Levoshild^® (Tablets) Instructions for Use

Marketing Authorization Holder

Biomate, LLC (Russia)

Manufactured By

Acme Generics, Pvt. Ltd. (India)

ATC Code

H03AA01 (Levothyroxine sodium)

Active Substance

Levothyroxine sodium (Rec.INN registered by WHO)

Dosage Forms

	Levoshild®	Tablets 25 mcg
		Tablets 50 mcg
		Tablets 75 mcg
		Tablets 88 mcg
		Tablets 100 mcg
		Tablets 125 mcg
		Tablets 137 mcg
		Tablets 150 mcg
		Tablets 200 mcg

Dosage Form, Packaging, and Composition

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Tablets

100 pcs. – bottles – cardboard packs (100 pcs.) – By prescription
14 pcs. – blisters (2 pcs.) – cardboard packs (28 pcs.) – By prescription
14 pcs. – blisters (4 pcs.) – cardboard packs (56 pcs.) – By prescription
14 pcs. – blisters (7 pcs.) – cardboard packs (98 pcs.) – By prescription

Clinical-Pharmacological Group

Thyroid drug

Pharmacotherapeutic Group

Drugs for the treatment of thyroid gland diseases; thyroid preparations; thyroid hormones

Pharmacological Action

Thyroid hormone drug. Synthetic levorotatory isomer of thyroxine. In small doses, it has an anabolic effect.

In medium doses, it stimulates growth and development, increases tissue oxygen demand, stimulates the metabolism of proteins, fats, and carbohydrates, and stimulates the activity of the cardiovascular system and central nervous system.

In high doses, it inhibits the production of thyrotropin-releasing hormone (TRH) by the hypothalamus and thyroid-stimulating hormone (TSH) by the pituitary gland.

Pharmacokinetics

After oral administration, it is absorbed from the gastrointestinal tract; absorption is 48-79%. Taking on an empty stomach increases the absorption of the active substance.

The maximum plasma concentration (C_max) is reached in approximately 6 hours. Binding to plasma proteins (thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin) is more than 99%. The volume of distribution (V_d) is 0.5 l/kg. Distribution occurs mainly in the liver, brain, and muscles.

In various tissues, about 80% of levothyroxine sodium undergoes monodeiodination to form triiodothyronine (T₃) and inactive products.

A small amount of the active substance undergoes deamination and decarboxylation to form tetraiodothyroacetic acid, as well as conjugation with sulfuric and glucuronic acids (in the liver).

The elimination half-life (T_1/2) is 6-7 days. About 15% is excreted by the kidneys and in bile unchanged and in the form of conjugates.

Indications

Hypothyroidism; euthyroid goiter; as replacement therapy and for the prevention of goiter recurrence after thyroid resection; thyroid cancer (after surgical treatment); diffuse toxic goiter: after achieving a euthyroid state with antithyroid drugs (as combination or monotherapy); as a diagnostic tool for the thyroid suppression test.

ICD codes

Dosage Regimen

Determine the dose individually based on the indication, patient’s clinical status, and thyroid function laboratory parameters.

Administer the total daily dose once daily, in the morning, on an empty stomach, at least 20-30 minutes before breakfast.

Swallow the tablet whole with a half-glass of water; do not chew or crush.

For adult hypothyroidism, initiate therapy with 12.5-25 mcg once daily. Increase the dose by 12.5-25 mcg increments at intervals of 2-4 weeks until euthyroidism is achieved.

The typical maintenance dose for most adults is 100-200 mcg once daily.

For elderly patients and those with long-standing hypothyroidism or known cardiovascular disease, initiate therapy with 12.5 mcg daily. Increase the dose more slowly and at longer intervals, monitoring for cardiac symptoms.

In severe long-standing hypothyroidism, start with 12.5 mcg daily; double the dose to 25 mcg daily after 2 weeks. Subsequently increase by 25 mcg every 2 weeks.

For the differential diagnostic thyroid suppression test, administer a single 3 mg (3000 mcg) dose. Alternatively, administer 200 mcg once daily for 14 days.

Adjust the dose based on periodic assessment of clinical response and serum TSH levels. Perform laboratory monitoring 6-8 weeks after initiation of therapy or any dose change.

When switching from another levothyroxine preparation, use the same dose. Monitor TSH levels and adjust the dose if necessary.

Adverse Reactions

Symptoms of hyperthyroidism are possible (when used in high doses, including when the dose is increased too quickly at the beginning of the course of treatment): tachycardia, palpitation, arrhythmias, angina attacks, headache, nervousness, tremor, sleep disorders, feeling of internal restlessness, muscle weakness and cramps, weight loss, diarrhea, menstrual cycle disorders, vomiting.

Contraindications

Hypersensitivity to levothyroxine sodium; untreated thyrotoxicosis; acute myocardial infarction, acute myocarditis; untreated adrenal cortex insufficiency.

With caution in cardiovascular diseases – coronary artery disease (atherosclerosis, angina, history of myocardial infarction), arterial hypertension, arrhythmia; in diabetes mellitus, severe long-standing hypothyroidism, malabsorption syndrome (dose adjustment may be required).

Use in Pregnancy and Lactation

During pregnancy and lactation (breastfeeding), Levothyroxine sodium should be used with caution, strictly in the recommended doses, under medical supervision.

The use in combination with thyrostatic agents during pregnancy is contraindicated due to an increased risk of hypothyroidism in the fetus.

Pediatric Use

It is possible to use in children according to indications in doses and dosage forms recommended for the respective age.

Geriatric Use

In elderly patients and with long-term hypothyroidism, treatment should be started gradually.

Special Precautions

Use with particular caution in patients with cardiovascular diseases (including coronary artery disease, heart failure, arterial hypertension). In such cases, Levothyroxine sodium should be used at a low initial dose, increasing it slowly and at longer intervals.

In hypothyroidism due to pituitary damage, it is necessary to determine whether there is concomitant adrenal cortex insufficiency. In this case, replacement therapy with glucocorticosteroids should be started before initiating treatment of hypothyroidism with thyroid hormones to avoid the development of acute adrenal insufficiency.

In elderly patients and with long-term hypothyroidism, treatment should be started gradually.

Use with caution in diabetes mellitus and diabetes insipidus.

When performing a differential diagnostic thyroid suppression test in patients with diabetes mellitus, it is recommended to increase the doses of antidiabetic agents.

In some cases, thyroid hormones may cause or exacerbate a pre-existing myasthenic syndrome.

Drug Interactions

Levothyroxine sodium potentiates the effect of indirect anticoagulants (coumarin derivatives) and reduces the effectiveness of oral hypoglycemic agents.

In patients with hypothyroidism and concomitant diabetes mellitus, at the beginning of replacement therapy with thyroid hormone preparations, an increased need for insulin or oral hypoglycemic agents is possible.

Salicylates, dicoumarol, furosemide (250 mg), clofibrate can displace levothyroxine from its binding to plasma proteins.

Sucralfate, aluminum hydroxide, calcium carbonate reduce the absorption of levothyroxine from the gastrointestinal tract.

Cholestyramine reduces the absorption of levothyroxine sodium from the gastrointestinal tract.

When using ritonavir, an increased need for levothyroxine is possible.

When using sertraline in patients with hypothyroidism, a decrease in the effects of levothyroxine sodium is possible.

With rapid intravenous administration of phenytoin while taking levothyroxine sodium, an increase in the level of free levothyroxine in the blood plasma is possible, and arrhythmias may be observed.

With simultaneous use of chloroquine, an increase in the metabolism of levothyroxine is possible, apparently due to the induction of liver microsomal enzymes by chloroquine. In patients receiving Levothyroxine sodium, when using proguanil or chloroquine, an increase in TSH concentration is possible.

The use of tricyclic antidepressants with levothyroxine sodium may lead to an enhancement of the effect of antidepressants.

Levothyroxine sodium reduces the effect of cardiac glycosides. With simultaneous use, cholestyramine, colestipol, and aluminum hydroxide reduce the plasma concentration of levothyroxine sodium by inhibiting its absorption in the intestine.

With simultaneous use with anabolic steroids, asparaginase, tamoxifen, pharmacokinetic interaction at the level of protein binding is possible.

Somatotropin, when used simultaneously with levothyroxine sodium, may accelerate the closure of epiphyseal growth zones.

Taking phenobarbital, carbamazepine, and rifampicin may increase the clearance of levothyroxine sodium and require a dose increase.

Estrogens increase the concentration of the thyroglobulin-bound fraction, which may lead to a decrease in the effectiveness of the drug.

Amiodarone, aminoglutethimide, para-aminosalicylic acid (PAS), ethionamide, antithyroid drugs, beta-adrenergic blockers, chloral hydrate, diazepam, levodopa, dopamine, metoclopramide, lovastatin, somatostatin affect the synthesis, secretion, distribution, and metabolism of levothyroxine sodium. Soy-containing products may reduce the absorption of levothyroxine sodium (dose adjustment may be required).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.