LUTRATE DEPOT TRIMESTRAL 22.5 mg POWDER AND SOLVENT FOR PROLONGED-RELEASE INJECTABLE SUSPENSION

Introduction

Package Leaflet: Information for the User

Lutrate Depot Trimestral 22.5 mg powder and solvent for prolonged-release injectable suspension

Leuprorelin acetate

Read all of this leaflet carefully before you start 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the package leaflet

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

1. What is Lutrate Depot Trimestral and what is it used for

Lutrate Depot Trimestral is a vial containing a white powder, which is reconstituted as a suspension for injection into a muscle. Lutrate Depot Trimestral contains the active substance leuprorelin (also known as leuprolide), which belongs to a group of medicines called gonadotropin-releasing hormone (LHRH) agonists, which are medicines that reduce testosterone (a male sex hormone).

Your doctor has prescribed Lutrate Depot Trimestral for the treatment of advanced prostate cancer.

Lutrate Depot Trimestral is also used for the treatment of locally advanced and localized hormone-dependent prostate tumors, in combination with radiotherapy.

2. What you need to know before you use Lutrate Depot Trimestral

Do not use Lutrate Depot Trimestral:

• If you are allergic (hypersensitive) to LHRH, LHRH agonists, or any of the other components of this medicine (listed in section 6). An allergic reaction may appear as a skin rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue.
• If you have undergone orchiectomy (removal of the testicles).
• If you are a woman or a child.
• Lutrate Depot Trimestral should not be used alone (as monotherapy) for the treatment of prostate cancer when the spinal cord is compressed or the cancer has spread to the spinal cord.

Warnings and precautions

Talk to your doctor or pharmacist before starting to take Lutrate Depot Trimestral:

• Tell your doctor if you have any heart or blood vessel condition or are being treated for it, including medications to control heart rhythm (arrhythmias). The risk of heart rhythm problems may increase when using leuprorelin acetate.

• It is possible that your disease may worsen during the first few weeks of treatment, but it should improve with continued treatment. The signs and symptoms include: temporary increase in testosterone (male hormone), hot flashes, bone pain, nervous system disorders (including depression) or urinary obstruction.
• If you think you are experiencing an allergic reaction (shortness of breath, asthma, rhinitis, swelling of the face, urticaria, skin rash), stop taking this medicine and inform your doctor.
• Tell your doctor if you have a risk of or are already suffering from any of the following diseases, as you may need more frequent check-ups:
• • Bruises or unexplained bleeding or if you experience general discomfort. Although rare, these can be symptoms of changes in the number of red or white blood cells.
  • Metabolic disease
  • Heart problems or palpitations
  • Diabetes
• Your doctor should be informed of any personal medical history of pituitary adenoma (non-cancerous tumor of the pituitary gland). Cases of pituitary apoplexy (partial loss of pituitary tissue) have been described after the initial administration of this type of medicine to patients with pituitary adenoma. Pituitary apoplexy may manifest as sudden headache, meningism, vision disorders or altered vision, including blindness, and occasionally a decrease in the level of consciousness.
• Your doctor should know if you suffer from a coagulation disorder, thrombocytopenia, or if you are being treated with anticoagulants. It may be necessary to monitor your liver function, as liver disorders and jaundice (yellowing of the eyes and skin) have been described with the administration of leuprorelin.
• Spinal fracture, paralysis, low blood pressure, and high blood pressure have been described with leuprorelin treatment.
• Depression has been reported in patients undergoing treatment with leuprorelin acetate, which can be severe. If you are using leuprorelin acetate and feel depressed, inform your doctor.
• A reduction in bone density (fragile or thinner bones) has been described after the administration of leuprorelin. Your doctor may consider adding an anti-androgen to the treatment with leuprorelin acetate. In this case, your doctor will be alert to detect the presence of vein inflammation (thrombophlebitis) and other signs of coagulation disorders and edema (swelling of hands, feet, or ankles) that are more likely to occur when anti-androgenic treatment is added to leuprorelin acetate.
• Tell your doctor if you feel pressure on the spinal cord and/or present urinary disorders and/or hematuria (blood in the urine); in such a case, your doctor will discuss the need for additional treatments to prevent neurological complications (e.g., tingling in hands and feet, paralysis) or urethral obstruction (the duct that connects the bladder to the outside of the body). You will be closely monitored during the first few weeks of treatment.
• Patients may experience metabolic changes (e.g., glucose intolerance or worsening of existing diabetes), weight changes, and cardiovascular disorders.
• Patients with metabolic or cardiovascular disease, and especially those with a history of congestive heart failure (a disease in which the heart can no longer pump enough blood to the rest of the body), should be monitored during treatment with leuprorelin.
• Consult your doctor, pharmacist, or nurse if you have fatty liver.
• During treatment, some blood tests will be performed to check if leuprorelin acetate is effective.
• You may experience a loss of interest in sexual relations, hot flashes, and occasionally a reduction in the size and function of the testicles.
• You may become fertile again when treatment with leuprorelin acetate is discontinued.
• Leuprorelin acetate may interfere with certain laboratory tests, so you should ensure that your doctor knows that you are using leuprorelin acetate.
• Seizures may occur in predisposed patients (patients with a history of seizures, epilepsy, cerebrovascular disorders, anomalies, or tumors of the central nervous system), in patients taking medications that can cause seizures, and to a lesser extent in patients who do not have these characteristics.
• Contact your doctor immediately if you experience severe or recurrent headaches, vision problems, or tinnitus (ringing in the ears).
• Severe skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), have been reported in association with leuprorelin. Discontinue the use of leuprorelin and seek immediate medical attention if you notice any of the symptoms related to these severe skin reactions described in section 4.

Using Lutrate Depot Trimestral with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. It may still be suitable to treat you with leuprorelin acetate; your doctor will decide what is suitable for you.

Leuprorelin acetate 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 for pain relief and for detoxification from other medicines), moxifloxacin (an antibiotic), antipsychotics used to treat severe mental illnesses).

Pregnancy and breastfeeding

The use of leuprorelin acetate is not indicated in women.

This medicine is contraindicated during pregnancy. Spontaneous abortions may occur if this medicine is administered during pregnancy.

Driving and using machines

Visual disturbances and dizziness may occur during treatment. If you are affected, do not drive or operate machinery.

Lutrate Depot Trimestral containsless than 23 mg of sodium (1 mmol) per dose; this is essentially “sodium-free”.

Lutrate Depot Trimestral contains Polysorbate 80

This medicine contains 3.8 mg of polysorbate 80 in each unit dose. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergy.

3. How to use Lutrate Depot Trimestral

Posology

Lutrate Depot Trimestral should only be administered by your doctor or nurse. They will be responsible for preparing the product.

Adults and the elderly:

The recommended dose of Lutrate Depot Trimestral is one injection every three months. The powder is reconstituted to form a suspension that is administered as an intramuscular injection (into a muscle) once every three months.

The injection site should be varied at regular intervals.

Lutrate Depot Trimestral should only be administered intramuscularly. It should not be administered by any other route.

The treatment schedule will be decided by your doctor.

Use in children:Lutrate Depot Trimestral is not indicated in children.

If you use more Lutrate Depot Trimestral than you should

This is unlikely, as your doctor or nurse will know what dose is suitable for you. However, if you suspect that you have received more medicine than you should, inform your doctor immediately so that the necessary measures can be taken.

In case of overdose or accidental ingestion, consult the Toxicological Information Service, telephone 91 562 04 20, indicating the medicine and the amount used.

If you forget to use Lutrate Depot Trimestral

It is important that you do not miss a dose of Lutrate Depot Trimestral. As soon as you realize that you have missed an injection, contact your doctor, who will administer the next injection.

If you stop using Lutrate Depot Trimestral

Since medical treatment involves the administration of Lutrate Depot Trimestral for a long period, if treatment is interrupted, you may experience a worsening of the symptoms related to the disease. Therefore, do not stop treatment prematurely without your doctor's permission.

If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Tell your doctor immediately if you notice any of the following symptoms:

• You suffer from wheezing, difficulty breathing, swelling of the eyelids, face, or lips, skin rash, or itching (especially if it affects your whole body) suddenly.
• Frequency not known (frequency cannot be estimated from the available data):
• If you notice circular or target-shaped red spots on your trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• Redness of the skin and rash with itching (toxic skin eruption).
• A skin reaction that causes red or target-shaped spots on the skin (erythema multiforme).

The following side effects have been reported:

Very common (may affect more than 1 in 10 people):

Hot flashes and reactions at the injection site.

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

Cold sweats, hyperhidrosis (increased sweating), pruritus (itching), fatigue, insomnia (not sleeping), decreased libido, dizziness, flushing, feeling of nausea, diarrhea, decreased appetite, erectile dysfunction, asthenia (lack or loss of strength), bone pain, joint pain, and reactions at the injection site such as pain, irritation, erythema (redness of the skin). Urinary tract pain, decreased urine flow, frequent urination, mood changes, and depression in prolonged treatments with leuprorelin, alteration of liver enzymes, hyperlipidemia (high levels of lipids in the blood), increased blood sugar.

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

High cholesterol, sleep disorders, restlessness, altered taste, tingling (altered skin sensitivity), headache, lethargy (drowsiness), blurred vision, pleurisy, tinnitus (ringing in the ears), upper abdominal pain, constipation, papule, rash, generalized pruritus (itching), nocturnal sweats, back pain, muscle pain, neck pain, breast pain, pelvic pain, testicular atrophy, testicular disorder, feeling of heat, mood changes, and depression in short-term treatments with leuprorelin. Changes in blood values and electrocardiogram (ECG) (prolongation of the QT interval). Reactions at the injection site such as urticaria, heat, and hemorrhage.

Not known (frequency cannot be estimated from the available data):

Lung inflammation, lung disease

Idiopathic intracranial hypertension (increased intracranial pressure around the brain characterized by headaches, diplopia, and other visual symptoms, tinnitus or ringing in one or both ears).

Reporting of side effects:

If you experience 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: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Lutrate Depot Trimestral

Your doctor or pharmacist will know how to store Lutrate Depot Trimestral.

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

Do not store above 25°C. Do not freeze.

Do not use this medicine after the expiry date which is stated on the carton, vial, and syringe after “EXP”. The syringe has the same expiry date as the vial. 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 Contents and Additional Information

Composition of Lutrate Depot Trimestral

The active ingredient is leuprolide acetate. Each vial contains 22.5 mg of leuprolide acetate.

The other components are: polysorbate 80, mannitol (E-421), sodium carmellose (E-466), triethyl citrate, and poly(lactic acid) (PLA).

The solvent contains (pre-filled syringe): mannitol, water for injectable preparations, sodium hydroxide (for pH adjustment), and hydrochloric acid (for pH adjustment).

Appearance of the Product and Container Contents

Each container contains a vial with 22.5 mg of leuprolide acetate, a pre-filled syringe with 2 ml of solvent, an adapter system, and a sterile 20G needle.

Marketing Authorization Holder and Manufacturer

GP-PHARM, S.A.

Pol. Ind. Els Vinyets – Els Fogars Sector 2

Carretera comarcal 244, km22

08777 Sant Quintí de Mediona

Spain

This Medicinal Product is Authorized in the Member States of the European Economic Area Under the Following Names:

Spain: Lutrate Depot Trimestral 22.5 mg powder and solvent for prolonged-release injectable suspension

France: Zeulide 22.5 mg powder and solvent for prolonged-release injectable suspension

Date of the Last Revision of this Leaflet:March 2025.

Other Sources of Information

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 Exclusively for Healthcare Professionals.

How to Prepare the Injection?

IMPORTANT: Read Carefully Before Administering the Product (Instructions for Use are Also Included in the Tray Containing the Kit Components).

Aseptic technique should be followed during the reconstitution procedure.

Use only the solvent included in the commercial kit.

Once mixed, the product should be administered immediately. By single intramuscular injection.

This medicinal product is for single use only. Any remaining suspension should be discarded.

Check the contents of the kit and ensure that it includes everything mentioned in the leaflet.

The Container Contains:

1 (one) vial of Lutrate Depot Trimestral 22.5 mg (leuprolide acetate) powder for injectable suspension.

1 (one) pre-filled syringe containing the solvent for the suspension (injectable mannitol 0.8% solution)

1 (one) single-use sterile reconstitution device, including 1 (one) single-use sterile needle.

Instructions for Use

To be Included in the Lid of the Tray Containing the Medicinal Product Kit Components

Lutrate Depot – Instructions for Use

Read Carefully Before Administering the Product

Reconstitute immediately before administering by single intramuscular injection

Use only the solvent included in the commercial kit.

Product intended for single injection only.

Any remaining suspension should be discarded.