Nebido

Patient Information Leaflet

Nebido 1000 mg/4 ml, solution for injection
Testosterone undecanoate
Please read all of this leaflet carefully before using 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.
• 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 this leaflet:

1. What Nebido is and what it is used for
2. What you need to know before using Nebido
3. How to use Nebido
4. Possible side effects
5. How to store Nebido
6. Contents of the pack and other information

1. What Nebido is and what it is used for

Nebido contains testosterone undecanoate, a male hormone, as its active substance. Nebido is injected into a muscle, where it can be stored and gradually released over time. Nebido is used in adult men as testosterone replacement therapy for the treatment of various conditions caused by a lack of testosterone in the body (male hypogonadism). Diagnosis of this condition requires two separate blood tests showing low testosterone levels, together with the following clinical symptoms:

• impotence,
• infertility,
• reduced libido,
• fatigue,
• depressive mood,
• loss of bone mass due to low hormone levels.

2. Important information before using Nebido

When not to use Nebido

• if the patient is allergic (hypersensitive) to testosterone undecanoate or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has androgen-dependent cancer or suspected cancer of the prostate gland or breast;
• if the patient currently has or has previously had liver tumour.

Nebido is not intended for use in women.
Warnings and precautions
Before starting treatment with Nebido, discuss this with your doctor. You must tell your doctor if the patient has or has ever had:

• epilepsy;
• heart, kidney or liver problems;
• migraine;
• episodes of interrupted breathing during sleep (apnoea), as these may worsen;
• cancer, therefore regular monitoring of blood calcium levels may be required;
• high blood pressure or if the patient is being treated for hypertension, as testosterone may increase blood pressure;
• blood clotting disorders;
• clotting disorders (such as haemophilia);
• thrombophilia (abnormal blood clotting increasing the risk of thrombosis – formation of blood clots in blood vessels);
• factors increasing the risk of venous blood clots: previous history of venous thrombosis; smoking; obesity; cancer; immobilisation; family history of blood clots in the leg, lung or other organ at a young age (e.g. under 50 years) in a close relative; advanced age of the patient. How to recognise a blood clot: painful swelling in one leg or sudden change in skin colour, e.g. pallor, redness or blueness; sudden shortness of breath; sudden unexplained cough, possibly with coughing up of blood; sudden chest pain; severe dizziness or vertigo; severe abdominal pain; sudden loss of vision. If any of these symptoms occur, seek immediate medical help. If the patient has severe heart, liver or kidney disease, treatment with Nebido may lead to serious complications, manifesting as fluid retention and sometimes (congestive) heart failure. The following blood tests should be ordered by the doctor before and during treatment: blood testosterone levels, full blood count.

Use in patients with liver function disorders
Studies have not been conducted in patients with liver function disorders. Nebido must not be prescribed if the patient currently has or has previously had liver tumour (see section When not to use Nebido).

Use in children and adolescents
Nebido is not intended for use in children and adolescents. There are no data on the use of this medicine in males under 18 years of age.

Use in elderly patients (over 65 years of age)
There is no need to change the dosage in patients over 65 years of age (see section Medical examination/Monitoring).

Muscle development and anti-doping tests
Nebido is not suitable for accelerating muscle development in healthy individuals or for enhancing physical performance.
Nebido may give positive results in anti-doping tests.

Misuse and dependence
This medicine must always be taken according to the doctor's instructions.
Misuse of testosterone, especially when excessive doses are used alone or in combination with other anabolic androgenic steroids, may lead to serious health problems affecting the heart and blood vessels (which may result in death), mental health and/or the liver. Individuals misusing testosterone may become dependent, which may lead to withdrawal symptoms following a significant dose reduction or abrupt discontinuation. Do not misuse this medicine either alone or in combination with other anabolic androgenic steroids, as this is associated with serious health risks (see section 4 "Possible side effects").

Medical examination/Monitoring
Male hormones may accelerate the development of prostate cancer and may cause enlargement of the prostate gland (benign prostatic hyperplasia). Before administering Nebido, the doctor will examine the patient to ensure there is no prostate cancer.
The doctor will regularly examine the prostate gland and breasts, particularly in elderly patients, and will also order blood tests.
Benign (non-malignant) and malignant (cancerous) liver tumours have been observed following the use of hormonal substances such as androgens.

Nebido with other medicines
You must tell your doctor or pharmacist about all medicines currently or recently taken, including those available without a prescription. The doctor may decide to adjust doses if the following medicines are used:

• adrenocorticotropic hormone (ACTH) or corticosteroids (used in various diseases such as rheumatism, arthritis, allergy and asthma): Nebido may increase the risk of fluid retention, especially in patients with impaired heart or liver function;
• blood-thinning tablets (oral anticoagulants, coumarin derivatives), as this may increase the risk of bleeding. The doctor will review the dosage;
• medicines used to treat diabetes. Adjustment of glucose-lowering medication dosage may be necessary. Like other androgens, testosterone may enhance the effect of insulin. Concomitant use of SGLT-2 inhibitors (such as empagliflozin, dapagliflozin or canagliflozin) with testosterone may increase the number of red blood cells in the blood. The doctor may need to order blood tests more frequently.

You must inform your doctor if the patient has blood clotting disorders, as this information is important for the doctor before deciding to administer Nebido injections.
Nebido may also affect the results of certain laboratory tests (e.g. thyroid function tests). You must inform your doctor or laboratory staff that Nebido is being used.

Pregnancy and breast-feeding
Nebido is not intended for women and must not be used in pregnant or breast-feeding women.

Effect on fertility
Regular treatment with preparations containing high doses of testosterone may reversibly suppress or reduce sperm production (see also "Possible side effects").

Driving and using machines
Nebido has no influence on the ability to drive and use machines.

Nebido contains benzyl benzoate
This medicine contains 2000 mg of benzyl benzoate per ampoule/vial in 4 ml solution, equivalent to 500 mg/ml solution.

3. How to use Nebido

Your doctor will prescribe a very slow intramuscular injection of Nebido (1 ampoule/vial).
The injection will be repeated every 10 to 14 weeks. This is sufficient to maintain testosterone
concentration at an appropriate level, without causing accumulation of the hormone in the blood.
Nebido is intended for intramuscular injection only. The person administering the injection will take care
not to inject the medicine into a blood vessel; see section “Method of administration”.

Starting treatment
Your doctor will assess your blood testosterone levels before starting treatment and in the early phase of
treatment. Your doctor may prescribe the next injection after only 6 weeks in order to rapidly achieve an
appropriate testosterone level. This will depend on your symptoms and testosterone concentrations.

Maintaining Nebido levels during treatment
The intervals between injections should remain within the recommended period of 10 to 14 weeks.
Your doctor will regularly check your blood testosterone levels towards the end of the interval between
injections to ensure they are correct. If the level is too low, your doctor may decide to administer the
medicine more frequently. If the level is too high, your doctor may decide to administer the medicine less
frequently. It is important to attend every scheduled injection appointment. Otherwise, optimal
testosterone levels cannot be maintained.
If you feel that the effect of Nebido is too strong or too weak, consult your doctor.

Use of a higher than recommended dose of Nebido
Symptoms of using a higher than recommended dose of Nebido may include:

• irritability,
• nervousness,
• increased body weight,
• prolonged or frequent erections.

If any of the above symptoms occur, consult your doctor. Your doctor may decide to administer
injections less frequently or discontinue treatment.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although they do not occur in everyone.
The most commonly occurring adverse reactions are acne and pain at the injection site.
Common adverse reactions (may occur in up to 1 in 10 patients):

• increased number of red blood cells;
• weight gain;
• hot flushes;
• acne;
• enlargement of the prostate gland and related problems;
• various reactions at the injection site (e.g. pain, bruising or irritation).

Uncommon adverse reactions (may occur in up to 1 in 100 patients):

• allergic reactions;
• increased appetite, changes in blood test results (e.g. increased blood sugar or fat levels);
• depression, emotional disturbances, insomnia, anxiety, aggression or irritability;
• headache, migraine or tremor;
• cardiovascular disorders, high blood pressure or dizziness;
• bronchitis, sinusitis, cough, shortness of breath, snoring or voice problems;
• diarrhoea, nausea;
• changes in liver function test results;
• hair loss or various skin reactions (e.g. itching, redness or dryness of the skin);
• joint pain, limb pain, muscle problems (e.g. cramps, pain or stiffness) or increased creatine phosphokinase activity in the blood;
• urinary disorders (e.g. reduced urine flow, urinary retention, need to urinate at night);
• prostate disorders (e.g. prostate dysplasia, sclerosis or prostatitis), changes in libido, testicular pain, pain, hardness or enlargement of the breasts or increased concentration of male and female sex hormones;
• fatigue, general weakness, excessive sweating or night sweats.

Rare adverse reactions (may occur in up to 1 in 1000 patients):

• The oil-based Nebido solution may enter the lungs (pulmonary oil microembolism), which rarely may lead to symptoms such as cough, shortness of breath, general malaise, excessive sweating, chest pain, dizziness, tingling or numbness, or fainting. These reactions may occur during or immediately after injection and are transient. Each patient should be observed during and immediately after each injection to enable early detection of objective and subjective symptoms that may indicate pulmonary oil microembolism.

Anaphylactic reactions have been observed following administration of Nebido.
With other testosterone-containing medicines, in addition to the adverse reactions listed above, the following have also been reported: nervousness, hostility, periodic breathing interruptions during sleep, various skin reactions including dandruff and oily skin, accelerated hair growth, more frequent erections, and very rarely yellowing of the skin and eyes (jaundice).
The use of high doses of testosterone often leads to suppression or reduction of sperm production in the body. These symptoms resolve after discontinuation of treatment. Testosterone replacement therapy in the treatment of impaired testicular function (hypogonadism) may rarely cause prolonged, painful erections (priapism). High doses or long-term administration of testosterone may occasionally lead to fluid retention and the development of oedema (swelling due to fluid retention).
The use of testosterone-containing products may be associated with a general risk of increased red blood cell count, haematocrit (percentage of red blood cells in the blood), and haemoglobin concentration (the oxygen-carrying component of red blood cells), as observed in periodic blood analyses.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, please inform your doctor or pharmacist. 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.: +48 22 4921301, fax: +48 22 4921309, website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
By reporting adverse reactions, additional information on the safety of this medicine can be collected.

5. How to store Nebido

Keep this medicine out of the sight and reach of children.
No special precautions for storage of the medicinal product.
Do not use this medicine after the expiry date stated on the carton and label following:
"Expiry date". The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Nebido contains
The active substance is testosterone undecylate 250 mg/ml (equivalent to 157.9 mg of testosterone).
One ampoule/vial contains 1000 mg of testosterone undecylate (equivalent to 631.5 mg of testosterone).
Additionally, the medicinal product contains: benzyl benzoate and refined castor oil.

What Nebido looks like and contents of the pack
Nebido is a clear, colourless to yellowish-brown oily solution.
The pack contains:
1 brown glass ampoule / brown glass vial with 4 ml of solution for injection.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Grünenthal Pharmaceuticals GmbH & Co. KG
Philipp-Ott-Strasse, 51373 Leverkusen, Germany

Manufacturers
Bayer AG
Müllerstrasse 178
D-13353 Berlin
Germany
or
EVER Pharma Jena GmbH
Brüsseler Strasse 18
07747 Jena
Germany
or
Grünenthal GmbH
Zieglerstrasse 6
52078 Aachen, Germany
or
Grünenthal Pharmaceuticals GmbH & Co. KG
Philipp-Ott-Straße 3
51373 Leverkusen, Germany

This medicinal product is authorised for marketing in the Member States of the European Economic Area under the following names:

• Cyprus, Czech Republic, Greece, Denmark, Luxembourg, Malta, Poland, and Portugal: Nebido
• Austria: Nebido 1000 mg/4 ml Injektionslösung
• Belgium: Nebido 1000 mg/4 ml, oplossing voor injectie
• Bulgaria: Небидо 250 mg/ml инжекционен разтвор
• Croatia: Nebido 1000 mg/4, ml otopina za injekciju
• Finland: Nebido 1000 mg/4 ml injektioneste, liuos
• France: Nebido 1000 mg/4 ml, solution injectable
• Germany: Nebido 1000 mg Injektionslösung
• Hungary: Nebido 250 mg/ml oldatos injekció
• Iceland: Nebido 1000 mg/4 ml stungulyf, lausn
• Italy: NEBID 1000 mg/4ml soluzione iniettabile
• Lithuania: Nebido 1000 mg/4 ml injekcinis tirpalas
• Netherlands: Nebido 1000 mg/4 ml
• Norway: Nebido 1000 mg/4 ml injeksjonsvæske, oppløsning
• Romania: Nebido 1000 mg/ 4 ml soluţie injectabilă
• Slovakia: Nebido 1000 mg/4 ml injekčný roztok
• Slovenia: Nebido 1000 mg/4 ml raztopina za injiciranje
• Spain: REANDRON 1000 MG/ 4 ML SOLUCIÓN INYECTABLE
• Sweden: Nebido, 1000 mg/4 ml injektionsvätska, lösning
• United Kingdom and Ireland: Nebido 1000mg/4ml, solution for injection

The following information is intended for healthcare professionals only:

During storage at low temperatures, the properties of this oil-based solution may temporarily change (e.g. increased viscosity, cloudiness). If the medicine has been stored at low temperatures, it should be brought to room temperature or body temperature before use.
The solution for intramuscular injection should be visually inspected before use; only solutions free from solid particles should be used.
The contents of the ampoule/vial must be administered intramuscularly immediately after opening.
Nebido is intended for single use only; any unused solution must be discarded.

Method of administration:
Extreme caution must be taken to avoid intravascular injection.
Like all oily solutions, Nebido must be administered intramuscularly and very slowly.
Pulmonary microemboli caused by oily solutions may rarely lead to symptoms such as: cough, dyspnea, malaise, excessive sweating, chest pain, dizziness, paresthesia, or fainting. These reactions may occur during or immediately after injection and are usually reversible. Treatment is typically supportive, e.g. by administering supplemental oxygen.
Anaphylactic reactions have been observed following administration of Nebido.

Warnings:
In patients treated with testosterone, careful and regular examinations of the prostate and breasts should be performed in accordance with recommended guidelines (digital rectal examination, PSA measurement). These examinations should be carried out at least once a year, and in elderly patients or those with increased risk (clinical and familial factors), twice a year.
In addition to laboratory measurements of testosterone concentrations, the following laboratory parameters should be periodically monitored in patients undergoing long-term androgen therapy: hemoglobin, hematocrit, liver function tests, and lipid profile.
In patients with severe heart, liver, or renal failure, or with ischemic heart disease, testosterone treatment may cause serious complications in the form of edema, with or without congestive heart failure. In such cases, treatment must be discontinued immediately.

Instructions for preparing/opening the OPC (One-Point-Cut) ampoule:
The ampoule has a scored line below the colored dot, which eliminates the need for scoring the neck. Before opening, ensure that the solution has flowed from the upper part of the ampoule to the lower part. To open, use both hands: hold the lower part of the ampoule with one hand and snap off the top part in the direction opposite to the colored dot.

Instructions for preparing the vial:
The vial is intended for single use only. The contents should be administered intramuscularly immediately after withdrawal into a syringe. After removing the plastic cap (A), do not remove the metal ring (B) or the flanged neck (C).