Package Insert: Information for the User

Lutrate Depot Trimestral 22.5 mg Powder and Diluent for Long-Acting Suspension Injectable

Leuprolide Acetate

Read this entire 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 or pharmacist.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What is Lutrate Depot Trimestral and how is it used

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

3. How to use Lutrate Depot Trimestral

4. Possible adverse effects

5. Storage of Lutrate Depot Trimestral

6. Contents of the package and additional information

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

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

No use Lutrate Depot Trimestral:

• If you are allergic (hypersensitive) to LHRH, LHRH agonists, or any of the other components of this medication (including those listed in section 6).A hypersensitivity reaction may manifest as 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 child.
• Lutrate Depot Trimestral should not be used alone (in 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

• Consult your doctor or pharmacist before starting to take Lutrate Depot Trimestral.

• Your condition may worsen during the first 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 obstructions.
• If you think you are experiencing an allergic reaction (shortness of breath, asthma, rhinitis, facial swelling, urticaria, skin rash), stop taking this medication and inform your doctor.
• Inform your doctor if you have a risk of developing, or have already developed, any of the following conditions, as you may need more frequent check-ups:
• • Bleeding or bruising without explanation, or if you experience general discomfort. Although rare, these may be symptoms of changes in the number of red or white blood cells.
  • Metabolic disease
  • Heart problems, or irregular heartbeat
  • Diabetes.
• Your doctor should be informed of any personal clinical history of pituitary adenoma (non-malignant tumor of the pituitary gland).Cases of pituitary apoplexy (partial loss of pituitary gland tissue) have been described after the initial administration of this type of medication to patients with pituitary adenoma.Pituitary apoplexy may manifest as sudden headache, meningism, visual disturbances, or altered vision, including blindness, and occasionally decreased level of consciousness.
• Your doctor should be aware if you suffer from a coagulation disorder, thrombocytopenia, or if you are being treated with anticoagulants. Your liver function may need to be monitored, as alterations of the liver and jaundice (yellowing of the eyes and skin) have been described with the administration of leuprorelina.
• Cases of spinal fracture, paralysis, low blood pressure, and high blood pressure have been described with leuprorelina treatment.
• Cases of depression have been reported in patients treated with Lutrate Depot Trimestral, which may be severe. If you are using Lutrate Depot Trimestral and feel depressed, inform your doctor.
• A reduction in bone density (fragile or thinner bones) has been described after the administration of leuprorelina.Your doctor may consider the possibility of adding an anti-androgen to the treatment with Lutrate Depot Trimestral.In this case, the doctor will be alert to detect the presence of inflammation of the veins (thrombophlebitis) and other signs of coagulation disorders and edema (swelling of the hands, feet, or ankles) that have a higher risk of occurring when anti-androgen treatment is added to Lutrate Depot Trimestral.
• Inform your doctor if you experience pressure on the spinal cord and/or urinary problems and/or hematuria (blood in the urine); in this case, your doctor will discuss the need for additional treatments to prevent neurological complications (e.g., numbness in the hands and feet, paralysis) or urethral obstruction (the tube that connects the bladder to the outside of the body).You will be closely monitored during the first 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 disease or cardiovascular disease, and especially those with a history of congestive heart failure (a condition in which the heart is no longer able to pump enough blood to the rest of the body), should be monitored during treatment with leuprorelina.
• Consult your doctor, pharmacist, or nurse if you have fatty liver.
• During treatment, some blood tests should be performed to check if Lutrate Depot Trimestral is effective.
• You may experience a loss of interest in sex, hot flashes, and occasionally a reduction in the size and function of the testicles.
• You may become fertile again when you stop treatment with Lutrate Depot Trimestral.
• Lutrate Depot Trimestral may interfere with certain laboratory tests, so make sure your doctor knows that you are using Lutrate Depot Trimestral.
• Seizures may occur in predisposed patients (patients with a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies, or tumors), in patients taking medications that can cause seizures, and to a lesser extent in patients without these characteristics.
• Inform your doctor if you have any heart or blood vessel disease or are being treated for it, including medications to control heart rhythm (arrhythmias). The risk of heart rhythm problems may increase when using Lutrate Depot Trimestral.
• Contact your doctor immediately if you experience intense or recurrent headaches, visual problems, and tinnitus or buzzing.
• Severe skin eruptions, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/NET), have been reported in association with leuprorelina. Stop using leuprorelina and seek medical attention immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.

Use of Lutrate Depot Trimestral with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.Lutrate Depot Trimestral may still be suitable for you; your doctor will decide what is best for you.

Lutrate Depot Trimestral 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 for pain relief and detoxification of other medications), moxifloxacino (an antibiotic), antipsychotics used to treat severe mental illnesses).

Pregnancy and breastfeeding

The use of Lutrate Depot Trimestral is not indicated in women.

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

Driving and operating machinery

No specific studies have been conducted on the effects of Lutrate Depot Trimestral on the ability to drive and operate machinery.

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

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

Dosage

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

Adults and 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 via intramuscular injection. 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 for children.

If you use more Lutrate Depot Trimestral than you should

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

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

If you forget to use Lutrate Depot Trimestral

It is essential 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 interrupt treatment with Lutrate Depot Trimestral

Since medical treatment involves the administration ofLutrate Depot Trimestralover a long period of time, interrupting treatment may result in an exacerbation of symptoms related to the disease.Therefore, do not interrupt treatment prematurely without your doctor's permission.

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

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

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

• You experience wheezing, difficulty breathing, swelling of the eyelids, face, or lips, skin rash, or itching (especially if it affects your entire body) suddenly.
• Unknown frequency (frequency cannot be estimated from available data):
• You notice circular or target-shaped patches on your trunk, red and not elevated, often with central blisters, skin peeling, mouth ulcers, throat, nose, genital, and eye ulcers. These severe skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome/toxic epidermal necrolysis).
• Redness of the skin and itchy rash (toxic skin eruption).
• A skin reaction that causes pimples or red patches on the skin, which may resemble a target, with a dark red center surrounded by rings of lighter red color (erythema multiforme).

The following side effects have been described:

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, excessive sweating, pruritus (itching), fatigue, insomnia, decreased libido, dizziness, flushing, sensation of dizziness (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 (skin redness). Urinary tract pain, decreased urine flow, frequent urination, mood changes, and depression in prolonged treatments with leuprorelin, liver enzyme alterations, hyperlipidemia (elevated blood lipid levels), increased blood sugar.

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

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

Unknown (frequency cannot be estimated from available data)

Pulmonary inflammation, pulmonary 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 any type of side effect, consult your doctor or pharmacist, even if it is not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Keepthis medicationout of the sight and reach of children.

Do not store at a temperature above25ºC. Do not freeze.

Do not use this medication after the expiration date that appears on the packaging, vial, and syringe after “CAD”. The syringe has the same expiration date as the vial.

The expiration date is the last day of the month indicated.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need at the SIGRE collection pointat the pharmacy. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

Composition of Lutrate Depot Trimestral

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

The concentration of the reconstituted product is 11.25 mg/ml. The other components are: polisorbate 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 contents of the package

Each package contains a vial with 22.5 mg of leuprorelin acetate, a pre-filled syringe with 2 ml of solvent, a mixing adapter system, and a sterile 20-gauge needle.

Holder of the marketing authorization and responsible for manufacturing

GP-PHARM, S.A.

Pol. Ind.Els Vinyets – Els Fogars Sector 2

Carretera comarcal 244, km22

08777 Sant Quintí de Mediona

Spain

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

Last review date of this leaflet: June 2024.

For detailed and updated information on this medicine, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/.

This information is intended solely for healthcare professionals.

How to prepare the injection?

IMPORTANT: Read carefully before administering the product (the Instructions for use are also included in the tray containing the components of the kit).

You should follow aseptic technique during the reconstitution procedure.

Use only the solvent included in the commercial kit.

Once mixed, the product must be administered immediately by single intramuscular injection.

This medicine is for single use only. Any remaining suspension must be discarded.

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

The package contains:

1 (one) vial of Lutrate Depot 22.5 mg (leuprorelin acetate) powder for injectable suspension

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

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

Instructions for use

Include in the cover of the tray containing the components of the Medicinal Product Kit

Lutrate®Depot –Instructions for use

Read carefully before administering the product

Reconstituteimmediately before administering by single intramuscular injection

Use only the solvent included in the commercial kit.

Product intended for single use only.

Any remaining suspension must be discarded.