Package Leaflet: Information for the User

Levotiroxina Sanofi 500 micrograms powder and solvent for solution for injection

Levotiroxina

Read this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist. See section 4.

1. What isLevotiroxina Sanofiand what it is used for

2. What you need to know before usingLevotiroxina Sanofi

3. How to useLevotiroxina Sanofi

4. Possible side effects

5. Storage ofLevotiroxina Sanofi

6. Contents of the pack and additional information

Levotiroxina Sanofibelongs to a group of medications known as thyroid hormones.

It is indicated for:

• Treatment of replacement or substitution in cases of malfunctioning of the thyroid gland, or lack of functioning of this gland, such as in cases of diseases such as: myxedema coma (hypothyroid), cretinism (congenital disease characterized by the arrest of physical and mental development), myxedema (deficient functioning of the thyroid gland that produces a hard edema extended to the face and limbs), non-toxic goiter (bulge in the anterior part of the neck due to an increase in the size of the thyroid gland, in this case without excess of thyroid hormones) or hypothyroidism in general (lack of thyroid hormones) (including hypothyroid states in children, during pregnancy or in old age).
• Hypothyroidism (lack of thyroid hormones) resulting from the surgical removal of the thyroid gland, or its deficient functioning, as a result of radiation application or treatment with antithyroid agents (medications for hyperthyroidism).
• Suppression of the secretion of thyrotropin (thyroid-stimulating hormone) required in the treatment of simple non-endemic goiter (increase in the size of the thyroid gland) and in lymphocytic thyroiditis (inflammation of the thyroid gland).
• Treatment of hyperthyroidism (excess of thyroid hormones), in combination with antithyroid agents, to prevent hypothyroidism.

No useLevotiroxina Sanofi

• If you are allergic to the active ingredient (levotiroxina) or any of the other components of this medication (listed in section 6).
• If you have any of the following conditions or conditions listed below:

• Untreated hyperthyroidism (excess of thyroid hormones).
• Adrenal insufficiency and do not have adequate replacement treatment.
• Untreated hypopituitarism (decreased function of the pituitary gland).
• Untreated hyperthyroidism (not receiving treatment from your doctor).
• Acute myocardial infarction.
• Acute myocarditis (inflammation of the heart muscle).
• Acute pancarditis (inflammation of all layers of the heart).

During pregnancy, Levotiroxina Sanofi should not be used at the same time as medications used to treat hyperactive thyroid (antithyroid medications).

Warnings and precautions

Consult your doctor or pharmacist before starting to use Levotiroxina Sanofi, especially in the following cases:

• If you have any cardiovascular disease, including angina pectoris, heart failure, myocardial infarction, arteriosclerosis (disease of the arteries) and hypertension (increased blood pressure). In case of worsening of your disease, your doctor may indicate a reduction in the dose of Levotiroxina Sanofi, a lower initial dose, smaller dose increments and longer time intervals between increments. Regular monitoring is very likely to be required.
• If you have goiter (enlargement of the thyroid gland) and are an elderly patient with normal thyroid function and have had a myocardial infarction or have heart failure, angina pectoris or arrhythmias with tachycardia.
• Inform your doctor if you have hypopituitarism (malfunction of the pituitary gland), if you are experiencing adrenal insufficiency, autonomous thyroid function (thyroid nodules that secrete hormones), iodine intolerance, tuberculosis, renal insufficiency (kidney dysfunction) or extreme thinness (anorexia).
• Replacement hormone therapy may trigger a decrease in hormone levels (acute adrenal crisis) in patients with problems with adrenal gland function (adrenal insufficiency) or pituitary gland function (hypopituitarism) without adequate corticosteroid coverage.
• Inform your doctor if you are hypothyroid (your thyroid hormone levels are low) or have myxedema (disease due to malfunction of the thyroid gland). Generally, people with these diseases are very sensitive to levotiroxina. Therefore, the initial dose prescribed by your doctor will be low, and then gradually increased. Your doctor will check your response to treatment through blood tests.
• If you are a postmenopausal woman, with a high risk of osteoporosis, and are being treated for hypothyroidism (decreased thyroid hormone levels), your doctor should adjust the dose to the lowest possible level and may require more frequent monitoring.
• Inform your doctor if you have hyperthyroidism (high thyroid hormone levels) and are being treated. Treatment with Levotiroxina Sanofi may not be suitable in this case.
• In case of needing surgery with general anesthesia, it is recommended to interrupt treatment with Levotiroxina Sanofi.
• If you have diabetes mellitus or diabetes insipidus (increased blood glucose levels) (see section “Other medications and Levotiroxina Sanofi”).
• If you are an elderly patient and have long-standing hypothyroidism.
• If you are being treated with anticoagulants (medications to prevent the formation of blood clots), as Levotiroxina Sanofi may potentiate their action.
• If you are a premature newborn with low birth weight. Extreme caution should be exercised when starting levotiroxina treatment, as it may cause circulatory collapse due to immature adrenal function (see section 4. “Possible side effects”). Regular monitoring of blood pressure will be performed when starting levotiroxina treatment in premature newborns with very low birth weight, as it may cause a rapid decrease in blood pressure (known as circulatory collapse).
• If you have a history of epilepsy, as the risk of seizures increases when levotiroxina is administered.
• Thyroid hormones are not suitable for weight loss. Taking thyroid hormones will not reduce your weight if your thyroid hormone level is within the normal range. Severe or even life-threatening side effects may occur if you increase the dose without consulting your doctor, especially when used with other medications for weight loss.
• Thyroid imbalance may occur if you need to switch to another product containing levotiroxina. Consult your doctor if you have any doubts about how to change your medication. Close monitoring (clinical and biological) is required during the transition period. Inform your doctor if you experience any side effects, as this may indicate that your dose needs to be adjusted up or down.
• Your doctor should adjust the dose according to thyroid function tests. Monitoring of patients should be performed according to clinical symptoms and thyroid function tests.
• Your doctor should monitor patients who are receiving levotiroxina and other medications (such as amiodarone, tyrosine kinase inhibitors, salicylates and high-dose furosemide) that may affect thyroid function (see section “Other medications and Levotiroxina Sanofi”).
• If you have protein loss, nephrotic syndrome, as this may increase the need for levotiroxina.
• If you experience an allergic reaction (see section 4. “Possible side effects”). Contact your doctor or healthcare professional immediately or go to the nearest hospital emergency room immediately.
• If you are undergoing laboratory tests to control your thyroid hormone levels, inform your doctor or laboratory personnel that you are taking or have recently taken biotin (also known as vitamin H, vitamin B7 or vitamin B8). Biotin may affect the results of laboratory tests. Depending on the test, the results may be falsely elevated or falsely reduced due to biotin. Your doctor may instruct you to stop taking biotin before the tests. You should also know that other products you may be taking, such as multivitamin preparations or supplements for hair, skin and nails, may also contain biotin. This may affect the results of laboratory tests. Inform your doctor or laboratory personnel if you are taking these products (see the information in section “Other medications and Levotiroxina Sanofi”).

Other warnings

In the case of mixedemic coma, consider the patient's history and laboratory values, as well as the clinical situation, to confirm the diagnosis of “hypothyroid coma”.

Monitor the comatose condition before initiating replacement therapy to treat thyroid hormone deficiency.

Other medications and Levotiroxina Sanofi

Inform your doctor or pharmacist if you are using, have used recently or may need to use any other medication.

The effect of Levotiroxina Sanofi is influenced by other medications, as indicated below:

• Catecholamines, as levotiroxina may potentiate their effect.
• Oral anticoagulants, as the dose of the oral anticoagulant may need to be reduced.
• Antidiabetic medications: levotiroxina may reduce the hypoglycemic effect of oral antidiabetic medications such as metformin, glimepiride and glibenclamide, as well as insulin, and therefore, blood glucose levels should be monitored, especially when starting or stopping hormone replacement therapy and may require adjustment of the antidiabetic dose.
• Rifampicin, carbamazepine, phenytoin, barbiturates, products containing hypericum: rifampicin (an antibiotic), carbamazepine (used to treat seizures), phenytoin (used to treat seizures and heart rhythm disorders), barbiturates (used for seizures, anesthesia; certain sleeping pills) and products containing hypericum (a plant-based medication) may weaken the effect of levotiroxina.
• Salicylates, dicumarol, high doses of furosemide (250 mg), clofibrate and other substances may displace levotiroxina sodium from plasma proteins, resulting in an increase in free T4 (fT4) levels.

Salicylates, especially at doses greater than 2.0 g/day, as well as high doses of furosemide (250 mg), may inhibit the binding of thyroid hormones to transport proteins, resulting in a transient initial increase in free thyroid hormones, followed by a general decrease in total thyroid hormone levels.

• Sertraline, chloroquine, proguanil: these substances reduce the effectiveness of levotiroxina and increase serum TSH levels.

• Protease inhibitors, such as lopinavir/ritonavir: cases of loss of therapeutic effect of levotiroxina have been reported when used together.
• Estradiol, such as in oral contraceptives, as they may lead to diagnostic and therapeutic errors. During treatment with oral contraceptives containing estradiol or during postmenopausal hormone replacement therapy, the dose of levotiroxina may need to be increased.
• Propylthiouracil, glucocorticoids, beta-sympatholytics (especially propranolol) inhibit peripheral conversion of T4 to T3 and may result in a decrease in serum T3 levels.
• Amiodarone and iodine-containing contrast media. Amiodarone inhibits peripheral conversion of T4 (levotiroxina) to T3, resulting in a decrease in serum T3 levels and an increase in serum TSH levels.
• Medications containing tyrosine kinase inhibitors (imatinib, sunitinib, sorafenib or motesanib), as they may reduce the effectiveness of levotiroxina.
• If you are taking or have recently taken biotin, inform your doctor or laboratory personnel when they are going to perform laboratory tests to control your thyroid hormone levels. Biotin may affect the results of laboratory tests (see “Warnings and precautions”).

Medications that, when administered orally, may decrease the absorption of levotiroxina

• Colestiramine and colestipol (medications for cholesterol treatment), calcium polystyrene sulfonate, sevelamer and sodium salts, as these medications reduce the absorption of levotiroxina by binding to thyroid hormones in the gastrointestinal tract, and therefore, these medications should be administered as far apart as possible from levotiroxina; wait at least 4-5 hours after levotiroxina administration for their use.

• Medications containing calcium carbonate, sucralfate and antacids, as they may reduce the effect of levotiroxina by reducing its absorption in the gastrointestinal tract, and therefore, their administration should be separated as much as possible.

• Colesevelam, a bile acid sequestrant, binds to levotiroxina and reduces its absorption in the gastrointestinal tract. Therefore, levotiroxina should be administered at least 4 hours before colesevelam.
• Iron salts reduce the absorption of levotiroxina in the gastrointestinal tract, and therefore, their administration should be separated as much as possible.
• Soja: in babies fed with soya and treated with levotiroxina for congenital hypothyroidism, an increase in TSH levels has been reported. Unusually, high doses of levotiroxina may be required to achieve normal serum TSH and T4 levels. During and after a soya diet, close monitoring of serum T4 and TSH levels is required, with the possibility of needing to adjust the levotiroxina dose.

Pregnancy and lactation

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

If you have hypothyroidism and are being treated with Levotiroxina Sanofi, do not interrupt treatment during pregnancy. Sometimes, your dose may need to be increased.

Thyroid function should be monitored both during and after pregnancy. Your dose may need to be adjusted.

It is essential to maintain normal thyroid hormone levels in pregnant women to ensure good health for both the mother and the fetus.

During pregnancy, it is contraindicated to use Levotiroxina Sanofi as a complement to treatment of hyperthyroidism with antithyroid medications. It may increase the required dose of these medications.

Levotiroxina Sanofi can be administered during lactation.

Driving and operating machinery

No effects of Levotiroxina Sanofi on the ability to drive vehicles and operate machinery have been described.

Levotiroxina Sanofi contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per 1 ml of injectable solution; it is essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

Your doctor will inform you of the duration of your treatment and the most suitable dose for you.

The treatment should be administered, always taking into account individual circumstances, during the period in which oral hormone administration is not possible.

Levotiroxina Sanofi is administered solely by intravenous or infusion route (see section 6 “Instructions for healthcare personnel”)

Treatment of mixed coma (hypothyroid):

Patients suffering from the most severe form of hypothyroidism (mixed coma (hypothyroid)) must undergo urgent treatment. The treatment will be directed at correcting electrolyte disorders or any potential infection, along with the administration of thyroid hormones.

Levotiroxina Sanofi may be administered initially by IV, over a period of 2-3 minutes at a dose of 500 micrograms of levotiroxine, given that the onset time of action, even with IV administration, may appear after several hours.

It is also possible to administer it by infusion, using a 50 ml syringe with a isotonic sodium chloride solution, over 30-60 minutes.

From the second day, 100 micrograms of levotiroxine per day should be administered, until the end of the mixed coma (hypothyroid).

- In elderly patients and patients with heart disease:

Treatment should be initiated with caution, for example, a low initial dose may be set and gradually increased at long intervals, with frequent monitoring of thyroid hormones.

Experience has shown that low doses are sufficient in patients with low weight.

Based on your individual circumstances, your doctor will choose the treatment during the period in which oral hormone administration is not possible. Consideration should be given to the administration of available oral formulations in other indications not related to mixed coma (hypothyroid), taking into account your individual circumstances.

If you use more Levotiroxina Sanofi than you should

Call your doctor, pharmacist, or go to the nearest hospital immediately.

The treatment of overdose will be symptomatic and supportive. Beta-blockers may be useful in controlling some symptoms.

In cases of intoxication with extremely high doses (suicide attempt), plasma exchange may be useful.

Overdose requires prolonged follow-up since symptoms may be delayed up to 6 days.

In case of overdose, serious complications with a threat to vital functions are not expected, except in cases of heart disease.

However, in cases of chronic or massive intoxication, cases of thyrotoxic crisis, muscle cramps, seizures, cardiac arrhythmias, heart failure, coma, and even death have been reported. Cases of sudden cardiac arrest in patients after many years of levotiroxine abuse have also been notified.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service. Phone 91 562 04 20, indicating the medication and the amount used.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

If you forgot to use Levotiroxina Sanofi

Do not use a double dose to compensate for the missed doses.

Like all medications,this medicationmay cause side effects, although not everyone will experience them.

Hypersensitivity to the active ingredient or to other components of Levotiroxina Sanofi

In case of hypersensitivity to levotiroxine or to any of the other components of Levotiroxina Sanofi,allergic reactions of the skin and respiratory tract (either immediately or after several days of medication administration) may occur, which can be life-threatening. Symptoms may include skin rash, itching, difficulty breathing, shortness of breath, facial swelling, lip, throat, or tongue swelling. Contact your doctor or healthcare professional immediately or go to the nearest hospital emergency room immediately.

Side effects have been grouped according to their frequency in accordance with the following classification:

Very frequent:may affect more than1 in 10 patients

Frequent:may affect up to1 in 10 patients

Infrequent:may affect up to1 in 100 patients

Rare:may affect up to1 in 1,000 patients

Very rare:may affect up to1 in 10,000 patients

Unknown frequency: cannot be estimated from available data.

These side effects are generally associated with excessive doses and correspond to symptoms of hyperthyroidism.

Immune system disorders:

Unknown frequency:hypersensitivity.

Blood and lymphatic system disorders:

Unknown frequency: cases of decreased white blood cell count (leucopenia) have been observed.

Endocrine disorders:

Frequent: increased thyroid hormones (hyperthyroidism).

Mental and behavioral disorders:

Very frequent: insomnia,

Frequent: nervousness,

Unknown frequency:excitability.

Nervous system disorders:

Very frequent:headache,

Unknown frequency: tremors, increased intracranial pressure (benign intracranial hypertension) especially in children.

Cardiac disorders:

Very frequent:palpitations,

Frequent:acceleration of heart rate(tachycardia),

Unknown frequency:chest pain that sometimes extends to the left arm (angina), alteration of heart rhythm (cardiac arrhythmias).

Vascular disorders:

Unknown frequency: hot flashes, circulatory collapse in premature newborns with low birth weight (see section 2. “Warnings and precautions”).

Gastrointestinal disorders:

Unknown frequency: vomiting and diarrhea.

Skin and subcutaneous tissue disorders:

Unknown frequency:allergic skin reactions (e.g. angioedema [difficulty breathing or facial, lip, throat, or tongue swelling], skin rash, urticaria, sweating).

Musculoskeletal and connective tissue disorders:

Unknown frequency: muscle weakness and cramps, osteoporosis especially in postmenopausal women, mainly when treated for a long period.

Reproductive and breast disorders:

Unknown frequency: irregular menstrual periods.

General disorders and administration site conditions:

Unknown frequency: fever, intolerance to heat.

Investigations:

Unknown frequency: weight loss.

All these reactions usually disappear when the dose is reduced or the treatment is temporarily suspended.

If the initial dose of levotiroxine is too high, alterations of heart rhythm (atrial or ventricular fibrillation) may precipitate, especially in sensitive patients.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in the leaflet. You can also report themdirectly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:https://www.notificaram.eshttps://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Store in refrigerator (between 2°C and 8°C).

Store in the original packaging to protect it from light.

Protect the prepared solution for use from direct light.

Expiration Date

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Shelf Life of the Reconstituted Solution:

- for intravenous administration: 24 hours at room temperature

- for administration by infusion: 2 hours at room temperature

From a microbiological point of view, unless the opening method excludes the risk of microbiological contamination, the product must be used immediately. If not used immediately, the time and storage conditions are the responsibility of the user.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty packaging and unused medications. This will help protect the environment.

Composition ofLevotiroxina Sanofi 500 micrograms powder and solvent for solution for injection

- The active ingredient is levotiroxine sodium. Each package contains 1 vial with 514 micrograms of levotiroxine sodium (equivalent to 500 micrograms of levotiroxine).

- The other components are:

Powder: hydrogen phosphate dihydrate of sodium, sodium chloride, mannitol (E-421), phosphoric acid and sodium hydroxide (for pH adjustment).

Solvent: water for injection preparations.

Appearance of the product and contents of the package

Vial: contains white powder.

Flask of solvent: contains a colorless solution.

Each Levotiroxina Sanofi package contains 1 vial of powder and 1 flask of solvent.

Instructions for healthcare personnel

Administer by intravenous route after reconstitution.

The powder must be dissolved in 5 ml of water for injection preparations (included in the package).

To use in intermittent short-term infusion, a sodium chloride isotonic solution (50 ml-250 ml) must be added.

Holder of the marketing authorization

sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

Responsible for manufacturing

SANOFI WINTHROP INDUSTRIE

30 – 36, avenue Gustave Eiffel

37100 Tours

France

Or

sanofi-aventis, S.A.

Ctra.C-35 (La Batlloria-Hostalric, Km. 63,09)

17404 Riells i Viabrea (Gerona)

Spain

Last review date of this leaflet: March 2023

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.