Eferox

Patient Information Leaflet

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 you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not share it with others. This medicine may harm other people, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Eferox is and what it is used for
2. What you need to know 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. Sodium levothyroxine is a synthetic form of this hormone.
Eferox is used to replace deficient thyroid hormone and/or to treat disorders of thyroid function.
Eferox is used:

• to replace thyroid hormone in all forms of hypothyroidism (underactive thyroid) or after thyroid gland removal,
• to prevent recurrence of goitre after surgical removal of the goitre in patients with normal thyroid function,
• to treat mild (benign) goitre in patients with normal thyroid function,
• in the treatment of malignant thyroid tumours, particularly after surgery, to suppress tumour 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 hyperthyroidism (hyperthyroidism, thyrotoxicosis);
• if the patient has 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 concomitantly with other antithyroid drugs (thyroid-suppressing drugs).

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

• coronary heart disease;
• chest pain with pressure (angina pectoris);
• fatty deposits in the arteries (atherosclerosis);
• high blood pressure (hypertension);
• conditions in which the pituitary gland and (or) adrenal glands do not produce sufficient amounts of 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 reducing body weight. Taking thyroid hormones will not lead to weight reduction 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 drugs (see section 2 "Eferox with other medicines").
When switching from one medicine to another containing levothyroxine, an imbalance in thyroid function may occur. If in doubt about 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 to adjust the dose (increase or decrease).
Before starting Eferox, discuss 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 drugs (e.g. fenprocoumon). The dose of this drug may need adjustment (see section 2 "Eferox with other medicines");
• if the patient is being treated for diabetes. The dose of antidiabetic medication may need adjustment, as levothyroxine may increase blood glucose levels (see section 2 "Eferox with other medicines");
• if the patient is in menopause. Thyroid function should be monitored more frequently to avoid elevated levothyroxine levels in the blood, which may lead to osteoporosis (bone fragility);
• if the patient has epilepsy (epileptic seizures). Seizures have been reported rarely during initiation of levothyroxine treatment or rapid dose escalation;
• if the patient has myxedema (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 drug absorption (malabsorption syndrome, e.g. celiac disease, lactose intolerance), which may require treatment to ensure Eferox works properly;
• if the patient has adrenal insufficiency (adrenal failure), pituitary dysfunction, or a certain type of thyroid disorder with uncontrolled overproduction of thyroid hormones, as appropriate treatment is required before

starting Eferox;

• if the patient is scheduled for laboratory tests measuring thyroid hormone levels, the patient should inform the doctor or laboratory staff about current or recent biotin intake (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 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 (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 adjusted carefully and individually. 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 the 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. This includes medicines without a prescription, herbal medicines, and vitamin preparations. Many other medicines may affect the action of Eferox. Levothyroxine may also affect the action of other medicines.
Before undergoing imaging tests using 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 drugs 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)
• rifampicin – a medicine used to treat infections
• imatinib, sunitinib, 5-fluorouracil – medicines used in the treatment of certain types of cancer
• beta-adrenergic blockers such as: propranolol, atenolol, and sotalol – medicines used to treat high blood pressure and heart diseases
• hormonal medicines containing estrogens, used in hormone replacement therapy and hormonal contraception ("birth control 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 edema
• 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 visualize 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 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 Eferox.

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

• calcium, magnesium, aluminum, or iron supplements, lanthanum
• cholestyramine, colestipol, or clofibrate – medicines used to reduce high blood cholesterol
• 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 ulcers.

Eferox may affect the action of the following medicines:

• anticoagulant drugs preventing blood clot formation, such as: warfarin, dicoumarol, and fenprocoumon
• 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
Soy-containing products and foods high in fiber may affect levothyroxine absorption. Therefore, the dose of levothyroxine may need to be adjusted by the treating physician.

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 medical supervision.
During pregnancy, the need for levothyroxine may increase due to elevated estrogen (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 treated with high doses of levothyroxine, the amount of thyroid hormone passing into breast milk during breastfeeding is very small and therefore harmless.
Thyroid 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 as directed by a doctor or pharmacist. If in doubt, consult a doctor or pharmacist.
In elderly patients, patients with ischemic heart disease, and patients with severe or chronic hypothyroidism, thyroid hormone therapy should be initiated with particular caution. In these patients, treatment should start with a low initial dose, which should then be gradually increased at longer intervals, with frequent monitoring of thyroid hormone levels. Experience indicates that lower doses are also sufficient in individuals with low body weight and in patients with a large goiter.

Dosing
For individualized treatment, Eferox tablets are available in graduated strengths from 25 to 200 micrograms, 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 clinical evaluation 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, laboratory tests will be ordered for the patient to 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,
because the active substance is better absorbed on an empty stomach than before or after a meal. 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 on the center of the tablet with your thumb.
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 goitre and to prevent recurrence of goitre, 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
anti-thyroid (thyrostatic) medication is being used.
In the treatment of mild goitre with normal thyroid function, the medicine should be taken for
6 months to 2 years. If treatment with Eferox does not yield 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 nearest hospital emergency department, or a poison control center immediately.
Symptoms of overdose may include: agitation, confusion, irritability, fever,
chest pain (angina), rapid or irregular heartbeat, accelerated breathing, muscle spasms, headache, restlessness,
hyperactivity, flushing, sweating, dilated pupils, diarrhoea, tremor, difficulty sleeping, anxiety or nervousness, feeling
of physical or emotional fatigue, and 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 is missed, take the usual dose at the time of the next scheduled dose. Do not take a double
dose to make up for a missed dose. If in doubt, consult a physician or pharmacist.
Discontinuation of Eferox treatment
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 there are any further doubts regarding the use of this medicine, consult a physician or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You must stop taking the tablets and go to hospital immediately if the patient experiences:

• 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 skin itching with raised lumps, joint pain, increased sensitivity to sunlight, general feeling of being unwell (frequency not known). The patient may require urgent medical attention.

Some patients may experience a severe reaction to high levels of thyroid hormone. This is known as "thyroid storm". You must stop taking the tablets immediately and go to the nearest hospital if the patient experiences any of the following symptoms (frequency not known):

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

You should inform your doctor or pharmacist if any of the following adverse reactions occur,
worsen, or if the patient notices any other 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 reducing the dose or stopping the tablets. You should inform your doctor if the patient experiences any adverse reactions. The doctor will decide whether to reduce the daily dose or temporarily discontinue treatment for a few days. However, you must not change the dose or stop taking the tablets without first consulting your doctor.
Frequency not known: frequency cannot be estimated from available data

• increased appetite
• anxiety, restlessness, difficulty sleeping (insomnia)
• tremor, headache, seizures
• chest pain (angina), palpitations, irregular or rapid heart rhythm, heart failure, heart attack
• 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 taking 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 tumour or other diseases (benign intracranial hypertension)

Frequency not known: frequency cannot be estimated from available data

• slowed or arrested growth in children due to changes in bone development
• transient hair loss in children
• skull deformity in infants due to 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 effects occur, including any adverse effects not listed in this leaflet, you should inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Eferox

Keep this medicine out of 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. This will help protect
the environment.

6. Contents of the pack and other information

What Eferox contains

• The active substance 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, breakable by pressure, with a dividing score on one side and a digital 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 box.
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 box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Aristo Pharma Sp. z o.o.
Baletowa 30 Street
02-867 Warsaw
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 in the United Kingdom (Northern Ireland) under the following names:
Austria Levothyroxin Aristo 112/125/137/175 Microgram Tablets
Germany L-Thyroxin Aristo 112/125/137/175 Microgram Tablets
Czech Republic Levothyroxine Aristo 112/125/137/175 microgram tablets
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 microgram tablets
Portugal Eferox 112/125/137/175 microgramas comprimidos
Italy Levotiroxina DOC 125 microgrammi compresse
Levotiroxina Aristo 112, 137, 175 microgrammi compresse