Tirosint - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf Life and Storage

Active ingredients: Levothyroxine (Levothyroxine sodium)

Tirosint® 50 micrograms tablets
Tirosint ® 100 micrograms tablets
Tirosint ® 100 micrograms / ml oral drops, solution

Tirosint package inserts are available for pack sizes:
  • Tirosint® 50 micrograms tablets, Tirosint® 100 micrograms tablets, Tirosint® 100 micrograms / ml oral drops, solution
  • Tirosint® 25 micrograms / 1ml oral solution, Tirosint® 50 micrograms / 1ml oral solution, Tirosint® 75 micrograms / 1ml oral solution, Tirosint ® 100 micrograms / 1ml oral solution

Why is Tirosint used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Thyroid hormones.

THERAPEUTIC INDICATIONS

States of hypothyroidism of any origin and nature: goiter, prophylaxis of relapses after strumectomy, thyroid hypofunction, inflammation of the thyroid, during therapy with antithyroid.

Contraindications When Tirosint should not be used

Hypersensitivity to the active substance or to any of the excipients.

Thyrotoxicosis, untreated adrenal insufficiency, untreated pituitary insufficiency. Tirosint treatment should not be initiated in acute myocardial infarction, acute myocarditis and pancarditis.

Precautions for use What you need to know before taking Tirosint

The product should be used with caution and under strict medical supervision in patients with cardiovascular diseases, such as myocardial infarction, angina pectoris, myocarditis, heart failure with tachycardia, hypertension, coronary insufficiency.

Before starting thyroid hormone therapy, or before performing a thyroid suppression test, the following conditions must be ruled out or treated: arteriosclerosis, pituitary or adrenal insufficiency, autonomy of the thyroid gland.

The induction of even mild hyperthyroidism in patients with coronary insufficiency, heart failure or tachyarrhythmias should be avoided. Therefore, frequent monitoring of thyroid hormone levels is necessary in these cases.

In elderly patients and in patients in whom hypothyroidism has been present for a long time, treatment with thyroid hormone should be initiated with particular caution, starting with a lower starting dose, and making gradual adjustments of the therapy.

Patients suffering from panhypopituitarism or other predisposing causes to adrenal insufficiency may react unfavorably to levothyroxine: therefore it is advisable to start corticosteroid therapy before treatment with Tirosint.

The product should also be used with caution in diabetic patients. (See paragraph "Interactions").

Interactions Which drugs or foods can modify the effect of Tirosint

Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.

Insulin and oral hypoglycemic agents. Levothyroxine may reduce the hypoglycemic action of insulin and oral hypoglycemic agents. Therefore, in diabetic patients, particularly at the beginning of therapy with thyroid hormones, the glycaemia should be regularly monitored, to highlight any phenomena of interaction and therefore to adapt the dosage of hypoglycemic drugs.

Coumarin derivatives. Levothyroxine may enhance the action of coumarin derivatives due to competition for binding to plasma albumin. In case of concomitant treatment, coagulation factors should be monitored regularly; eventually, the dosage of the anticoagulant will have to be adapted.

Ion exchange resins. Ion exchange resins, such as cholestyramine and colestipol, reduce the absorption of levothyroxine; therefore, the administration of these resins must take place 4 - 5 hours after that of Tirosint.

Antacids based on aluminum, sucralfate, medicines based on iron or calcium carbonate. These drugs reduce the absorption of levothyroxine, reducing its effect. Therefore Tirosint should be taken at least four hours before taking these drugs.

Salicylates, dicumarol, furosemide, clofibrate, phenytoin. Salicylates, dicumarol, high-dose furosemide (250 mg), clofibrate, phenytoin and other substances can displace sodium levothyroxine from plasma proteins, thus resulting in a "high fT4 fraction.

Propylthiouracil, glucocorticoids, beta-sympatholytics. These substances inhibit the peripheral conversion of T4 to T3.

Soy-based products. They can reduce the intestinal absorption of levothyroxine. Therefore, especially at the beginning and after the interruption of a diet rich in soy, it may be necessary to adjust the dosage of Tirosint.

Inducers of metabolizing enzymes. Barbiturates, rifampicin, carbamazepine, phenytoin and other hepatic enzyme inducers may increase the hepatic clearance of levothyroxine.

Phenytoin (diphenylhydantoin) should not be administered intravenously during treatment with Tirosint

Propranolol. Levothyroxine accelerates the metabolism of propranolol.

Estrogen. The concomitant use of estrogenic or estrogen contraceptives for postmenopausal hormone replacement therapy may necessitate an increase in levothyroxine dosage.

Sertraline, chloroquine, proguanil. These substances reduce the effectiveness of levothyroxine and increase the serum TSH level.

Amiodarone and iodine-based contrast media. Due to the high iodine content, these drugs can cause hyperthyroidism or hypothyroidism. Particular caution should be observed in case of stroma with possible functional autonomy of the thyroid.

Orlistat. Hypothyroidism and / or impaired control of hypothyroidism may occur following concomitant administration of orlistat and levothyroxine.

Warnings It is important to know that:

The use of drugs having hormonal activity on the thyroid gland for the treatment of obesity is dangerous, since, at the necessary doses, it can cause secondary reactions, even of considerable seriousness. Since rare cases of hepatic dysfunction have been reported in subjects treated with thyroid preparations, it is recommended to reduce the dosage or discontinue treatment if fever, muscle weakness or abnormal liver function laboratory tests occur during therapy.

In "primary hypothyroidism" TSH levels alone (measured by a sensitive method) should be used to monitor therapy.

The cause of secondary hypothyroidism should be established prior to administration of replacement therapy and, if necessary, replacement therapy should be initiated for compensated "adrenal insufficiency."

In cases where thyroid autonomy is suspected, the physician should evaluate the need for a TRH test or a suppression scan before initiating therapy.

In postmenopausal women with hypothyroidism and a high risk of osteoporosis, it is necessary to avoid serum levels of levothyroxine above the physiological ones; therefore, thyroid function must be closely monitored.

The frequency of TSH checks during the dose adjustment phase depends on the clinical situation, but is generally recommended at 6-8 week intervals until desired levels are achieved. In particular, in patients with differentiated carcinoma of the thyroid who begin treatment following thyroidectomy and possible radio isotope therapy, the TSH dosage is recommended 2 months after the start of treatment to confirm the suppression of TSH and check-ups after about 6 and 12 months. In individuals judged to be in complete remission, it is recommended that the level of TSH suppression be adjusted based on medical judgment.

In patients whose TSH levels have reached the desired level and in those whose levothyroxine medicinal product or dosage has been changed, the TSH concentration should be checked after 8-12 weeks and the dosage adjusted according to the results. obtained. Once the maintenance dose is reached, clinical and biochemical checks should be repeated every 6-12 months based on medical judgment.

Important information about some of the ingredients of Tirosint

Tirosint oral drops contains 28.8 vol% ethanol (ethyl alcohol). Each 100 μg (1 ml) dose therefore contains 243 mg of ethanol (ethyl alcohol). Harmful for those suffering from alcoholism. Consider for treatment during pregnancy and lactation and for the treatment of children and high-risk patients, such as patients with liver disease or epilepsy.

For those who carry out sporting activities, the use of medicines containing ethyl alcohol can determine positive doping tests in relation to the alcohol concentration limits indicated by some sports federations.

Pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine.

PREGNANCY

In pregnant women and during the lactation period, the administration of the product should not be interrupted, however its administration, as for other drugs administered during pregnancy, should be carried out only in case of real need and under the direct supervision of the doctor.

The dosages needed may also increase during pregnancy.

Experience has shown that there is no evidence of drug induced teratogenicity and / or fetal toxicity in humans at recommended therapeutic dosages. Excessively high doses of levothyroxine during pregnancy can have a negative effect on fetal and postnatal development.

During pregnancy, levothyroxine should not be administered in combination with drugs for hyperthyroidism (antithyroid drugs), as the addition of levothyroxine may require a higher dose of antithyroid drug.

Since antithyroid drugs, in contrast to levothyroxine, can cross the placenta in sufficient quantities to exert pharmacological effects, concomitant therapy with levothyroxine requiring a higher dosage of antithyroid drug could induce hypothyroidism in the fetus. Consequently, antithyroid drugs must always be administered alone in hyperthyroidism in pregnancy.

FEEDING TIME

Levothyroxine is secreted into breast milk during lactation but the concentrations reached at recommended therapeutic doses are not sufficient to cause the development of hyperthyroidism or the suppression of TSH secretion in the newborn.

Please note that Tirosint oral drops contain ethanol.

Driving and using machines

There are no known effects on the ability to drive and use machines. However, due to the possible onset of headache, caution is advised when driving vehicles or performing activities that require special vigilance.

Dosage and method of use How to use Tirosint: Dosage

It is always advisable to carefully check the treatment by the doctor who will adjust the doses and duration of therapy according to the needs of the individual patient.

In elderly patients, in those with coronary artery disease and in patients in whom hypothyroidism has been present for a long time, treatment with thyroid hormone should be initiated with particular caution, ie it is necessary to choose a lower starting dosage, increasing it slowly over time and carrying out frequent dosages of thyroid hormones.

The number of drops of Tirosint Drops required to obtain the different dosages and the correspondence with the number of Tirosint tablets 50 and 100 micrograms are shown in the following table:


Levothyroxine Sodium mcg N ° drops ml No. tablets 50 mcg 100 mcg 25 7 0.25 ½ - 50 14 0.5 1 ½ 75 21 0.75 1 and ½ - 100 28 1 2 1 125 35 1.25 2 and ½ - 150 42 1.5 3 1 and ½ 200 56 2 - 2 300 84 3 - 3

The indicative dosage schedule is as follows:

Adults

Goiter:

100-150 micrograms per day.

Prophylaxis of relapses after strumectomy:

100 micrograms per day.

Thyroid inflammation:

100-150 micrograms per day.

During therapy with antithyroid: The administration of 50-100 micrograms per day will be sufficient.

Thyroid hypofunction:

Adults

50 micrograms per day as a starting dose (for about two weeks); the daily dose will be increased by 50 micrograms at intervals of approximately 14-15 days, until the maintenance dose of 100-200 micrograms per day is reached (on average 2-2.5 micrograms / kg body weight / day).

Pediatric patients

The maintenance dose is generally 100 to 150 micrograms per m2 of body surface area.

For newborns and infants with congenital hypothyroidism, in whom rapid replacement therapy is important, the recommended starting dosage is 10 to 15 micrograms / kg body weight / day for the first 3 months. Thereafter, the dose should be individually adjusted based on the clinical response and determination of plasma levels of thyroid hormones and TSH.

For children with acquired hypothyroidism, the recommended starting dosage is 12.5-50 micrograms per day. The dose should be gradually increased every 2-4 weeks based on clinical response and determination of plasma levels of thyroid hormones and TSH until a dose that ensures full replacement has been reached.

For infants, the full daily dose should be given at least 30 minutes before the first meal of the day.

Tirosint tablets.

The tablets must be dissolved in a little water (10-15 mL) and the resulting suspension, which must be prepared at the time of use, must be administered with the addition of other liquid (5-10 mL).

Method of administration

The daily dosage should be taken in a single administration, in the morning, preferably on an empty stomach.

Tablets

The tablets should be swallowed with a sip of water.

Oral drops, solution

Before administering the medicine, test the proper functioning of the dropper by taking the solution from the bottle and verifying the dispensing in drops. To correctly dose the medicine, keep the dropper in an upright position.

The drops must be dissolved in a little water

Overdose What to do if you have taken too much Tirosint

An increase in the level of T3 is a more reliable indicator of overdose than an increase in the levels of T4 or fT4.

Moderate to severe symptoms of impaired metabolism occur in the event of overdose and intoxication (see "Undesirable Effects"). In these cases, an interruption of the intake and a follow-up visit is indicated, depending on the extent of the overdose.

The cases of attempted suicide with levothyroxine have shown the safety of taking doses of levothyroxine up to 10 mg. Unless coronary heart disease is present, an overdose of levothyroxine does not suggest compromising vital functions (breathing and circulation). Single cases of sudden cardiac arrest have been reported in patients who have abused levothyroxine for years.

In case of acute overdose, gastrointestinal absorption can be reduced by administering charcoal. Treatment is usually symptomatic and supportive. In case of severe beta-sympathomimetic effects such as tachycardia, fear, agitation and hyperkinesias, symptoms can be reduced by "taking beta-blockers. Thyrostats are not indicated, as the thyroid is already completely at rest

In case of extremely high dosages (suicide attempt), plasmapheresis can be useful.

An overdose of levothyroxine requires a prolonged monitoring period. Due to the gradual transformation of levothyroxine into liothyronine, symptoms can last up to 6 days.

In case of accidental ingestion / intake of an excessive dose of Tirosint, notify your doctor immediately or go to the nearest hospital.

If you have any further questions on the use of Tirosint, ask your doctor or pharmacist.

Side Effects What are the side effects of Tirosint

Like all medicines, Tirosint can cause side effects, although not everybody gets them. Cardiac symptoms (eg anginal manifestations, cardiac arrhythmias, palpitations) and cramps of the skeletal muscles may occur occasionally, especially at the beginning of therapy or in case of overdose.

The following were also reported:

  • restlessness, excitability, insomnia
  • headache, cerebri pseudotumor, tremor
  • tachycardia, palpitations, cardiac arrhythmias, anginal manifestations
  • vomiting, diarrhea, weight loss
  • excessive sweating
  • muscle weakness, skeletal muscle cramps
  • hot flashes, changes in the menstrual cycle
  • fever

In these cases it is advisable, on medical advice, to reduce the daily dosage or to suspend the treatment for a few days.

In case of hypersensitivity, allergic reactions can occur.

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.

Warning: do not use the medicine after the expiry date shown on the package.

Store the medicine below 25 ° C.

Tirosint Oral drops, solution: the shelf life after first opening the bottle is 1 month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

Keep this medicine out of the reach and sight of children.

COMPOSITION

Tablets


Each tablet of Tirosint 50 mcg Tirosint 100 mcg contains Sodium Levothyroxine 50 mcg 100 mcg equal to Levothyroxine 48.62 mcg 97.24 mcg

Excipients: Anhydrous Bibasic Calcium Phosphate, Sodium Carboxymethyl Starch, Magnesium Stearate, Microcrystalline Cellulose, Talc, Citric Acid, Corn Starch.

Drops


1 ml of solution (equal to 28 drops) of Tirosint drops contains Sodium Levothyroxine 100.00 mcg equal to Levothyroxine 97.24 mcg

One drop of solution contains 3.57 micrograms of Levothyroxine Sodium.

Excipients: Ethanol 96%, glycerol 85%

PHARMACEUTICAL FORM AND CONTENT

Tablets

Carton containing 50 tablets of 50 micrograms (2 blisters of 25 tablets)

Carton containing 50 tablets of 100 micrograms (2 blisters of 25 tablets)

Oral drops, solution

20 ml bottle T

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.

Further information on Tirosint can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other Forms of interaction04.6 Pregnancy and lactation Pregnancy04.7 Effects on ability to drive and use machines04.8 Undesirable effects04.9 Overdose05.0 PHARMACOLOGICAL PROPERTIES05.1 Pharmacodynamic properties05.2 Pharmacokinetic properties05.3 Preclinical safety data06.0 INFORMATION PHARMACEUTICALS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the immediate packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER08 .0 MARKETING AUTHORIZATION NUMBER 09.0 DATE DE THE FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIOPharmaceuticals, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIATION DRUGS, FURTHER DETAILED INSTRUCTIONS ON QUALITY PREPARATION

01.0 NAME OF THE MEDICINAL PRODUCT

TIROSINT

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

Tablets


Each tablet of Tirosint 50 mcg Tirosint 100 mcg contains Sodium Levothyroxine 50 mcg 100 mcg equal to Levothyroxine 48.62 mcg 97.24 mcg

For the full list of excipients, see section 6.1

Drops


1 ml of solution (equal to 28 drops) of Tirosint drops contains Sodium Levothyroxine 100.00 mcg equal to Levothyroxine 97.24 mcg

One drop of solution contains 3.57 mcg of Levothyroxine Sodium.

Excipients

Ethanol 96%

For the full list of excipients, see section 6.1

03.0 PHARMACEUTICAL FORM

Tablets

Oral drops, solution

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

States of hypothyroidism of any origin and nature: goiter, prophylaxis of relapses after strumectomy, thyroid hypofunction, inflammation of the thyroid, during therapy with antithyroid.

04.2 Posology and method of administration

It is always advisable to carefully check the treatment by the doctor who will adjust the doses and duration of therapy according to the needs of the individual patient.

In elderly patients, in those with coronary artery disease and in patients in whom hypothyroidism has been present for a long time, treatment with thyroid hormone should be initiated with particular caution, ie it is necessary to choose a lower starting dosage, increasing it slowly over time and carrying out frequent dosages of thyroid hormones.

The number of drops of Tirosint Drops required to obtain the different dosages and the correspondence with the number of Tirosint tablets 50 and 100 mcg are shown in the following table:


Levothyroxine Sodium mcg N ° drops ml No. tablets 50 mcg 100 mcg 25 7 0.25 ½ - 50 14 0.5 1 ½ 75 21 0.75 1 and ½ - 100 28 1 2 1 125 35 1.25 2 and ½ - 150 42 1.5 3 1 and ½ 200 56 2 - 2 300 84 3 - 3

The indicative dosage schedule is as follows:

Adults

Goiter:

100-150 mcg per day.

Prophylaxis of relapses after strumectomy:

100 mcg per day

Thyroid inflammation:

100-150 mcg per day.

During antithyroid therapy:

The administration of 50-100 mcg per day will be sufficient.

Thyroid hypofunction:

Adults

50 mcg per day as a starting dose (for about two weeks); the daily dose will be increased by 50 mcg per day at intervals of approximately 14-15 days, until the maintenance dose of 100-200 mcg per day is reached (on average 2-2.5 mcg / kg body weight / day).

Pediatric patients

The maintenance dose is generally 100 to 150 mcg per m2 of body surface area.

For newborns and infants with congenital hypothyroidism, in whom rapid replacement therapy is important, the recommended starting dosage is 10 to 15 micrograms / kg body weight / day for the first 3 months. Thereafter, the dose should be individually adjusted based on the clinical response and determination of plasma levels of thyroid hormones and TSH.

For children with acquired hypothyroidism, the recommended starting dosage is 12.5-50 mcg per day. The dose should be gradually increased every 2-4 weeks based on clinical response and determination of plasma levels of thyroid hormones and TSH until a dose that ensures full replacement has been reached.

For infants, the full daily dose should be given at least 30 minutes before the first meal of the day.

Tirosint tablets. The tablets must be dissolved in a little water (10-15 mL) and the resulting suspension, which must be prepared at the time of use, must be administered with the addition of other liquid (5-10 mL).

Method of administration

The daily dosage should be taken in a single administration, in the morning, preferably on an empty stomach.

The drops must be dissolved in a little water.

The tablets should be swallowed with a sip of water.

04.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Thyrotoxicosis.

Untreated adrenal insufficiency.

Untreated pituitary insufficiency

Tirosint treatment should not be initiated in acute myocardial infarction, acute myocarditis and pancarditis.

04.4 Special warnings and appropriate precautions for use

The product should be used with caution and under strict medical supervision in patients with cardiovascular diseases, such as myocardial infarction, angina pectoris, myocarditis, heart failure with tachycardia, hypertension, coronary insufficiency.

Before starting thyroid hormone therapy, or before performing a thyroid suppression test, the following conditions must be ruled out or treated: arteriosclerosis, pituitary or adrenal insufficiency, autonomy of the thyroid gland.

The induction of even mild hyperthyroidism in patients with coronary insufficiency, heart failure or tachyarrhythmias should be avoided. Therefore, frequent monitoring of thyroid hormone levels is necessary in these cases.

In elderly patients and in patients in whom hypothyroidism has been present for a long time, treatment with thyroid hormone should be initiated with particular caution, starting with a lower starting dose, and making gradual adjustments of the therapy (see section 4.2 Posology and method). of administration).

The use of drugs having hormonal activity on the thyroid gland for the treatment of obesity is dangerous, since, at the necessary doses, it can cause secondary reactions even of considerable severity. Since rare cases of hepatic dysfunction have been reported in subjects treated with thyroid preparations, it is recommended to reduce the dosage or discontinue treatment if fever, muscle weakness or abnormal liver function laboratory tests occur during therapy.

Patients suffering from panhypopituitarism or other predisposing causes to adrenal insufficiency may react unfavorably to levothyroxine: therefore it is advisable to start corticosteroid therapy before treatment with Tirosint.

In "primary hypothyroidism" TSH levels alone (measured by a sensitive method) should be used to monitor therapy.

The cause of secondary hypothyroidism should be established prior to administration of replacement therapy and, if necessary, replacement therapy should be initiated for compensated "adrenal insufficiency."

In cases where thyroid autonomy is suspected, the physician should evaluate the need for a TRH test or a suppression scan before initiating therapy.

In postmenopausal women with hypothyroidism and a high risk of osteoporosis, it is necessary to avoid serum levels of levothyroxine above the physiological ones; therefore, thyroid function must be closely monitored.

The frequency of TSH checks during the dose adjustment phase depends on the clinical situation, but is generally recommended at 6-8 week intervals until desired levels are achieved.

In particular, in patients with differentiated carcinoma of the thyroid who begin treatment following thyroidectomy and possible radioisotope therapy, the TSH dosage is recommended 2 months after the start of treatment to confirm the suppression of TSH and visits control after about 6 and 12 months. In individuals judged to be in complete remission, it is recommended that the level of TSH suppression be adjusted based on medical judgment.

In patients whose TSH levels have reached the desired level and in those whose levothyroxine medicinal product or dosage has been changed, the TSH concentration should be checked after 8-12 weeks and the dosage adjusted according to the results. obtained. Once the maintenance dose is reached, clinical and biochemical checks should be repeated every 6-12 months based on medical judgment.

The product should also be used with caution in diabetic patients. (See section 4.5 Interactions with other medicinal products and other forms of interaction).

Tirosint oral drops contains 28.8 vol% ethanol (ethyl alcohol). Each 100 mcg (1 ml) dose therefore contains 243 mg of ethanol (ethyl alcohol). Harmful for those suffering from alcoholism. Consider for treatment during pregnancy and lactation and for the treatment of children and high-risk patients, such as patients with liver disease or epilepsy.

04.5 Interactions with other medicinal products and other forms of interaction

Insulin and oral hypoglycemic agents. Levothyroxine may reduce the hypoglycemic action of insulin and oral hypoglycemic agents. Therefore, in diabetic patients, particularly at the beginning of therapy with thyroid hormones, the glycaemia should be regularly monitored, to highlight any phenomena of interaction and therefore to adapt the dosage of hypoglycemic drugs.

Coumarin derivatives . Levothyroxine may enhance the action of coumarin derivatives due to competition for binding to plasma albumin. In case of concomitant treatment, coagulation factors should be monitored regularly; eventually, the dosage of the anticoagulant will have to be adapted.

Ion exchange resins . Ion exchange resins, such as cholestyramine and colestipol, reduce the absorption of levothyroxine; therefore, the administration of these resins must take place 4 - 5 hours after that of Tirosint.

Antacids based on aluminum, sucralfate, medicines based on iron or calcium carbonate. These drugs reduce the absorption of levothyroxine, reducing its effect. Therefore Tirosint should be taken at least four hours before taking these drugs.

Salicylates, dicumarol, furosemide, clofibrate, phenytoin : Salicylates, dicumarol, high dose furosemide (250 mg), clofibrate, phenytoin and other substances can displace sodium levothyroxine from plasma proteins, thus resulting in a "high fT4 fraction.

Propylthiouracil, glucocorticoids, beta-sympatholytics : these substances inhibit the peripheral conversion of T4 to T3.

Soy-based products. They can reduce the intestinal absorption of levothyroxine. Therefore, especially at the beginning and after the interruption of a diet rich in soy, it may be necessary to adjust the dosage of Tirosint.

Inducers of metabolizing enzymes . Barbiturates, rifampicin, carbamazepine, phenytoin and other hepatic enzyme inducers may increase the hepatic clearance of levothyroxine.

Phenytoin (diphenylhydantoin) should not be administered intravenously during treatment with Tirosint.

Propranolol . Levothyroxine accelerates the metabolism of propranolol.

Estrogen . The concomitant use of estrogenic or estrogen contraceptives for postmenopausal hormone replacement therapy may necessitate an increase in levothyroxine dosage.

Sertraline, chloroquine, proguanil . These substances reduce the effectiveness of levothyroxine and increase the serum TSH level.

Amiodarone and iodine-based contrast media . Due to the high iodine content, these drugs can cause hyperthyroidism or hypothyroidism. Particular caution should be observed in case of stroma with possible functional autonomy of the thyroid.

Orlistat : Hypothyroidism and / or impaired control of hypothyroidism may occur following concomitant administration of orlistat and levothyroxine.

04.6 Pregnancy and breastfeeding

Pregnancy

In pregnant women and during the lactation period, the administration of the product should not be interrupted, however its administration, as for other drugs administered during pregnancy, should be carried out only in case of real need and under the direct supervision of the doctor.

The dosages needed may also increase during pregnancy.

Experience has shown that there is no evidence of drug induced teratogenicity and / or fetal toxicity in humans at recommended therapeutic dosages. Excessively high doses of levothyroxine during pregnancy can have a negative effect on fetal and postnatal development.

During pregnancy, levothyroxine should not be administered in combination with drugs for hyperthyroidism (antithyroid drugs), as the addition of levothyroxine may require a higher dose of antithyroid drug.

Since antithyroid drugs, in contrast to levothyroxine, can cross the placenta in sufficient quantities to exert pharmacological effects, concomitant therapy with levothyroxine requiring a higher dosage of antithyroid drug could induce hypothyroidism in the fetus. Consequently, antithyroid drugs must always be administered alone in hyperthyroidism in pregnancy.

Pregnancy

Levothyroxine is secreted into breast milk during lactation but the concentrations reached at recommended therapeutic doses are not sufficient to cause the development of hyperthyroidism or the suppression of TSH secretion in the newborn.

Please note that Tirosint oral drops contain ethanol (see section 4.4 Special warnings and precautions for use).

04.7 Effects on ability to drive and use machines

There are no known effects on the ability to drive and use machines. However, due to the possible onset of headache, caution is advised when driving vehicles or performing activities that require special vigilance.

04.8 Undesirable effects

Cardiac symptoms (eg angina, cardiac arrhythmias, palpitations) and skeletal muscle cramps may occur occasionally, especially at the beginning of therapy, or in the case of overdose. Tachycardia, insomnia, diarrhea, excitability, headache have also been reported. , hot flashes, muscle weakness, weight loss, fever, vomiting, changes in the menstrual cycle, pseudotumor cerebri, tremor, restlessness and hyperhidrosis. In these cases it is advisable, on medical advice, to reduce the daily dosage or to suspend the treatment for a few days.

Frequency classes are defined as follows: very common (≥ 1/10); common (≥ 1/100,

MedDRA classification Frequency Preferential term Psychiatric disorders Not known Restlessness, excitability, insomnia Nervous system disorders Not known Headache, pseudotumor cerebri, tremor Cardiac pathologies Not known Tachycardia, palpitations, cardiac arrhythmias, anginal manifestations Gastrointestinal disorders Not known Vomiting, diarrhea, weight loss Skin and subcutaneous tissue disorders Not known Hyperhidrosis Musculoskeletal and connective tissue disorders Not known Muscle weakness, skeletal muscle cramps Diseases of the reproductive system and breast Not known Hot flashes, changes in the menstrual cycle General disorders and administration site conditions Not known Fever

In case of hypersensitivity, allergic reactions can occur.

04.9 Overdose

An increase in the level of T3 is a more reliable indicator of overdose than an increase in the levels of T4 or fT4.

Moderate to severe symptoms of impaired metabolism occur in the event of overdose and intoxication (see section 4.8 Undesirable effects). In these cases, an interruption of the intake and a follow-up visit is indicated, depending on the extent of the overdose.

The cases of attempted suicide with levothyroxine have shown the safety of taking doses of levothyroxine up to 10 mg. Unless coronary heart disease is present, an overdose of levothyroxine does not suggest compromising vital functions (breathing and circulation). Single cases of sudden cardiac arrest have been reported in patients who have abused levothyroxine for years.

In case of acute overdose, gastrointestinal absorption can be reduced by administering charcoal. Treatment is usually symptomatic and supportive. In case of severe beta-sympathomimetic effects such as tachycardia, fear, agitation and hyperkinesias, symptoms can be reduced by "taking beta-blockers. Thyrostats are not indicated, as the thyroid is already completely at rest.

In case of extremely high dosages (suicide attempt), plasmapheresis can be useful.

An overdose of levothyroxine requires a prolonged monitoring period. Due to the gradual transformation of levothyroxine into liothyronine, symptoms can last up to 6 days.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: thyroid hormones ATC code: H03AA01

Thyroxine is a physiologically produced hormone by the thyroid. The hormonal activity of the thyroid is carried out by the iodinated amino acid derivatives of thyronine, ie levothyroxine (T4) and triiodothyronine (T3), present in the glycoprotein thyroglobulin. The thyroid hormones determine an increase in oxygen consumption, in the metabolism of carbohydrates, fats and proteins, promote the growth and differentiation of the immature organism, inhibit the secretion of pituitary thyrotropin. Both triiodothyronine and levothyroxine correct the alterations of hypothyroidism and therefore the therapeutic practice of administering exogenous hormone molecules is now universally widespread, offering the advantages of a more direct dose proportionality, in relation to the actual metabolic needs.

05.2 Pharmacokinetic properties

Levothyroxine is rapidly and incompletely absorbed in the upper tract of the small intestine. Its binding to plasma proteins is almost complete: the free share is 0.05%. The t½ is approximately 190 hours, with a slight increase in "hypothyroidism and with a modest reduction in hyperthyroidism. Levothyroxine is metabolised for more than 80% by deiodination in peripheral tissues. Some is metabolised in the liver by conjugation with glucuronides and sulphates and excreted in the bile.A small amount is excreted unchanged. Thyroid hormones hardly cross the placental barrier and are excreted in breast milk only in minimal quantities.

05.3 Preclinical safety data

There is no information, deriving from preclinical data, of significant importance to the physician that has not already been reported in the sections of the Summary of Product Characteristics.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

TABLETS: Anhydrous dibasic calcium phosphate, sodium carboxymethyl starch, magnesium stearate, microcrystalline cellulose, talc, citric acid, corn starch

ORAL DROPS : Ethanol 96%, Glycerol 85%

06.2 Incompatibility

Not relevant.

06.3 Period of validity

TABLETS: 18 months

ORAL DROPS: 2 years

Tirosint Gocce: the shelf life after first opening the bottle is 1 month.

06.4 Special precautions for storage

Store the medicine below 25 ° C.

06.5 Nature of the immediate packaging and contents of the package

TABLETS: Blister of PVC / Aclar UltRx 3000 coupled with heat-sealable aluminum.

ORAL DROPS: Amber glass bottle, sealed with polypropylene cap and polyethylene gasket in contact with the product. The cap is removed after the first opening and the system is screwed in its place, consisting of: polypropylene capsule with polyethylene gasket / rubber pump / glass dropper.

06.6 Instructions for use and handling

No special instructions.

Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.

07.0 MARKETING AUTHORIZATION HOLDER

IBSA Farmaceutici Italia Srl, via Martiri di Cefalonia, 2, 26900 Lodi

08.0 MARKETING AUTHORIZATION NUMBER

Tirosint 50 mcg tablets - 50 tablets A.I.C. n. 034368050

Tirosint 100 mcg tablets - 50 tablets A.I.C. n. 034368047

Tirosint 100 mcg / ml oral drops, solution - bottle 20 ml A.I.C. n. 034368062

09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION

First authorization: 06 December 1999

Last renewal: 06 December 2009

10.0 DATE OF REVISION OF THE TEXT

September 2012

11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY

12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL

none:  infectious diseases fatigue fever