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 that occur 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 other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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's blood.
• Preventing the formation of blood clots in the patient's blood in the following situations:
  • Before and after surgical procedures
  • During acute illness when the patient has limited mobility
  • In patients who have had blood clots caused by cancer, to prevent further clots
  • In unstable angina (a condition in which insufficient blood reaches the heart)
  • After myocardial infarction (heart attack)
• Preventing clot formation in the dialysis filter tubing (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 previously 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 is known as heparin-induced thrombocytopenia — within the past 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 dosing instructions.
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, epidural anaesthesia or lumbar puncture (see "Surgical procedures and anaesthetics"): the appropriate time interval between administration of Crusia and the procedure must be considered
• the patient has had a heart valve replacement
• the patient has endocarditis (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 has diabetes-related eye vessel problems (diabetic retinopathy)
• the patient has recently undergone eye or brain surgery
• the patient is elderly (over 65 years of age), particularly 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 with other medicines")

Before starting this medicine, and periodically during treatment, the patient may undergo blood tests to monitor platelet count (the blood cells responsible for clotting) and blood potassium levels.
Children and adolescents:
The safety and efficacy of enoxaparin have not been established in children and adolescents.
Crusia with other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or 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 medicine")
• Dextran injections – used as a blood substitute
• 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, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, 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 developing blood clots. The doctor should discuss this issue with the patient.
Women who are breastfeeding or intend to breastfeed should consult their doctor before starting treatment with this medicine.
Driving and using machines
Crusia has no influence on the ability to drive and use machines.
It is recommended that the doctor documents 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, i.e. this medicine is considered "sodium-free".

3. How to use Crusia

This medicine should always be used exactly as directed by your doctor or pharmacist. If you are unsure,
you should 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 using Crusia and to 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 out of the body (into the so-called arterial line) at the beginning of a dialysis session. Crusia must not be given by intramuscular injection.

Dose of medicine

• Your doctor will decide how much Crusia you should receive. The dose depends on the reason for treatment.
• If you have kidney disease, you 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 patient's blood in the following situations:
  • Surgery or periods of limited mobility due to illness
• The dose depends on the individual patient's risk of developing blood clots. You will receive Crusia at a dose of 2000 IU (20 mg) or 4000 IU (40 mg) daily.
• If surgery is planned, 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 heart attack Crusia may be used in two different 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 of Crusia 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 of 3000 IU (30 mg) will be given as an intravenous injection.
• Crusia will also be administered as a subcutaneous injection. 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 of Crusia 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
administer an additional dose of Crusia before the percutaneous coronary intervention procedure.
The medicine will then be given by intravenous injection.

3. Prevention of blood clots in dialyzer tubing
   • The usual dose of Crusia is 100 IU (1 mg) per kilogram of body weight.
   • Crusia is injected into the tubing carrying blood out of 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 injection
If you are able to self-administer Crusia, your doctor or nurse will show you how to do it. Do not
attempt to self-inject without proper instruction.
If you are unsure about any step, you should immediately speak with your doctor or
nurse. Proper administration of the subcutaneous injection (called a "subcutaneous injection") will help
reduce pain and bruising at the injection site.
Before self-administering 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 another syringe.
• Confirm the correct dose to be administered.
• 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-administering Crusia injection:
(Instructions for pre-filled syringes without 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.
• You should alternate 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, relaxed position. Ensure the injection site is clearly visible. A chair, examination table, or bed with pillows for support is suitable.
   Selecting the dose
4. Carefully remove the needle cap from the syringe. Discard the cap.

• Do not press the plunger before injection 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 gently tapping the syringe held 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 index finger and thumb, creating 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. This will deliver 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 reach of children. If the container is full, dispose of it according to your doctor’s or pharmacist’s instructions.
   Any unused medicines or waste materials should 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 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.
• You should alternate 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, relaxed position. Ensure the injection site is clearly visible. A chair, examination table, or bed with pillows for support is suitable.
   Selecting the dose
4. Carefully remove the needle cap from the syringe. Discard the cap.

• Do not press the plunger before injection 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 gently tapping the syringe held 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 index finger and thumb, creating 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. This will deliver 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, while still keeping your fingers on the plunger. Keep the needle away from yourself and others. The safety mechanism 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 safety 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 reach of children. If the container is full, dispose of it according to your doctor’s or pharmacist’s instructions.
   Any unused medicines or waste materials should 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 anticoagulant medicines known as vitamin K antagonists (e.g. warfarin) Your doctor will recommend blood tests to monitor your INR value and will inform you when to stop taking Crusia based on the results.
• Switching from vitamin K antagonist anticoagulants (e.g. warfarin) to Crusia Discontinue the vitamin K antagonist medicine. Your doctor will recommend blood tests to monitor your INR value and will inform you when to start taking Crusia based on the results.
• Switching from Crusia to direct oral anticoagulants Discontinue Crusia. Begin taking the direct oral anticoagulant 0–2 hours before the next scheduled injection; then continue taking the medicine as usual.
• Switching from direct oral anticoagulant therapy to Crusia Discontinue the direct oral anticoagulant. Crusia therapy may be started 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 do not notice any problems. In case of accidental injection or ingestion of Crusia by a child, go immediately to the hospital emergency department.
Missed dose of Crusia
If you miss a dose, take it as soon as possible. Do not use a double dose to make up for a missed dose. Keeping a diary can help ensure you do not miss doses.
Stopping use of Crusia
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 advises you to stop. Stopping treatment may lead to the formation of a blood clot, which could be very dangerous.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, 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 (increased weakness, fatigue, paleness, dizziness, headaches or unexplained sweating), medical advice should be sought immediately. The doctor may decide to subject the patient to closer monitoring or to change the medication.

Treatment with enoxaparin should be discontinued and immediate medical assistance 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, extensive rash with subcutaneous nodules and blisters, accompanied by fever.

Contact a doctor immediately:

• If the patient experiences any signs of blood vessel blockage 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 under the skin that do not fade upon pressure. The doctor may order blood tests to determine platelet count.

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

• Bleeding.
• Increased liver enzyme activity.

Common (may affect up to 1 in 10 people)

• Greater than usual tendency to bruising. This may be caused by reduced platelet count.
• Pink spots on the skin. These changes are more likely at sites where Crusia injections are administered.
• Skin rash (urticaria).
• Itchy, red skin.
• Bruising or pain at the injection site.
• Decreased number of red blood cells.
• Increased platelet count.
• Headaches.

Uncommon (may affect up to 1 in 100 people)

• Sudden, severe headache. This may indicate intracranial bleeding.
• Feeling 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 people with kidney disease or diabetes. The doctor may check this by performing a blood test.
• Increased number of eosinophils in the blood. The doctor may check this by performing 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 nodule at the injection site.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects 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 effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to 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.
Keep the medicine out of the 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 must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Crusia contains

• The active substance in this medicine is enoxaparin sodium.

Each pre-filled syringe contains enoxaparin sodium in an amount corresponding to 2000 IU
anti-Xa activity (equivalent to 20 mg) in 0.2 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium in an amount corresponding to 4000 IU
anti-Xa activity (equivalent to 40 mg) in 0.4 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium in an amount corresponding to 6000 IU
anti-Xa activity (equivalent to 60 mg) in 0.6 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium in an amount corresponding to 8000 IU
anti-Xa activity (equivalent to 80 mg) in 0.8 ml of water for injections.
Each pre-filled syringe contains enoxaparin sodium in an amount corresponding to 10,000 IU
anti-Xa activity (equivalent 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, injectable solution, supplied in a pre-filled syringe made of colourless type I glass with a chlorobutyl rubber stopper, plunger, and needle in a protective cap, with or without an automatic safety 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 graduation marks.
Pack sizes: 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 graduation marks.
Pack sizes: 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 sizes: 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 sizes: 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 sizes: 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 Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following trade 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/