In the course of preparation of requirements to the safety and efficacy of medicines based on up-to-date scientifically grounded information on the clinical use of drugs containing as an active substance levothyroxine sodium, tablets 25 mcg, 50 mcg, 75 mcg, 100 mcg, 150 mcg, it was found necessary to unify and supplement the instructions for the use of these medications with the following information.
The section "Pharmacokinetics" under "Distribution" and "Excretion" should be supplemented with the following information: "Estimated volume of distribution is 10-12 liters" and "Metabolic clearance is about 1.2 liters of blood plasma per day, respectively.
The section "Indications for use" should be submitted in the following edition:
hypothyroidism;
- euthyroid goiter;
- as a substitution 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 anti thyroid agents (in the form of combined or monotherapy);
- as a diagnostic tool in the test of thyroid suppression. "
The section "Contraindications" should be presented in the following edition:
"~ increased individual sensitivity to any of the components of the drug;
- untreated thyrotoxicosis;
- untreated pituitary insufficiency;
- untreated adrenal insufficiency;
- use during pregnancy in combination with antithyroid means;
You should not start treatment with the drug in the presence of acute myocardial infarction, acute myocarditis, acute pankardita ".
The section "With caution" should be submitted in the following edition:
"Levothyroxine sodium should be used with caution in diseases of the cardiovascular system: ischemic heart disease (atherosclerosis, angina, myocardial infarction), hypertension, arrhythmia, diabetes, severe long-existing hypothyroidism, malabsorption syndrome (may require dose adjustment) at patients with predisposition to psychotic reactions.
Section "Pregnancy and lactation" must be supplemented and to read as follows:
"Pregnancy
During pregnancy, therapy with levothyroxine sodium, prescribed for hypothyroidism, should continue.
During pregnancy, an increase in the dose of levothyroxine sodium may be required due to an increase in the thyroxine-binding globulin content. There are no data on the occurrence of teratogenic and fetotoxic effects when taking levothyroxine sodium in recommended therapeutic doses. Taking levothyroxine sodium during pregnancy in excessively high doses can adversely affect the fetus and postnatal development.
The use of levothyroxine sodium in pregnancy in combination with antithyroid drugs is contraindicated, since taking levothyroxine sodium may require an increase in the doses of antithyroid drugs. Since antithyroid drugs, in contrast to levothyroxine sodium, can penetrate the placenta, the fetus may develop hypothyroidism.
Breastfeeding period
During breastfeeding levothyroxine sodium should be taken strictly in recommended doses, under the supervision of a doctor. When administered at recommended therapeutic doses, the concentration of thyroid hormone,secreted with breast milk during lactation, is insufficient to cause hyperthyroidism and suppression of TSH secretion in a child.
The section "Method of administration and dose" should be submitted in the following edition:
"The daily dose is determined individually depending on the indications, the clinical condition of the patient and the data of the laboratory examination.
The daily dose of levothyroxine sodium is taken by mouth in the morning on an empty stomach, at least 30 minutes before a meal, with a small amount of liquid (half a cup of water) and without chewing.
When carrying out substitution therapy for hypothyroidism in patients younger than 55 years with no cardiovascular disease, levothyroxine sodium apply in a daily dose of 1.6-1.8 μg per 1 kg of body weight; in patients older than 55 years or with cardiovascular diseases - 0.9 μg per 1 kg of body weight.
| The initial stage of replacement therapy for hypothyroidism |
| Patients without cardiovascular disease younger than 55 years | Initial dose: - women - 75-100 mcg / day; - men - 100-150 mcg / day |
| Patients with cardiovascular disease or over 55 years of age | - Initial dose - 25 mcg / day - Increase 25 μg with an interval of 2 months before the normalization of the TSH in the blood When cardiovascular system symptoms appear or worsen, cardiovascular diseases |
Recommended doses of levothyroxine sodium for treatment congenital hypothyroidism
| Age | Daily dose (mcg) | Dose based on body weight (μg / kg) |
| 0-6 months | 25-50 | 10-15 |
| 6-12 months | 50-75 | 6-8 |
| 1-5 years | 75-100 | 5-6 |
| 6-12 years old | 100-150 | 4-5 |
| > 12 years | 100-200 | 2-3 |
| Indications | Recommended doses levothyroxine sodium (mcg / day) |
| Treatment of euthyroid goiter | 75-200 |
| Prevention of relapse after surgical treatment of euthyroid goiter | 75-200 |
| In the complex therapy of thyrotoxicosis | 50-100 |
| Suppressive Thyroid Cancer Therapy | 150-300 |
| Thyroid suppression test | 4 weeks before the test
| 3 weeks before the test
| 2 weeks before the test
| 1 week before the test
|
| 75 | 75 | 150-200 | 150-200 |
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. The tablet is dissolved in water to a fine suspension, which is prepared immediately before taking the drug.
In patients with severe long-term hypothyroidism, treatment should be started with extreme caution, from small doses - from 12.5 μg / day,the dose is increased to the supporting one at longer intervals - by 12.5 μg / day every 2 weeks and the concentration of TSH in the blood is more often determined.
With hypothyroidism levothyroxine sodium take, as a rule, throughout life. With thyrotoxicosis levothyroxine sodium They are used in complex therapy with antithyroid drugs after reaching the euthyroid state. In all cases, the duration of treatment with the drug is determined by the doctor.
For accurate dosing, the most suitable dosage of left-hand thyroxin sodium should be used. "
Section "Side effect" should be submitted in the following edition:
With proper use of levothyroxine sodium under the supervision of a doctor, side effects are not observed. There have been reported cases of allergic reactions in the form of angioedema.
The section "Overdose" should be presented in the following edition:
"Symptoms
With an overdose of levothyroxine sodium, a significant increase in metabolic rate is observed. Clinical signs of hyperthyroidism may occur in case of an overdose if the individual threshold of tolerability of levothyroxine sodium is exceeded or if its dose increases too quickly from the beginning of therapy.Symptoms typical of hyperthyroidism: cardiac arrhythmias, tachycardia, palpitations, angina, headache, muscle weakness and muscle twitching, hyperemia (especially face), fever, vomiting, menstrual irregularity, benign intracranial hypertension, tremor, anxiety, insomnia, hyperhidrosis , weight loss, diarrhea.
Overdosage of levothyroxine sodium can lead to the appearance of symptoms of acute psychosis, especially in patients with a predisposition to psychotic disorders.
There were reported cases of sudden cardiac arrest in patients who were taking excessively high doses of levothyroxine sodium for many years. In predisposing patients, individual cases of seizures were noted when the individual threshold of tolerance was exceeded.
Treatment
Depending on the severity of symptoms, the doctor may recommend a reduction in the daily dose of levothyroxine sodium, a break in treatment for several days, the appointment of beta-blockers. When you receive extremely high doses may be prescribed plasmapheresis. After the disappearance The side effects of treatment should be started with caution with a lower dose. "
The section "Interaction with other medicinal products" should be supplemented with new information and presented in the following edition:
"The use of tricyclic antidepressants with levothyroxine sodium may lead to an increase in the effect of antidepressants.
Levotiroksin sodium reduces the action of cardiac glycosides.
With simultaneous application colestramine and colestipol (ion exchange resins) reduce the plasma concentration of levothyroxine sodium by inhibiting its absorption in the intestine. Concerning levothyroxine sodium should be used 4-5 hours before taking these drugs.
When used simultaneously with anabolic steroids, asparaginase, tamoxifen, pharmacokinetic interaction at the level of binding to plasma proteins is possible.
Protease inhibitors (eg, ritonavir, indinavir, lopinavir) may affect the efficacy of levothyroxine sodium. It is recommended to carefully monitor the concentration of thyroid hormones. If necessary, adjust the dose of levothyroxine sodium.
Phenytoin may affect the efficacy of levothyroxine sodium due to the displacement of levothyroxine sodium from the binding to plasma proteins, which may lead to an increase in the concentration of free T4 and T3. On the other hand, phenytoin increases the intensity of metabolism of levothyroxine sodium in the liver. It is recommended to carefully monitor the concentration of thyroid hormones.
Levothyroxine sodium may help reduce the effectiveness of hypoglycemic drugs. Therefore, frequent monitoring of the concentration of glucose in the blood from the time of the initiation of thyroid hormone replacement therapy. If necessary, the dose of hypoglycemic drug should be adjusted.
Levothyroxine sodium can enhance the effect of anticoagulants (coumarin derivatives) by displacing them from the bond with plasma proteins, which can increase the risk of bleeding, for example, cerebral hemorrhage or gastrointestinal bleeding, especially in elderly patients. Therefore, regular monitoring of coagulation parameters at the beginning and during combined therapy with these drugs is necessary.If necessary, the dose of anticoagulant should be adjusted.
Salicylates, dicoumarol, furosemide in high doses (250 mg), clofibrate and other drugs can displace levothyroxine sodium from the connection with plasma proteins, which leads to an increase in the concentration of the fraction of free T4.
Sevelamer can reduce absorption of levothyroxine sodium. 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 concomitant therapy, these drugs are recommended to monitor the change in thyroid function in patients. If necessary, the dose of levothyroxine sodium is adjusted.
Aluminum-containing drugs (antacids, sucralfate), are described in the literature as potentially decreasing the efficacy of levothyroxine sodium. Therefore, it is recommended to take levothyroxine sodium, at least 2 hours before the application of these drugs. This recommendation also applies to the use of medicines, containing salts of iron and calcium.
Somatropin, when used concomitantly with levothyroxine sodium, can accelerate the closure of epiphyseal growth zones.
Propylthiouracil, glucocorticosteroids, beta-sympatholytics, iodine-containing contrast agents and amiodarone inhibit the peripheral transformation of T4 in T3. In view of the high content of iodine, the use of amiodarone may be accompanied by the development of both hyperthyroidism and hypothyroidism. Particular attention should be paid to nodular goiter with possible development of unrecognized functional autonomy.
Sertraline, chloroquine / proguanil reduce the effectiveness of levothyroxine sodium and increase the concentration of TGH in serum.
Medications that promote the induction of hepatic enzymes (eg, barbiturates, carbamazepine), can promote hepatic clearance of levothyroxine sodium.
In women using estrogen-containing contraceptives, or in postmenopausal women receiving hormone replacement therapy, the need for levothyroxine sodium may increase.
The use of sosesoderzhaschih products can help reduce absorption in the intestine of levothyroxine sodium. Therefore, dose adjustment may be required, especially at the beginning or after stopping the use of products containing soy.
With the simultaneous use of orlistat and levothyroxine sodium hypothyroidism may develop and / or a decrease in the control of hypothyroidism may occur.The reason for this may be a decrease in the absorption of iodine salts and / or levothyroxine sodium. Patients receiving levothyroxine sodium, should consult a physician before applying orlistat, since it may be necessary to take orlistat and levothyroxine sodium at different times of the day and adjust the dose of levothyroxine sodium. In the future, it is recommended to monitor the function of the thyroid gland. "
The section "Special instructions" should be presented in the following edition:
"Before the beginning of thyroid hormone replacement therapy or before the test of thyroid suppression, the following diseases or pathological conditions should be excluded or treated: acute coronary insufficiency, angina pectoris, atherosclerosis, arterial hypertension, pituitary insufficiency or adrenal insufficiency. To exclude or conduct treatment of functional autonomy of the thyroid gland.
In patients at risk of developing psychotic disorders, it is recommended to start therapy with a low dose of levothyroxine sodium followed by a slow increase in the initiation of therapy. It is recommended that patients be monitored.In case of signs of psychotic disorders, the dose of levothyroxine should be adjusted. It is necessary to exclude the possibility of even a slight drug-induced hyperthyroidism in patients with coronary insufficiency, cardiac insufficiency or tachyarrhythmias. Therefore, in these cases, regular monitoring of the concentration of thyroid hormones is necessary.
Before carrying out substitution therapy with thyroid hormones, it is necessary to find out the etiology of secondary hypothyroidism. If necessary, start substitution therapy to compensate for adrenal insufficiency.
If there is a suspicion of the development of functional autonomy of the thyroid gland before the start of therapy, it is recommended that the TGH test or suppressive scintigraphy be performed.
In postmenopausal women with hypothyroidism and an increased risk of osteoporosis, it is necessary to exclude the presence of concentrations of levothyroxine sodium in the serum exceeding physiological levels. In this case, careful monitoring of thyroid function is recommended.
The use of levothyroxine sodium is not recommended in the presence of metabolic disorders, accompanied by hyperthyroidism. An exception is the concomitant use of antithyroid drugs during drug therapy for hyperthyroidism.
Since initiating therapy with levothyroxine sodium in the case of a transition from one drug to another it is recommended to adjust the dose depending on the patient's clinical response to therapy, and results of laboratory inspection. "
Section "Influence on the ability to drive vehicles, mechanisms" should be presented in the following edition:
"Studies of the effect of sodium levothyroxine on the ability to drive vehicles and mechanisms have not been carried out, however, since levothyroxine sodium is identical to the natural thyroid hormone, the effect on the ability to drive vehicles and mechanisms is not expected. "