REANDRON 1000 mg/4 ml INJECTABLE SOLUTION

2. What you need to know before you are given Reandron

Do not use Reandron

• 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 suspect you may have prostate or breast cancer.
• if you have or have had a liver tumor;

Reandron is not indicatedfor use in women.

Warnings and precautions

Tell your doctorbefore you start using Reandron if you have or have ever had:

• epilepsy
• heart, liver, or kidney problems
• migraine
• breathing interruptions during sleep (apnea) as it may worsen with treatment
• cancer, as calcium levels in the blood should be determined
• high blood pressure or if you are being treated for high blood pressure, as testosterone may cause an increase in blood pressure.
• bleeding problems
• bleeding disorders (e.g., hemophilia)
• thrombophilia (a blood clotting abnormality that increases the risk of blood clots in blood vessels)
• factors that increase the risk of blood clots in a vein: previous blood clots in a vein, smoking, obesity, cancer, inactivity, if a close relative has had a blood clot in a leg, lung, or other organ at a young age (e.g., below 50 years of age), or as you get older.

How to recognize a blood clot: painful swelling of a leg or sudden change in skin color, for example, becoming pale, red, or blue, sudden difficulty breathing, sudden and unexplained cough that may bring up blood, or sudden chest pain, severe dizziness or fainting, severe stomach pain, sudden loss of vision. Seek urgent medical attention if you experience any of these symptoms.

If you have severe heart, liver, or kidney failure,treatment with Reandron may cause you to have serious complications in the form of fluid retention, which may occasionally be accompanied by congestive heart failure.

Before starting treatment and during treatment, your doctor will check the following parameters in your blood test: testosterone level and complete blood count.

If your liver is not working properly

No formal studies have been conducted in patients with liver failure. If you have ever had a liver tumor, you will not be prescribed Reandron (see "Do not use Reandron").

Children and adolescents

Reandron is notindicatedfor use in children and adolescents. There is no available information on the use of Reandron in males under 18 years of age.

Older people (65 years or older)

No dose adjustment is necessary if you are over 65 years old. (See "Medical examination/Follow-up").

Muscle building and doping tests

Reandron is notindicated for increasing muscle mass in healthy individuals or for increasing physical strength.

Reandron may give positive results in doping tests.

Substance abuse and dependence

Always use this medicine exactly as your doctor or pharmacist has told you.

Abuse of testosterone, especially if you take too much of this medicine alone or in combination with other anabolic androgenic steroids, can cause serious health problems with your heart and blood vessels (which can be fatal), your mental health, and/or your liver.

People who have abused testosterone may become dependent and may experience withdrawal symptoms when the dose is significantly changed or when use is suddenly stopped. Do not abuse this medicine because it can cause serious health problems, whether used alone or in combination with other anabolic androgenic steroids. (see "Possible side effects")

Medical examination / Follow-up

Male hormones can increase the growth of prostate cancer or increase the size of the prostate gland (benign prostatic hyperplasia). Before starting treatment with Reandron, your doctor should perform a medical examination to rule out the risk of existing prostate cancer.

Your doctor should carefully monitor your prostate and breasts, especially in older patients. Your doctor will also perform periodic blood tests.

Benign (non-cancerous) and malignant (cancerous) liver tumors have been reported in patients treated with hormonal products such as androgenic compounds.

Using Reandron with other medicines

Tell your doctor or pharmacistif you are using or have recently used or might use any other medicines, including those obtained without a prescription. Your doctor may need to adjust the dose if you are taking other medicines, such as:

• Adrenocorticotropic hormone (ACTH) or corticosteroids (used to treat various diseases such as rheumatism, arthritis, allergic reactions, and asthma). Reandron may increase the risk of fluid retention, especially if you have heart or liver problems.
• Medicines that make your blood more fluid (oral anticoagulants, coumarin derivatives) as they may increase the risk of bleeding. Your doctor will check your dose.
• Medicines for the treatment of diabetes. It may be necessary to adjust the dose of your antidiabetic medicine. Like other androgens, testosterone may increase the effect of insulin.

Tell your doctor if you have any coagulation disorders,as it is important for your doctor to know this information to decide whether you can be treated with Reandron.

Reandron may also affect the results of laboratory tests (e.g., thyroid gland tests). Inform your doctor or laboratory personnel that you are being treated with Reandron.

Pregnancy and breastfeeding

Reandron is not indicated for use in women and should not be used in pregnant or breastfeeding women.

Fertility

Treatment with high doses of testosterone medicines can interrupt or reduce sperm production in a reversible way (see also "Possible side effects").

Driving and using machines

No effects on the ability to drive or use machines have been observed.

Reandron contains benzyl benzoate

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

3. How to use Reandron

Your doctor will inject Reandron (1 ampoule/vial) intramuscularly, very slowly. The treatment will be repeated every 10-14 weeks, which is sufficient time to maintain testosterone levels without accumulation in the blood.

Reandron should only be administered intramuscularly. Special care should be taken not to inject the product into a blood vessel (see "Administration").

Starting treatment

Before starting treatment and during the first part of treatment, your doctor will determine your blood testosterone levels. Your doctor may give you a second injection, as early as 6 weeks after the first injection, in order to quickly reach the necessary testosterone level. This will depend on your symptoms and testosterone levels.

Maintaining Reandron levels during treatment

The interval between injections should be maintained within the recommended limit of 10 to 14 weeks. Your doctor will regularly check your testosterone levels at the end of an injection interval to ensure that the levels are correct. If the levels are too low, your doctor may increase the frequency of injections. If the levels are too high, your doctor may decrease the frequency of injections. Remember your treatment days, as otherwise your testosterone levels will not be properly controlled.

If you think the effect of Reandron is too strong or too weak, tell your doctor.

If you use more Reandron than you should

Symptoms of having received too much Reandron include:

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

Tell your doctor if you have any of the above symptoms. Your doctor will reduce the frequency of injections or stop 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 red blood cell counts
• weight gain
• hot flushes
• acne
• prostate enlargement and associated problems
• various reactions at the injection site, such as pain, bruising, or irritation

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

• allergic reaction
• increased appetite, changes in some blood test results, such as increased sugar or fat
• depression, emotional changes, insomnia, restlessness, aggression, or irritability
• headache, migraine, or tremors
• cardiovascular changes, high blood pressure, or dizziness
• bronchitis, sinusitis, cough, shortness of breath, wheezing, or voice changes
• diarrhea or nausea
• changes in liver test results
• hair loss or various skin reactions (e.g., itching, redness, or dry skin)
• joint or limb pain, muscle problems (e.g., spasms, pain, or stiffness), or increased creatine phosphokinase in the blood
• urinary tract changes (e.g., decreased urine flow, urinary retention, urgent need to urinate at night)
• prostate changes (e.g., prostatic dysplasia, hardening, or inflammation), changes in sexual desire, testicular pain, pain, hardening, or enlargement of the breasts, or increased levels of male and female hormones
• fatigue, generalized weakness, excessive sweating, or night sweats

Rare side effects(may affect up to 1 in 1,000 patients)

• The oily liquid of Reandron may reach the lungs (pulmonary microembolism of oily solutions) and in rare cases may cause signs and symptoms such as cough, shortness of breath, discomfort, excessive sweating, chest pain, dizziness, or fainting. These reactions can occur during or immediately after injection and are reversible.

Suspected anaphylactic reactions have been reported after injection of Reandron.

In addition to those mentioned above, the following side effects have been observed after treatment with testosterone-containing products: nervousness, hostility, brief interruptions of breathing during sleep (apnea), skin reactions such as dandruff and seborrhea, excessive hair growth, more frequent erections, and in very rare cases, yellowing of the skin and eyes (jaundice).

Treatment with high doses of testosterone usually interrupts or reduces sperm production, although it returns to normal after treatment is stopped. Testosterone replacement therapy in cases of low testicular function (hypogonadism) may rarely cause persistent and painful erections (priapism). Long-term or high-dose testosterone treatment may occasionally cause increased fluid retention and edema (swelling due to fluid retention).

In general, with testosterone-based medicines, a frequent 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, identified by periodic blood tests.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Agency's website: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Reandron

Keep this medicine out of the sight and reach of children.

This medicine does not require any special storage conditions.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.

Medicines should 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. Container Content and Additional Information

Reandron Composition

The active ingredient is testosterone undecanoate 250 mg/ml (corresponding to 157.9 mg of testosterone). 1 ampoule/vial contains 1,000 mg of testosterone undecanoate (which corresponds to 631.5 mg of testosterone).

The other components are: benzyl benzoate and refined castor oil.

Product Appearance and Container Content

Reandron is a clear oily solution, between colorless and light yellowish-brown. It is presented in topaz-colored glass ampoules/vials, which contain 4 ml of injectable solution.

Marketing Authorization Holder and Manufacturer

This medicinal product is authorized 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: ?????? 250 mg/ml ??????????? ???????
• Croatia: Nebido 1000 mg/4 ml otopina za injekcij
• 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: NEBIDO 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 solutie injectabila
• Slovakia: Nebido 1000 mg/4 ml injekcný 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

Date of the last revision of this leaflet:October 2022

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

--------------------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals:

At cold storage temperatures, the properties of this oily solution may change temporarily (e.g., increased viscosity, turbidity). If stored at cold temperatures, the product should be brought to room temperature or body temperature before use.

The solution for intramuscular injection should be inspected visually before use and only clear solutions free of particles should be used.

The contents of an ampoule/vial should be injected intramuscularly immediately after opening the ampoule/vial.

The medicinal product is for single use only, and any unused solution should be discarded.

Administration

Great care should be taken not to inject the medicinal product into a blood vessel.

As with all oily solutions, Reandron should be injected only intramuscularly and very slowly. Pulmonary microembolism related to oily solutions can rarely cause signs and symptoms such as cough, dyspnea, discomfort, hyperhidrosis, chest pain, dizziness, paresthesia, or syncope. These reactions can occur during or immediately after injection and are reversible. Treatment is usually supportive, e.g., administration of supplemental oxygen.

Suspected anaphylactic reactions have been reported after administration of Reandron.

Warnings

A careful regular check of the prostate and breasts should be performed according to established methods (digital rectal examination and PSA determination in serum) in patients receiving testosterone treatment, at least once a year and twice a year in elderly patients and those at risk (those with clinical or family factors).

In addition to laboratory tests to determine testosterone concentration in blood in patients undergoing long-term treatment, the following laboratory tests should be performed periodically: hemoglobin, hematocrit, liver function tests, and lipid profile.

In patients with severe heart, liver, or kidney failure or with ischemic heart disease, treatment with testosterone may cause serious complications, characterized by edema with or without congestive heart failure. In this case, treatment should be discontinued immediately.

Instructions for Opening Reandron Ampoule with "One-Point Cut" (UPC) Opening System

The ampoule has a mark below the colored point. Before opening, ensure that no solution remains in the top part of the ampoule. Use both hands to open it; hold the lower part of the ampoule with one hand and use the other hand to press outward and break the top part of the ampoule in the direction opposite the colored point.

Instructions for Opening Reandron Vial

The vial is for single use. The contents of the vial should be injected intramuscularly immediately after loading into the syringe. After removing the plastic cap (A), do not remove the metal ring (B) or the rim cap (C).