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. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, 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 indicated:

• for replacement therapy in all forms of hypothyroidism (thyroid hormone deficiency) or after thyroidectomy (surgical removal of the thyroid gland),
• for prevention of recurrence of goitre after surgical removal of goitre in patients with normal thyroid function,
• for treatment of 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 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 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 hormones (pituitary insufficiency and (or) adrenal cortical insufficiency);
• areas in the thyroid gland producing 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 medicines (see section 2 "Eferox with other medicines").
When switching from one medicine to another containing levothyroxine, a disturbance in thyroid function balance may occur. In case of any questions regarding switching the medicine, 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 Eferox, discuss this 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 require adjustment (see section 2 "Eferox with other medicines");
• if the patient is being treated for diabetes. The dose of antidiabetic medicine may require 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 increased levothyroxine levels in the blood, which may lead to osteoporosis (bone fragility);
• if the patient has epilepsy (epileptic seizures). During initiation of levothyroxine treatment or rapid dose increase, epileptic seizures have been reported with frequency: rarely;
• 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 a small intestine disease, as it may impair absorption of the medicine (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 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 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 elevated or falsely decreased due to biotin intake. The doctor may advise the patient to stop taking biotin before laboratory tests. It is also important to remember that other products the patient may be taking, 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 carefully and individually adjusted. The doctor should monitor such patients.
Blood tests
Before starting levothyroxine, the doctor will perform a blood test to check how much thyroxine the patient's thyroid gland produces and what dose of medicine will be needed. After starting the medicine, the doctor will recommend regular blood tests to monitor whether 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 also includes over-the-counter medicines, 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 iodinated 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:

• medicines used for epilepsy, such as: carbamazepine, phenytoin, primidone, and barbiturates
• medicines containing St. John's wort (some herbal medicines)
• sertraline, lithium – medicines used for 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 to treat 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 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 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 Eferox dose.

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

• calcium, magnesium, aluminium, iron, or lanthanum supplements
• 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 dothiepin
• 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
Products and foods containing soy or high in fiber may affect levothyroxine absorption. Therefore, the dose of levothyroxine may need to be adjusted by the treating doctor.
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 requirement 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 should be appropriately adjusted.
Even when taking high doses of levothyroxine, the amount of thyroid hormone passing into breast milk during breastfeeding is very small and therefore harmless.
During pregnancy and breastfeeding, suppression tests must not be performed.
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. In case of
doubt, consult a doctor or pharmacist.
In elderly patients, patients with ischemic heart disease, and in patients with severe
or chronic hypothyroidism, thyroid hormone therapy 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 indicates that lower doses are
also sufficient in individuals with low body weight and in patients with a large goiter.

Dosing
Tablets of Eferox with graduated strengths from 25 to 200 micrograms are available for individual treatment, meaning that in most cases only one tablet per day should 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, 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,
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 in 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 is being used.
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 yield the desired results within this period,
alternative treatment options should be considered.
Administration 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, seek immediate medical advice from a doctor,
the emergency department of the nearest hospital, or a poison control center.
Symptoms of overdose may include: restlessness, confusion, irritability, fever,
chest pain (angina), rapid or irregular heartbeat, accelerated
breathing, muscle spasms, headache, anxiety, hyperactivity,
flushing, sweating, dilated pupils, diarrhea, tremor, difficulty sleeping,
restlessness 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
the medical staff can clearly identify 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 doctor or pharmacist.
Discontinuation of Eferox treatment
For treatment to be effective, Eferox should be taken regularly at the doses prescribed by the doctor.
Under no circumstances should the prescribed treatment be changed, interrupted, or discontinued without consulting a doctor, as symptoms may recur.
If you have any further doubts regarding 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.
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 itching of the skin with raised lumps, joint pain, increased sensitivity to sunlight, general malaise (frequency unknown). The patient may require urgent medical attention.

In some patients, a severe reaction to high levels of thyroid hormone may occur. This is known as "thyroid storm". You must immediately stop taking the tablets and go to the nearest hospital if the patient experiences any of the following symptoms (frequency unknown):

• 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 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 the doctor if the patient experiences any adverse reactions. The doctor will decide whether to reduce the daily dose or temporarily discontinue the medicine for a few days. However, do not change the dose or stop taking the tablets without first consulting your doctor.
Frequency not known: frequency cannot be determined from available data

• increased appetite
• anxiety, restlessness, sleep disturbances (insomnia)
• tremor, headache, seizures
• chest pain (angina), palpitations, irregular or rapid heartbeat, heart failure, heart attack
• high blood pressure (hypertension), sudden flushing
• shortness of breath (dyspnoea)
• diarrhoea, feeling sick (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 determined from 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 skull 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, tell your doctor, pharmacist, or nurse. Adverse reactions can also be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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 authorization holder.
Reporting adverse reactions helps provide more information on the safety of this 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 and carton: EXP. The expiry date refers to the last day of the specified 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. Such measures help protect the environment.

6. Contents of the packaging 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, scored tablets divisible by hand pressure, with a dividing groove on one side and an engraved numerical code corresponding to the strength (i.e. 112, 125, 137, 175) 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 microgram tablets
Netherlands Levothyroxinenatrium Aristo 112/125/137/175 microgram tablets
Ireland Levothyroxine sodium Aristo 112/125/137/175 microgram tablets
Poland Eferox 112/125/137/175 microgram tablets
Portugal Eferox 112/125/137/175 microgram tablets
Italy Levotiroxina DOC 125 microgram tablets
Levotiroxina Aristo 112, 137, 175 microgram tablets