Metizol (Tablets) Instructions for Use

Marketing Authorization Holder

ICN Polfa Rzeszow, S.A. (Poland)

ATC Code

H03BB02 (Thiamazole)

Active Substance

Thiamazole (Rec.INN registered by WHO)

Dosage Form

Metizol

Tablets 5 mg: 50 pcs.

Dosage Form, Packaging, and Composition

25 pcs. – blister packs (2) – cardboard packs.

Clinical-Pharmacological Group

Antithyroid drug

Pharmacotherapeutic Group

Antithyroid agent

Pharmacological Action

Antithyroid agent. It blocks the peroxidase enzyme involved in the iodination of thyroid hormones, which leads to a disruption in the synthesis of thyroxine and triiodothyronine. This property allows for symptomatic therapy of thyrotoxicosis, except in cases of thyrotoxicosis due to hormone release after the destruction of thyroid cells (after treatment with radioactive iodine or in thyroiditis). Thiamazole does not affect the process of release of synthesized thyronines from the thyroid follicles. This explains the latent period of varying duration that may precede the normalization of T3 and T4 levels in the blood plasma, i.e., the improvement of the clinical picture.

Thiamazole reduces the basal metabolic rate, accelerates the excretion of iodides from the thyroid gland, increases the reciprocal activation of the synthesis and release of thyroid-stimulating hormone by the pituitary gland, which may be accompanied by some hyperplasia of the thyroid gland.

Pharmacokinetics

After oral administration, it is rapidly and almost completely absorbed. C_max in plasma is reached within 0.4 – 1.2 hours. It practically does not bind to plasma proteins. It accumulates in the thyroid gland, where it is slowly metabolized. It is excreted in small amounts in breast milk. T_1/2 is 3-6 hours. No dependence of pharmacokinetic parameters on the functional state of the thyroid gland was found. Metabolism occurs in the kidneys and liver, it is excreted in the urine and bile. 70% of thiamazole is excreted by the kidneys within 24 hours (7-12% unchanged).

Indications

Thyrotoxicosis, preparation for surgical treatment of thyrotoxicosis, preparation for treatment of thyrotoxicosis with radioactive iodine, therapy during the latent period of radioactive iodine action (carried out before the onset of radioactive iodine action – for 4-6 months). In exceptional cases – long-term maintenance therapy of thyrotoxicosis, when radical treatment is impossible due to the general condition or individual reasons. Prevention of thyrotoxicosis when prescribing iodine preparations (including cases of using iodine-containing X-ray contrast agents) in the presence of latent thyrotoxicosis, autonomous adenomas, or a history of thyrotoxicosis.

ICD codes

Dosage Regimen

Administer orally. The dosage is individualized based on disease severity, therapeutic goal, and patient age.

For initial treatment of thyrotoxicosis in adults, prescribe 20-40 mg daily, divided into 2-3 doses.

For severe thyrotoxicosis, initiate therapy at the higher end of the dosage range.

For maintenance therapy, reduce the dose to 5-20 mg daily, typically as a single dose or divided into two doses.

For preparation before thyroid surgery or radioactive iodine therapy, use a similar initial dosing strategy.

For pediatric patients over 3 years of age, initiate therapy at 0.3-0.7 mg per kg of body weight per day, divided into doses.

Adjust all doses based on regular monitoring of clinical response and thyroid function tests.

Gradually titrate the dose to the minimum effective level for long-term control.

Abruptly discontinuing therapy may precipitate a relapse of thyrotoxicosis.

Adverse Reactions

From the hematopoietic system: infrequently – agranulocytosis; very rarely – thrombocytopenia, pancytopenia, generalized lymphadenopathy.

From the metabolism: very rarely – autoimmune insulin syndrome (AIS), with a pronounced decrease in plasma glucose concentration.

From the nervous system: rarely – taste disorders (dysgeusia, ageusia); very rarely – neuritis, polyneuropathy.

From the digestive system: very rarely – acute salivary gland edema.

From the liver and biliary tract: very rarely – isolated cases of cholestatic jaundice or toxic hepatitis.

From the immune system: very often – itching, rash, urticaria; rarely – drug fever; very rarely – severe forms of allergic skin reactions up to generalized dermatitis, drug-induced lupus erythematosus.

From the skin and subcutaneous tissues: very rarely – alopecia.

From the musculoskeletal system: often – arthralgia.

Contraindications

Hypersensitivity to thiamazole; agranulocytosis during previous therapy with carbimazole or thiamazole, granulocytopenia (including in history), cholestasis before the start of treatment; children under 3 years of age. Therapy with thiamazole in combination with levothyroxine sodium during pregnancy.

With caution in patients with very large goiter with tracheal narrowing (only short-term treatment during preparation for surgery), with hepatic insufficiency.

Use in Pregnancy and Lactation

During pregnancy and breastfeeding, it should be used only after consultation with a doctor, in cases where the intended benefit to the mother outweighs the potential risk to the fetus or infant. The use of thiamazole in combination with levothyroxine sodium is contraindicated during pregnancy.

Lack of treatment for hyperthyroidism during pregnancy can lead to serious complications, such as premature birth, fetal malformations. Hypothyroidism caused by treatment with inadequate doses of thiamazole can lead to miscarriage.

Thiamazole crosses the placental barrier and in the fetal blood can reach the same concentration as in the mother. In this regard, during pregnancy, Thiamazole should be prescribed in the minimum effective dose (up to 10 mg/day) without additional intake of levothyroxine sodium.

Doses of thiamazole significantly exceeding the recommended ones can cause goiter formation and hypothyroidism in the fetus, as well as low birth weight.

Thiamazole passes into breast milk and can reach a concentration corresponding to its level in the mother’s blood. The development of hypothyroidism in the newborn is possible. It is necessary to regularly monitor the thyroid function in newborns.

Use in Hepatic Impairment

Should be used with caution in hepatic insufficiency. Thiamazole is prescribed in the minimum effective dose under careful medical supervision.

Pediatric Use

Contraindicated for use in children under 3 years of age.

Special Precautions

During treatment with thiamazole, regular monitoring of the peripheral blood picture is necessary.

For patients with a significant enlargement of the thyroid gland that narrows the tracheal lumen, Thiamazole is prescribed short-term in combination with levothyroxine sodium, since long-term use may lead to an increase in the goiter and further compression of the trachea.

Careful monitoring of the patient (control of TSH level, tracheal lumen) is necessary.

Thiamazole and thiourea derivatives may reduce the sensitivity of thyroid tissue to radiation therapy.

Before starting treatment, the patient should be warned about the need to consult a doctor if fever, sore throat, inflammation of the oral mucosa, or boils appear, as these phenomena may be symptoms of agranulocytosis.

If subcutaneous hemorrhages or bleeding of unclear origin, generalized skin rash and itching, persistent nausea or vomiting, jaundice, severe epigastric pain, and pronounced weakness appear during treatment with thiamazole, discontinuation of thiamazole is required.

In case of early discontinuation of treatment, a relapse of the disease is possible.

In rare cases, after the end of treatment, late hypothyroidism may occur, which is not a side effect of thiamazole, but is associated with inflammatory and destructive processes in the thyroid tissue occurring within the framework of the underlying disease.

Drug Interactions

When prescribing thiamazole after the use of high-dose iodine-containing X-ray contrast agents, a weakening of the effect of thiamazole is possible.

In patients with iodine deficiency, the pharmacological action of thiamazole is enhanced; in patients with excess iodine (for example, against the background of simultaneous use of medications containing large amounts of iodine) – it is weakened.

In patients taking Thiamazole for the treatment of thyrotoxicosis, after achieving a euthyroid state, i.e., normalization of thyroid hormone levels in the blood serum, it may be necessary to reduce the doses of cardiac glycosides (digoxin and digitoxin), aminophylline, as well as increase the doses of warfarin and other anticoagulants – derivatives of coumarin and indandione (pharmacodynamic interaction).

With simultaneous use, lithium preparations, beta-blockers, reserpine, amiodarone enhance the effect of thiamazole.

With simultaneous use of thiamazole with sulfonamides, sodium metamizole, and myelotoxic drugs, the risk of leukopenia increases.

Leukogen and folic acid, when used simultaneously with thiamazole, reduce the risk of leukopenia.

With simultaneous use, gentamicin enhances the antithyroid effect of thiamazole.

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.