Levotiroxine Sanofi 500 micrograms powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Levotiroxina Sanofi 500 micrograms powder and solvent for solution for injection

Levothyroxine

Read all of 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, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Levotiroxina Sanofi is and what it is used for
2. What you need to know before using Levotiroxina Sanofi
3. How to use Levotiroxina Sanofi
4. Possible side effects
5. How to store Levotiroxina Sanofi
6. Contents of the pack and other information

1. What Levotiroxina Sanofi is and what it is used for

Levotiroxina Sanofi belongs to a group of medicines called thyroid hormones.

It is indicated for:

• Replacement therapy in cases of impaired or absent thyroid gland function, such as in diseases including: myxedema coma (hypothyroid coma), cretinism (a congenital disease characterized by physical and mental development arrest), myxedema (deficient function of the thyroid gland causing firm edema affecting face and extremities), nontoxic goiter (swelling in the front part of the neck due to an enlarged thyroid gland, in this case without excess 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 surgical removal of the thyroid gland, or from deficient function due to radiation therapy or treatment with antithyroid agents (medications for hyperthyroidism).
• Suppression of thyrotropin (thyroid-stimulating hormone) secretion, required in the treatment of simple nonendemic goiter (enlargement of the thyroid gland) and lymphocytic thyroiditis (inflammation of the thyroid gland).
• Treatment of thyrotoxicosis (excess of thyroid hormones), in combination with antithyroid agents, to prevent hypothyroidism.

2. What you need to know before using Levotiroxina Sanofi

Do not use Levotiroxina Sanofi

• If you are allergic to the active substance (levotiroxina) or to any of the other components of this medicine (listed in section 6).

• if you have any of the following disorders or conditions listed below:

• excess thyroid hormones (untreated thyrotoxicosis),

• underactive adrenal gland (adrenal insufficiency) without adequate replacement therapy,

• untreated pituitary insufficiency (decreased pituitary function),

• untreated hyperthyroidism (you are not receiving treatment from your doctor),

• acute myocardial infarction,

• acute inflammation of the heart muscle (myocarditis),

• acute inflammation of all layers of the heart (pancarditis).

During pregnancy, Levotiroxina Sanofi must not be used simultaneously with medications used to treat overactive thyroid (antithyroid drugs).

Warnings and precautions

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

• If you have any cardiovascular disease, including angina pectoris, heart failure, myocardial infarction, arteriosclerosis (artery disease), or hypertension (high blood pressure). If your condition worsens, your doctor may recommend an immediate reduction in the dose of Levotiroxina Sanofi, a lower starting dose, smaller dose increments, and longer intervals between dose increases. Regular monitoring will likely be required.
• If you have goiter (enlarged thyroid gland) and are elderly with normal thyroid function, and have had a myocardial infarction or have heart failure, angina pectoris, or tachyarrhythmias.
• Inform your doctor if you have pituitary insufficiency (impaired pituitary function), adrenal hypofunction (adrenal insufficiency), thyroid autonomy (thyroid nodules that secrete hormones), iodine intolerance, tuberculosis, renal insufficiency (impaired kidney function), or extreme thinness (anorexia).
• Thyroid hormone replacement therapy may trigger a drop in hormone levels (acute adrenal crisis) in patients with impaired adrenal gland function (adrenal insufficiency) or impaired pituitary function (pituitary insufficiency) who are not adequately treated with corticosteroids.
• Inform your doctor if you have hypothyroidism (low thyroid hormone levels) or suffer from myxedema (a disease caused by poor thyroid function). Generally, people with these conditions are highly sensitive to levotiroxina. Therefore, your doctor will prescribe a low initial dose, gradually increasing it. Your doctor will monitor your response to treatment through blood tests.
• If you are a postmenopausal woman at high risk of osteoporosis and are being treated for hypothyroidism (low 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 (very high thyroid hormone levels) and are receiving treatment. Treatment with Levotiroxina Sanofi may not be appropriate in this case.
• If you require surgery under general anesthesia, it is advisable to discontinue treatment with Levotiroxina Sanofi.
• If you have diabetes mellitus or diabetes insipidus (elevated blood glucose) (see section “Other medicines and Levotiroxina Sanofi”).
• If you are elderly and have long-standing hypothyroidism.
• If you are being treated with anticoagulants (medications to prevent blood clots), as Levotiroxina Sanofi may enhance their effect.
• If treating a premature newborn with low birth weight. Extreme caution is required when initiating levotiroxina therapy, as circulatory collapse may occur due to immature adrenal function (see section 4. “Possible adverse effects”). Blood pressure should be monitored periodically when starting levotiroxina in very low birth weight premature infants, as rapid drops in blood pressure (known as circulatory collapse) may occur.
• If you have a history of epilepsy, as the risk of seizures increases when levotiroxina is administered.
• Thyroid hormones are not suitable for weight reduction. Taking thyroid hormones will not reduce your weight if your thyroid hormone levels are within the normal range. Serious or even life-threatening adverse effects may occur if the dose is increased without your doctor’s specific advice, especially when used in combination with other weight-loss medications.
• Thyroid imbalance may occur if you need to switch your medication to another product containing levotiroxina. Consult your doctor if you have any doubts about switching medications. Close monitoring (clinical and biological) is required during the transition period. Inform your doctor if you experience any adverse effects, as this may indicate the need to adjust your dose up or down.
• Your doctor must adjust the dose based on thyroid function tests. Patient monitoring should be based on clinical symptoms as well as thyroid function tests.
• Your doctor should monitor patients receiving concomitant levotiroxina and other medications (such as amiodarone, tyrosine kinase inhibitors, salicylates, and high-dose furosemide) that may affect thyroid function (see section “Other medicines and Levotiroxina Sanofi”).
• If you have a condition involving protein loss, such as nephrotic syndrome, as this may increase your levotiroxina requirements.
• If you experience an allergic reaction (see section 4. “Possible adverse effects”). Contact your doctor or healthcare professional immediately or go to the nearest hospital emergency room.
• If you are undergoing laboratory tests to monitor your thyroid hormone levels, inform your doctor or laboratory staff that you are taking or have recently taken biotin (also known as vitamin H, vitamin B7, or vitamin B8). Biotin can affect laboratory test results. Depending on the test, results may be falsely elevated or falsely reduced due to biotin. Your doctor may instruct you to stop taking biotin before blood tests. Also note that other products you may be taking, such as multivitamins or supplements for hair, skin, and nails, may also contain biotin. This could affect laboratory test results. Inform your doctor or laboratory staff if you are taking these products (refer to the information in section “Other medicines and Levotiroxina Sanofi”).

Other warnings

In cases of myxedema coma, the patient’s history, laboratory values, and clinical condition should be considered to confirm the diagnosis of “hypothyroid coma.”

The comatose condition should be stabilized before initiating thyroid hormone replacement therapy to treat thyroid hormone deficiency.

Other medicines and Levotiroxina Sanofi

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

The effect of Levotiroxina Sanofi may be influenced by other medicines, as follows:

• Catecholamines, as levotiroxina may enhance their effect.
• Oral anticoagulants, as a reduction in the dose of the oral anticoagulant may be required.
• Antidiabetic agents: levotiroxina may reduce the hypoglycemic effect of oral antidiabetic drugs such as metformin, glimepiride, and glibenclamide, as well as insulin; therefore, blood glucose levels should be monitored, especially when starting or stopping thyroid hormone treatment, and a dose adjustment of the antidiabetic agent may be necessary.
• Rifampicin, carbamazepine, phenytoin, barbiturates, and products containing St. John’s wort: rifampicin (an antibiotic), carbamazepine (used to treat seizures), phenytoin (used to treat seizures and cardiac arrhythmias), barbiturates (used in seizures, anesthesia, and certain sleeping pills), and products containing St. John’s wort (a herbal medicine) may reduce the effect of levotiroxina.
• Salicylates, dicoumarol, high doses of furosemide (250 mg), clofibrate, and other substances may displace sodium levothyroxine from plasma proteins, leading to an increase in free T4 (fT4) fraction.

Salicylates, especially at doses above 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 efficacy of levotiroxina and increase serum TSH concentration.

• Protease inhibitors, such as lopinavir/ritonavir: cases of reduced therapeutic effect of levotiroxina have been reported when co-administered.

• Estrogens, such as those in oral contraceptives, as they may lead to diagnostic and therapeutic errors. During treatment with estrogen-containing contraceptives or postmenopausal hormone replacement therapy, an increased dose of levotiroxina may be required.

• Propylthiouracil, glucocorticoids, beta-adrenergic blockers (especially propranolol) inhibit the peripheral conversion of T4 to T3 and may lead to a reduced serum concentration of T3.

• Amiodarone and iodine-containing contrast agents. Amiodarone inhibits the peripheral conversion of T4 (levotiroxina) to T3, leading to reduced serum T3 concentration and increased serum TSH levels.

• Medications containing tyrosine kinase inhibitors (imatinib, sunitinib, sorafenib, or motesanib), as they may reduce the efficacy of levotiroxina.

• If you are taking or have recently taken biotin, inform your doctor or laboratory staff when undergoing laboratory tests to monitor thyroid hormone levels. Biotin may affect laboratory test results (see “Warnings and precautions”).

Medicines taken orally that may decrease levothyroxine absorption

• Cholestyramine and colestipol (medications for the treatment of cholesterol), polystyrene sulfonate calcium, sevelamer, and sodium salts, as these medications reduce levothyroxine absorption by binding to thyroid hormones in the gastrointestinal tract; therefore, these drugs should be administered as far apart as possible from levothyroxine. A minimum interval of 4–5 hours should be maintained after levothyroxine administration before taking them.

• Medications containing calcium carbonate, sucralfate, and antacids, as they may reduce the effect of levothyroxine by decreasing its gastrointestinal absorption; therefore, administration should be separated as much as possible.

• Bile acid sequestrants (colesevelam), which bind to levothyroxine and reduce its gastrointestinal absorption. Therefore, levothyroxine should be administered at least four hours before colesevelam.

• Iron salts reduce levothyroxine absorption in the gastrointestinal tract; therefore, administration should be separated as much as possible.

• Soy: In infants fed soy-based formulas and treated with levothyroxine for congenital hypothyroidism, increased TSH levels have been reported. Unusually high doses of levothyroxine may be required to achieve normal serum TSH and T4 levels. Close monitoring of serum T4 and TSH levels is required during and after soy-based feeding, and dose adjustments of levothyroxine may be necessary.

Pregnancy and lactation

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

If you have hypothyroidism and are being treated with Levotiroxina Sanofi, you should not discontinue treatment during pregnancy. Sometimes, it may be necessary to increase your dose.

Thyroid function should be monitored both during and after pregnancy. Dose adjustments may be required.

Maintaining normal thyroid hormone levels in pregnant women is vital to ensure good health for both mother and fetus.

During pregnancy, the use of Levotiroxina Sanofi is contraindicated as a supplement to antithyroid drug therapy for hyperthyroidism, as it may increase the required dose of these medications.

Levotiroxina Sanofi may be administered during lactation.

Driving and use of machines

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

Levotiroxina Sanofi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 1 ml of injectable solution; hence, it is essentially "sodium-free".

3. How to use Levotiroxina Sanofi

Follow exactly the administration instructions for this medicine as given by your doctor. If in doubt, consult your doctor again.

Your doctor will indicate the duration of your treatment and the most appropriate dose for you.

Treatment should be administered, always taking individual circumstances into account, during the period when oral administration of hormones is not possible.

Levotiroxina Sanofi is administered only intravenously or by infusion (see section 6 "Instructions for healthcare professionals").

Treatment of myxedema coma (hypothyroidism):

Patients suffering from the most severe form of hypothyroidism (myxedema coma (hypothyroidism)) must be treated urgently. Treatment should aim to correct water and electrolyte imbalances or any concurrent infection, along with the administration of thyroid hormones.

Levotiroxina Sanofi may initially be administered intravenously over a period of 2–3 minutes at a dose of 500 micrograms of levothyroxine, since the onset of action—even with IV administration—may occur several hours later.

It may also be administered by infusion, using a 50 ml syringe with an isotonic sodium chloride solution, over 30–60 minutes.

From the second day onwards, 100 micrograms of levothyroxine per day should be administered until the end of the myxedema coma (hypothyroidism).

• In elderly patients and in patients with heart disease:

Treatment should be initiated cautiously; for example, if necessary, a low initial dose should be used and gradually increased at long intervals, with frequent monitoring of thyroid hormone levels.

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

Based on your individual circumstances, your doctor will choose the treatment during the period when oral administration of hormones is not possible. The use of available oral formulations in other indications unrelated to myxedema coma (hypothyroidism) should be considered, 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.

Treatment of overdose will be symptomatic and supportive. Beta-blockers may be useful to control certain symptoms.

In cases of poisoning with extremely high doses (suicide attempt), plasmapheresis may be helpful.

Overdose requires a prolonged period of monitoring, as symptoms may be delayed up to 6 days.

In cases of overdose, serious complications threatening vital functions are not expected, except in patients with heart disease.

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

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

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

If you forget to use Levotiroxina Sanofi

Do not use a double dose to make up for forgotten doses.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

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

In case of hypersensitivity to levothyroxine or to any of the other components of Levotiroxina Sanofi, allergic reactions of the skin and respiratory tract may occur (either immediately or after several days of administration), which may be life-threatening. Symptoms may include skin rash, itching, difficulty breathing, shortness of breath, swelling of the face, lips, throat, or tongue. Contact your doctor or healthcare professional immediately or go to the nearest hospital emergency room without delay.

Adverse effects have been grouped according to their frequency based on the following classification:

Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Frequency not known: cannot be estimated from the available data.

These adverse effects are generally associated with excessive dosage and correspond to symptoms of hyperthyroidism.

Immune system disorders:

Frequency not known: hypersensitivity.

Blood and lymphatic system disorders:

Frequency not known: cases of decreased white blood cell count (leucopenia) have been observed.

Endocrine disorders:

Common: increased thyroid hormones (hyperthyroidism).

Psychiatric disorders:

Very common: insomnia,
Common: nervousness,
Frequency not known: excitability.

Nervous system disorders:

Very common: headache,
Frequency not known: tremors, increased intracranial pressure (benign intracranial hypertension), especially in children.

Cardiac disorders:

Very common: palpitations,
Common: increased heart rate (tachycardia),
Frequency not known: chest pain sometimes radiating to the left arm (anginal pain), disturbance in heart rhythm (cardiac arrhythmias).

Vascular disorders:

Frequency not known: hot flushes, circulatory collapse in premature newborns with low birth weight (see section 2. "Warnings and precautions").

Gastrointestinal disorders:

Frequency not known: vomiting and diarrhoea.

Skin and subcutaneous tissue disorders:

Frequency not known: skin allergic reactions (e.g. angioedema [difficulty breathing or swelling of the face, lips, throat or tongue], skin rash, urticaria, sweating).

Musculoskeletal and connective tissue disorders:

Frequency not known: muscle weakness and cramps, osteoporosis especially in postmenopausal women, mainly when treated for a long period.

Reproductive system and breast disorders:

Frequency not known: menstrual irregularities.

General disorders and administration site conditions:

Frequency not known: fever, heat intolerance.

Investigations:

Frequency not known: weight loss.

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

If the initial dose of levothyroxine is too high, disturbances in heart rhythm (atrial or ventricular fibrillation) may be precipitated, especially in susceptible patients.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.eshttps://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Levothyroxine Sanofi

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

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

Keep in the original packaging to protect from light.

Protect the prepared solution from direct light.

Expiry

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Stability period of the reconstituted solution:

• for intravenous administration: 24 hours at room temperature
• for infusion administration: 2 hours at room temperature

From a microbiological standpoint, unless the method of opening excludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, the duration and conditions of storage are the responsibility of the user.

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

6. Contents of the container and other information

Composition of Levothyroxine Sanofi 500 micrograms powder and solvent for injectable solution

• The active substance is sodium levothyroxine. Each package contains 1 vial with 514 micrograms of sodium levothyroxine (equivalent to 500 micrograms of levothyroxine).
• The other components are:

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

Solvent: water for injections.

Appearance of the product and contents of the container

Vial: contains white powder.

Solvent ampoule: contains a colorless solution.

Each Levothyroxine Sanofi carton contains 1 vial of powder and 1 ampoule of solvent.

Instructions for healthcare professionals

Administer intravenously after reconstitution.

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

For short-term intermittent infusion use, an isotonic sodium chloride solution (50 ml–250 ml) should be added.

Marketing Authorization Holder

sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

Manufacturer

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 (Girona)

Spain

Date of latest review of this leaflet: March 2023

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.