommended to adjust the daily dose depending on clinical symptoms and laboratory data.

Effect on the ability to drive transp. cf. and fur:

Investigations of the drug L-Tiroxin 125 Berlin-Chemie on the ability to drive vehicles and mechanisms was not carried out. Nevertheless, since levothyroxine sodium is identical to the natural hormone of the thyroid gland, the effect of the drug L-Throxin 125 Berlin-Chemie when applied in therapeutic doses to the ability to drive vehicles and mechanisms is not expected.

Form release / dosage:Tablets 125 mcg.

Packaging:

For 25 tablets in a contour mesh package (blister) [PVC / PVDH / aluminum foil or aluminum foil / aluminum foil].

For 1, 2 or 4 blisters with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children!

Shelf life:

2 years.

Do not apply but the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001807/08

Date of registration:17.03.2008 / 21.01.2015

Expiration Date:Unlimited

The owner of the registration certificate:Berlin-Chemie / A. Menarini, LLCBerlin-Chemie / A. Menarini, LLC Russia

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

Information update date: & nbsp28.06.2016

Illustrated instructions

Instructions

L-thyroxine 125 Berlin-Chemie (L-Thyroxin 125 Berlin Chemi)