Package Insert: Information for the User

Procrin Semiannual 30 mg Powder and Diluent for Injectable Suspension in Preloaded Syringe

Leuprolide Acetate

Procrin Semestral is a medication that belongs to a group of gonadotropin-releasing hormone analogs and is used to reduce circulating levels of testosterone and estrogens in the body.

Procrin Semestral is indicated for the palliative treatment of advanced hormone-dependent prostate cancer and for the treatment of high-risk and locally advanced hormone-dependent prostate cancer in combination with radiation therapy.

Procrin Semestral should be administered in patients who have previously been treated with one of the following medications: natural gonadotropin-releasing hormone analogs (GnRH or LH-RH) and/or antiandrogens.

No use Procrin Semestral:

• If you are allergic to leuprorelin acetate or similar nonapeptides, or to any of the other components of this medication (listed in section 6).
• After surgical removal of your testicles.
• As a single treatment, if you experience symptoms related to spinal cord pressure or a spinal column tumor.
• If you are a woman or child.

This is a medication indicated only for men, but since the same active ingredient is used in other doses in women, it is essential to note that it cannot be used in women:

• If you have undiagnosed vaginal bleeding.

• If you are pregnant or believe you may be pregnant during treatment.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Procrin Semestral

• Generally, there is an increase in blood levels of the male sex hormone (testosterone) during the first week of treatment. This may lead to a temporary worsening of symptoms related to the disease and the appearance of new symptoms that had not been experienced until then. These symptoms include, especially, bone pain, urinary disorders, and spinal cord pressure. These symptoms usually subside as treatment continues. If symptoms do not subside or worsen, you should contact your doctor immediately.
• If you experience sudden headache, vomiting, visual disturbances, or alteration of mental state, seek immediate medical attention in the first weeks of treatment, as you may be experiencing a severe condition called pituitary apoplexy (disease caused by a decrease in blood flow to a brain area).

• If you experience urinary tract obstruction, blood in the urine, or vertebral and/or cerebral metastatic lesions. In these cases, your doctor should monitor you frequently, and additionally evaluate the possibility of starting daily PROCRIN treatment for the first two weeks of treatment to facilitate discontinuation if necessary.
• It may cause loss of bone mineral density with a risk of osteoporosis-related fractures.
• Seizures may occur in patients predisposed to them due to their underlying disease, in patients receiving medications that can cause seizures, and to a lesser extent in patients not included in either of the two previous groups.
• If you are diabetic, as treatment with leuprorelin may affect blood glucose control.
• If you have or have had heart problems, inform your doctor.
• If you were born with or have a history of prolonged QT interval on the electrocardiogram (electrical activity of the heart), electrolyte imbalance in the blood, or taking medications that can cause changes in the electrocardiogram (seeUse of other medications). Inform your doctor.
• 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 Procrin Semestral.
• Depression has been reported in patients using Procrin, which can be severe. If you are using Procrin and have a depressed mood, inform your doctor.
• If you have a history of hyperglycemia, diabetes, hypercholesterolemia, and/or fatty liver, your doctor should closely monitor you to detect possible changes/metabolic syndrome.
• If you have fatty liver.

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

Use of Procrin Semestral with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Procrin Semestral 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, for example, methadone (used for pain relief and for detoxification of other medications), moxifloxacine (an antibiotic), and antipsychotics used to treat mental disorders.

Interference with laboratory tests:

Changes in the results of various laboratory tests may occur; it is normal for these fluctuations to occur as treatment progresses, and it is the doctor who must evaluate this behavior.

Pregnancy, breastfeeding, and fertility

This medication is intended exclusively for male patients.

If, by accident, it is administered to women, it should be noted that Procrin Semestral is contraindicated in pregnant women or those who may be pregnant and during the lactation period. There is a possibility of spontaneous abortion if administered during pregnancy.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

Your ability to drive and operate machinery may be impaired due to fatigue, dizziness, vertigo, and visual disturbances, which may be possible adverse reactions to treatment or a consequence of the underlying disease.

Use in athletes:

This medication contains leuprorelin acetate, which may produce a positive result in doping control tests.

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

Procrin Semestral is administered via subcutaneous injection (injecting the medication into the tissue located immediately beneath the skin).

The normal dose is a single subcutaneous injection once every six months.

Your doctor will decide what dose of Procrin Semestral you should receive and when you should receive it. You should receive the specified dose from your doctor.

Your doctor may perform blood tests to check the effect of Procrin Semestral.

In some cases, your doctor may prescribe an additional medication from the antiandrogen group to control symptoms caused by the elevation of testosterone levels (male sex hormone) in the first weeks of treatment.

If you estimate that the action of Procrin Semestral is too strong or too weak, inform your doctor or pharmacist.

If you use more Procrin Semestral than you should

There is no clinical experience of the effects of an acute overdose of leuprorelin acetate. In animal studies, administration of doses approximately 133 times higher than the recommended dose for human use resulted in dyspnea (shortness of breath), decreased activity, and local irritation at the injection site. In case of overdose, the patient should be monitored and accompanied.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91.562.04.20, indicating the medication and the amount administered.

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

Like all medications, this medication may cause side effects, although not everyone will experience them.

The majority of side effects observed with leuprorelin acetate are due to the drug's own action that produces increases and/or decreases in male hormone levels.

Side effects at the beginning of treatment:

During clinical trials in prostate cancer, at the beginning of treatment, there is a transient increase in blood testosterone (male hormone) in patients who have not been previously treated with hormonal therapy, which is occasionally associated with a worsening of symptoms, usually a transient increase in bone pain. In patients with vertebral metastases and/or urinary obstruction or hematuria, there may be neurological problems such as temporary weakness and/or abnormal sensation of itching, coldness, tingling, etc. in the legs or worsening of urinary symptoms. If the presence of these symptoms seems important to you, inform your doctor.

The side effects collected during clinical trials and after the commercialization of the medication are presented below, classified by frequency:

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

Erythema (superficial skin inflammation, characterized by red patches),erythema at the injection site.

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

Exacerbation of prostate tumor1, worsening of prostate tumor1, anemia, increased appetite,diabetes mellitus(excess glucose in the blood)2,glucose intolerance2, increase in blood fat (increase in cholesterol)2, increase in low-density lipoproteins (LDL)2in blood, increase in triglycerides2(a type of fat), decreased sexual desire1, increased sexual desire1, mood changes2, depression2,headache1, dilation of arteries or veins1, hot flashes1,hypotension(low blood pressure)1, sudden decrease in blood pressure when standing (orthostatic hypotension)1,abnormal accumulation of fluid in the lungs, excessive sweating (hyperhidrosis)1,dry skin1, skin rash1, urticaria1, abnormal hair growth1, hair disorder1, nocturnal sweating1, hair loss1,discoloration1,cold sweats1,excessive hair growth on the face or body (hirsutism)1, muscle weakness1,osteoporosis(disease in which bone mineral density is low and bones may have fractures or microfractures)2, inability to achieve erection1, testicular atrophy1,breast growth in men1,congestion of the mammary gland1, testicular pain1,breast growth and enlargement1,breast pain1, prostate pain1, penile inflammation1, penile disorder1,fatigue (sensation of tiredness), reaction at the injection site, inflammation at the injection site, pain at the injection site, induration at the injection site,abscess at the injection site,dry mucous membranes1,increase in transaminases,gain or loss of weight1,increase in prostate-specific antigen (PSA)1, decrease in bone density1.

1Side effects associated frequently with the drug's own pharmacological action.

2Side effects associated frequently with the drug's own pharmacological actionin prolonged treatments (6 to 12 months).

Uncommon (may affect up to 1 in 1000 people)::

Abnormal weight gain, sleep disorders, mood changes3, depression3, dizziness,heart failure (the heart loses its ability to pump blood effectively),nausea, itching, nocturnal sweating, partial hair loss,increased frequency of urination,difficulty urinating, peripheral edema (accumulation of fluid in the legs, feet, and ankles),abnormal liver function test.

3Side effects associated frequently with the drug's own pharmacological actionin short treatments.

Frequency unknown (cannot be estimated from available data):

infection, urinary tract infection, pharyngitis, pneumonia, skin cancer,anaphylactic reaction (generalized immune reaction, usually severe), goiter (enlargement of the thyroid gland), pituitary apoplexy (death of an area of the pituitary gland tissue), low blood sugar, dehydration, high blood phosphorus, low protein levels in the blood, nervousness, insomnia, anxiety, delirium, suicidal thoughts, attempt at suicide, dizziness, numbness or tingling in some parts of the body (paresthesia), lethargy, alteration of memory, alteration of taste (dysgeusia), decreased sensitivity (hypoesthesia), fainting, peripheral neuropathy (disorder of the peripheral nerves), stroke, loss of consciousness, transient ischemic attack, paralysis, neuromuscular disorders, seizures, blurred vision, eye disorders, decreased vision, amblyopia (decreased vision in one or both eyes), dry eyes, tinnitus, decreased hearing, congestive heart failure (the heart loses its ability to pump blood effectively), alteration of heart rhythm, myocardial infarction, angina pectoris, increased heart rate, bradycardia, sudden cardiac death, changes in the electrocardiogram (ECG) (prolongation of the QT interval), lymphedema (accumulation of lymphatic fluid in the tissues), hypertension (high blood pressure), phlebitis (inflammation of a vein caused by a blood clot), arterial thrombosis (blockage of an artery by a blood clot),varicose veins (swollen and painful veins due to abnormal accumulation of blood),pleural rub (sound produced by the contact of the two inflamed pleural leaves), pulmonary fibrosis (scarring or thickening of lung tissue), nasal bleeding, respiratory difficulty, coughing up blood, cough, pleural effusion (fluid in the chest), pulmonary infiltrate, respiratory disorders, nasal congestion, pulmonary embolism, interstitial lung disease (inflammatory disorder of the lower airways), constipation, vomiting, gastrointestinal bleeding, abdominal inflammation, diarrhea, difficulty swallowing, dry mouth, duodenal ulcer, gastrointestinal disorder, peptic ulcer, rectal polyps, abnormal liver function, yellow skin and eyes (jaundice),non-alcoholic fatty liver disease,severe liver damage, hair loss,red skin patches (ecchymosis), photosensitivity reaction, urticaria, dermatitis, skin lesions, erythema multiforme, eczema, dermatitis exfoliativa, Stevens-Johnson syndrome, Toxic Epidermal Necrolysis,muscle pain, bone inflammation, joint disorders, joint pain, ankylosing spondylitis (inflammatory disease that affects the vertebrae), tenosynovitis (inflammation of the tendon sheath), urinary incontinence, sudden and powerful urge to urinate, presence of blood in the urine, bladder spasms, urinary tract disorders, obstruction of the urinary tract,breast growth in men,testicular disorder, generalized pain,edema (swelling), generalized fatigue, essential fever (pyrexia), sterile abscess at the injection site, hematoma at the injection site, chills, nodule, thirst, inflammation, pelvic fibrosis, increase in urea in the blood, increase in uric acid in the blood, increase in creatinine in the blood, increase in calcium in the blood, abnormal electrocardiogram, signs of myocardial ischemia (lack of blood flow to a part of the myocardium in the heart) on the electrocardiogram, decrease in platelets, decrease in potassium in the blood, increase in white blood cells, decrease in white blood cells, increase in prothrombin time, increase in activated partial thromboplastin time, heart murmur (sound that indicates a malfunction of the heart), increase in low-density lipoproteins in the blood (a type of fat),increase in triglyceridesin the blood, increase in bilirubin in the blood,vertebral column fracture.

Seek immediate medical attention if you notice any of the following symptoms:

If you notice circular or target-shaped red patches on the trunk, 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).

Redness of the skin and rash with itching (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).

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 prospectus. You can also report them directly through theSpanish 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 medication.

Keep out of sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Dispose of packaging and unused medications at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of packaging and unused medications. In this way, you will help protect the environment.

Composition of Procrin Semestral

The active principle is leuprorelin acetate. Each preloaded syringe contains 30 mg of leuprorelin (as acetate) equivalent to 28.58 mg of leuprorelin.

The other components are:

Powder: Polylactic acid and mannitol.

Solvent: Carboxymethylcellulose sodium, mannitol, polysorbate 80, and water for injectable preparations.

1BAppearance of the product and contents of the packaging

Each package contains a preloaded syringe with a double-chamber syringe with a 23 G single-use needle, a plunger, and an isopropyl alcohol 70% impregnated wipe.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

AbbVie Spain S.L.U.,

Avenida de Burgos 91,

28050 Madrid,

Spain.

Responsible for manufacturing

ABBVIE LOGISTICS B.V.

Zuiderzeelaan 53 8017 Zwolle,

Netherlands

or

AbbVie Deutschland GmbH&Co.KG,

Knollstrasse,

67061 Ludwigshafen,

Germany

Last review date of this leaflet: February 2025

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

2BAdditional information for the healthcare professional

Instructions for the correct administration of the preparation: