Eligard Semestral 45 mg powder and solvent for solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

Eligard 6-Month 45 mg

Powder and solvent for injectable solution

Leuprorelin acetate.

Read the entire patient information leaflet carefully before you start using this medicine, as it contains important information for you. Keep this leaflet as you may need to read it again. If you have any questions, consult your doctor, pharmacist, or nurse. This medicine has been prescribed for you only; do not give it to other people, 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 adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet:

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

1. What Eligard semestral is and what it is used for

The active substance in Eligard semestral belongs to the group of gonadotropin-releasing hormone analogues. These medicines are used to reduce the production of certain sex hormones (testosterone).

Eligard semestral is used to treat metastatic hormone-dependent prostate carcinoma in adult males and for the treatment of high-risk non-metastatic hormone-dependent prostate carcinoma in combination with radiotherapy.

2. What you need to know before starting to use Eligard semiannual

Do not use Eligard semiannual

• If you are a woman or a child.
• If you are hypersensitive (allergic) to the active substance leuprorelin acetate, to medicines with activity similar to natural gonadotropin-releasing hormone, or to any of the other components of Eligard semiannual (listed in section 6).
• After surgical removal of your testicles, since in this case Eligard semiannual does not lead to a further decrease in serum testosterone concentrations.
• As monotherapy if you have symptoms related to pressure on the spinal cord or a tumor in the spine. In this case, Eligard semiannual may only be used in combination with other medications for prostate carcinoma.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Eligard semiannual

• If you have: any heart or blood vessel disorder, including heart rhythm problems (arrhythmias), or if you are being treated with medications to correct these conditions. The risk of heart rhythm problems may be increased with the use of Eligard semiannual.

• If you have difficulty urinating. You should be closely monitored during the first weeks of treatment.

• If you start experiencing pressure on the spinal cord or difficulty urinating. Serious cases (associated with other medicines that have a mechanism of action similar to Eligard semiannual) of pressure on the spinal cord and narrowing of the tubes between the kidneys and the urinary bladder have been reported, which may lead to symptoms resembling paralysis. If these complications occur, standard treatment for such conditions should be initiated.

• If, within two weeks after receiving Eligard semiannual, you experience sudden headache, vomiting, altered mental status, and sometimes cardiac collapse, notify your doctor or medical team. Rarely, such cases have been reported with OTHER MEDICINES that have a similar mechanism of action to Eligard semiannual, known as pituitary apoplexy.

• If you have diabetes mellitus (high blood glucose levels). You should be monitored frequently during treatment.

• Treatment with Eligard semiannual may increase the risk of fractures due to osteoporosis (reduced bone density).

• Cases of depression have been reported in patients using Eligard semiannual. If you are using Eligard semiannual and begin to experience depressive mood, inform your doctor.

• Cases of cardiovascular effects have been reported in patients using medicines similar to Eligard semiannual; it is unknown whether these are related to the medicines. If you are using Eligard semiannual and develop signs or symptoms of cardiovascular problems, inform your doctor.

• Cases of epileptic seizures have been reported in patients after administration of Eligard semiannual. If you are using Eligard semiannual and begin to experience epileptic seizures, inform your doctor.

• Contact your doctor immediately if you experience severe or recurrent headaches, visual disturbances, or tinnitus (ringing in the ears).

• You have fatty liver.

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

Complications at the start of treatment

During the first week of treatment, there is usually a brief increase in the male sex hormone, testosterone, in the blood. This may lead to a temporary worsening of disease-related symptoms and may also cause new symptoms not previously experienced. These symptoms include especially bone pain, urinary disturbances, pressure on the spinal cord, or presence of blood in the urine. These symptoms usually resolve as treatment continues. If symptoms do not resolve, you should contact your doctor.

If you do not improve with Eligard semiannual

A proportion of patients will have tumors that are not sensitive to reduced serum testosterone concentrations. If you feel that the effect of Eligard semiannual is not as expected, inform your doctor.

Use of Eligard semiannual with other medicines

This medicine may interfere with certain drugs 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 certain medicines (e.g., methadone (used for pain relief and as part of drug addiction detoxification), moxifloxacin (an antibiotic), antipsychotics used for serious mental illnesses).

Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription.

Pregnancy and breastfeeding

This medicine is contraindicated in women.

Driving and using machines

Fatigue, dizziness, and visual disturbances are possible side effects of treatment with Eligard semiannual or may occur due to the underlying disease. If you experience these adverse effects, take care when driving or operating machinery.

3. How to use Eligard 6-month

Dosage

Follow exactly the instructions for administration of this medicine as given by your doctor or pharmacist. If in doubt, please consult your doctor or pharmacist again.

Unless otherwise prescribed by your doctor, this medicine is administered once every six months.

The injected solution forms a depot of active substance from which the active ingredient, leuprorelin acetate, is continuously released over a period of six months.

Additional tests

The response to treatment with this medicine must be reviewed by your doctor by checking specific clinical values and determining blood concentrations of prostate-specific antigen (PSA).

Method of administration

This medicine must only be administered by your doctor or nurse. They are responsible for its preparation.

After preparation, Eligard 6-month is administered as a subcutaneous injection (an injection into the tissue beneath the skin). Intraarterial (into an artery) or intravenous (into a vein) injection must be completely avoided. As with other active substances administered by subcutaneous injection, the injection site should be changed periodically.

If you receive more Eligard 6-month than you should

Since the injection is normally administered by your doctor or qualified personnel, overdose is not expected.

Nevertheless, if a larger than intended amount has been administered, contact your doctor so that you can be closely monitored and receive additional treatment as necessary, or contact the Toxicology Information Service. Telephone 91 562 04 20.

If you forget to administer Eligard 6-month

Talk to your doctor if you think you have missed your scheduled six-month administration of the medicine.

Effects when treatment with Eligard 6-month is interrupted

As a general rule, treatment of prostate cancer with this medicine is prolonged. Therefore, treatment should not be stopped, even if symptoms improve or disappear completely.

If treatment with this medicine is stopped prematurely, worsening of disease-related symptoms may occur.

Do not stop treatment prematurely without first consulting your doctor.

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

4. Possible adverse effects

Like all medicines, Eligard semestral may cause adverse effects, although not everyone experiences them.

The adverse effects observed during treatment with Eligard semestral are mainly attributed to the specific action of the active substance, leuprorelin acetate, particularly the increase and decrease of certain hormones. The most frequently reported adverse effects are hot flushes (in approximately 58% of patients), nausea, malaise, fatigue, and temporary local irritation at the injection site.

Adverse effects at the beginning of treatment

During the first weeks of treatment with Eligard semestral, specific symptoms of the disease may worsen, because initially there is a brief increase in the male sex hormone testosterone in the blood. Therefore, your doctor may administer an appropriate antiandrogen (a substance that inhibits the effect of testosterone) during the initial phase of treatment to reduce possible undesirable effects. (See also Section 2 Before using Eligard semestral, Complications at the beginning of treatment).

Local adverse effects

Local adverse effects reported after injection of Eligard semestral are typically those often associated with similar preparations administered subcutaneously (preparations injected into the tissue beneath the skin). Mild burning immediately after injection is very common. Stinging and pain after injection, as well as bruising at the injection site, are common. Redness of the skin at the injection site has been frequently reported. Tissue hardening and ulceration are uncommon.

These local adverse effects following subcutaneous injection are mild and have been described as short-lived. They do not recur between individual injections.

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

• Hot flushes
• Spontaneous bleeding in the skin or mucous membranes, redness of the skin
• Fatigue, injection-related adverse effects (See also local adverse effects above)

Common adverse effects (may affect up to 1 in 10 people)

• Nasopharyngitis (common cold symptoms)
• Nausea, malaise, diarrhoea, inflammation of the stomach and intestines (gastroenteritis/colitis)
• Itching, night sweats
• Joint pain
• Irregular urination (including at night), difficulty starting to urinate, pain when urinating, reduced urine volume
• Breast tenderness, breast enlargement, testicular shrinkage, testicular pain, infertility, erectile dysfunction, reduction in penis size
• Rigidity (episodes of exaggerated shivering with high fever), weakness
• Prolonged bleeding time, changes in blood values, reduction in red blood cells/low red blood cell count

Uncommon adverse effects (may affect up to 1 in 100 people)

• Urinary tract infection, local skin infection
• Worsening of diabetes mellitus
• Abnormal dreams, depression, decreased libido
• Dizziness, headache, skin sensation disorders, insomnia, taste disturbance, smell disturbance
• Hypertension (increased blood pressure), hypotension (decreased blood pressure)
• Shortness of breath
• Constipation, dry mouth, dyspepsia (indigestion, feeling of fullness, stomach pain, belching, nausea, vomiting, burning sensation in the stomach), vomiting
• Feeling of warmth, increased sweating
• Low back pain, muscle cramps
• Haematuria (blood in urine)
• Bladder spasms, increased frequency of urination, inability to urinate
• Gynecomastia (enlargement of male breast tissue), impotence
• Lethargy (drowsiness), pain, fever
• Weight gain
• Loss of balance, dizziness
• Loss of muscle mass/muscle tissue loss after prolonged use

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

• Abnormal involuntary movements
• Sudden loss of consciousness, fainting
• Flatulence, belching
• Hair loss, skin rash (skin pimples)
• Breast pain
• Ulceration at the injection site

Very rare adverse effects (may affect up to 1 in 10,000 people)

• Necrosis at the injection site

Not known (frequency cannot be estimated from available data)

• Changes in electrocardiogram (prolongation of QT interval)
• 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)
• If you notice circular or target-shaped, reddish, non-elevated spots on your trunk, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe skin rashes 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 causing bumps or red spots on the skin, which may resemble targets, with a dark red center surrounded by rings of lighter red (erythema multiforme)

Other adverse effects

Other adverse effects reported with leuprorelin, the active substance in Eligard semestral, include oedema (fluid accumulation in tissues, appearing as swelling of hands and feet), pulmonary embolism (causing symptoms such as breathlessness, difficulty breathing, and chest pain), palpitations (awareness of heartbeats), muscle weakness, chills, skin rash, memory loss, and deterioration in vision. An increased loss of bone tissue (osteoporosis) can be expected after prolonged treatment with Eligard semestral. Due to osteoporosis, the risk of fractures increases.

Severe allergic reactions causing difficulty breathing or dizziness have rarely been reported following administration of products of the same class as Eligard semestral.

Seizures have been reported following administration of products of the same class as Eligard semestral.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Eligard Semestral

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Storage instructions

Store in a refrigerator (between 2°C and 8°C).

Keep in the original packaging to protect from moisture.

This product must be brought to room temperature before injection. Remove from the refrigerator approximately 30 minutes before use. After removal from the refrigerator, this product may be stored in its original packaging at room temperature (below 25°C) for up to 4 weeks.

Once the tray has been opened, the product must be prepared immediately and used promptly. For single use only.

Instructions for disposal of unused or expired Eligard Semestral containers

Medicines must not be disposed of via wastewater or household waste. Return unused or expired containers and medicines to your pharmacy’s SIGRE point. If in doubt, ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Eligard Semestral

The active substance is leuprolide acetate.

One pre-filled syringe (Syringe B) contains 45 mg of leuprolide acetate.

The other components are poly(DL-lactic-co-glycolic) acid (85:15) and N-methyl-2-pyrrolidone in the pre-filled syringe with injectable solution (Syringe A).

Appearance of Eligard Semestral and contents of the pack

Powder and solvent for injectable solution.

It is available in the following pack sizes:

• One thermoformed tray and one sterile 18-gauge needle inserted into a cardboard holder. The tray contains a desiccant bag and a pre-connected syringe system consisting of:

• Syringe A pre-filled with solvent

• Syringe B pre-filled with powder

• A connector with a locking button for Syringes A and B

• A multiple pack containing 2 pre-connected syringe system kits.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Recordati Industria Chimica e Farmaceutica S.p.A.
Via Matteo Civitali, 1
20148 Milan
Italy

Manufacturer

Recordati Industria Chimica e Farmaceutica S.p.A.
Via Matteo Civitali, 1
20148 Milan
Italy

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Casen Recordati, S.L.
Autovía de Logroño, km 13.300
50180 Utebo - Zaragoza
Spain

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

Austria: Eligard Depot 45 mg
Belgium: Depo-Eligard 45 mg
Bulgaria: Eligard 45 mg
Cyprus: Eligard
Czech Republic: Eligard
Denmark: Eligard
Estonia: Eligard
Finland: Eligard
France: Eligard 45 mg
Germany: Eligard 45 mg
Hungary: Eligard 45 mg
Iceland: Eligard
Ireland: Eligard 45 mg
Italy: Eligard
Latvia: Eligard 45 mg
Lithuania: Eligard 45 mg
Luxembourg: Depo-Eligard 45 mg
Netherlands: Eligard 45 mg
Norway: Eligard
Poland: Eligard 45 mg
Portugal: Eligard 45 mg
Romania: Eligard 45 mg
Slovakia: Eligard 45 mg
Slovenia: Eligard 45 mg
Spain: Eligard semestral 45 mg
Sweden: Eligard

Date of the most recent review of this leaflet: 10/2024

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicinal Products and Health Products (AEMPS): http://www.aemps.es/

This information is intended for healthcare professionals only:

Allow the medicine to reach room temperature by removing it from the refrigerator approximately 30 minutes before use.

Please first prepare the patient for injection, then prepare the medicine following the instructions given below. If the medicine is not prepared using the correct technique, it must not be administered, as incorrect reconstitution may result in lack of clinical efficacy.

Step 1

On a clean surface, open the tray by peeling back the aluminum foil at the corner to remove the contents. Discard the desiccant bag. Remove the pre-connected syringe system (Figure 1.1) from the tray. Open the safety needle package (Figure 1.2) by removing the paper tab. Note: Syringe A and Syringe B should not be aligned yet.

Figure 1.1 Tray contents: pre-connected syringe system	Figure 1.2 Under the tray: safety needle and cap

Step 2

Hold the connector's locking button with your index finger and thumb and press (Figure 2) until you hear a click. The two syringes will be aligned. No specific orientation of the syringe system is required to activate the connector. Do not bend the syringe system (please note that some medication may leak out if the syringes are partially unscrewed).

Figure 2

Step 3

Hold the syringes horizontally. Transfer the liquid contents from syringe A into the leuprorelin acetate powder contained in syringe B. Mix the product thoroughly for 60 cycles by gently pushing the contents back and forth between both syringes (one cycle equals one plunger push for syringe A and one plunger push for syringe B), keeping the syringes in a horizontal position, until a homogeneous and viscous solution is obtained (Figure 3). Do not bend the syringe system (please note that some of the medication may be lost if the syringes are partially unscrewed).

Figure 3

When thoroughly mixed, the viscous solution will have a color ranging from colorless to white-yellowish (which may include shades from white to pale yellow).

Important: after mixing, proceed immediately to the next step, as the viscosity of the product increases over time. Do not refrigerate the medication once reconstituted.

Please note: The medication must be mixed as described; shaking will not yield an adequate mixture.

Step 4

After mixing, hold the syringes vertically with syringe B at the bottom. The syringes must remain securely connected. Transfer the entire contents into syringe B (wide syringe) by pushing the plunger of syringe A while slightly retracting the plunger of syringe B (Figure 4).

Figure 4

Step 5

While ensuring that the plunger of syringe A is fully pressed down, hold the connector and unscrew it from syringe B. Syringe A will remain attached to the connector (Figure 5). Make sure the contents do not spill out, as otherwise the needle will not fit properly when attached.

Please note: It is acceptable if a large air bubble or several small ones remain after preparation. Please do not purge the air bubbles from syringe B at this stage, as this would result in loss of medication!

Figure 5

Step 6

• Keep syringe B in an upright position and hold back the white plunger to prevent loss of medication.

• Attach the safety needle to syringe B by holding the syringe and gently turning the needle clockwise approximately three-quarters of a turn until securely fixed (Figure 6).

Do not over-tighten, as this may crack the needle hub and cause medication to leak during injection. The safety cap may also be damaged if the needle is screwed on too tightly.

The medication must not be used if the needle hub is cracked, damaged, or leaking contents. A damaged needle must not be replaced or substituted, and the medication must not be injected. All components of the administration device must be safely discarded.

If the needle hub becomes damaged, the medication must be replaced with a new one.

Figure 6

Step 7

Immediately before administration, pull the safety cover away from the needle and remove the needle protective cap (Figure 7).

Important: Do not handle the safety needle mechanism before administration. If the needle appears damaged or is leaking, the product MUST NOT be used. A damaged needle MUST NOT be replaced, and the medication MUST NOT be injected. If the needle is damaged, use another ELIGARD kit.

Figure 7

Step 8

Before administration, purge any large air bubbles from Syringe B. Administer the medication subcutaneously while keeping the safety shield away from the needle.

Administration procedure:

• Select an injection site on the abdomen, upper buttocks, or another area with adequate amounts of subcutaneous tissue that has no excess pigmentation, nodules, lesions, or hair, and that has not been used recently.
• Clean the injection site area with an alcohol swab (not included).
• Using your thumb and index finger, pinch and hold the skin around the injection site.
• Using your dominant hand, insert the needle quickly at a 90° angle relative to the skin surface. The depth of penetration will depend on the amount and thickness of the subcutaneous tissue and on the needle length. After inserting the needle, release the skin.
• Inject the medication by slowly and steadily pushing the plunger until the syringe is empty. Be sure to inject the full dose from Syringe B before removing the needle.
• Remove the needle quickly at the same 90° angle used for insertion, while maintaining pressure on the plunger.

Figure 8

Step 9

After injection, lock the safety mechanism using one of the activation methods described below.

1. Closing against a flat surface

Press the safety shield with the slider facing downward against a flat surface (Figure 9a) to cover the needle and lock the shield.

Verify the locked position by an audible and tactile "click." The locked position will completely cover the needle tip.

2. Closing with your thumb

Place your thumb on the safety shield (Figure 9b) and slide it forward to cover the needle tip and lock the shield.

Verify the locked position by an audible and tactile "click." The locked position will completely cover the needle tip.

Figure 9a Closing on a flat surface	Figure 9b Closing with your thumb

Once the safety shield is locked, immediately dispose of the needle and syringe in an authorized sharps container.