Thyreocomb^® (Tablets) Instructions for Use

Marketing Authorization Holder

Berlin-Chemie AG/Menarini Group (Germany)

ATC Code

H03AA03 (Levothyroxine in combination with liothyronine)

Active Substances

Potassium iodide (Ph.Eur. European Pharmacopoeia)

Liothyronine (Rec.INN registered by WHO)

Levothyroxine sodium (Rec.INN registered by WHO)

Dosage Form

Thyreocomb®

Tablets 70 mcg+10 mcg+150 mcg: 20, 40, 50 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets white, round, flat-cylindrical, with a beveled edge.

Excipients : lactose monohydrate, corn starch, gelatin, magnesium stearate, colloidal silicon dioxide, glycerol 85%, sodium hydroxide, talc, methylparaben, propylparaben.

10 pcs. – blisters (2) – carton packs.
25 pcs. – blisters (2) – carton packs.
25 pcs. – blisters (4) – carton packs.
40 pcs. – glass bottles (1) – carton packs.

Clinical-Pharmacological Group

Thyroid hormone preparation in combination with iodine

Pharmacotherapeutic Group

Thyroid agent

Pharmacological Action

[I] – Instructions for medical use approved by the Pharmacological Committee of the Ministry of Health of the Russian Federation

A preparation of synthetic thyroid hormones (levothyroxine and liothyronine) and potassium iodide, which is a structural element in the synthesis of thyroid hormones (thyroxine and triiodothyronine).

The preparation compensates for the deficiency of thyroid hormones. It increases tissue oxygen demand, stimulates their growth and differentiation, and increases the level of basal metabolism (proteins, fats, and carbohydrates). In small doses, it has an anabolic effect, and in large doses, it has a catabolic effect. It inhibits the production of thyroid-stimulating hormone. It enhances energy processes, has a positive effect on the functions of the nervous and cardiovascular systems, liver and kidneys.

Pharmacokinetics

When taken orally, levothyroxine is absorbed almost exclusively in the upper part of the small intestine (up to 80% of the dose taken on an empty stomach).

C_max in blood serum is reached approximately 6 hours after oral administration. After absorption, more than 99% of the preparation is bound to serum proteins (thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin). The therapeutic effect is observed 3-5 days after the start of oral therapy. Levothyroxine is metabolized mainly in the liver, kidneys, muscles, and brain tissues. Metabolites are excreted in the urine and bile. T_1/2 of levothyroxine is 6-7 days.

After oral administration, Liothyronine is absorbed mainly in the small intestine in an amount of 78-95% of the dose taken.

C_max in plasma is reached approximately after 2-3 days. The therapeutic effect ceases 7-9 days after the end of therapy. 90.7% of liothyronine is bound to thyroxine-binding globulin and in small amounts to thyroxine-binding prealbumin, as well as albumin. During pregnancy or after estrogen treatment, the binding capacity increases; in severe hypoproteinemia, the binding capacity may decrease. Liothyronine is metabolized mainly in the liver, kidneys, muscles, and brain tissues. T_1/2 of liothyronine is 24 hours.

The absorption of inorganic iodine in the small intestine is almost 100%. Iodine is excreted in the urine.

Indications

• Hypothyroidism;
• Treatment of euthyroid goiter;
• Prevention of goiter recurrence after thyroid resection.

ICD codes

Dosage Regimen

The daily dose of the preparation is selected individually by the attending physician based on clinical and laboratory data.

Usually, treatment begins with 1/2 tab. of Thyreocomb^® per day. Depending on individual needs, the initial dose can be gradually increased every 1-2 weeks to a maintenance dose of 1-2 tablets per day. In elderly patients with cardiovascular diseases, in patients with adrenal cortex insufficiency, and in persons suffering from epilepsy, the period of dose selection and adaptation to it may increase to 4-6 weeks or more. The entire daily dose of the preparation is taken once, in the morning, at least 30 minutes before breakfast, without chewing, with a small amount of liquid. The preparation should be taken regularly. The duration of use of the preparation is determined by the attending physician. Patients are not recommended to independently change or stop the treatment prescribed by the doctor.

Adverse Reactions

With the correctly selected dose of the preparation, no side effects are observed. Allergic reactions, progression of heart failure and angina pectoris may be observed.

Very rare hypersensitivity reactions in combination with “iodine” rhinitis; iododerma, exfoliative dermatitis, angioedema; very rarely – iodine fever, iodine acne, swelling of the salivary glands. If adverse reactions occur, it is necessary to stop taking Thyreocomb^® and inform the attending physician.

Contraindications

• Increased individual sensitivity to the preparation;
• Thyrotoxicosis;
• Acute myocardial infarction;
• Angina pectoris III-IV functional class;
• Acute myocarditis;
• Untreated adrenal cortex insufficiency;
• Dermatitis herpetiformis (Duhring’s disease).

With caution the preparation should be prescribed for cardiovascular diseases: coronary artery disease (atherosclerosis, angina pectoris I-II functional class, history of myocardial infarction), heart failure, arterial hypertension, tachycardia, tachyarrhythmia; diabetes mellitus; diabetes insipidus; severe long-standing hypothyroidism; malabsorption syndrome; elderly patients (dose adjustment may be required).

Use in Pregnancy and Lactation

During pregnancy and breastfeeding, therapy with thyroid hormones prescribed for hypothyroidism should be continued.

The amount of thyroid hormones secreted in breast milk during lactation (even when treated with high doses of the preparation) is not sufficient to cause any disorders in the child. However, during breastfeeding, the preparation should be taken with caution, strictly in the recommended doses, under medical supervision.

Pediatric Use

When using the preparation in children suffering from epilepsy, the possibility of an increase in the number of seizures should be taken into account.

Geriatric Use

Particular caution should be exercised when prescribing the preparation to elderly patients. Treatment in them should be carried out with lower doses.

Special Precautions

In coronary artery disease, heart failure, or tachyarrhythmias, more frequent monitoring of thyroid hormone levels is required.

Particular caution should be exercised when prescribing the preparation to elderly patients. Treatment in them should be carried out with lower doses. When using the preparation in children suffering from epilepsy, the possibility of an increase in the number of seizures should be taken into account.

The use of Thyreocomb^® in patients with diabetes mellitus, diabetes insipidus, or adrenal cortex insufficiency may lead to an increase in the severity of these diseases. During this period, careful selection of treatments for these diseases is required.

In hypothyroidism caused by pituitary damage, it is necessary to find out if there is simultaneous adrenal cortex insufficiency. In this case, replacement therapy with glucocorticosteroids should be started before the start of treatment of hypothyroidism with thyroid hormones to avoid the development of acute adrenal insufficiency.

Effect on the ability to drive vehicles and mechanisms

The preparation does not affect professional activities related to driving vehicles and operating mechanisms.

Overdose

In case of overdose (especially with too rapid dose increase at the beginning of treatment), symptoms of thyrotoxicosis may be observed: palpitations, cardiac arrhythmia, finger tremor, internal restlessness, insomnia, increased sweating, weight loss, diarrhea.

Depending on the severity of the symptoms, the doctor may recommend a reduction in the daily dose of the preparation, a break in treatment for several days, or the prescription of beta-blockers. After the side effects disappear, treatment should be started cautiously with a lower dose.

In case of acute overdose and intoxication, it is recommended to stop taking the preparation and conduct a control examination. The appointment of thyrostatic agents is not recommended. When using the preparation in very high doses, plasmapheresis is indicated.

Drug Interactions

With simultaneous use with phenytoin, salicylates, dicumarol, clofibrate, furosemide in high doses (250 mg), the effect of Thyreocomb^® is enhanced, because the content of thyroid hormones not bound to plasma proteins increases.

Thyreocomb^® enhances the effect of indirect anticoagulants, which may require a reduction in their dose.

The use of tricyclic antidepressants with Thyreocomb^® may lead to an enhancement of the effect of antidepressants.

Thyroid hormones may increase the need for insulin and oral hypoglycemic drugs. More frequent monitoring of blood glucose levels is recommended during the periods of starting treatment with the preparation, as well as when changing its dosage regimen.

With simultaneous use with potassium-sparing diuretics, Potassium iodide may lead to an increase in blood potassium levels. Thyreocomb^® reduces the effect of cardiac glycosides.

With simultaneous use, cholestyramine, colestipol, and aluminum hydroxide reduce the plasma concentration of the preparation by inhibiting its absorption in the intestine, so Thyreocomb^® should be taken 4-5 hours before taking these drugs.

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

Taking estrogen-containing drugs increases the content of thyroxine-binding globulin, which may increase the need for Thyreocomb^® in some patients. Somatropin, when used simultaneously with Thyreocomb^®, may accelerate the closure of epiphyseal growth zones.

Taking phenobarbital, carbamazepine, and rifampicin may increase the clearance of levothyroxine and require an increase in the dose of Thyreocomb^®.

Storage Conditions

In a dry place, protected from light, at a temperature of 15 to 25°C (77°F).

Keep out of reach of children.

The expiration date of the preparation is indicated on the folding carton box. After this date, the preparation must not be used.

Shelf Life

Shelf life – 3 years.

Dispensing Status

The preparation is dispensed by prescription.

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.