LEPTOPROL TRIMESTRAL 5 mg IMPLANT IN PRE-FILLED SYRINGE

2. What you need to know before you use Leptoprol Trimestral

Do not use Leptoprol Trimestral:

• if you are allergic to leuprorelin or any of the other ingredients of this medicine (listed in section 6),
• if you are allergic to substances similar to leuprorelin, such as goserelin or buserelin,
• if your cancer is not affected by hormones,
• if you are a woman or a child.

Warnings and precautions

Talk to your doctor or nurse before starting treatment with Leptoprol Trimestral if:

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

Contact your doctor immediately if you experience severe or recurrent headaches, vision problems, and ringing or buzzing in the ears.

Depression has been reported in patients undergoing treatment with leuprorelin, which can be severe. If you are using leuprorelin and develop depression in your mood, inform your doctor.

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

Severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), have been reported in association with leuprorelin. Stop using leuprorelin and seek immediate medical attention if you notice any symptoms related to these severe skin reactions described in section 4.

Important information for athletes

Athletes are warned that this medicine contains a component that may result in a positive doping test.

Other medicines and Leptoprol Trimestral

Tell your doctor, pharmacist, or nurse if you are using, have recently used, or might use any other medicines.

Leuprorelin may interfere with some medicines 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 medicines (e.g., methadone (used to alleviate pain and as part of drug addiction detoxification treatment), moxifloxacin (an antibiotic), antipsychotics used for severe diseases).

Children and adolescents

Leuprorelin is only indicated for adult patients.

Pregnancy and breastfeeding

Leuprorelin is indicated only for male patients.

Driving and using machines

This medicine and the tumor disease may cause fatigue. This is more frequent with the use of alcohol.

Therefore, do not drive or use machineswithout your doctor's consent if this applies to you.

3. How to use Leptoprol Trimestral

Use of Leptoprol Trimestral

• clean the area where the implant is to be injected,
• a local anesthetic can be applied to alleviate the pain of the implant injection,
• inject Leptoprol Trimestral under the skin (subcutaneously) in the stomach area.
• Leptoprol Trimestral should only be administered by your doctor or nurse. They will be responsible for preparing the product.

How much to administer

The recommended dose is 1 implant of Leptoprol Trimestral with 5 mg of leuprorelin 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. If the next injection is delayed in exceptional cases up to 4 weeks, the therapeutic effect is usually not affected,
• inject the contents of a pre-filled syringe,
• the syringe contains an implant with a dose of 5 mg of leuprorelin.

Blood tests

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

Duration of treatment

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 medicine 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 the 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 too much is accidentally applied, 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 Toxicology Information Service, phone: 91 562 04 02, indicating the medicine and the amount ingested.

If you forget to use Leptoprol Trimestral

Talk to your doctor if you think your quarterly dose of leuprorelin has been forgotten.

If you stop treatment with Leptoprol Trimestral

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

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

If you have any further questions on the use of this product, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• allergic reactions (anaphylactic reactions). Symptoms can include:
• sudden onset of: feeling of heat, rash, itching, or hives on the skin and/or mucous membranes,
• swelling of the face, lips, or tongue or other parts of the body,
• shortness of breath, wheezing, or breathing problems,
• drop in blood pressure, rapid heartbeat, convulsions, and in severe cases,
• failure of the cardiovascular system 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 heartbeat, blue-tinged skin
• and discolorationdue to a blood clot in the lungs.

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

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

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

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

This increase in symptoms usually subsides after discontinuation of treatment with this medicine.

At the start 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 decrease to a very low level. As a consequence, in certain patients, the following side effects appear:

Very common:may affect more than 1 in 10 people

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

Common:may affect up to 1 in 10 people

• increase in breast size in men,
• 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 when urinating,
• fatigue,
• swelling 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

• generalized allergic reactions such as fever, itching, increased eosinophil cells in the blood, skin rash,
• diarrhea,
• dry skin or mucous membranes,
• testicular pain,
• inability to empty the bladder completely on its own,
• increased nocturnal sweating.

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

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

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

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

Frequency not known:frequency cannot be estimated from the available data

• non-infectious lung disease (pneumonia) (mainly registered in Japan),
• in isolated cases, an abscess has appeared at the injection site,
• changes in the electrocardiogram (ECG) (QT prolongation),
• lung inflammation, lung disease,
• seizures,
• idiopathic intracranial hypertension (increased intracranial pressure around the brain characterized by headaches, double vision, and other visual symptoms, ringing or buzzing in one or both ears),
• if you notice circular or target-shaped, reddish-colored, non-raised spots on the trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome/toxic epidermal necrolysis),
• redness of the skin and rash with itching (toxic skin rash),
• a skin reaction that causes grains or red spots on the skin, which can look like 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 in the blood of the male sex hormone (testosterone) and performing other blood tests (acid phosphatase, PSA=prostate-specific antigen). Testosterone levels first increase at the start of treatment and then decrease over the next two weeks. After 2 to 4 weeks, the testosterone concentration reached is similar to that observed after removal of both testicles, remaining constant throughout the treatment period.

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

The decrease in testosterone, as occurs after removal of the testicles or with treatment with medicines that inhibit sex hormones (such as leuprorelin), can cause a reduction in bone density with a high risk of bone fractures (see Warnings and precautions). The reduction in bone density after removal of the testicles is, however, more marked than after administration of leuprorelin. Your doctor will consider the administration of a medicine to regulate calcium metabolism (known as bisphosphonates).

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Leptoprol Trimestral

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

Do not store above 30°C.

Do not use this medicine after the expiry date which is stated on the carton, as well as on the sterile bag and the label on the syringe after EXP. The expiry date is the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicine in the SIGRE collection point at the pharmacy. If you have any doubts, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Contents and Additional Information

Composition ofLeptoprol TrimestralThe active ingredient is leuprorelin (as leuprorelin acetate).

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

The other component is polylactic acid.

Appearance of the Product and Container Contents

Prefilled plastic syringes made of polycarbonate with an acrylonitrile-butadiene-styrene copolymer plunger and a needle in a sealed polyethylene terephthalate/aluminum/PE bag.

Package 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)

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

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

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

Phone: 0034 669596174

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

Czech Republic: Leptoprol 5 mg

Finland: Leuprorelin Sandoz 5 mg implant

France: Leptoprol

Germany: Leptoprol

Greece: Leuprorelin/Sandoz

Latvia: Leptoprol 5 mg implants

Romania: Leptoprol

Slovenia: Leptoprol 5 mg implant in a prefilled syringe

Spain: Leptoprol Trimestral 5 mg implant in a prefilled syringe

Date of the last revision of this leaflet:August 2024.

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"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."

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

This information is intended only for 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 repository (see framed area). To verify, examine the applicator against the light or gently shake it.

1. Pull the plunger of the applicator completely back until you can see a full line in the second window.

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

1. Remove the needle cap.

1. 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 the needle opening facing up, insert the entire needle. Do this at a slight angle, almost parallel to the skin in the subcutaneous tissue.

1. Carefully pull the applicator back about 1 cm. This creates the puncture channel for the implant.

1. Inject the implant into the puncture channel by pushing the plunger completely forward until it clicks into place and you hear a "click".

1. Withdraw the needle. To ensure that the implant has been injected correctly, check that the light blue tip of the plunger is visible at the tip of the needle.

Forinformation on dosing, go to section 3.How to useLeptoprol Trimestral).