Active ingredients: Thiamazole
TAPAZOLE 5 mg tablets
Why is Tapazole used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Antithyroid belonging to the class of sulfur-containing imidazole derivatives.
THERAPEUTIC INDICATIONS
Medical therapy of hyperthyroidism.
Long-term therapy can induce remission of the disease. Tapazole can be used to prepare for subtotal thyroidectomy and radioactive iodine therapy. Tapazole is also indicated when thyroidectomy is contraindicated or not recommended.
Contraindications When Tapazole should not be used
Known individual hypersensitivity to the active substance or to any of the excipients. Tapazole is contraindicated during breastfeeding.
Precautions for use What you need to know before taking Tapazole
Patients being treated with Tapazole should be closely monitored and reported immediately to their doctor any symptoms such as: sore throat, rash, fever, migraine (a particular type of headache characterized by violent painful crises localized in one half of the head ) or general malaise. In such cases, in fact, it is necessary to carry out a blood test (complete blood count with leukocyte formula) to exclude the diagnosis of agranulocytosis. Even more careful medical supervision must be carried out in patients who are simultaneously taking drugs that can cause agranulocytosis.
Laboratory tests
Since methimazole can cause hypoprothrombinemia (decreased levels of prothrombin in the blood) and bleeding, the prothrombin time should be checked periodically during drug therapy, especially before surgery. Periodic monitoring of thyroid function is essential: if the values of the thyroid stimulating hormone (TSH) are elevated, a decrease in the dosage of methimazole is necessary.
Carcinogenesis, mutagenesis and alterations of fertility
Rats treated for 2 years with methimazole showed thyroid hyperplasia, adenoma formation and thyroid carcinoma. Such findings are observed with continued withdrawal of thyroid function by sufficient doses of various antithyroid agents.
Pituitary gland adenomas have also been observed.
Interactions What medications or foods can change the effect of Tapazole
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Interaction studies have not been conducted in pediatric age. Anticoagulants (oral): the activity of anticoagulants can be enhanced by an anti-vitamin K action attributed to methimazole.
Beta-blockers: Hyperthyroidism can cause increased clearance of beta-blockers with a high extraction rate. When a hyperthyroid patient becomes euthyroid, a reduction in the dosage of beta-blockers may be necessary.
Digitalis glycosides: plasma levels of digitalis drugs may be increased when hyperthyroid patients on continuous treatment with digitalis glycosides become euthyroid; in such cases it may be necessary to reduce the dosage of digitalis glycosides.
Theophylline: clearance of theophylline may decrease when hyperthyroid patients on continuous treatment with theophylline become euthyroid; in such cases a reduction of the theophylline dosage may be necessary.
Warnings It is important to know that:
Patients should report any symptoms suggesting agranulocytosis, such as fever or sore throat, to their physician. Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur.
The drug should be discontinued in the presence of agranulocytosis, aplastic anemia, hepatitis or exfoliative dermatitis. The hematopoietic function (ability to produce the figurative elements of blood) of the patient must be carefully checked periodically.
Due to the hepatic toxicity of Tapazole and propylthiouracil, attention should be paid to severe hepatic reactions occurring with these drugs. Cases of fulminant hepatitis, hepatic necrosis (death of liver cells), encephalopathy (central nervous system disorder) and death have been observed rarely. Upon the appearance of symptoms that may indicate impaired hepatic function (marked loss of appetite, itching, right upper abdominal pain, etc.) a liver function check should be performed.
In the event of clinically significant evidence of the existence of hepatic abnormalities, including transaminase values that exceed three times the upper limit of normal, drug treatment should be promptly discontinued.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine. IN PREGNANT WOMEN AND IN THE VERY EARLY CHILDHOOD, THE DRUG MUST BE ADMINISTERED IN CASE OF ACTUAL NEED AND UNDER DIRECT MEDICAL CONTROL.
Methimazole can cause fetal harm as it quickly crosses the placental barrier and can cause goiter (enlargement of the thyroid gland) in the fetus and even cretinism. In addition, the following birth defects have rarely occurred in infants whose mothers were treated with methimazole during pregnancy: aplasia cutis (scalp defect), esophageal atresia (occlusion of the "esophagus) with tracheoesophageal fistula (abnormal communication between the trachea and esophagus), choanal atresia (occlusion of one or both nasal passages) with absence or incomplete development of the nipples.
If methimazole is used during pregnancy, or conception occurs during treatment with this drug, the patient should be made aware of the potential risks to the fetus.
Since the aforementioned congenital defects have occurred in the offspring of patients treated with methimazole, in pregnant women requiring treatment for hyperthyroidism the physician will have to carefully evaluate possible therapeutic alternatives.
To date, no scalp defects and other specific congenital malformations have been described in neonates of patients treated with propylthiouracil; therefore this drug may be preferable to methimazole in pregnant women who require antithyroid therapy, always bearing in mind the risk of goiter and hypothyroidism in the fetus.
In many women, the degree of thyroid dysfunction tends to decrease as pregnancy progresses, which may allow for a reduction in the dose. In some cases, the administration of Tapazole may be stopped 2 or 3 weeks before delivery.
In nursing mothers, Tapazole is contraindicated, due to the passage of the drug into breast milk.
Effects on ability to drive and use machines
No effects of Tapazole on driving skills and use of machines have been reported.
Dosage and method of use How to use Tapazole: Dosage
Tapazole is generally administered orally in three equal doses at 8 hour intervals.
Adults - The starting daily dose is 15 mg for mild hyperthyroidism, 30-40 mg for moderate hyperthyroidism and 60 mg for severe hyperthyroidism. The maintenance dose usually ranges from 5 to 15 mg per day.
Pediatric population
Use in children and adolescents (3-17 years)
The starting dose for the treatment of children over 3 years of age and adolescents should be calculated in relation to their body weight. Generally, the starting daily dose is 0.5 / mg / kg divided into two or three equal doses. For maintenance therapy, the daily dose may be reduced according to the patient's response to therapy. Additional treatment with levothyroxine may be needed to avoid hypothyroidism. Do not exceed a dose of 40 mg per day.
Use in children (age 2 years and younger)
The safety and efficacy of methimazole in children under 2 years of age has not been systematically established. Therefore its use is not recommended in this age group. Daily dosing can be implemented by breaking the tablet.
Overdose What to do if you have taken too much Tapazole
Signs and symptoms
They can include: nausea, vomiting, stomach pain, headache, fever, joint pain, itching and edema. Aplastic anemia or agranulocytosis can occur within hours or days.
Less frequently, hepatitis, nephrotic syndrome, exfoliative dermatitis, neuropathies (disorders affecting the peripheral nervous system), stimulation or reduction of central nervous system activity may occur.
Although the mechanism that triggers agranulocytosis is not yet known, the phenomenon is generally associated with the intake of methimazole doses greater than or equal to 40 mg in patients over 40 years of age.
Treatment
For up-to-date information on the treatment of overdose, contact the Regional Poison Control Center.
In evaluating overdose, the possibility of multiple drug overdoses, drug interactions, and particular pharmacokinetics in the patient should be considered.
The patient must be followed carefully, particularly checking the state of the airways, ensuring ventilation and perfusion.
Carefully check and maintain the patient's vital signs (blood pressure, heart rate and respiratory activity), blood gas analysis, serum electrolytes, etc. within acceptable limits. The patient's hematopoietic function should be checked periodically. The intestinal absorption of the drug can be reduced by administering activated charcoal which, in many cases, is more effective than induced vomiting or gastric lavage; therefore, consider activated charcoal as an alternative treatment or in addition to gastric lavage. Repeated administration of charcoal. active may facilitate the elimination of other drugs that may have been taken. Carefully check the patient's airways during gastric lavage and the use of activated charcoal.
It is not known whether forced diuresis, peritoneal dialysis, hemodialysis and activated charcoal hemoperfusion are beneficial to the patient for the treatment of methimazole overdose.
In case of accidental ingestion / intake of an excessive dose of Tapazole, notify your doctor immediately or go to the nearest hospital.
Side Effects What are the side effects of Tapazole
Like all medicines, Tapazole can cause side effects, although not everybody gets them.
Non-serious side effects include: rash, hives, nausea, vomiting, epigastric disorder (stomach pain), arthralgia (joint pain), paraesthesia (altered sensation), loss of taste, hair loss, myalgia (muscle pain), headache, itching, drowsiness, neuritis (inflammatory or degenerative process affecting a nerve), edema, dizziness, skin discoloration, sialoadenopathy and lymphadenopathy (increase in size and / or pain affecting the salivary and lymphatic glands).
Serious adverse reactions (occurring much less frequently than non-serious adverse reactions) include inhibition of bone marrow function (agranulocytosis, granulocytopenia and thrombocytopenia), aplastic anemia, drug fever, a lupus-like syndrome, an autoimmune syndrome towards insulin (which can cause hypoglycemic coma), hepatitis (jaundice may persist for several weeks after discontinuation of the drug), periarteritis (inflammatory process affecting the wall of an artery) and hypoprothrombinemia (with risk of bleeding).
Very rarely, nephritis occurs (an inflammatory process affecting the kidney).
It should be borne in mind that in about 10% of patients with untreated hyperthyroidism there is a decrease in white blood cells (less than 4,000 per mm3), often with a relative decrease in granulocytes.
Pediatric population
The frequency, type and severity of adverse reactions in children appear to be comparable to those in adults. Severe skin hypersensitivity reactions have been reported in both adults and pediatric patients, including Stevens-Johnson syndrome (very rare) and isolated cases of severe generalized dermatitis.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact packaging, correctly stored.
CAUTION: DO NOT USE THE MEDICINAL PRODUCT AFTER THE EXPIRY DATE INDICATED ON THE PACKAGE
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN
Composition and pharmaceutical form
COMPOSITION
Active principle:
Methimazole 5 mg
Excipients: lactose monohydrate, corn starch, magnesium stearate, talc
PHARMACEUTICAL FORM AND CONTENT
Tablets. Pack containing 100 divisible tablets of 5 mg, packed in blisters.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
TAPAZOLE 5 MG TABLETS
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each breakable tablet contains:
Active principle:
Methimazole 5 mg
Excipients:
Lactose monohydrate
For the full list of excipients, see section 6.1
03.0 PHARMACEUTICAL FORM
Tablets
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Medical therapy of hyperthyroidism.
Long-term therapy can induce remission of the disease. Tapazole can be used to prepare for subtotal thyroidectomy and radioactive iodine therapy.
Tapazole is also indicated when thyroidectomy is contraindicated or not recommended.
04.2 Posology and method of administration
Adults
The starting daily dose is 15 mg for mild hyperthyroidism, 30-40 mg for moderate hyperthyroidism and 60 mg for severe hyperthyroidism. The daily amount should be divided into three doses to be administered at intervals. 8 hours The maintenance dose varies from 5 to 15 mg per day.
Pediatric population
Use in children and adolescents (3-17 years)
The starting dose for the treatment of children over 3 years of age and adolescents should be calculated in relation to their body weight. Generally, the starting daily dose is 0.5 / mg / kg divided into two or three equal doses.
For maintenance therapy, the daily dose can be reduced based on the patient's response to therapy. Additional treatment with levothyroxine may be needed to avoid hypothyroidism. Do not exceed a dose of 40 mg per day.
Use in children (age 2 years and younger)
The safety and efficacy of methimazole in children under 2 years of age has not been systematically established and therefore its use is not recommended in this age group.
04.3 Contraindications
Hypersensitivity to antithyroid drugs.
Feeding time.
04.4 Special warnings and appropriate precautions for use
Agranulocytosis is a potentially serious side effect. Patients should be advised to report any symptoms suggestive of agranulocytosis, such as fever or sore throat, to their physician. Leukopenia, thrombocytopenia and aplastic anemia may also occur. presence of agranulocytosis, aplastic anemia, hepatitis or exfoliative dermatitis The patient's hematopoietic function should be carefully monitored.
Due to the hepatic toxicity of methimazole and propylthiouracil, attention should be paid to severe hepatic reactions occurring with these drugs. Rare cases of fulminant hepatitis, hepatic necrosis, encephalopathy and death have been reported.The appearance of symptoms suggestive of hepatic involvement (anorexia, pruritus, pain in the right upper abdominal quadrant, etc.) must therefore lead to a "careful evaluation of liver function.
The presence of evident manifestations of hepatic dysfunction (including an increase in transaminases of 3 times the upper limit of normal or greater) makes prompt discontinuation of methimazole necessary.
Patients should be closely monitored, paying particular attention to any symptoms or signs of illness they report, particularly sore throat, fever, rash, headache or general malaise. In these cases, a complete blood count with a leukocyte formula should be performed in order to exclude the possibility of agranulocytosis. These precautions are even more necessary if the patient is receiving other potentially myelotoxic drugs.
Since methimazole can cause hypoprothrombinemia and bleeding, the prothrombin time should be monitored, especially before surgery.
Finally, it is necessary to monitor thyroid function in order to make appropriate reductions in the dosage of methimazole following high TSH values.
This medicine contains lactose: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Interaction studies have not been conducted in pediatric age.
Anticoagulants (oral): the activity of anticoagulants can be enhanced by an anti-vitamin K action attributed to methimazole.
Beta blockers: Hyperthyroidism can cause increased clearance of beta-blockers with a high extraction index. When a hyperthyroid patient becomes euthyroid, a reduction in the dosage of beta-blockers may be necessary.
Digitalis glycosides: plasma levels of digitalis drugs may be increased when hyperthyroid patients on continuous treatment with digitalis glycosides become euthyroid; in such cases it may be necessary to reduce the dosage of digitalis glycosides.
Theophylline: clearance of theophylline may decrease when hyperthyroid patients on continuous theophylline become euthyroid; in such cases a reduction of the theophylline dosage may be necessary.
04.6 Pregnancy and lactation
IN PREGNANT WOMEN AND IN THE VERY EARLY CHILDHOOD, THE DRUG MUST BE ADMINISTERED IN CASES OF ACTUAL NEED AND UNDER DIRECT MEDICAL CONTROL.
Methimazole can cause fetal harm by rapidly crossing the placental barrier and can cause goiter (enlargement of the thyroid gland) and even cretinism in the fetus. In addition, the following birth defects have rarely occurred in infants whose mothers were treated with methimazole during pregnancy: aplasia cutis (scalp defect), esophageal atresia (occlusion of the "esophagus) with tracheoesophageal fistula (abnormal communication between the trachea and esophagus), choanal atresia (occlusion of one or both nasal passages) with absence or incomplete development of the nipples.
If methimazole is used during pregnancy, or conception occurs during treatment with this drug, the patient should be made aware of the potential risks to the fetus.
Since the aforementioned congenital defects have occurred in the offspring of patients treated with methimazole, in pregnant women requiring treatment for hyperthyroidism the physician will have to carefully evaluate possible therapeutic alternatives.
To date, no scalp defects and other specific congenital malformations have been described in neonates of patients treated with propylthiouracil; therefore this drug may be preferable to methimazole in pregnant women who require antithyroid therapy, always bearing in mind the risk of goiter and hypothyroidism in the fetus.
In many women, the degree of thyroid dysfunction tends to decrease as pregnancy progresses, which may allow for a reduction in the dose. In some cases, the administration of Tapazole may be stopped 2 or 3 weeks before delivery.
In nursing mothers, Tapazole is contraindicated, due to the passage of the drug into breast milk.
04.7 Effects on ability to drive and use machines
No effect of methimazole on the ability to drive and use machines has been reported.
04.8 Undesirable effects
Non-serious side effects include: skin rashes, hives, nausea, vomiting, epigastralgia, arthralgia, paraesthesia, loss of sense of taste, hair loss, myalgia, headache, itching, drowsiness, neuritis, edema, dizziness, skin pigmentation, jaundice , sialoadenopathy and lymphadenopathy.
More serious adverse reactions (occurring much less frequently than non-serious ones) include: inhibition of myelopoiesis (agranulocytosis, granulocytopenia and thrombocytopenia), aplastic anemia, drug fever, lupus-like syndrome, hepatitis (jaundice may persist for several weeks after drug withdrawal), an autoimmune insulin syndrome (which can result in hypoglycemic coma), periarteritis and hypoprothrombinemia. Rarely, nephritis may occur.
It should be noted that approximately 10% of untreated hyperthyroid patients have leukopenia with relative granulocytopenia.
Pediatric population
The frequency, type and severity of adverse reactions in children appear to be comparable to those in adults. Severe skin hypersensitivity reactions have been reported in both adults and pediatric patients, including Stevens-Johnson syndrome (very rare) and isolated cases of severe generalized dermatitis.
04.9 Overdose
Signs and symptoms: Signs and / or symptoms such as nausea, vomiting, epigastralgia, headache, fever, pruritus, edema and joint pain have been reported. Exfoliative dermatitis, hepatitis, nephrotic syndrome, neuropathies, central nervous system stimulation or depression may occur less frequently.
Aplastic anemia and agranulocytosis may occur within hours or days. Although the mechanism that triggers agranulocytosis is not yet known, the phenomenon is generally associated with the intake of methimazole doses greater than or equal to 40 mg in patients over 40 years of age.
Treatment: In the evaluation of overdose, the possibility of overdoses due to multiple drugs, drug interactions and particular pharmacokinetics in the patient should be considered.
The patient should be followed carefully, checking in particular the state of the airways ensuring ventilation and perfusion. Monitor and maintain patient vital signs, blood gas analysis, serum electrolytes and hematopoietic function within acceptable limits.
Intestinal absorption of the drug can be reduced by administering activated charcoal which, in many cases, is more effective than emesis or gastric lavage. Consider using activated charcoal as an alternative treatment or in addition to gastric lavage. Repeated administration of activated charcoal may facilitate the elimination of other drugs that may have been taken. Carefully check the patient's airways during gastric lavage and the use of activated charcoal.
It is not known whether forced diuresis, peritoneal dialysis, hemodialysis and activated charcoal hemoperfusion can be effective for the treatment of methimazole overdose.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Tapazole exerts its action by blocking the synthesis of thyroid hormone at the level of the oxidation of inorganic iodine (I-) to the organic form (I +) and at the level of its incorporation in the tyrosine residues of the thyroglobulin molecule. It also determines an inhibition of the production of TSH antireceptor and antimicrosomal antibodies. The drug is electively concentrated in the thyroid, where it would act on thyroid lymphocytes, the main source of antibody synthesis.
The drug does not inactivate thyroxine and triiodothyronine already synthesized and present in the colloid or circulating in the blood, nor does it interfere with the activity of thyroid hormones administered orally or parenterally.
05.2 Pharmacokinetic properties
Methimazole is readily absorbed from the gastrointestinal tract, rapidly metabolized and excreted via the urine; frequent administrations are therefore necessary.
Effective concentrations are achieved in 30 minutes. Only 0.5 mg of methimazole is needed to block thyroid hormone synthesis; dosages of 10-25 mg inhibit synthesis for 24 hours.
The half-life of methimazole ranges from 6 to 13 hours.
Methimazole electively concentrates in the thyroid and crosses the fetal-placental barrier.
05.3 Preclinical safety data
Rats treated for 2 years with methimazole presented thyroid hyperplasia, adenoma and thyroid carcinoma. Such effects have been observed with continued suppression of thyroid function by sufficient doses of various antithyroid agents. Pituitary gland adenomas have also been observed.
Therapeutic regimens that have been studied in this regard include antithyroid drugs such as matimazole, but also conditions such as dietary iodine deficiency, subtotal thyroidectomy, implantation of autonomous thyroid hormone-secreting pituitary tumors, and administration of goitigenic substances.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Lactose monohydrate, corn starch, magnesium stearate, talc.
06.2 Incompatibility
Not relevant
06.3 Period of validity
The validity period is 2 years.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Carton containing 100 divisible tablets packed in blisters.
06.6 Instructions for use and handling
No special instructions
07.0 MARKETING AUTHORIZATION HOLDER
TEOFARMA S.r.l.
Via F.lli Cervi, 8
27010 Salimbene Valley (PV)
08.0 MARKETING AUTHORIZATION NUMBER
AIC N °: 005472028
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
13.10.2005 / June 2010
10.0 DATE OF REVISION OF THE TEXT
April 2012
