Package Insert: Information for the User

Leptoprol Trimestral 5 mg Preloaded Syringe Implant

leuprorelin acetate

Read this package insert carefully before starting to use this medication, as it contains important information for you.

-Keep this package insert, as you may need to refer to it again.

-If you have any questions, consult your doctor, pharmacist, or nurse.

-This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

1.What is Leptoprol Trimestral and what is it used for

2.What you need to knowbefore starting to useLeptoprol Trimestral

3.How to use Leptoprol Trimestral

4.Possible adverse effects

5.StorageofLeptoprol Trimestral

6.Contents of the package and additional information

The active ingredient of Leptoprol Trimestral (leuprorelin acetate) belongs to the group of inhibitors of certain sex hormones.

Leuprorelin acts on the pituitary gland, stimulating it briefly and stopping the production of hormones that control the production of sex hormones in the testicles.

This means that the concentration of sex hormones decreases and, with continued administration, remains at that level. After the interruption of treatment with leuprorelin, the concentration of sex hormones and pituitary hormones returns to normal values.

Leptoprol Trimestral is used for the symptomatic treatment of advanced hormone-dependent prostate cancer in adult males (prostate carcinoma).

Leptoprol Trimestral is also used for the treatment of locally advanced and localized hormone-dependent prostate tumors in combination with or after radiation therapy.

No use Leptoprol Trimestral:

-if you areallergicto leuprorelina or any of the other components of this medication (listed in section 6),

-if you are allergic to substances similar to leuprorelina, such as goserelina or buserelina,

-if your cancer is not hormone-sensitive,

-if you are a woman or a child.

Warnings and Precautions

Consult your doctor,or nurse before starting to use Leptoprol Trimestral if:

• you have high blood pressure. In this case, your doctor will monitor you regularly,
• if you have had your testicles surgically removed. In this case, leuprorelina does not produce any additional decrease in the concentration of male sex hormones in the blood,
• if you have had symptoms in the nervous system (back pressure, metastases in the spine) or urinary difficulties due to displacement of the urinary tract. You must inform your doctor immediately: he will examine you thoroughly in the first weeks, if possible in a hospital,
• if the symptoms of the disease return (such as pain, difficulty urinating, or weakness in the legs with prolonged use of leuprorelina). In this case, your doctor will analyze the success of the treatment regularly through clinical examinations (digital rectal examination of the prostate, scanner) and analyzing blood values (alkaline phosphatase and prostate-specific antigen (PSA) and male sex hormone (testosterone)),
• if there is a risk of developing osteoporosis. Your doctor will provide additional medication when possible, to prevent bone loss,
• if you have diabetes. In this case, your doctor will perform regular checks,
• you have fatty liver (a condition where excess fat accumulates in the liver).

Immediately contact your doctor if you experience intense or recurring headaches, visual problems, and tinnitus or buzzing.

Cases of depression have been reported in patients treated with leuprorelina, which can be severe. If you are using leuprorelina and develop depression, inform your doctor.

Inform your doctor if you have any of the following problems: blood vessel or heart problems, including arrhythmia, or if you are being treated with medications for these problems. The risk of arrhythmia may be increased when using leuprorelina.

Severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/NET), have been reported in association with leuprorelina. Discontinue the use of leuprorelina and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Important Information for Athletes

Warning to athletes: this medication contains a component that may result in a positive analytical control for doping.

Other Medications and Leptoprol TrimestralInform your doctor, pharmacist, or nurse if you are using,have used recentlyor may need to use any other medication.

Leuprorelina may interfere with some medications used to treat heart rhythm problems (e.g., quinidine, procainamide, amiodarone, and sotalol) or may increase the risk of heart rhythm problems when used with other medications (e.g., methadone (used to relieve pain and as part of addiction treatment), moxifloxacino (an antibiotic), and antipsychotics used for severe diseases).

Children and Adolescents

Leuprorelina is only indicated for adult patients.

Pregnancy and Breastfeeding

Leuprorelina is only indicated for male patients.

Driving and Operating Machines

This medication and the tumor disease may causefatigue. This is more frequent with alcohol use.

Thereforedo not drive or operate machineswithout your doctor's consentif this applies to you.

Use of Leptoprol Trimestral

• Clean the area where the implant will be injected.
• An anesthetic can be applied locally to alleviate the pain of the implant injection.
• Inject Leptoprol Trimestral under the skin (subcutaneously) in the abdominal area.
• Leptoprol Trimestral should only be administered by your doctor or nurse. They will be responsible for preparing the product.

How much should be administered

The recommended dose is 1 implant of Leptoprol Trimestral with 5 mg of leuprorelina every 3 months.

• Follow your doctor's warnings about when to use Leptoprol Trimestral and the time between each injection.
• Leptoprol Trimestral injections will be applied every 3 months. In exceptional cases, if the next injection is delayed up to 4 weeks, the therapeutic effect is usually not affected.
• Inject the contents of a pre-loaded syringe.
• The syringe contains an implant with a dose of 5 mg of leuprorelina.

Blood tests

Your doctor will need to perform regular blood tests to check the effect of this medication. After 3 months of treatment, your doctor will usually inform you if your prostate cancer is treatable with leuprorelina. Your doctor should also analyze the prostate-specific antigen (PSA) and testosterone levels.

Treatment duration

This will be decided by your doctor. Treatment should be continued, even if the symptoms related to the cancer have decreased or the cancer has improved.

Prostate cancer can be treated with this medication for several years. Therefore, if it is effective and you can tolerate it, it can be used continuously. Your doctor will perform regular analyses to evaluate the treatment, particularly if symptoms recur, such as:

- Pain

- Difficulty urinating

- Weakness in the legs

If you use more Leptoprol Trimestral than you should

It is unlikely that your doctor or nurse will administer too much medication.

If you accidentally receive too much, your doctor will monitor you and, if necessary, provide appropriate treatment.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 02, indicating the medication and the amount ingested.

If you forget to use Leptoprol Trimestral

Discuss this with your doctor if you think your quarterly dose of leuprorelina has been forgotten.

If you interrupt treatment with Leptoprol Trimestral

If treatment is interrupted without your doctor's consent, symptoms associated with your disease may worsen.

Treatment should not be interrupted prematurely without your doctor's consent.

If you have any other questions about the use of this medication, consult your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Contact your doctor or go immediately to the nearest hospital if you experience the following severe side effects:

• allergic reactions (anaphylactic reactions). Symptoms may include:
• the sudden appearance of: a feeling of heat, rash, itching, or hives on the skin and/or mucous membranes,
• inflammation of the face, lips, or tongue, or other parts of the body,
• shortness of breath, wheezing, or difficulty breathing,
• low blood pressure, rapid pulse, seizures, and in severe cases,
• cardiovascular system failure with mortal danger,
• inflammation and pain in a part of the bodydue to a blood clot in a vein,
• difficulty breathing, chest pain, fainting, rapid heart rate, blue skin discoloration
• and discolorationdue to a blood clot in the lungs.

Uncommon side effects (may affect up to 1 in 1,000 people)

There is initially a short-term increase in male sex hormones (testosterone) in the blood.

As a result, the following disease-related symptoms may temporarily worsen:

• appearance or increase in bone pain,
• difficulty urinating due to displacement of the urinary tract,
• pressure on the spine,
• weakness in the legs,
• inflammation due to the appearance of fluid in the tissues impeding circulation
• (lymphatic edema).

This increase in symptoms usually subsides after the treatment with this medicine is discontinued.

At the beginning of treatment, the administration of an antagonist (anti-androgen) of male sex hormones should be considered to minimize the possible consequences of the initial increase in male sex hormones.

During treatment, male sex hormones fall to very low levels. As a consequence, in certain patients, the following side effects may occur:

Very common:may affect more than 1 in 10 people

• hot flashes,
• increased sweating,
• bone pain,
• reduced or lost libido and sexual potency,
• reduction in testicle size,
• weight gain,
• local reactions in the skin, such as redness or induration, pain, swelling, and
• itching at the injection site, which usually subsides when treatment continues; in isolated cases, abscesses have appeared.

Common:may affect up to 1 in 10 people

• male breast enlargement,
• decreased appetite,
• increased appetite,
• depression, mood changes,
• sleep disturbances,
• headaches,
• strange sensations such as tingling and/or numbness,
• nausea/vomiting,
• back or joint pain,
• muscle weakness,
• increased need to urinate at night,
• excessive frequency of the need to urinate during the day,
• difficulty and pain urinating,
• fatigue,
• inflammation of the ankles, feet, or toes (peripheral edema),
• weight loss,
• increase in liver enzyme levels in the blood (ALT, AST, gamma-GT) and other enzymes (LDH, alkaline phosphatase).

Uncommon:may affect up to 1 in 100 people

• general allergic reactions such as fever, itching, increased eosinophilic blood cells, skin rash,
• diarrhea,
• dry skin or mucous membranes,
• testicular pain,
• inability to empty the bladder spontaneously,
• increased nocturnal sweating.

Rare:may affect up to 1 in 1,000 people

• increase or decrease in blood sugar levels,
• dizziness,
• temporary changes in taste,
• increase or decrease in blood pressure,
• hair loss.

Very rare: may affect up to 1 in 10,000 people

• like with other medicines in this class of substances: pituitary infarction after the first administration in patients with pituitary tumor.

Frequency notknown:the frequencycannot be estimated from the available data

• non-infectious lung disease (pneumonia) (mainly reported in Japan),
• in isolated cases, an abscess has appeared at the injection site,
• changes in the electrocardiogram (ECG) (prolongation of QT),
• lung inflammation, lung disease,
• seizures,
• idiopathic intracranial hypertension (increase in intracranial pressure around the brain characterized by headaches, diplopia, and other visual symptoms, tinnitus or ringing in one or both ears),
• if you notice that on the trunk there are circular or target-shaped, reddish, and
• not elevated, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome/toxic epidermal necrolysis),
• skin redness and rash with itching (toxic skin eruption),
• a skin reaction that causes pimples or red spots on the skin, which may resemble a target, with a dark red center surrounded by lighter red rings (erythema

multiforme).

Special information:

The effect of treatment with Leptoprol Trimestral can be monitored by measuring the concentration of male sex hormone (testosterone) in the blood and performing other blood tests (acid phosphatase, PSA=prostate-specific antigen). Testosterone levels first rise at the beginning of treatment and then fall within 2 weeks. After 2 to 4 weeks, the testosterone concentration reached is similar to that observed after a bilateral orchiectomy, remaining constant throughout the entire treatment period.

Temporary increases in acid phosphatase levels in the blood may occur during the initial phase of treatment. Normal or almost normal levels are reached after a few weeks.

The decrease in male sex hormone, as occurs after orchiectomy or treatment with medications that inhibit sex hormones (such as leuprorelin), may cause a reduction in bone density with a high risk of bone fractures (see Warnings and Precautions). The reduction in bone density after orchiectomy is, however, more pronounced than after leuprorelin administration. Your doctor will consider administering a medication to regulate calcium metabolism (known as bisphosphonates).

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSistema Español de Farmacovigilancia de Medicamentos de Uso Humano: https://www.notificaram.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not store at a temperature above 86°F (30°C).

Do not use this medication after the expiration date that appears on the box, as well as on the sterile bag and the syringe label after CAD. The expiration date is the last day of the month indicated.

Medicines should not be disposed of through drains or in the trash. Dispose of the containers and medicines you no longer need at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. By doing so, you will help protect the environment

Composition ofLeptoprol Trimestral
The active principle is leuprorelin (as leuprorelin acetate).

1implant contains 5 mg of leuprorelin (as leuprorelin acetate).

The other component is polylactic acid.

Appearance of the product and contents of the pack

Preloaded syringes of polycarbonate plastic with a copolymer of acrylonitrile-butadiene-styrene piston and a needle in a sealed polyethylene terephthalate/aluminum/PE bag.

Pack sizes:

1x1 implant with 5 mg of leuprorelin (as leuprorelin acetate)

2x1 implants with 5 mg of leuprorelin (as leuprorelin acetate)

3x1 implants with 5 mg of leuprorelin (as leuprorelin acetate)

5x1implants with5 mgofleuprorelina(asleuprorelin acetate)

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Marketing authorization holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer responsible

EVER Pharma Jena GmbH

Otto-Schott-Strasse 15

07745 Jena

Germany

or

EBEWE Pharma Ges.m.b.H Nfg.KG

Mondseestrasse 11

4866 Unterach

Austria

or

Sandoz GmbH,

Biochemiestraße 10

6250 Kundl

Austria

or

EVER Pharma Jena GmbH

Brüsseler Strasse 18

07747 Jena

Germany

Local Representative:

EVER Pharma Therapeutics Spain S.L.

C/ Toledo 170

28005 Madrid

Spain

Tel.: 0034 669596174

This medicinal product is authorized in the member states of the European Economic Area with the following names:

Republic of Czech: Leptoprol 5 mg

Finland: Leuprorelin Sandoz 5 mg implant

France: Leptoprol

Germany: Leptoprol

Greece: Leuprorelin/Sandoz

Latvia: Leptoprol 5 mg implants pilnšlirce

Romania: Leptoprol

Slovenia: Leptoprol 5 mg implantat v napolnjeni injekcijski brizgi

Spain: Leptoprol Trimestral 5 mg implant in preloaded syringe

Last review date of this leaflet:August 2024.

----------------------------------------------------------------------------------------------------------------“Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es.”

You can access detailed and updated information on how to administer this medicinal product by scanning the QR code included in the carton with your smartphone. You can also access this information at the following internet address: www.cima.aemps.es/info/79581.

This information is intended solely for medical professionals or healthcare professionals:

Read the instructions carefully, as the applicator provided with this medicinal product may be different from others you have used.

Instructions for use

1.Disinfect the injection site on the anterior abdominal wall below the navel line.

2.Remove the applicator from the sterile bag and check that the implant is visible in the reservoir (see the framed area). To verify, examine the applicator under light or gently shake it.

3.Pull the piston of the applicatorcompletely back until you can see a complete line in the second window.

Note: The piston can only be pushed forward to inject the implant if it has been pulled back completely beforehand.

4.Remove the needle cap.

5.Hold the main body of the applicator with one hand. With the other hand, pinch the patient's skin on the anterior abdominal wall, below the navel line. See illustration.

With theneedle opening upwards, insert the entire needle. Do this at a slight angle, almost parallel to the skin in the subcutaneous tissue.

6.Remove the applicator carefully, approximately1 cm back. This creates the puncture channel for the implant.

7.Inject the implant into the puncture channel by pushing the pistoncompletely forwarduntil it fits in place andyou hear a “click”.

8.Remove the needle. To ensure that the implant has been injected correctly, check that the blue tip of the piston is visible at the end of the needle.

For information on dosage, see the section “How to use Leptoprol Trimestral”.