Eligard 45 mg

Package leaflet: Information for the user

Eligard 45 mg,
powder and solvent for solution for injection
Leuprorelin acetate
Please read all of this leaflet carefully before 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, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Eligard is and what it is used for

The active substance in Eligard belongs to a group of medicines called gonadoliberins. These medicines are used to suppress the production of certain sex hormones (testosterone).
Eligard is used in adult men for the treatment of metastatic prostate cancer that is hormone-sensitive, and in combination with radiotherapy – for the treatment of high-risk, non-metastatic prostate cancer that is hormone-sensitive.

2. Important information before using Eligard

When not to use Eligard

• In women and children.
• If the patient is allergic to the active substance – leuprorelin acetate, to any compound acting similarly to the naturally occurring hormone gonadotropin-releasing hormone (GnRH), or to any of the other ingredients of Eligard (listed in section 6).
• After surgical removal of the testes, because Eligard does not further reduce serum testosterone concentration.
• As the sole treatment if the patient has symptoms related to spinal cord compression or spinal metastases. In such cases, Eligard may only be used in combination with other medications used in the treatment of prostate cancer.

Warnings and precautions
Before starting treatment with Eligard, discuss the following with your doctor, pharmacist, or nurse:

• If you have any of the following conditions: any heart or blood vessel disorders, including heart rhythm disorders (arrhythmia), or if you are taking medications for these conditions. The risk of heart rhythm disturbances may increase during treatment with Eligard.
• If you have difficulty urinating. In such cases, the patient's condition should be monitored during the first weeks of treatment.
• If symptoms of spinal cord compression or difficulty urinating worsen. When drugs similar in action to Eligard are used concomitantly, severe cases of spinal cord compression and ureteral obstruction have been observed, which may lead to symptoms resembling paralysis. In such cases, standard treatment must be initiated.
• If the patient experiences sudden headache, vomiting, change in mental status, or circulatory collapse within two weeks after administration of Eligard. In such cases, contact your doctor or medical personnel immediately. These are symptoms of a rare condition called pituitary apoplexy, which has been reported in association with other drugs similar in action to Eligard.
• If the patient has diabetes (elevated blood sugar levels). In such cases, the patient's condition should be monitored during treatment.
• Treatment with Eligard may increase the risk of fractures due to osteoporosis (reduced bone density).
• There have been reports of depression in patients receiving Eligard. If depressive symptoms occur during treatment with Eligard, inform your doctor.
• There have been reports of cardiovascular disorders in patients receiving drugs similar to Eligard; it is not known whether their occurrence is related to the use of these drugs. If cardiovascular symptoms develop during treatment with Eligard, inform your doctor.
• There have been reports of seizures in patients receiving Eligard. If seizures occur during treatment with Eligard, inform your doctor.
• If the patient experiences severe or recurring headaches, visual disturbances, or ringing or buzzing in the ears, seek medical advice immediately.
• If the patient has fatty liver disease (hepatic steatosis).

Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), have been reported with leuprorelin use. If any symptoms of serious skin reactions described in section 4 occur, leuprorelin should be discontinued immediately and medical advice sought without delay.

Complications occurring during the initial phase of Eligard treatment
During the first week of treatment, a transient increase in blood testosterone levels may occur, which may lead to a temporary worsening of disease symptoms or the appearance of new symptoms not previously present. These symptoms include, in particular: bone pain, urinary disturbances, spinal cord compression, and presence of blood in urine. These symptoms usually resolve during continued treatment. If symptoms do not resolve, contact your treating physician.

Lack of effectiveness of Eligard
In some patients, tumors may be present that are not sensitive to reduced serum testosterone levels. If you feel that Eligard is not providing adequate effect, inform your treating physician.

Eligard with other medicines
Eligard may affect the action of certain drugs used to treat heart rhythm disorders (e.g. quinidine, procainamide, amiodarone, and sotalol) or may increase the risk of heart rhythm disturbances when used with certain other drugs (e.g. methadone (used for pain relief and detoxification in drug addicts), moxifloxacin (an antibiotic), antipsychotics used in the treatment of severe psychiatric disorders).

Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken, including those obtained without a prescription.

Pregnancy and breastfeeding
Eligard is contraindicated in women.

Driving and operating machinery
Fatigue, dizziness, and visual disturbances may be adverse effects of Eligard or may result from the underlying disease. If any of the adverse effects listed above occur, caution should be exercised when driving or operating machinery.

3. How to use Eligard

Dosage
This medicine should always be used as directed by a physician or pharmacist. If in doubt,
consult a physician or pharmacist.
Unless otherwise directed by the physician, Eligard is administered once every 6 months.
After injection, the solution forms a depot of the active substance, from which leuprorelin acetate is continuously released over a period of 6 months.

Additional monitoring
The response to treatment with Eligard should be monitored by the treating physician based on clinical symptoms and blood levels of prostate-specific antigen (PSA).

Method of administration
Eligard must be administered exclusively by a physician or nurse, who will also prepare the product.
After preparation, Eligard is given as a subcutaneous injection (injection into the tissue beneath the skin). Intravascular (intra-arterial or intravenous) injection must be strictly avoided. As with other active substances administered by subcutaneous injection, the injection site should be rotated periodically.

Use of a higher than recommended dose of Eligard
Since the medicine is usually administered by a physician or appropriately trained medical personnel, overdose appears unlikely.
However, if a higher than recommended dose is administered, the treating physician will advise patient monitoring and appropriate treatment, if necessary.

Missed dose of Eligard
If there is a suspicion that a 6-month dose of the medicine has been missed, the treating physician should be informed immediately.

Discontinuation of Eligard treatment
Long-term administration of Eligard is required for the treatment of advanced prostate cancer.
Therefore, treatment should not be interrupted, even if the patient's condition improves or disease symptoms subside.
Premature discontinuation of treatment may result in worsening of disease symptoms.
Treatment must not be stopped prematurely without prior consultation with the physician.

If you have any further questions concerning the use of this medicine, consult your physician,
pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, Eligard may cause adverse reactions, although not everyone will experience them.
Adverse reactions observed during the use of Eligard are primarily due to the specific action of leuprorelin acetate, which increases or decreases the concentration of certain hormones. The most commonly observed adverse reactions are hot flushes (in approximately 58% of patients), nausea, malaise and fatigue, and transient injection site reactions.

Adverse reactions during the initial treatment period
During the first weeks of treatment with Eligard, symptoms of the disease may temporarily worsen due to an initial, short-term increase in blood levels of the male sex hormone testosterone. Therefore, your doctor may prescribe an appropriate antiandrogen (a substance that reduces the effects of testosterone) at the beginning of treatment to minimize this effect of the drug (see also section 2. Important information before using Eligard; Complications occurring during the initial period of treatment).

Local adverse reactions
Local adverse reactions described after injection of Eligard are similar to those commonly observed after subcutaneous injection (injection into the tissue beneath the skin) of similar drugs. A mild burning sensation immediately after injection occurs very commonly. A pricking sensation and pain at the injection site, as well as bruising at the injection site, occur commonly. Redness at the injection site has been reported commonly. Tissue hardening and ulceration at the injection site occur uncommonly.
The above-mentioned local adverse reactions following subcutaneous administration are mild and described as transient. They do not recur between subsequent injections.

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

• Hot flushes
• Spontaneous bleeding from skin and mucous membranes, skin redness
• Fatigue, injection site reactions (see above: Local adverse reactions)

Common adverse reactions (may affect less than 1 in 10 people)

• Nasopharyngitis (cold-like symptoms)
• Nausea, malaise, diarrhoea, gastroenteritis (inflammation of the stomach and intestines/colon)
• Itching, night sweats
• Joint pain
• Irregular urination (including at night), difficulty in urinating, painful urination, reduced urine volume
• Breast tenderness, breast swelling, testicular atrophy, testicular pain, infertility, erection disorders, reduced penis size
• Chills (episodes of shivering with high fever), weakness
• Prolonged bleeding time, changes in blood parameter values, decreased number of red blood cells/low number of red blood cells

Uncommon adverse reactions (may affect less than 1 in 100 people)

• Urinary tract infections, local skin infections
• Worsening of diabetes symptoms
• Vivid dreams, depression, decreased libido
• Dizziness, headache, disturbances in skin sensation, insomnia, taste disturbances, smell disturbances
• Hypertension (high blood pressure), hypotension (low blood pressure)
• Shortness of breath
• Constipation, dry mouth, dyspepsia (impaired digestion with a feeling of fullness in the stomach, stomach pain, belching, nausea, vomiting, burning sensation in the stomach), vomiting
• Increased skin moisture, excessive sweating
• Back pain, muscle cramps
• Haematuria (presence of blood in urine)
• Bladder spasm, increased frequency of urination, inability to urinate
• Gynaecomastia (breast enlargement in men), impotence
• Lethargy (drowsiness), pain, fever
• Weight gain
• Loss of balance, feeling of emptiness in the head
• Muscle atrophy/muscle tissue loss after long-term use

Rare adverse reactions (may affect less than 1 in 1000 people)

• Involuntary movements
• Sudden loss of consciousness, fainting
• Bloating with flatulence, belching
• Hair loss, skin eruptions (skin pimples)
• Breast pain
• Ulceration at the injection site

Very rare adverse reactions (may affect less than 1 in 10,000 people)

• Necrosis at the injection site

Frequency not known (cannot be estimated from available data)

• Changes in electrocardiogram (prolongation of QT interval)
• Pneumonia, lung disease
• Idiopathic intracranial hypertension (increased intracranial pressure around the brain, characterized by headache, double vision and other visual disturbances, and ringing or buzzing in one or both ears)
• Red, non-raised, target-shaped or round lesions on the trunk, often with blisters in the center, skin peeling, ulceration of the mouth, throat, nose, genital organs and eyes. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Skin redness and itchy rash (toxic skin eruptions)
• Skin reaction causing red spots or lesions that may resemble a bull's-eye with a dark red center surrounded by lighter red rings (erythema multiforme)

Other adverse reactions
Other adverse reactions described in the literature as associated with leuprorelin treatment—the active substance in Eligard—include peripheral oedema (fluid accumulation in tissues, manifesting as swelling of hands and feet), pulmonary embolism (manifesting as breathlessness, difficulty breathing and chest pain), palpitations (awareness of heart beating), decreased muscle strength, chills, rash, memory disturbances and visual disturbances. With long-term treatment with Eligard, an increased frequency of symptoms related to decreased bone density (osteoporosis) may be expected. Due to osteoporosis, the risk of fractures is increased.
Severe allergic reactions causing difficulty in breathing or dizziness have been rarely reported with products belonging to the same group as Eligard.
Seizures have been reported with products belonging to the same group as Eligard.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Eligard 45 mg

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after EXP.
The expiry date refers to the last day of the stated month.
Storage instructions
Store in a refrigerator (2°C to 8°C).
Store in the original packaging to protect from moisture.
Before injection, the medicinal product must be at room temperature. Remove it from the refrigerator approximately 30 minutes before preparation. After removal from the refrigerator, the product may be stored in its original packaging at room temperature (below 25°C) for up to 4 weeks.
After first opening the plastic tray sealed with foil, the solution should be prepared immediately and administered to the patient as soon as possible. The product is for single use only.
Instructions for disposal of unused or expired Eligard 45 mg
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. Such measures will help protect the environment.

6. Contents of the pack and other information

What Eligard contains
The active substance in Eligard is leuprorelin acetate.
One pre-filled syringe (Syringe B) contains 45 mg of leuprorelin acetate.
The other ingredients are poly(DL-lactic-co-glycolic acid) (85:15) and N-methylpyrrolidone, contained in the pre-filled syringe with solvent for preparation of injection solution (Syringe A).

What Eligard looks like and contents of the pack
Eligard is a powder and solvent for solution for injection.
Eligard 45 mg is available in the following pack sizes:

• A set consisting of a thermoformed tray sealed with foil, containing a desiccant pouch and a connected syringe system, together with a sterile 18G needle, in a cardboard box. The tray contains:
  – Syringe A, containing the solvent,
  – Syringe B, containing the powder,
  – A connector with a snap button to join syringes A and B.
• A multipack containing 2 of the above sets, each set comprising one connected syringe system.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Recordati Industria Chimica e Farmaceutica S.p.A.
Via Matteo Civitali 1
20148 Milan
Italy

For further information, please contact the local representative of the Marketing Authorisation Holder:
Recordati Polska sp. z o.o.
Al. Armii Ludowej 26
00-609 Warsaw
tel: +48 22 206 84 50

This medicinal product is authorised in the Member States of the European Economic Area 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

Information intended exclusively for healthcare professionals:

Before opening, allow the medicinal product to reach room temperature by removing it from the refrigerator approximately 30 minutes prior to use.
First prepare the patient for administration of the product, then prepare the solution according to the instructions below. If the solution is not prepared using the correct technique, do not administer it to the patient, as improper reconstitution of the medicinal product may result in lack of clinical efficacy.

Step 1
On a clean surface, open the tray by peeling off the foil starting from the corners to remove the contents. Remove the moisture-absorbing packet. Take out the connected syringe system (Fig. 1.1) from the tray. Open the package containing the needle with safety shield (Fig. 1.2) by peeling off the paper part of the packaging.
Note: Syringe A and Syringe B should not yet be aligned in a straight line.
Fig. 1.1 Fig. 1.2
Contents of the tray: connected syringe system
Under the tray: Needle with safety shield and adapter

Step 2
Using your finger and thumb, press the locking clip on the connector (Fig. 2) until you hear and feel a click. The two syringes will become aligned in a straight line. Activation of the connector does not require any specific positioning of the connected syringe system. Do not bend the connected syringe system (note that this could cause leakage, as the syringes may become partially unscrewed).

Step 3
Holding the syringes horizontally, transfer the liquid content of Syringe A into the leuprolide acetate powder contained in Syringe B. Mix thoroughly for 60 cycles by gently moving the contents back and forth between both syringes (one cycle equals one push of the plunger of Syringe A and one push of the plunger of Syringe B), with the syringes held horizontally, until a uniform, viscous solution is obtained (Fig. 3). Do not bend the connected syringe system (note that this could cause leakage, as the syringes may become partially unscrewed).

Repeat 60 times
After thorough mixing, the viscous solution should be colorless to white or pale yellow (shades from white to pale yellow).
Important: Immediately proceed to the next step after mixing, as viscosity increases over time. Do not freeze the mixed product.
Note: The product must be mixed according to these instructions; shaking will NOT ensure proper mixing.

Step 4: After mixing, hold the syringes vertically with Syringe B on the bottom. The syringes should remain properly connected. Transfer the entire mixed product into Syringe B (the wider syringe) by pushing the plunger of Syringe A while slightly pulling back the plunger of Syringe B (Fig. 4).
Fig. 4

Step 5
Ensuring that the plunger of Syringe A is fully depressed, hold the connector and unscrew it from Syringe B. Syringe A will remain attached to the connector (Fig. 5). Ensure that no product leaks, as otherwise the needle, once attached, may not properly secure the syringe.
Note: One large or several small air bubbles may remain in the mixture – this is normal.
Do NOT remove air bubbles from Syringe B at this stage, as this may result in product loss!
Fig. 5

Step 6

• Hold Syringe B vertically and hold the white plunger to prevent product loss.
• Attach the needle with safety shield to Syringe B by holding the syringe and gently twisting the needle approximately three-quarters of a turn clockwise until firmly secured (Fig. 6). Do NOT overtighten, as this may cause the needle hub to crack and lead to product leakage during injection. Excessive force may also damage the safety shield.

If the needle hub is cracked or appears damaged, or if leakage is observed, do not administer the medicinal product. Do not replace or substitute the damaged needle, and do not inject the product. All unused components must be safely discarded.
In case of damage to the needle hub, a new medicinal product must be administered.

Step 7
Bend back the safety shield from the needle and remove the protective cap covering the needle tip immediately before administering the medicinal product (Fig. 7).
Important: Do not manipulate the needle safety shield mechanism before administration. If the needle hub appears damaged or leakage is observed, DO NOT use the product. Do NOT replace the damaged needle with another one, and DO NOT administer the product. In case of damage to the needle hub, use a new Eligard medicinal product kit.
Fig. 7

Step 8
Before administering the medicinal product, remove all large air bubbles from Syringe B. Administer this product subcutaneously with the safety shield bent away from the needle.
Administration procedure: Fig. 8

• Select an injection site not recently used, on the abdomen, upper buttock area, or another location with sufficient subcutaneous tissue and free of discoloration, nodules, lesions, or hair.
• Clean the injection site using an alcohol swab (not included).
• Using your thumb and index finger, pinch and hold the skin around the injection site.
• With your dominant hand, quickly insert the needle at a 90° angle to the skin surface. Depth of penetration will depend on the amount and density of subcutaneous tissue and needle length. Release the skin after needle insertion.
• Inject the product slowly and evenly by pressing the plunger until the syringe is completely empty. Before removing the needle, ensure that the entire content of Syringe B has been administered.
• While maintaining pressure on the plunger, quickly withdraw the needle at the same 90° angle used for insertion.

Step 9
After administering the medicinal product, close the needle safety shield using one of the methods described below.

1. Closing on a flat surface

Press the safety shield, with the lever facing downward, against a flat surface (Fig. 9a) to cover the needle and lock the safety shield.
The shield is closed when you hear and feel a click. In the closed position, the needle tip will be completely covered.

2. Closing with the thumb

Place your thumb on the safety shield (Fig. 9b), cover the needle tip, and close the safety shield.
The shield is closed when you hear and feel a click. In the closed position, the needle tip will be completely covered.
Fig. 9a Fig. 9b
Closing on a flat surface Closing with the thumb

After closing the safety shield, immediately dispose of the needle and syringe into a sharps container.