Crusia

Package leaflet: Information for the patient

Crusia, 2000 IU (20 mg)/0.2 ml, solution for injection in pre-filled pen
Crusia, 4000 IU (40 mg)/0.4 ml, solution for injection in pre-filled pen
Crusia, 6000 IU (60 mg)/0.6 ml, solution for injection in pre-filled pen
Crusia, 8000 IU (80 mg)/0.8 ml, solution for injection in pre-filled pen
Crusia, 10,000 IU (100 mg)/1 ml, solution for injection in pre-filled pen
This medicinal product will be subject to additional monitoring. This will allow for rapid
identification of new safety information. Patients can also help by reporting any adverse reactions experienced after using the medicine. For information on how to report adverse reactions – see section 4.
Enoxaparin sodium
Please read all of this leaflet carefully before 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 further questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Crusia is and what it is used for

Crusia contains the active substance enoxaparin sodium, which is a low molecular weight heparin (LMWH).
Crusia works in two ways:

1. It prevents existing blood clots from growing larger. This helps the body dissolve existing clots, so they are no longer harmful.
2. It prevents the formation of new blood clots in the patient's blood.
   Crusia may be used for:

• Treating existing blood clots in the patient.
• Preventing the formation of blood clots in the patient in the following situations:
  • Before and after surgical procedures
  • During acute illness when the patient has limited mobility
  • If the patient has developed blood clots due to cancer, to prevent further clots
  • In unstable angina (a condition where insufficient blood reaches the heart)
  • After myocardial infarction (heart attack)
• Preventing clot formation in the dialysis filter (used in patients with severe kidney dysfunction).

2. Important information before using Crusia

When not to use Crusia

• If the patient is allergic to enoxaparin sodium or any of the other ingredients of this medicine (listed in section 6). Symptoms of an allergic reaction may include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue.
• If the patient has had an allergic reaction to heparin or other low molecular weight heparins, such as nadroparin, tinzaparin or dalteparin.
• If the patient has previously experienced a reaction to heparin that caused a serious drop in the number of blood cells responsible for blood clotting (platelets) – this reaction is known as heparin-induced thrombocytopenia – within the last 100 days, or if the patient has antibodies against enoxaparin in the blood.
• If the patient has active bleeding or a medical condition associated with an increased risk of bleeding (e.g. stomach ulcers, recent brain or eye surgery), including recent hemorrhagic stroke.
• If the patient is being treated with Crusia for blood clots and a spinal or epidural anaesthesia or lumbar puncture is planned within 24 hours.

Warnings and precautions
Crusia must not be used interchangeably with other medicines belonging to the group of low molecular weight heparins. This is because they are not exactly the same and differ in activity and instructions for use.
Before starting treatment with Crusia, discuss with your doctor or pharmacist if:

• the patient has ever had a reaction to heparin that caused a significant drop in platelet count
• the patient is scheduled to receive spinal or epidural anaesthesia or lumbar puncture (see "Surgical procedures and anaesthetics"): the appropriate time interval between administration of Crusia and the procedure must be taken into account
• the patient has had a heart valve implanted
• the patient has endocarditis (an infection of the inner lining of the heart)
• the patient has had or currently has stomach ulcers
• the patient has recently had a stroke
• the patient has high blood pressure
• the patient has diabetes or diabetic eye disease (so-called diabetic retinopathy)
• the patient has recently undergone eye or brain surgery
• the patient is elderly (over 65 years), especially if over 75 years of age
• the patient has kidney disease
• the patient has liver disease
• the patient is underweight or overweight
• the patient has elevated potassium levels in the blood (this can be checked with a blood laboratory test)
• the patient is currently taking medicines that may cause bleeding (see section below "Crusia and other medicines")

Before starting treatment with this medicine and periodically during treatment, the patient may undergo blood tests to monitor platelet count (blood cells responsible for clotting) and potassium levels in the blood.
Children and adolescents:
The safety and efficacy of enoxaparin have not been established in children and adolescents.
Crusia and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

• Warfarin – a medicine used to thin the blood
• Aspirin (also known as acetylsalicylic acid or ASA), clopidogrel, or other medicines used to prevent blood clots (see also section 3 "Changing anticoagulant therapy")
• Dextran injections – used as a blood volume expander
• Ibuprofen, diclofenac, ketorolac, or other medicines known as non-steroidal anti-inflammatory drugs (NSAIDs), used to treat pain and swelling in arthritis and other conditions
• Prednisolone, dexamethasone, or other medicines used to treat asthma, rheumatoid arthritis, and other conditions
• Medicines that increase potassium levels in the blood, such as potassium salts, diuretics, and certain medicines used for heart conditions.

Surgical procedures and anaesthetics
If the patient is scheduled for a lumbar puncture or surgery under epidural or spinal anaesthesia, inform the doctor that the patient is using Crusia. See section "When not to use Crusia". Additionally, inform the doctor of any spinal problems or if the patient has ever had spinal surgery.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Women who are pregnant and have a mechanical heart valve may be at increased risk of blood clots. The doctor should discuss this issue with the patient.
Women who are breastfeeding or intend to breastfeed should seek medical advice before starting treatment with this medicine.
Driving and operating machinery
Crusia has no effect on the ability to drive or operate machinery.
It is recommended that the doctor records the brand name and batch number of the product used.
Crusia contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, meaning it is considered "sodium-free".

3. How to use Crusia

This medicine should always be used exactly as prescribed by your doctor or pharmacist. If in doubt,
please consult your doctor or pharmacist.
Taking the medicine

• Crusia is usually administered by a doctor or nurse. This is because it must be given by injection.

• After returning home, you may need to continue treatment with Crusia and administer it yourself (see the administration instructions below).

• Crusia is usually given as a subcutaneous injection.

• Crusia may be given as an intravenous injection following certain types of heart attack or after surgery.

• Crusia may be administered into the dialysis tubing that carries blood away from the body (into the so-called arterial line) at the beginning of a dialysis session. Crusia must not be given by intramuscular injection.

Dosage

• Your doctor will decide the dose of Crusia you should receive. The dose depends on the reason for treatment.

• Patients with kidney disease may receive a lower dose of Crusia.

  1. Treatment of blood clots in the patient's blood

• The usual dose is 150 IU (1.5 mg) per kilogram of body weight once daily or 100 IU (1 mg) per kilogram of body weight twice daily.

• Your doctor will decide how long you should continue receiving Crusia.

  2. Prevention of blood clots in the following situations:
     • Surgery or periods of limited mobility due to illness

• The dose depends on the individual patient's risk of clot formation. You will receive Crusia at a dose of 2000 IU (20 mg) or 4000 IU (40 mg) daily.

• If you are scheduled for surgery, the first injection is usually given 2 hours or 12 hours before the procedure.

• If you have limited mobility due to illness, you usually receive Crusia at a dose of 4000 IU (40 mg) daily.

• Your doctor will decide how long you should continue receiving Crusia.

  • After a heart attack
    Crusia can be used in two types of heart attack: ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). The dose of Crusia will depend on the patient's age and the type of heart attack.

NSTEMI heart attack:

• The usual dose is 100 IU (1 mg) per kilogram of body weight every 12 hours.
• Your doctor will usually also recommend taking aspirin (acetylsalicylic acid).
• Your doctor will decide how long you should continue receiving Crusia.

STEMI heart attack in patients under 75 years of age:

• An initial dose of Crusia 3000 IU (30 mg) will be given by intravenous injection.
• Crusia will also be administered subcutaneously. The usual dose is 100 IU (1 mg) per kilogram of body weight every 12 hours.
• Your doctor will usually also recommend taking aspirin (acetylsalicylic acid).
• Your doctor will decide how long you should continue receiving Crusia.

STEMI heart attack in patients aged 75 years or older:

• The usual dose is 75 IU (0.75 mg) per kilogram of body weight every 12 hours.
• The maximum dose of Crusia in the first two doses is 7500 IU (75 mg).
• Your doctor will decide how long you should continue receiving Crusia.

Patients undergoing percutaneous coronary intervention (PCI):
Depending on when the last dose of Crusia was administered, your doctor may decide to give an additional dose of Crusia before the PCI procedure. The medicine will then be given by intravenous injection.

3. Prevention of blood clots in dialyzer tubing
   • The usual dose is 100 IU (1 mg) per kilogram of body weight.
   • Crusia is injected into the tubing carrying blood away from the body (into the so-called arterial line) at the start of the dialysis session. This dose is usually sufficient for a 4-hour dialysis session. However, if necessary, your doctor may administer an additional dose of 50 IU to 100 IU (0.5 to 1 mg) per kilogram of body weight.

Instructions for using pre-filled syringes
Self-administration of Crusia injections
If you are able to self-administer Crusia, your doctor or nurse will show you how to do it. Do not attempt to inject the medicine yourself until you have received proper instruction. If you are unsure what to do, speak to your doctor or nurse immediately. Correctly performing a subcutaneous injection (called a "subcutaneous injection") can help reduce pain and bruising at the injection site.
Before self-injecting Crusia

• Gather the necessary supplies: syringe, alcohol swab or soap and water, and a sharps container.
• Check the expiry date on the packaging. Do not use the medicine after the expiry date.
• Check that the syringe is undamaged and that the liquid is clear. If not, use a new syringe.
• Confirm the correct dose to be injected.
• Examine the abdomen to check whether the previous injection caused redness, skin discoloration, swelling, oozing, or if it is still painful. If so, consult your doctor or nurse.

Instructions for self-injecting Crusia:
(Instructions for pre-filled syringes without a safety system)
Preparing the injection site

1. Choose an injection site on the right or left side of the abdomen. The injection site should be at least 5 cm away from the navel, towards the sides.

• Do not inject within 5 cm of the navel or near existing scars or bruises.
• Rotate injection sites between the left and right sides of the abdomen, depending on the previous injection site.

2. Wash your hands. Clean (do not rub) the injection site with an alcohol swab or soap and water.
3. Sit or lie down in a comfortable position to relax. Ensure the injection site is clearly visible. A chair, examination table, or bed with supportive pillows is suitable.
   Selecting the dose
4. Carefully remove the needle cap from the syringe. Discard the cap.

• Do not press the plunger before injecting to remove air bubbles. This may reduce the administered dose.
• After removing the cap, do not touch the needle. This ensures the needle remains clean (sterile).

2. If the amount of medicine in the syringe matches the prescribed dose, no dose adjustment is needed. You may proceed with the injection.
3. If the dose depends on body weight, you may need to adjust the dose in the syringe according to the prescribed amount. In this case, remove the excess medicine by holding the syringe downward (to keep air bubbles in the syringe) and expel the excess into a container.
4. A drop may appear at the needle tip. In this case, remove the drop before injection by tapping the syringe with the needle pointing downward. You may now proceed with the injection.
   Injection
5. Hold the syringe in the hand you write with (like a pencil). With the other hand, gently pinch the cleaned abdominal skin between your thumb and index finger to create a skin fold.

• Make sure you maintain the skin fold during the injection.

2. Hold the syringe with the needle pointing downward (vertically at a 90° angle). Insert the full length of the needle into the skin fold.

3. Press the plunger with your thumb to inject the medicine into the fatty tissue of the abdomen. Inject the entire contents of the syringe.
4. Remove the needle straight out from the injection site. Keep the needle away from yourself and others. You may now release the skin fold.

After the injection

1. To avoid bruising, do not rub the injection site after the injection.
2. Dispose of the used syringe in a sharps container. Close the container lid and store it out of sight and out of reach of children. If the container is full, dispose of it according to your doctor's or pharmacist's instructions.
   Any unused medicine or waste must be disposed of in accordance with local regulations.
   If you feel the dose is too strong (e.g., unexpected bleeding) or too weak (e.g., the dose does not seem to be working), consult your doctor or pharmacist.
   Instructions for pre-filled syringes with a safety system:
   Preparing the injection site
3. Choose an injection site on the right or left side of the abdomen. The injection site should be at least 5 cm away from the navel, towards the sides.

• Do not inject within 5 cm of the navel or near existing scars or bruises.
• Rotate injection sites between the left and right sides of the abdomen, depending on the previous injection site.

2. Wash your hands. Clean (do not rub) the injection site with an alcohol swab or soap and water.
3. Sit or lie down in a comfortable position to relax. Ensure the injection site is clearly visible. A chair, examination table, or bed with supportive pillows is suitable.
   Selecting the dose
4. Carefully remove the needle cap from the syringe. Discard the cap.

• Do not press the plunger before injecting to remove air bubbles. This may reduce the administered dose.
• After removing the cap, do not touch the needle. This ensures the needle remains clean (sterile).

2. If the amount of medicine in the syringe matches the prescribed dose, no dose adjustment is needed. You may proceed with the injection.
3. If the dose depends on body weight, you may need to adjust the dose in the syringe according to the prescribed amount. In this case, remove the excess medicine by holding the syringe downward (to keep air bubbles in the syringe) and expel the excess into a container.
4. A drop may appear at the needle tip. In this case, remove the drop before injection by tapping the syringe with the needle pointing downward. You may now proceed with the injection.
   Injection
5. Hold the syringe in the hand you write with (like a pencil). With the other hand, gently pinch the cleaned abdominal skin between your thumb and index finger to create a skin fold.

• Make sure you maintain the skin fold during the injection.

2. Hold the syringe with the needle pointing downward (vertically at a 90° angle). Insert the full length of the needle into the skin fold.

3. Press the plunger with your thumb to inject the medicine into the fatty tissue of the abdomen. Inject the entire contents of the syringe.
4. Remove the needle straight out from the injection site, keeping your fingers on the plunger. Keep the needle away from yourself and others. The safety system is activated by firmly pressing the plunger. The protective shield will automatically cover the needle, and you will hear a distinct "click" confirming activation of the protective shield. You may now release the skin fold.

After the injection

1. To avoid bruising, do not rub the injection site after the injection.
2. Dispose of the used syringe in a sharps container. Close the container lid and store it out of sight and out of reach of children. If the container is full, dispose of it according to your doctor's or pharmacist's instructions.
   Any unused medicine or waste must be disposed of in accordance with local regulations.
   If you feel the dose is too strong (e.g., unexpected bleeding) or too weak (e.g., the dose does not seem to be working), consult your doctor or pharmacist.
   Changing anticoagulant therapy

• Switching from Crusia to vitamin K antagonist anticoagulants (e.g., warfarin)
  Your doctor will order blood tests to monitor your INR and will inform you when to stop taking Crusia.
• Switching from vitamin K antagonist anticoagulants (e.g., warfarin) to Crusia
  Stop taking the vitamin K antagonist medicine. Your doctor will order blood tests to monitor your INR and will inform you when to start taking Crusia.
• Switching from Crusia to direct oral anticoagulants (DOACs)
  Stop taking Crusia. Start taking the direct oral anticoagulant 0–2 hours before the next scheduled injection; then continue taking the medicine as usual.
• Switching from a direct oral anticoagulant to Crusia
  Stop taking the direct oral anticoagulant. Treatment with Crusia may begin only 12 hours after the last dose of the direct oral anticoagulant.

Using more than the recommended dose of Crusia
If you think you have used too much or too little Crusia, contact your doctor, nurse, or pharmacist immediately, even if you have no symptoms. In case of accidental injection or ingestion of Crusia by a child, go immediately to the nearest hospital emergency department.
Missed dose of Crusia
If you miss a dose, take it as soon as possible. Do not take a double dose to make up for a missed dose. Keeping a diary can help ensure you do not miss doses.
Stopping Crusia treatment
If you have any further questions about using this medicine, consult your doctor, pharmacist, or nurse.
It is important to continue administering Crusia injections until your doctor tells you to stop. Stopping treatment may lead to the formation of a blood clot, which could be very dangerous.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Similarly to other similar medicines (used to reduce blood clotting), Crusia may cause bleeding, which could potentially be life-threatening. In some cases, bleeding may not be immediately visible.
If any bleeding occurs that does not stop spontaneously, or if signs of excessive bleeding appear (severe weakness, fatigue, paleness, dizziness, headache or unexplained sweating), medical advice must be sought immediately. The doctor may decide to monitor the patient more closely or to change the treatment.

Treatment with enoxaparin should be discontinued and immediate medical help sought if any of the following symptoms occur:

• Any symptoms of acute allergic reaction (such as difficulty breathing, swelling of the lips, mouth, throat or eyes).
• Red, scaly, widespread rash with lumps under the skin and blisters, accompanied by fever.

Immediate contact with a doctor is necessary:

• If the patient experiences any signs of a blood vessel blocked by a blood clot, such as:
  • Cramping pain, redness, increased warmth or swelling in one of the lower limbs – these are symptoms of deep vein thrombosis
  • Shortness of breath, chest pain, fainting or coughing up blood – these are symptoms of pulmonary embolism
• If the patient develops painful skin rash or dark red spots on the skin that do not fade when pressed. The doctor may order blood tests to determine the platelet count.

List of possible adverse reactions:
Very common (may affect more than 1 in 10 people)

• Bleeding.
• Increased liver enzyme activity.

Common (may affect up to 1 in 10 people)

• Increased tendency to bruising compared to normal. This may be due to a reduced number of platelets.
• Red spots on the skin. These changes are more likely at the injection sites of Crusia.
• Skin rash (urticaria).
• Itchy, red skin.
• Bruising or pain at the injection site.
• Decreased number of red blood cells.
• Increased number of platelets.
• Headache.

Uncommon (may affect up to 1 in 100 people)

• Sudden, severe headache. This may indicate bleeding into the brain.
• Sensation of tenderness and swelling in the stomach. This may indicate gastrointestinal bleeding.
• Large, irregularly shaped red skin lesions, with or without blisters.
• Skin irritation (local irritation).
• The patient may notice yellowing of the skin or eyes and darker urine. This may indicate liver disease.

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

• Severe allergic reaction. Symptoms may include: rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue.
• Increased potassium levels in the blood. This is more likely in patients with kidney disease or diabetes. The doctor may check this with a blood test.
• Increased eosinophil count in the blood. The doctor may check this with a blood test.
• Hair loss.
• Osteoporosis (a condition in which bones are more prone to fractures) after long-term use of the medicine.
• Tingling, numbness, and muscle weakness (especially in the lower part of the body) after lumbar puncture or spinal/epidural anaesthesia.
• Loss of bladder or bowel control (a condition in which the patient cannot control when they need to go to the toilet).
• Hardening or lump at the injection site.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a 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 provide more information on the safety of the medicine.

5. How to store Crusia

Store below 25°C. Do not freeze.
Crusia pre-filled syringes are single-dose containers – any unused portion of the product should be discarded.
The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Do not use the medicine if the pre-filled syringe is damaged or if the solution is not clear.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures help protect the environment.

6. Contents of the package and other information

What Crusia contains

• The active substance is enoxaparin sodium.

Each pre-filled syringe contains enoxaparin sodium equivalent to 2000 IU anti-Xa activity (corresponding to 20 mg) in 0.2 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium equivalent to 4000 IU anti-Xa activity (corresponding to 40 mg) in 0.4 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium equivalent to 6000 IU anti-Xa activity (corresponding to 60 mg) in 0.6 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium equivalent to 8000 IU anti-Xa activity (corresponding to 80 mg) in 0.8 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium equivalent to 10,000 IU anti-Xa activity (corresponding to 100 mg) in 1.0 ml of water for injections.

• The other ingredient is water for injections.

What Crusia looks like and contents of the pack
Crusia is a clear, colourless to pale yellow solution for injection, supplied in a colourless type I glass pre-filled syringe with a chlorobutyl rubber stopper, plunger, and needle in a protective sheath, with or without an automatic needle protection device. It is available in the following presentations:
Crusia 2000 IU (20 mg)/0.2 ml solution for injection in a 0.5 ml pre-filled syringe without graduations.
Pack size: 2, 6, 10, 20 and 50 pre-filled syringes.
Crusia 4000 IU (40 mg)/0.4 ml solution for injection in a 0.5 ml pre-filled syringe without graduations.
Pack size: 2, 6, 10, 20, 30 and 50 pre-filled syringes.
Crusia 6000 IU (60 mg)/0.6 ml solution for injection in a 1 ml pre-filled syringe.
Pack size: 2, 6, 10, 12, 24, 30 and 50 pre-filled syringes.
Crusia 8000 IU (80 mg)/0.8 ml solution for injection in a 1 ml pre-filled syringe.
Pack size: 2, 6, 10, 12, 24, 30 and 50 pre-filled syringes.
Crusia 10,000 IU (100 mg)/1 ml solution for injection in a 1 ml pre-filled syringe.
Pack size: 2, 6, 10, 12, 24, 30 and 50 pre-filled syringes.
Not all pack sizes may be marketed.
In certain pack sizes, the pre-filled syringes may be equipped with a safety device.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder:
Laboratorios Farmacéuticos Rovi, S.A.
Julián Camarillo, 35
28037 Madrid
Spain
Tel.: (+48) 699 711 147

Manufacturer:
ROVI Pharma Industrial Services S.A.
Julián Camarillo, 35
28037 Madrid
Spain

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria, Denmark, Finland, Netherlands, Germany, Norway, Sweden, United Kingdom (Northern Ireland), Spain, Portugal, Greece, Bulgaria, Czech Republic, Estonia, Croatia, Hungary, Latvia, Poland, Romania, Slovakia: Crusia
France: Enoxaparine Crusia
Italy: Rovinadil
Belgium, Ireland, Slovenia, Luxembourg: Teuro

Further information
Detailed information about this medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: http://www.urpl.gov.pl/