Package leaflet: Information for the patient

Letrox 25 micrograms, 25 micrograms, tablets
Levothyroxinum natricum
Please read carefully the entire leaflet before use, as it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

What Letrox 25 micrograms is and what it is used for
Important information before taking Letrox 25 micrograms
How to take Letrox 25 micrograms
Possible side effects
How to store Letrox 25 micrograms
Contents of the pack and other information

1. What Letrox 25 micrograms is and what it is used for

Letrox 25 micrograms is a medicine containing the thyroid hormone levothyroxine as the active substance.
It has the same effect as the hormone naturally produced by the body.
The purpose of treatment with Letrox 25 micrograms is to replace deficient thyroid hormone and (or) to alleviate thyroid function disorders.
Letrox 25 micrograms is used:

To replace thyroid hormone deficiency in all forms of hypothyroidism.
To prevent recurrence of goitre (thyroid enlargement) after surgical treatment in patients with normal thyroid function.
For treatment of benign goitre in patients with normal thyroid function.
As an adjunct in the treatment of hyperthyroidism in combination with antithyroid drugs (medicines that suppress thyroid function), after achieving normal thyroid function.
In the treatment of malignant thyroid tumours, particularly after surgical removal of the thyroid gland, to suppress tumour growth and to replace deficient thyroid hormones.

Letrox 25 micrograms is indicated for use in all age groups.

2. Important information before using Letrox 25 micrograms

When not to use Letrox 25 micrograms

If the patient is allergic to sodium levothyroxine or any of the other ingredients of this medicine (listed in section 6).
If the patient has any of the following diseases or conditions:
untreated hyperthyroidism
untreated adrenal insufficiency
untreated pituitary insufficiency, if it leads to adrenal insufficiency requiring treatment
recent myocardial infarction (heart attack)
acute myocarditis (inflammation of the heart muscle)
acute inflammation of all layers of the heart wall (acute pancarditis).

During pregnancy, Letrox 25 micrograms must not be taken at the same time as drugs that
inhibit thyroid function (so-called antithyroid drugs) (see also section “Pregnancy,
breastfeeding and fertility”).

Medical history regarding other diseases
Before starting treatment with Letrox 25 micrograms, the doctor should exclude or treat the
following disorders or conditions:

coronary heart disease
chest pain with pressure (angina pectoris)
high blood pressure (hypertension)
pituitary and/or adrenal insufficiency
areas in the thyroid gland that uncontrollably produce thyroid hormones (autonomous nodule).

Warnings and precautions
Before starting to take Letrox 25 micrograms, discuss this with your doctor or pharmacist.
Exercise particular caution when taking Letrox 25 micrograms:

in patients with a history of myocardial infarction, coronary heart disease, impaired heart function, cardiac arrhythmias (tachycardia), myocarditis without acute phase, or in case of long-standing hypothyroidism. In such cases, excessive concentration of thyroid hormones in the blood should be avoided. Monitoring of thyroid hormone levels should be performed more frequently. If mild symptoms of hyperthyroidism occur related to the use of Letrox 25 micrograms, discuss this with your doctor (see section 4. “Possible side effects”).
if the patient has adrenal insufficiency.
in patients with hypothyroidism caused by pituitary insufficiency. In case of coexisting adrenal insufficiency, the doctor should first initiate treatment of adrenal insufficiency (hydrocortisone therapy). Without appropriate treatment, acute adrenal insufficiency (Addisonian crisis) may occur.
if there is suspicion of autonomously functioning thyroid tissue producing hormones. This should be investigated by additional thyroid function tests before starting treatment.
in postmenopausal women at increased risk of bone loss (osteoporosis). The treating physician should monitor thyroid function more frequently to avoid excessive serum thyroid hormone concentrations and ensure the use of the lowest effective dose.
in patients with diabetes. For further information, see section “Letrox 25 micrograms and other medicines”.
in patients treated with anticoagulant drugs (e.g. dicoumarol) and drugs affecting the thyroid (e.g. amiodarone, tyrosine kinase inhibitors [drugs used in cancer treatment], salicylates, and high doses of furosemide). For further information, see section “Letrox 25 micrograms and other medicines”.
if, for example, a dialysed patient is being treated with sevelamer due to high phosphate levels in the blood, the treating physician may consider monitoring certain blood parameters to assess the effectiveness of levothyroxine therapy (see also: “Letrox 25 micrograms and other medicines”).
if the patient has ever had epilepsy, due to increased risk of seizures.
if the patient experiences an allergic reaction (see section 4. “Possible side effects”). The patient should immediately contact a doctor or healthcare professional or go immediately to the emergency department of the nearest hospital.
if the patient is to undergo laboratory tests measuring thyroid hormone levels, the patient should inform the doctor or laboratory staff about current or recent use of biotin (also known as vitamin H, vitamin B7 or vitamin B8). Biotin may affect laboratory test results. Depending on the type of test, results may be falsely elevated or falsely decreased due to biotin intake. The doctor may advise the patient to stop taking biotin before laboratory testing. It should also be remembered that other products taken by the patient, such as multivitamin preparations or supplements for hair, skin, and nails, may also contain biotin. This may affect laboratory test results. If the patient takes such products, they should inform the doctor or laboratory staff (refer to information in section “Letrox 25 micrograms and other medicines”).

Improper use
Letrox 25 micrograms must not be used for weight reduction. In patients with normal serum
thyroid hormone levels, additional intake of thyroid hormones will not lead to weight loss.
Taking additional amounts of thyroid hormones or increasing the dose without specific medical
advice may cause serious, even life-threatening adverse effects, especially when combined with
other weight-reducing drugs.

Changing treatment
When switching from one medicine to another containing levothyroxine, thyroid function balance
may be disturbed. If you have any questions regarding switching medication, discuss this with your
doctor. Patients should be closely monitored (clinically and biologically) during the transition period.
Inform your doctor if any adverse effects occur, as this may indicate the need to adjust the dose
(increase or decrease).

Elderly patients
In elderly patients (especially those with heart problems), the dose should be increased cautiously,
and patients should undergo medical check-ups more frequently.

Children and adolescents
When starting levothyroxine treatment in preterm infants with very low birth weight, blood pressure
should be monitored regularly, as sudden drop in blood pressure (so-called circulatory collapse) may
occur (see section 4. “Possible side effects”).

Letrox 25 micrograms and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently
taken, as well as any medicines the patient plans to take.

Letrox 25 micrograms affects the action of the following medicinal substances and drug groups:

Antidiabetic drugs (drugs lowering blood sugar such as metformin, glimepiride, glibenclamide, and insulin): In patients with diabetes, blood glucose levels should be monitored regularly, especially at the beginning and after completion of thyroid hormone therapy. If necessary, the doctor may adjust the dose of the blood glucose-lowering drug, as levothyroxine may weaken its effect.
Coumarin derivatives (anticoagulant drugs):
When Letrox 25 micrograms is taken concomitantly with coumarin derivatives (e.g. dicoumarol), blood coagulation parameters should be monitored regularly. If necessary, the doctor may reduce the dose of the anticoagulant, as levothyroxine may enhance its effect.

The following medicines may affect the action of Letrox 25 micrograms:

Ion-exchange resins: Medicines used to lower blood lipid levels (e.g. cholestyramine, colestipol) or to reduce high potassium levels in the blood (calcium or sodium salts of polystyrene sulfonate) should be taken 4 to 5 hours after taking Letrox 25 micrograms. Otherwise, these drugs inhibit the absorption of levothyroxine from the intestines and thus reduce its effectiveness.
Proton pump inhibitors: Proton pump inhibitors (such as omeprazole, esomeprazole, pantoprazole, rabeprazole, and lansoprazole) used to reduce stomach acid production may inhibit the intestinal absorption of levothyroxine and thus reduce its effectiveness. If the patient is taking levothyroxine during treatment with proton pump inhibitors, the doctor should monitor thyroid function and, if necessary, adjust the dose of Letrox 25 micrograms.
Sevelamer and lanthanum carbonate: Sevelamer and lanthanum carbonate (medicines used to lower elevated serum phosphate levels in dialysed patients) may reduce the absorption and effectiveness of levothyroxine. The treating physician will perform more frequent monitoring of thyroid function (see also section “Warnings and precautions”).
Bile acid-binding agents: Colesevelam (a drug used to lower high cholesterol levels in the blood) binds levothyroxine and thus reduces its intestinal absorption. Therefore, Letrox 25 micrograms should be taken 4 hours before colesevelam.
Antacids containing aluminium, iron-containing drugs, calcium-containing drugs: Letrox 25 micrograms should be taken at least 2 hours before antacids containing aluminium (antacids, sucralfate), iron-containing drugs, or calcium-containing drugs. Otherwise, these drugs may reduce the intestinal absorption of levothyroxine and thus reduce its effectiveness.
Propylthiouracil, glucocorticosteroids, beta-blockers (especially propranolol): Propylthiouracil (used in hyperthyroidism), glucocorticosteroids (adrenal cortex hormones, “cortisone”), and beta-blockers (drugs slowing heart rate and reducing blood pressure) inhibit the conversion of levothyroxine to the more active form triiodothyronine (liothyronine) and may therefore reduce the effectiveness of Letrox 25 micrograms.
Amiodarone and iodine-containing contrast agents: Amiodarone (used in the treatment of cardiac arrhythmias) and iodine-containing contrast agents (mainly used in X-ray diagnostics) may, due to their high iodine content, cause both hypothyroidism and hyperthyroidism. Particular attention should be paid to patients with nodular goitre, in whom undiagnosed autonomous thyroid nodules (autonomy) releasing hormones uncontrollably may be present. Amiodarone inhibits the conversion of levothyroxine to the more active form liothyronine and thus affects the action of Letrox 25 micrograms. If necessary, the treating physician will adjust the dose of Letrox 25 micrograms.
The following drugs may affect the action of Letrox 25 micrograms:
- Salicylates, especially doses above 2 g per day (antipyretic and analgesic drugs)
- Dicoumarol (anticoagulant drug)
- Furosemide (diuretic) in high doses (250 mg)
- Clofibrate (drug used to lower elevated blood lipid levels)
Oral contraceptives and hormone replacement therapy: Estrogen-containing oral contraceptives (“birth control pills”) and postmenopausal hormone replacement therapy may increase the requirement for levothyroxine.
Sertraline, chloroquine / proguanil: Sertraline (used in depression treatment) and chloroquine and proguanil (used in malaria and rheumatoid arthritis treatment) reduce the effectiveness of levothyroxine.
Rifampicin, carbamazepine, phenytoin, barbiturates, St. John’s wort-containing products: Rifampicin (antibiotic), carbamazepine (used in epilepsy treatment), phenytoin (used in epilepsy and cardiac arrhythmia treatment), barbiturates (used in epileptic seizures, anesthesia; some sleeping pills), and products containing St. John’s wort (herbal medicinal product) may reduce the effectiveness of levothyroxine.
Protease inhibitors (drugs used in HIV and chronic hepatitis C virus infection treatment): The doctor should closely monitor disease symptoms and thyroid function in patients taking levothyroxine concomitantly with protease inhibitors (lopinavir, ritonavir). Concurrent use of levothyroxine with lopinavir and/or ritonavir may reduce its effectiveness.
Tyrosine kinase inhibitors (drugs used in cancer treatment): The doctor should closely monitor clinical symptoms and thyroid function in patients taking levothyroxine concomitantly with tyrosine kinase inhibitors (e.g. imatinib, sunitinib, sorafenib, motesanib). The effectiveness of levothyroxine may be reduced; if necessary, the doctor will adjust the levothyroxine dose.
Semaglutide: If the patient is taking levothyroxine at the same time as semaglutide (antidiabetic drug), this may affect levothyroxine levels, and the doctor may recommend monitoring thyroid hormone levels and adjusting the dose of Letrox 25 micrograms.
Orlistat: Orlistat (used in obesity treatment) may reduce the absorption of levothyroxine.
Biotin (also known as vitamin H, vitamin B7 or vitamin B8): If the patient is currently taking or has recently taken biotin, they must inform the doctor or laboratory staff if thyroid hormone laboratory tests are to be performed. Biotin may affect laboratory test results (see “Warnings and precautions”).

Letrox 25 micrograms with food and drink
Do not take Letrox 25 micrograms with food, especially with a diet rich in calcium (e.g. milk and dairy
products), as this may significantly reduce the absorption of levothyroxine.
In case of a soy-containing diet, the doctor will monitor thyroid hormone levels in the blood more
frequently. During and after such a diet, adjustment of the dose of Letrox 25 micrograms by the doctor
(more often higher doses) may be necessary, as soy-containing products interfere with the intestinal
absorption of levothyroxine, thus reducing its effectiveness.
Do not take Letrox 25 micrograms with coffee, as this may reduce the intestinal absorption of
levothyroxine and thus reduce its effectiveness. After taking Letrox 25 micrograms, wait at least
30 minutes to 1 hour before drinking coffee. Patients taking levothyroxine are advised not to change
their coffee-drinking habits without checking and monitoring levothyroxine levels by the treating
physician.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child,
she should consult her doctor or pharmacist before using this medicine.
Proper thyroid hormone therapy is particularly important for the health of the mother and the fetus
during pregnancy and breastfeeding. Therefore, treatment should be continued uninterrupted under
the supervision of the treating physician. Despite the widespread use of levothyroxine during
pregnancy, any negative effect on pregnancy or on the health of the fetus or newborn remains
unknown.
Thyroid function should be monitored both during and after pregnancy. The doctor may adjust the
dose, as the requirement for thyroid hormone may increase during pregnancy due to elevated
estrogen levels in the blood (female sex hormone).
During pregnancy, Letrox 25 micrograms must not be used simultaneously with drugs that inhibit
thyroid function (thyrostatic drugs), as this would necessitate higher doses of thyrostatic drugs.
Thyrostytics (unlike levothyroxine) can cross the placenta into the fetal circulation and may cause
hypothyroidism in the unborn child. In case of hyperthyroidism during pregnancy, the doctor should
use only small doses of thyrostatic drugs.
If the patient is breastfeeding, levothyroxine intake should be continued as recommended by the
doctor. Even when treating with high doses of levothyroxine during breastfeeding, the amount of
levothyroxine passing into breast milk is very small and therefore harmless.
Hypothyroidism or hyperthyroidism may affect fertility.
During treatment of patients with hypothyroidism, the dose of Letrox 25 micrograms should be
adjusted based on laboratory test results, as an insufficient dose may not correct hypothyroidism,
and overdosing may lead to hyperthyroidism.

Driving and using machines
No studies on the effect of Letrox 25 micrograms on the ability to drive and use machines have been
conducted.

Letrox 25 micrograms contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is considered “sodium-free”.

3. How to use Letrox 25 micrograms

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Your doctor will determine the daily dose for each patient based on follow-up tests.
Dosage
Tablets with different strengths of the active substance (25–150 micrograms of sodium levothyroxine) are available to allow individualized treatment, meaning most patients will take one tablet per day.
Depending on symptoms, your doctor will adjust the dose according to the following recommendations:

In the treatment of hypothyroidism, the initial dose for adult patients is 25–50 micrograms of sodium levothyroxine per day. Your doctor may recommend increasing the dose by 25–50 micrograms of sodium levothyroxine at 2–4 week intervals until reaching a daily dose of 100–200 micrograms of sodium levothyroxine.
For prevention of goiter recurrence after its removal and in the treatment of benign goiter, the daily dose is 75–200 micrograms of sodium levothyroxine.
As an adjunct in the treatment of hyperthyroidism in combination with antithyroid drugs (thyreostatics), the daily dose is 50–100 micrograms of sodium levothyroxine.
After surgical removal of the thyroid due to malignant thyroid tumors, the daily dose is 150–300 micrograms of sodium levothyroxine.

A lower dose of thyroid hormone may also be appropriate.
Use in children and adolescents
The maintenance dose during long-term treatment of hypothyroidism (congenital or acquired) is usually 100 to 150 micrograms of sodium levothyroxine per m² of body surface area per day.
In newborns and infants with congenital hypothyroidism, prompt initiation of treatment is particularly important to achieve normal mental and physical development. The recommended initial dose is 10 to 15 micrograms of sodium levothyroxine per kg of body weight per day for the first 3 months. Thereafter, your doctor will individually adjust the daily dose based on clinical findings (particularly blood levels of thyroid hormones).
In children with acquired hypothyroidism, the recommended initial dose is 12.5 to 50 micrograms of sodium levothyroxine per day. Your doctor will gradually increase the daily dose at 2–4 week intervals until the full replacement dose is achieved. During this process, your doctor will particularly monitor thyroid hormone levels in the blood.
Elderly patients, patients with ischemic heart disease, patients with hypothyroidism
In elderly patients, patients with ischemic heart disease, and patients with severe or long-standing hypothyroidism, treatment with thyroid hormones should be initiated with particular caution (a low starting dose, which should then be increased slowly at long intervals, with frequent monitoring of thyroid hormone levels).
Patients with low body weight and patients with large goiter
Experience shows that lower doses are also sufficient in patients with low body weight and in patients with large goiter.
Method of administration
The entire daily dose should be taken in the morning, with a large amount of liquid, preferably a glass of water, on an empty stomach, at least half an hour before breakfast. The active substance is better absorbed on an empty stomach than before or after a meal.
Children should receive their total daily dose at least half an hour before the first meal. Tablets may also be dissolved in an appropriate amount of water (10–15 mL), and the resulting suspension (tablets must always be dissolved immediately before administration!) may be given with a small additional amount of liquid (5–10 mL).
Duration of treatment
Letrox 25 micrograms is usually taken for life in cases of hypothyroidism and after surgical removal of the thyroid due to malignant thyroid tumors. In the treatment of benign goiter and prevention of goiter recurrence, treatment may last several months or years, possibly for life. In adjunctive therapy of hyperthyroidism, Letrox 25 micrograms should be taken as long as antithyroid drugs (thyreostatics) are used. Treatment of benign goiter with normal thyroid function should last from 6 months to 2 years. If during this period treatment with Letrox 25 micrograms does not produce the expected effect, your doctor will consider alternative treatment options.
Taking more than the recommended dose of Letrox 25 micrograms
Symptoms of overdose are described in section 4, "Possible side effects." If such symptoms occur, consult your doctor.
Missing a dose of Letrox 25 micrograms
If a patient takes too low a dose or misses a dose, they must not take a double dose to make up for the missed dose. Continue taking the medicine as prescribed by your doctor.
Stopping treatment with Letrox 25 micrograms
To achieve the desired therapeutic effects, Letrox 25 micrograms must be taken regularly at the dose prescribed by your doctor. Under no circumstances should the dose be changed, treatment interrupted, or discontinued prematurely without consulting your doctor, as symptoms may recur.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Hypersensitivity to the active substance or any of the other components of Letrox 25 micrograms
In case of hypersensitivity to levothyroxine or any of the other components of Letrox 25 micrograms,
skin allergic reactions and allergic reactions related to the respiratory system may occur (either
immediately or within a few days after administration), which may be life-threatening. These symptoms
may include rash, itching, difficulty breathing, shortness of breath, swelling of the face, lips, throat, or tongue.
You should immediately contact a doctor or healthcare professional or seek urgent medical attention at
the nearest hospital emergency department.
Intolerance to the administered dose, overdose
In individual cases when the recommended dose is not tolerated or when the medicine has been
overdosed, particularly in cases of too rapid dose escalation at the beginning of treatment, typical
symptoms of hyperthyroidism may occur.
Very common: may affect more than 1 in 10 patients

Palpitations
Insomnia
Headache

Common: may affect up to 1 in 10 patients

Rapid heartbeat (tachycardia)
Nervousness

Rare: may affect up to 1 in 1,000 patients

Increased intracranial pressure (especially in children)

Frequency not known: cannot be estimated from the available data

Hypersensitivity
Cardiac arrhythmias
Chest pain with a feeling of pressure (angina pectoris)
Skin allergic reactions (e.g. angioedema [difficulty breathing or swelling of the face, lips, throat, or tongue], rash, urticaria)
Restlessness
Muscle weakness, muscle cramps
Osteoporosis during long-term use of high doses of levothyroxine, particularly in postmenopausal women
Feeling of warmth, intolerance to high temperature, circulatory collapse in preterm infants with low birth weight (see section 2. "Warnings and precautions")
Menstrual disorders
Diarrhea
Vomiting
Nausea
Weight loss
Tremor
Excessive sweating
Fever

You should inform your doctor if any adverse reactions occur. The doctor will decide whether the daily
dose should be reduced or whether treatment should be temporarily discontinued for a few days. Once
the adverse reactions have subsided, the doctor may resume treatment, carefully adjusting the dose.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your
doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Letrox 25 micrograms

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the outer carton after: "EXP". The expiry date refers to the last day of the stated month.
Store below 30°C.
Store in the original blister to protect from light.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Letrox 25 micrograms contains
The active substance is levothyroxine sodium.
Each tablet contains 25 micrograms of levothyroxine sodium.
The other ingredients are:
cysteine hydrochloride monohydrate (partially present in the tablet as cystine), microcrystalline cellulose, maize starch, pregelatinized starch, light magnesium oxide, talc.

What Letrox 25 micrograms looks like and contents of the pack
Letrox 25 micrograms is white to beige, round, slightly convex tablets.
The pack contains 28, 50 or 100 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
BERLIN – CHEMIE AG
Glienicker Weg 125
12489 Berlin, Germany
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Berlin - Chemie/Menarini Polska Sp. z o.o.
Tel.: +48 22 566 21 00
Fax: +48 22 566 21 01

This medicinal product is authorised in the European Economic Area countries under the following names:
Bulgaria: L-Thyroxin 25 Berlin-Chemie
Czech Republic: Letrox
Germany: L-Thyroxin BC 25 Mikrogramm
Latvia: Levothyroxine sodium Berlin-Chemie 25 mikrogrami tabletes
Lithuania: L-Thyroxin Berlin-Chemie 25
Poland: Letrox 25 micrograms
Slovakia: L-Thyroxin 25 Berlin-Chemie