Eferox

Package leaflet: Information for the patient

Eferox, 100 micrograms, tablets
Levothyroxinum natricum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, 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

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 in the body by the thyroid gland. 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 of thyroid hormone in all forms of hypothyroidism or after thyroidectomy,
• for prevention of goitre recurrence after goitre removal in patients with normal thyroid function,
• for treatment of mild (benign) goitre in patients with normal thyroid function,
• as combination therapy with antithyroid drugs in hyperthyroidism, after achieving normal thyroid metabolic status,
• in malignant thyroid cancers, particularly after surgical procedures, to suppress tumour growth and to replace deficient thyroid hormone,
• in thyroid function suppression tests.

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 together with other antithyroid drugs (thyroid-suppressing medications).

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) 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 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 drugs (see section 2 "Eferox with other medicines").

When switching from one medicine to another containing levothyroxine, thyroid function imbalance may occur. 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 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 suffered a heart attack;
• if the patient is taking anticoagulant drugs (e.g. phenprocoumon). The dose of this drug may need to be adjusted (see section 2 "Eferox with other medicines");
• if the patient is being treated for diabetes. The dose of antidiabetic medication may need to be adjusted, 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 (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; appropriate treatment is required before starting Eferox;
• 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 reduced due to biotin intake. The doctor may advise the patient to stop taking biotin before laboratory testing. Also note 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 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 experiences symptoms of psychotic disorders.
When starting levothyroxine treatment in premature 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 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 an imaging test 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 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 to treat certain types of cancer
• beta-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 male hormone replacement therapy
• 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 drugs 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 to treat 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 to treat gastric ulcer.

Eferox may affect the action of the following medicines:

• anticoagulant drugs preventing blood clots, 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
Soy-containing products and high-fiber foods may affect levothyroxine absorption. Therefore, the doctor 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 become pregnant, she should consult her doctor or pharmacist before using this medicine.
Continuous thyroid hormone therapy 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 estrogen (female sex hormone) levels in the blood. Therefore, thyroid function should be monitored both 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.
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 according to the doctor's or pharmacist's instructions.
If in doubt, consult your 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 shows that
lower doses are also sufficient in patients 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 individualized
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 tablet splitting

Place the tablet on a hard, flat surface
with the dividing groove facing upwards. To split the tablet,
press directly in the centre 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 life.
In supportive therapy for hyperthyroidism, Eferox should be taken for as long as antithyroid (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.
To perform thyroid function suppression tests, 150 or 200 micrograms of Eferox should be taken daily for 14 days.
Taking more Eferox than recommended
If a patient (or another person) has swallowed more tablets than intended, or if there is suspicion that a child has ingested any amount of tablets, contact a doctor,
the emergency department of the nearest hospital, or a poison control centre 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, diarrhoea, 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 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.
Stopping 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 doctor, as symptoms may otherwise return.
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 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, 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". 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 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 any adverse reactions occur. The doctor will decide whether to reduce the daily dose or temporarily discontinue treatment for a few days. However, do not change the dose or stop taking the tablets without first consulting your doctor.
Frequency unknown: frequency cannot be estimated from the available data

• increased appetite
• anxiety, restlessness, difficulty sleeping (insomnia)
• tremor, headache, seizures
• chest pain (angina pectoris), palpitations, irregular or rapid heartbeat, 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 a tumour or other diseases (benign intracranial hypertension).

Frequency unknown: frequency cannot be estimated from the available data

• slowed or halted 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 the medicine 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 and the cardboard
package 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 will help
protect the environment.

6. Contents of the pack and other information

What Eferox contains

• The active substance is levothyroxine sodium anhydrous.

Eferox 100 micrograms tablets
Each tablet contains 100 micrograms of levothyroxine sodium.

• The other ingredients are: microcrystalline cellulose, maize starch, heavy magnesium oxide, 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 which can be divided by applying pressure, with a dividing groove on one side and an embossed numerical code corresponding to the strength (i.e. 100) on the other side. The tablets have a diameter of approximately 7 mm and a height of approximately 3 mm.
Eferox 100 microgram tablets are available in blister packs containing 15, 20, 25, 30, 50, 60, 84, 90 and 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
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 100 Mikrogramm Tabletten
Germany L-Thyroxin Aristo 100 Mikrogramm Tabletten
Czech Republic Levothyroxine Aristo 100 mikrogramů tablety
Finland Levothyroxine Aristo 100 mikrog tablettia
Spain Levotiroxina Aristo 100 microgramos comprimidos EFG
Netherlands Levothyroxinenatrium Aristo 100 microgram tabletten
Ireland Levothyroxine sodium Aristo 100 microgram tablets
Poland Eferox 100 microgram tablets
Portugal Eferox 100 microgramas comprimidos
Sweden Levothyroxine Aristo 100 mikrogram tabletter
Italy Levotiroxina DOC 100 mikrogrammi compresse