NEBID 1000 mg /4 Ml Injectable Solution

Зміст інструкції

1. NEBID 1000 mg/4 ml injectable solution
   1. What is Nebid and what is it used for
   2. What you need to know before using Nebid
   3. How to use Nebid
   4. Possible side effects
   5. How to store Nebid
   6. Contents of the pack and other information

Procedure: Transfer of ownership from Bayer to Grunenthal Srl

AIFA/Silenzio Assenso approval date: Official Gazette n° XX of dd/mm/yyyy

NEBID 1000 mg/4 ml injectable solution

Testosterone undecanoate

contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What is Nebid and what is it used for

Nebid contains testosterone as its active ingredient, a male hormone. Nebid is injected into a
muscle, where it remains stored and from which it is gradually released over a certain period of
time. Nebid is used to replace testosterone in adult men, for the treatment of various
health problems due to testosterone deficiency (male hypogonadism). This condition
must be confirmed with two distinct testosterone measurements in the blood and must include
clinical symptoms such as:

• impotence
• infertility
• low libido
• fatigue
• depressed mood
• loss of bone tissue due to low hormone levels

2. What you need to know before using Nebid

DO NOT use Nebid:

• if you are allergic to testosterone undecanoate or any of the other ingredients of this medicine (listed in section 6).
• if you have androgen-dependent cancer, or suspected cancer, of the prostate or the mammary gland.
• if you have or have had a liver tumor.

Nebid is notintended for use in women.

Warnings and precautions
Talk to your doctorbefore using Nebid if you suffer from or have suffered in the past from:

• epilepsy
• heart, kidney or liver problems
• migraine
• temporary interruptions of breathing during sleep (sleep apnoea), because they may worsen
• cancer, because it may be necessary to regularly check the level of calcium in the blood
• high blood pressure or if you are being treated for high blood pressure, as testosterone may cause an increase in blood pressure.
• blood coagulation disorders
• bleeding disorders (i.e. haemophilia)
• thrombophilia (an abnormality of blood coagulation that increases the risk of thrombosis - blood clots in the veins)
• factors that increase the risk of blood clots in a vein: previous blood clots in a vein; smoking; obesity; cancer; inactivity; if one of your close relatives has had a blood clot in a leg, a lung or other organ at a young age (e.g. under about 50 years of age); or with advancing age.

How to recognise a blood clot: painful swelling of a leg or a sudden change in the
skin colour, for example becoming pale, red or blue, sudden shortness of breath, sudden unexplained
coughing up blood; or sudden chest pain, severe dizziness or lightheadedness, severe stomach pain, sudden loss of vision. Seek immediate medical attention if you experience any of these symptoms.

If you suffer from severe heart, liver or kidney disease, treatment with Nebid may
cause serious complications in the form of fluid accumulation in the body, sometimes accompanied by
heart failure (congestion).
Before and during treatment, the doctor must perform the following blood tests: testosterone levels in the blood, complete blood count.

If you have liver problems
Formal studies have not been conducted in patients with impaired liver function. You will not
be prescribed Nebid if you have suffered from liver cancer (see “Do not use Nebid”).

Children and adolescents
Nebid must notbe used in children and adolescents. There are no data available on the use of
Nebid in male patients under 18 years of age.

Elderly patients (65 years and over)
If you are over 65 years of age, your doctor does not need to adjust your dosage (see “Medical examinations/

checks”)

Muscle development and anti-doping tests
Nebid is notindicated to promote muscle development in healthy subjects or to improve
physical performance.

Misuse of the medicine and dependence
Always take the medicine exactly as your doctor or pharmacist has told you.
Abuse of testosterone, especially if you take too much on your own or with other anabolic androgenic steroids, can cause serious health problems with the heart and blood vessels (which can be
fatal), mental health and/or the liver.
Individuals who have abused testosterone may develop dependence and may experience
withdrawal symptoms when the dosage is changed significantly or stopped abruptly. Do not
abuse this medicine on your own or with other anabolic androgenic steroids as it causes
serious health risks. (see “Possible side effects”).

Doping
For athletes: the use of the drug without therapeutic need constitutes doping and may
still result in a positive anti-doping test.

Medical examinations/checks
Male hormones can promote the growth of prostate cancer and enlarged prostate gland (benign prostatic hyperplasia). Before injecting Nebid, your doctor will examine you to ensure you do not have prostate cancer.
Your doctor will subject you to regular checks of the prostate and mammary glands, especially if
you are elderly. They will also subject you to regular blood tests.
Following the use of hormonal substances such as androgenic compounds, the onset of
benign (non-cancerous) and malignant (cancerous) liver tumors has been observed.

Other medicines and Nebid
Tell your doctor or pharmacistif you are taking or have recently taken or might take

any other medicines, including those available without a prescription.
It is possible that the doctor may need to adjust your dosage if you are using any of the following medicines:

• the hormone ACTH or corticosteroids (used to treat various conditions, such as rheumatism, arthritis, allergies and asthma): Nebid may increase the risk of fluid retention, especially if your heart and liver are not functioning well
• tablets to thin the blood (coumarin derivatives, oral anticoagulants) as this may increase the risk of bleeding. The doctor will check your dosage.
• Medicines used to treat diabetes. It may be necessary to adjust the dosage of your medicine to lower blood sugar. Like other androgens, testosterone can increase the effect of insulin.

Please make sure to inform your doctor if you have a blood clotting disorder, because it
is important that the doctor knows this before deciding to inject Nebid.
Nebid may also affect the results of certain laboratory tests (e.g. those for the thyroid). Tell
your doctor or laboratory personnel that you are using Nebid.

Pregnancy and breastfeeding
The use of Nebid is not indicated in women and the medicine must not be used during pregnancy or
breastfeeding.

Fertility
Treatment with high doses of testosterone-based preparations usually can reversibly block or
reduce sperm production (see also “Possible side effects”).

Driving and using machines
Nebid has no known effects on the ability to drive vehicles or operate machinery.

Nebid contains benzyl benzoate
This medicine contains 2000 mg of benzyl benzoate in each vial/ampoule of 4 ml equivalent to
500mg/ml.

3. How to use Nebid

Your doctor will inject Nebid (1 vial/ ampoule) very slowly into a muscle. You will receive an
injection every 10-14 weeks. This frequency allows maintaining sufficient levels of
testosterone without leading to an accumulation of testosterone in the blood.
Nebid must be strictly administered by intramuscular injection.
Particular attention will be paid to avoiding injecting the medicine into a blood vessel (see
“ Administration”).

Start of treatment
Before starting treatment, and in its early stages, your doctor will measure your testosterone levels in
your blood. Your doctor may give you the second injection after only six weeks, in order to quickly
reach the necessary testosterone level. This will depend on your symptoms and your initial
testosterone levels.

Maintaining Nebid levels during treatment
The interval between injections must always remain between 10 and 14 weeks, as
recommended.
Your doctor will regularly measure your testosterone levels at the end of an interval between one
injection and the next, to ensure they are correct. If the values found are too low, your doctor may
decide to increase the frequency of injections. If, conversely, the values are high, your doctor may
decide to decrease the frequency of injections. Do not miss your injection appointments,
otherwise it will not be possible to maintain optimal testosterone levels.
If you think that the effect of Nebid is too strong or too weak, talk to your doctor.

If you use more Nebid than you should
The symptoms of an overdose of Nebid are:

• irritability
• nervousness
• weight gain
• prolonged or frequent erections

Inform your doctor if you experience any of these symptoms. Your doctor will space out the injections or
stop the treatment.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The most common side effectsare acne and pain at the injection site.

Common side effects(may affect up to 1 in 10 people):

• abnormally high levels of red blood cells
• weight gain
• hot flushes
• acne
• enlarged prostate and associated disorders
• various reactions at the injection site (e.g. pain, bruising or irritation)

Uncommon side effects(may affect up to 1 in 100 people):

• allergic reaction
• increased appetite, changes in some blood tests (e.g. increased sugar or fats in the blood)
• depression, emotional disturbances, insomnia, restlessness, aggressiveness, irritability
• headache, migraine, tremor
• cardiovascular disorders, high blood pressure, dizziness
• bronchitis, sinusitis, cough, shortness of breath, snoring, changes in voice
• diarrhoea, nausea
• changes in liver function tests
• hair loss, various skin reactions (e.g. itching, redness or dry skin)
• joint pain, pain in the extremities, muscle problems (e.g. spasm, pain or stiffness), or an increase in creatine phosphokinase in the blood
• urinary disorders (e.g. decreased urine flow, urinary retention, need to urinate at night)
• prostate disorders (e.g. prostate dysplasia, hardening or inflammation of the prostate), changes in sexual desire, testicular pain, pain hardening or enlargement of the breasts, increased levels of male and female hormones
• fatigue, general feeling of weakness, excessive sweating, night sweats

Rare side effects(may affect up to 1 in 1000 people):

• Nebid, which is an oily liquid, can reach the lungs (pulmonary microembolism of oily solutions) and this, in rare cases, can lead to signs and symptoms such as cough, dyspnea, general malaise, excessive sweating, chest pain, dizziness, tingling or fainting. These reactions can occur during or immediately after the injection and are reversible.

Cases of suspected anaphylactic reaction have been reported after Nebid injection.
In addition to those listed above, the following side effects have been reported following treatment with preparations containing testosterone: nervousness, hostility, brief interruptions of breathing during
sleep, various skin reactions, including dandruff and oily skin, increased hair growth, more frequent erections and
very rare cases of yellowing of the skin and eyes (jaundice).
Commonly, treatment with testosterone preparations at high doses stops or reduces
sperm production, even if this returns to normal after discontinuation of treatment. Testosterone replacement therapy for reduced testicular function (hypogonadism) can cause, in
rare cases, persistent and painful erections (priapism). The administration of testosterone at high doses or
for prolonged periods may occasionally lead to more frequent manifestations of fluid retention
and edema (swelling due to fluid retention).
For testosterone-containing products in general, a common risk of increased
red blood cell count, hematocrit (percentage of red blood cells in the blood) and hemoglobin (the
component of red blood cells that carries oxygen) has been observed, highlighted by periodic blood tests.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through
the national reporting system at https://www.aifa.gov.it/content/segnalazioni-
reazioni-avverse . By reporting side effects you can help provide more
information on the safety of this medicine.

5. How to store Nebid

Keep this medicine out of the sight and reach of children.
This medicine does not require any particular storage conditions.

Do not usethis medicine after the expiry date which is stated on the carton and the label after
“Exp”. The expiry date refers to the last day of that month.

Do not dispose ofany medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Nebid contains
The active ingredient is testosterone undecanoate 250 mg/ml (corresponding to 157.9 mg of testosterone).
One vial/bottle contains 1000 mg of testosterone undecanoate (corresponding to 631.5 mg of
testosterone).
The other ingredients are benzyl benzoate and refined castor oil.

Description of the appearance of Nebid and contents of the pack
Nebid is a clear, oily liquid, from colourless to yellowish-brown. The pack contains:
1 brown glass vial/1 brown glass bottle containing 4 ml of injectable solution.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
GRÜNENTHAL ITALIA S.r.l.
Via Vittor Pisani 16 - 20124 Milan
Manufacturer
Bayer AG
13342 Berlin
Germany

This medicinal product is authorised in the Member States of the EEA with the following denominations:

• Cyprus, Czech Republic, Greece, Denmark, Estonia, Latvia, Luxembourg, Malta, Poland and Portugal: Nebido
• Austria: Nebido 1000 mg/4 ml Injektionslösung
• Belgium: Nebido 1000 mg/4 ml, solution for injection
• 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 injekcióIceland: Nebido 1000 mg/4 ml stungulyf, lausn
• Italy: NEBID 1000 mg/4ml soluzione iniettabileLithuania: Nebido 1000 mg/4 ml injekcinis tirpalas
• Netherlands: Nebido 1000 mg/4 mlNorway: 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

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The following information is intended exclusively for healthcare professionals:
Under conditions of storage at low temperatures, the properties of this oil-based solution
may temporarily change (e.g. increased viscosity, turbidity). If stored at low
temperature, the product must be brought to room or body temperature before use.
The injectable solution for intramuscular use must be visually inspected before use;
only clear solutions free from particulate matter must be used.
The contents of one vial/bottle must be injected intramuscularly immediately after opening
the vial/bottle.
The medicine is for single use only; any unused solution must be discarded.
Administration:
Take particular care to avoid intravascular injection.
Like all oily solutions, Nebid must be injected strictly intramuscularly and
very slowly. The formation of pulmonary microemboli of oily solutions can, in rare cases, give
rise to signs and symptoms such as cough, dyspnoea, malaise, hyperhidrosis, chest pain, a feeling of instability,
paresthesia or syncope. These reactions can occur during or immediately after the injection and are
reversible. Treatment is usually supportive, consisting, for example, in the administration of
oxygen.
Cases of suspected anaphylactic reaction have been reported following the injection of Nebid.
Warning:
Patients taking testosterone therapy must be subject to careful and regular monitoring of the
prostate gland (rectal examination and serum PSA determination) and breasts, according to recommended methods, at least once a year and twice a year for elderly patients and those at risk (those with clinical or family history).
In patients undergoing long-term androgen therapy, in addition to laboratory tests relating
to testosterone concentration, the following laboratory parameters must be checked periodically: haemoglobin, haematocrit and liver function tests and lipid profile.
In patients with severe heart, liver or kidney failure or ischaemic heart disease, treatment with testosterone may induce serious complications, characterised by oedema with or without
congestive heart failure. In such cases, treatment must be discontinued immediately.

Notes on handling the OPC (One-Point Cut) vial:
Below the coloured point, the vial has a pre-score, which eliminates the need to use
a saw for opening it. Before opening, make sure that any solution present
in the upper part of the vial has flowed into the lower part. Use both hands to open;
holding the lower part of the vial with one hand, detach the upper part with the other, in the direction
opposite the coloured point.

Notes on handling the bottle:
The bottle is for single use. The contents of the bottle must be injected intramuscularly immediately
after aspiration into the syringe. After removing the plastic cap (A), do not remove
the metal ring (B) or the screw cap (C).