Eferox

Package leaflet: Information for the patient

Eferox, 112 micrograms, tablets
Eferox, 125 micrograms, tablets
Eferox, 137 micrograms, tablets
Eferox, 175 micrograms, tablets
Levothyroxinum natricum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for the patient.

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

Contents of the leaflet

1. What Eferox is and what it is used for
2. Important information before taking Eferox
3. How to take Eferox
4. Possible side effects
5. How to store Eferox
6. Contents of the pack and other information

1. What Eferox is and what it is used for

Thyroxine is a hormone naturally produced by the thyroid gland in the body. Sodium levothyroxine is a synthetic form of this hormone.
Eferox is used to replace deficient thyroid hormone and/or to manage thyroid disorders.
Eferox is indicated:

• for replacement therapy in all forms of hypothyroidism (thyroid hormone deficiency) or after thyroidectomy,
• for prevention of goiter recurrence after goiter removal in patients with normal thyroid function,
• for treatment of benign (non-malignant) goiter in patients with normal thyroid function,
• in the management of malignant thyroid cancers, particularly after surgical procedures, to suppress tumor growth and to replace missing thyroid hormone.

2. Important information before using Eferox

When not to use Eferox

• if the patient is allergic to levothyroxine or any of the other ingredients of this medicine (listed in section 6);
• if the patient has untreated overactivity of the thyroid gland (hyperthyroidism, thyrotoxicosis);
• if the patient has untreated adrenal insufficiency (adrenal failure) and is not receiving appropriate replacement therapy;
• if the patient has untreated pituitary insufficiency;
• if the patient has any of the following diseases or conditions:
  • acute myocardial infarction
  • acute inflammation of the heart muscle (myocarditis)
  • acute inflammation of all layers of the heart wall (pancarditis)
• during pregnancy, Eferox must not be taken together with other medicines for hyperthyroidism (antithyroid drugs).

The following diseases or conditions must be excluded or treated before starting treatment with Eferox:

• coronary heart disease;
• chest pain with a feeling of pressure (angina pectoris);
• fatty deposits in the arteries (atherosclerosis);
• high blood pressure (hypertension);
• conditions in which the pituitary gland and (or) the adrenal glands do not produce sufficient hormones (pituitary insufficiency and (or) adrenal cortical insufficiency);
• areas in the thyroid gland that produce uncontrolled amounts of thyroid hormone (autonomous thyroid function).

Warnings and precautions
Thyroid hormones are not suitable for use in weight reduction. Taking thyroid hormones will not lead to weight loss in patients with normal thyroid hormone levels. Taking additional thyroid hormones without medical indication may cause severe, even life-threatening, adverse effects, especially when combined with other weight-reducing medicines (see section 2 "Eferox with other medicines").
When switching from one medicine to another containing levothyroxine, thyroid function imbalance may occur. If there are any questions regarding switching medicines, 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 for dose adjustment (increasing or decreasing the dose).
Before starting treatment with Eferox, discuss the following with your doctor or pharmacist:

• if the patient has had hypothyroidism for a long time, for example since birth or if the disease appeared in childhood;
• if the patient has heart disease, including angina pectoris, coronary heart disease, weakened heart muscle, cardiac arrhythmias, or high blood pressure or atherosclerosis;
• if the patient recently had a heart attack;
• if the patient is taking anticoagulant medicines (e.g. phenprocoumon). The dose of this medicine may need to be adjusted (see section 2 "Eferox with other medicines");
• if the patient is being treated for diabetes. The dose of antidiabetic medicine may need to be adjusted, as levothyroxine may increase blood glucose levels (see section 2 "Eferox with other medicines");
• if the patient is postmenopausal. Thyroid function should be monitored more frequently to avoid increased levothyroxine levels in the blood, which may lead to osteoporosis (bone fragility);
• if the patient has epilepsy (seizures). During initiation of levothyroxine treatment or rapid dose increase, seizures have been reported with frequency - rarely;
• if the patient has myxoedema (swelling of the skin and subcutaneous tissue), as the dose of Eferox may need to be reduced;
• if the patient has small intestine disease, as it may impair absorption of the medicine (malabsorption syndrome, e.g. coeliac disease, lactose intolerance), which may require treatment to ensure that Eferox works properly;
• if the patient has adrenal insufficiency (adrenal failure), pituitary dysfunction, or a certain type of thyroid dysfunction with uncontrolled excessive production of thyroid hormones, as appropriate treatment is required before

starting Eferox treatment;

• 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 increased or falsely decreased due to biotin intake. The doctor may advise the patient to stop taking biotin before laboratory tests. It should also be remembered that other products the patient may be taking, such as multivitamin preparations or hair, skin and nail supplements, may also contain biotin. This may affect laboratory test results. If the patient is taking such products, they should inform the doctor or laboratory staff (see information in section 2: "Eferox with other medicines").

Talk to your doctor if the patient has symptoms of psychotic disorders.
When starting levothyroxine treatment in preterm infants with very low birth weight, blood pressure should be monitored regularly, as a sudden drop in blood pressure (so-called circulatory collapse) may occur.
In elderly patients, e.g. those with heart disease, the dose should be carefully and individually adjusted. The doctor should monitor such patients.
Blood tests
Before starting levothyroxine, the doctor will perform a blood test to determine how much thyroxine the patient's thyroid gland produces and what dose of medicine is needed. After starting the medicine, the doctor will recommend regular blood tests to ensure the medicine is working properly.
Eferox with other medicines
Tell 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 or use. This includes also non-prescription medicines, herbal remedies and vitamin preparations. Many other medicines may affect the action of Eferox. Levothyroxine may also affect the action of other medicines.
Before undergoing an examination with iodine-containing contrast agents, inform the doctor about taking Eferox.
If the patient is currently taking or has recently taken biotin, they must inform the doctor and (or) laboratory staff if thyroid hormone laboratory tests are to be performed. Biotin may affect laboratory test results (see "Warnings and precautions").
The following medicines may affect the action of levothyroxine:

• antiepileptic medicines such as: carbamazepine, phenytoin, primidone and barbiturates
• medicines containing St. John's wort (some herbal medicines)
• sertraline, lithium – medicines used in depression, mood disorders and anxiety
• statins such as simvastatin and lovastatin (medicines used to treat high blood cholesterol levels);
• rifampicin – a medicine used to treat infections
• imatinib, sunitinib, 5-fluorouracil – medicines used in the treatment of certain types of cancer
• beta-adrenergic blocking agents such as: propranolol, atenolol and sotalol – medicines used to treat high blood pressure and heart diseases
• hormonal medicines containing oestrogens, used in hormone replacement therapy and hormonal contraception ("the contraceptive pill")
• hormonal medicines containing androgens, used in hormone replacement therapy in men
• glucocorticosteroids such as: cortisone, hydrocortisone, prednisolone and dexamethasone – medicines

used to treat inflammatory conditions

• amiodarone – a medicine used to treat irregular heart rhythm
• anti-inflammatory medicines such as: phenylbutazone or acetylsalicylic acid
• methadone – a medicine used in opioid substitution therapy
• furosemide – a medicine used to treat high blood pressure or oedema
• propylthiouracil – a medicine used to treat hyperthyroidism
• iodide – used to protect the thyroid gland from radiation
• oral contrast agents – taken before certain imaging tests to better visualise body parts
• chloroquine or proguanil – used for malaria prophylaxis and rheumatic diseases
• ritonavir – a medicine used to control HIV infection and chronic hepatitis C virus infection
• orlistat – a medicine used to treat obesity;
• proton pump inhibitors (such as omeprazole, esomeprazole, pantoprazole, rabeprazole and lansoprazole) used to reduce stomach acid production, which may impair levothyroxine absorption from the intestine and make it less effective. If the patient is taking levothyroxine during treatment with proton pump inhibitors, the doctor should monitor thyroid function and, if necessary, modify the dose of Eferox.

Eferox should be taken at least 4 to 5 hours before taking the following medicines:

• calcium, magnesium, aluminium or iron supplements, lanthanum
• cholestyramine, colestipol or clofibrate – medicines used to reduce high blood cholesterol levels
• sodium polystyrene sulfonate – used in the treatment of kidney diseases
• orlistat – used for weight loss
• cimetidine – used to inhibit excessive gastric acid secretion
• proton pump inhibitors such as: omeprazole, esomeprazole – medicines used to inhibit excessive gastric acid secretion
• sucralfate, antacids – used in the treatment of gastric ulcer.

Eferox may affect the action of the following medicines:

• anticoagulant medicines preventing blood clot formation, such as: warfarin, dicoumarol and phenprocoumon
• medicines used to treat diabetes, such as: insulin and metformin
• tricyclic antidepressants such as: amitriptyline, imipramine and doxepin
• medicines that stimulate the sympathetic nervous system, such as: adrenaline (used to treat severe allergic reactions) or phenylephrine (a medicine reducing mucosal congestion found in many cold and flu medicines)
• digoxin – a medicine used to treat heart diseases
• phenytoin – a medicine used to treat epilepsy.

Eferox with food and drink
Foods and products containing soya or high in fibre may affect levothyroxine absorption. Therefore, the doctor in charge may need to adjust the levothyroxine dose.
Pregnancy and breastfeeding
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.
Continuous thyroid hormone treatment is particularly important during pregnancy and breastfeeding and must therefore be continued under the supervision of the treating doctor.
During pregnancy, the need for levothyroxine may increase due to elevated oestrogen (female sex hormone) levels in the blood. Therefore, thyroid function should be monitored during and after pregnancy, and the levothyroxine dose adjusted accordingly.
Even when taking high doses of levothyroxine, the amount of thyroid hormone passing into breast milk during breastfeeding is very small and therefore harmless.
Suppression tests must not be performed during pregnancy and breastfeeding.
Driving and operating machinery
Eferox is not expected to have any effect on the ability to drive or operate machinery, as the levothyroxine contained in this medicine is identical to the thyroid hormone naturally present in the body.
Eferox contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Eferox

This medicine should always be taken exactly as directed by the doctor or pharmacist. In case of
doubt, consult your doctor or pharmacist.
In elderly patients, patients with ischemic heart disease, and patients with severe or chronic
hypothyroidism, treatment with thyroid hormones should be initiated with particular caution. In
these patients, treatment should begin with a low starting dose, which should then be gradually
increased at longer intervals, with frequent monitoring of thyroid hormone levels. Experience
shows that lower doses are also sufficient in individuals with low body weight and in patients with
a large goiter.

Dosing
Eferox tablets with graduated strengths from 25 to 200 micrograms are available for individual
treatment, meaning that in most cases only one tablet per day needs to be taken.
The doctor will determine the individual dose for the patient based on conducted examinations and
laboratory test results. Treatment usually starts with a low dose, which is increased every 2 to
4 weeks until the full, individually adjusted dose is reached. During the first weeks of treatment,
the patient will be instructed to undergo laboratory tests, which will allow the doctor to adjust the
appropriate dose.

Method of administration
The entire daily dose should be taken in the morning on an empty stomach, at least half an hour before breakfast,
since the active substance is better absorbed on an empty stomach than before or after a meal. The tablets should be
swallowed whole, without chewing, with a glass of water.
Infants should receive the entire daily dose at least half an hour before the first meal, preferably with a small amount of water to facilitate swallowing. If necessary,
the tablet may be divided.
Crushing the tablet or preparing a suspension in water or other liquids is not recommended,
as this may lead to incorrect dosing.
Eferox tablets may be divided into equal doses.
Instructions for dividing the tablet

Place the tablet on a hard, flat surface with the dividing groove facing upwards. To divide the tablet,
press directly with the thumb onto the center of the tablet.
Duration of treatment
The medicine should be taken for as long as directed by the physician.
If the patient has hypothyroidism or has undergone surgery due to malignant thyroid cancer,
they will usually need to take Eferox for life.
In the treatment of mild goiter and to prevent recurrence, Eferox should be taken
for several months or years, and even for the rest of the patient's life.
In supportive therapy for hyperthyroidism, Eferox should be taken for as long as
antithyroid medication (thyrostatics) is being administered.
In the treatment of mild goiter with normal thyroid function, the medicine should be taken for
6 months to 2 years. If treatment with Eferox does not achieve the desired results within this period,
alternative treatment options should be considered.
Use of a higher than recommended dose of Eferox
If a patient (or another person) has swallowed more tablets than prescribed, or if there is suspicion that
a child has ingested any amount of tablets, contact a physician, the emergency department of the nearest hospital, or a poison control center immediately.
Symptoms of overdose may include: excitation, confusion, irritability, fever,
chest pain (angina), rapid or irregular heartbeat, accelerated breathing,
muscle spasms, headache, restlessness, hyperactivity, flushing, sweating,
dilated pupils, diarrhea, tremor, difficulty falling asleep, anxiety or nervousness, feeling
of physical or emotional fatigue, seizures.
These symptoms may last up to 6 days. Bring any remaining tablets and this leaflet with you so that
medical personnel know exactly which medicine the patient has taken.
Missed dose of Eferox
If a dose of the medicine is missed, take the usual dose at the time of the next scheduled dose. Do not take a double dose to make up for the missed dose. If in doubt, consult a physician or pharmacist.
Stopping treatment with Eferox
For treatment to be effective, Eferox must be taken regularly at the doses prescribed by the physician. Under no circumstances should the prescribed treatment be changed, interrupted, or discontinued without consulting a physician, as symptoms may otherwise return.
If you have any further questions regarding the use of this medicine, consult your physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Treatment with tablets should be discontinued and immediate hospitalisation sought if the patient develops:

• an allergic reaction such as: swelling of the face, tongue, lips and (or) throat and (or) difficulty swallowing or hives causing breathing difficulties (angioedema), severe itching of the skin with raised lumps, joint pain, photosensitivity, general malaise (frequency unknown). The patient may require urgent medical attention.

Some patients may experience a severe reaction to high concentrations of thyroid hormone.
This is known as "thyroid storm". Treatment with tablets should be immediately discontinued and the patient should go to the nearest hospital if any of the following symptoms occur (frequency unknown):

• very high fever, rapid heartbeat, irregular heartbeat, low blood pressure, heart failure, jaundice, confusion, seizures and coma.

Inform the doctor or pharmacist if any of the following adverse reactions occur,
worsen, or if the patient notices any adverse reactions not listed here.
Most adverse reactions resemble symptoms of hyperthyroidism (when the thyroid gland produces too much thyroxine) and are caused by taking too high a dose of the medicine. Symptoms usually resolve after dose reduction or temporary discontinuation of the tablets. Inform the doctor if any adverse reactions occur. The doctor will decide whether to reduce the daily dose or discontinue treatment for a few days. However, do not change the dose or stop taking the tablets without first consulting a doctor.
Frequency unknown: frequency cannot be estimated from the available data

• increased appetite
• anxiety, restlessness, difficulty sleeping (insomnia)
• tremor, headache, seizures
• chest pain (angina), palpitations, irregular or rapid heartbeat, heart failure, myocardial infarction
• high blood pressure (hypertension), sudden flushing
• shortness of breath (dyspnoea)
• diarrhoea, nausea, vomiting, abdominal pain
• increased sweating, itching, skin rash, urticaria
• muscle cramps, muscle weakness, joint pain
• decreased bone density (osteoporosis), especially in postmenopausal women receiving high doses of the medicine for a prolonged period
• in women: irregular menstruation
• fever (high temperature), swelling, general malaise
• weight loss
• hyperthyroidism

Additional adverse reactions in children
Rare: may affect up to 1 in 1,000 patients

• increased intracranial pressure in children not caused by a tumour or other diseases (benign intracranial hypertension).

Frequency unknown: frequency cannot be estimated from the available data

• slowed or arrested growth in children due to changes in bone development
• transient hair loss in children
• skull deformity in infants caused by premature closure of cranial sutures in children (craniosynostosis)
• heat intolerance.

In case of hypersensitivity to levothyroxine or any of the other ingredients of Eferox,
allergic reactions affecting the skin and respiratory tract may occur.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the 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 authorisation holder.
Reporting of adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Eferox

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and the cardboard
box after: EXP. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. These measures help protect
the environment.

6. Contents of the pack and other information

What Eferox contains

• The active substance in this medicine is levothyroxine sodium anhydrous.

Eferox 112 micrograms tablets
Each tablet contains 112 micrograms of levothyroxine sodium anhydrous.
Eferox 125 micrograms tablets
Each tablet contains 125 micrograms of levothyroxine sodium anhydrous.
Eferox 137 micrograms tablets
Each tablet contains 137 micrograms of levothyroxine sodium anhydrous.
Eferox 175 micrograms tablets
Each tablet contains 175 micrograms of levothyroxine sodium anhydrous.

• The other ingredients are: microcrystalline cellulose, maize starch, magnesium oxide heavy, sodium carboxymethyl starch (type A) and magnesium stearate.

What Eferox looks like and contents of the pack
Eferox tablets are white, round, uncoated, designed to be split by pressing, with a dividing groove on one side and a numerical imprint corresponding to the strength (i.e. 112, 125, 137, 175) embossed on the other side. The tablets have a diameter of approximately 7 mm and a height of approximately 3 mm.
Eferox 125 micrograms is available in blister packs containing 20, 25, 30, 50, 60, 90 or 100 tablets in a cardboard carton.
Eferox 112 micrograms, 137 micrograms and 175 micrograms are available in blister packs containing 25, 30, 50, 60, 90 or 100 tablets in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Aristo Pharma Sp. z o.o.
Baletowa 30 Street
02-867 Warsaw
Poland
Tel: +48 22 855 40 93

Manufacturer
Aristo Pharma GmbH
Wallenroder Straße 8–10
13435 Berlin
Germany
Lindopharm GmbH
Neustraße 82
40721 Hilden
Germany

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
Austria Levothyroxin Aristo 112/125/137/175 Mikrogramm Tabletten
Germany L-Thyroxin Aristo 112/125/137/175 Mikrogramm Tabletten
Czech Republic Levothyroxine Aristo 112/125/137/175 mikrogramů tablety
Spain Levotiroxina Aristo 112/125/137/175 microgramos comprimidos
Netherlands Levothyroxinenatrium Aristo 112/125/137/175 microgram tabletten
Ireland Levothyroxine sodium Aristo 112/125/137/175 microgram tablets
Poland Eferox 112/125/137/175 mikrogramów tabletki
Portugal Eferox 112/125/137/175 microgramas comprimidos
Italy Levotiroxina DOC 125 mikrogrammi compresse
Levotiroxina Aristo 112, 137, 175 mikrogrammi compresse