Clexane forte

Package leaflet: Information for the user

Clexane Forte, 12,000 IU (120 mg)/0.8 ml, solution for injection
Clexane Forte, 15,000 IU (150 mg)/1 ml, solution for injection
Enoxaparin sodium
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 only. Do not pass it on to others. It may harm other people, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Clexane Forte is and what it is used for

Clexane Forte contains a substance called enoxaparin sodium. It belongs to a group of medicines known as low molecular weight heparins (LMWHs).

How Clexane Forte works

Clexane Forte works in two ways:

1. It prevents existing blood clots from getting larger. This helps the body to dissolve existing clots, so they are no longer harmful.

2. It prevents the formation of new blood clots in the patient.

What Clexane Forte is used for

Clexane Forte may be used:

• To treat existing blood clots in the patient.
• To prevent the formation of blood clots in the patient in the following situations:
  • Before and after surgical procedures
  • During a short-term illness when the patient is unable to move around for some time
  • In patients who have developed blood clots due to cancer, to further prevent the formation of new clots
• To prevent blood clots in unstable angina (when insufficient blood is reaching the heart muscle) or after a heart attack
• To prevent clotting in the dialysis machine tubing (used in patients with severe kidney problems)

2. Important Information Before Using Clexane Forte

Do not use Clexane Forte if:

• the patient is allergic to:

  • enoxaparin sodium or any of the other ingredients of this medicine (listed in section 6)
  • heparin or other low-molecular-weight heparins, such as nadroparin, tinzaparin, or dalteparin.
    Symptoms of an allergic reaction may include: rash, difficulty breathing or swallowing, swelling of the face, lips, tongue, mouth, throat, or eyes.

• the patient has had a reaction to heparin in the last 100 days which caused a serious drop in the number of blood cells responsible for blood clotting (platelets).

• the patient has antibodies against enoxaparin in the blood.

• the patient has active bleeding or a medical condition associated with an increased risk of bleeding, for example:

  • stomach ulcers
  • recent brain or eye surgery
  • recent hemorrhagic stroke.

• the patient is being treated with Clexane Forte for blood clots and a procedure is planned within the next 24 hours:

  • lumbar puncture
  • surgical procedure under spinal or epidural anaesthesia.

Do not use Clexane Forte in the above-mentioned patients. If in doubt, consult a doctor or pharmacist before starting treatment with Clexane Forte.

Warnings and Precautions
Clexane Forte must not be interchanged with other low-molecular-weight heparins such as nadroparin, tinzaparin, or dalteparin. This is because they are not exactly the same and differ in activity and dosing instructions.
Before starting treatment with Clexane Forte, consult a doctor or pharmacist if:

• the patient has ever had a reaction to heparin that caused a significant drop in the number of blood cells responsible for blood clotting (platelets)
• the patient has a prosthetic heart valve
• 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 diabetic eye disease affecting blood vessels (diabetic retinopathy)
• the patient has recently undergone eye or brain surgery
• the patient is elderly (over 65 years of age), especially if over 75 years old
• 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 in a blood laboratory test)
• the patient is currently taking medications that may cause bleeding (see section 2 “Clexane Forte and Other Medicines”)
• the patient has spinal problems or has undergone spinal surgery.

If any of the above conditions apply, or if the patient has any doubts, consult a doctor or pharmacist before starting treatment with Clexane Forte.

For patients receiving doses higher than 210 mg/day, this medicine contains more than 24 mg of sodium (the main component of table salt) per dose. This corresponds to 1.2% of the maximum recommended daily dietary sodium intake for adults.

Monitoring and Tests
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 blood potassium levels.

Use in Children and Adolescents
The safety and efficacy of Clexane Forte in children and adolescents have not been established.

Clexane Forte and Other Medicines
Inform the doctor or pharmacist about all medicines currently used, recently used, or planned for use, including:

• 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 section 3 “Switching Anticoagulant Therapy”)
• dextran injections – used as a plasma substitute
• ibuprofen, diclofenac, ketorolac, or other non-steroidal anti-inflammatory drugs (NSAIDs) used to treat pain and inflammation 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 supplements, diuretics, or certain medicines used in heart conditions.

Surgical Procedures and Anaesthetics
If the patient is scheduled for a lumbar puncture or a surgical procedure under epidural or spinal anaesthesia, inform the doctor that the patient is using Clexane Forte. See section “When Not to Use Clexane Forte”.

Pregnancy and Breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a 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 seek medical advice before starting treatment with this medicine.

Driving and Operating Machinery
Clexane Forte has no influence on the ability to drive or operate machinery.

It is recommended that the doctor document the brand name and batch number of the product used.

3. How to use Clexane Forte

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

• Clexane Forte is usually administered to the patient by a doctor or nurse. This is because it requires injection.
• Clexane Forte is usually given as subcutaneous injections.
• Clexane Forte may be administered as an intravenous injection following certain types of heart attack or after surgery.
• Clexane Forte may be introduced into the dialysis tubing carrying blood away from the body (into the so-called arterial line) at the beginning of a dialysis session.
• Clexane Forte must not be administered by intramuscular injection.

Dosage

• Your doctor will decide how much Clexane Forte you should receive. The dose depends on the reason for using the medicine.
• In case of kidney disease, you may receive a lower dose of Clexane Forte.
  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 Clexane Forte.

2) Prevention of blood clot formation in the patient during surgical procedures
or during periods of limited mobility due to illness

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

• If undergoing planned 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 Clexane Forte at a dose of 4000 IU (40 mg) daily.

• Your doctor will decide how long you should continue receiving Clexane Forte.
  3) Prevention of clot formation in patients with unstable angina or after
  myocardial infarction

• Clexane Forte can be used in two different types of heart attack.

• The dose of Clexane Forte will depend on the patient's age and the type of heart attack that occurred.

Myocardial infarction of type NSTEMI (non-ST-elevation myocardial infarction):

• 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 Clexane Forte.

Myocardial infarction of type STEMI (ST-elevation myocardial infarction) in patients under 75 years of age:

• The initial dose of Clexane Forte, 3000 IU (30 mg), will be administered as an intravenous injection.
• Clexane Forte will also be given 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 Clexane Forte.

Myocardial infarction of type STEMI 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 Clexane Forte for the first two doses is 7500 IU (75 mg).
• Your doctor will decide how long you should continue receiving Clexane Forte.

Patients undergoing percutaneous coronary intervention (PCI):

• Depending on when the last dose of Clexane Forte was administered, your doctor may decide to give an additional dose of Clexane Forte before the percutaneous coronary intervention. The medicine will then be administered as an intravenous injection.

4) Prevention of blood clot formation in dialyser tubing

• The usual dose is 100 IU (1 mg) per kilogram of body weight.
• Clexane Forte 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.

Self-administration of Clexane Forte injections
If you are able to self-administer Clexane Forte injections, your doctor or nurse will demonstrate how to do it. Do not attempt to inject yourself unless you have been trained to do so. If you have any doubts about how to perform the injection, consult your doctor or nurse immediately. Correct subcutaneous injection (called "subcutaneous injection") may reduce pain and bruising at the injection site.
Before self-injecting Clexane Forte

• Prepare all necessary items: syringe, alcohol swab or soap and water, and a sharps disposal 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 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-administering Clexane Forte injections:
(Instructions for pre-filled syringes without safety device)
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 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, recliner, 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 needle sterility.

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, dose adjustment in the syringe may be necessary according to the prescribed dose. In this case, remove excess medicine by holding the syringe downward (to retain air bubbles in the syringe) and expel excess medicine into a container.
4. A drop may appear at the needle tip. In this case, remove the drop before injection by tapping the syringe held needle-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 to create a skin fold.

• Ensure the skin fold is maintained during 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 abdominal fatty tissue. 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. Release the skin fold.

After injection

1. To avoid bruising, do not rub the injection site after injection.
2. Dispose of the used syringe in a sharps disposal 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 should be disposed of in accordance with local regulations.
   (Instructions for pre-filled syringes with ERIS™ safety device)
   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 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, recliner, 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 needle sterility.

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, dose adjustment in the syringe may be necessary according to the prescribed dose. In this case, remove excess medicine by holding the syringe downward (to retain air bubbles in the syringe) and expel excess medicine into a container.
4. A drop may appear at the needle tip. In this case, remove the drop before injection by tapping the syringe held needle-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 to create a skin fold.

• Ensure the skin fold is maintained during 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 abdominal fatty tissue. Inject the entire contents of the syringe.
4. Remove the needle straight out from the injection site. The protective shield will automatically cover the needle. Release the skin fold. The safety device activates the protective shield only when the syringe is fully emptied by pressing the plunger completely to the end.

After injection

1. To avoid bruising, do not rub the injection site after injection.
2. Dispose of the used syringe in a sharps disposal 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 should be disposed of in accordance with local regulations.
   (Instructions for pre-filled syringes with PREVENTIS™ safety device)
   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 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, recliner, 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 needle sterility.

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, dose adjustment in the syringe may be necessary according to the prescribed dose. In this case, remove excess medicine by holding the syringe downward (to retain air bubbles in the syringe) and expel excess medicine into a container.
4. A drop may appear at the needle tip. In this case, remove the drop before injection by tapping the syringe held needle-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 to create a skin fold.

• Ensure the skin fold is maintained during 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 abdominal fatty tissue. Inject the entire contents of the syringe.
4. Remove the needle straight out from the injection site, while still holding your fingers on the plunger. Keeping the needle away from yourself and others, firmly press the plunger to activate the safety device. The protective shield will automatically cover the needle. You will hear an audible "click" confirming activation of the protective shield. Release the skin fold.

After injection

1. To avoid bruising, do not rub the injection site after injection.
2. Dispose of the used syringe in a sharps disposal 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 should be disposed of in accordance with local regulations.
   Switching anticoagulant medicines

• Switching from Clexane Forte to vitamin K antagonists (such as warfarin)
  Your doctor will order blood tests to measure your INR and inform you when to stop taking Clexane Forte.
• Switching from vitamin K antagonists (such as warfarin) to Clexane Forte
  Discontinue the vitamin K antagonist medicine. Your doctor will order a blood test to measure your INR and inform you when to start taking Clexane Forte.
• Switching from Clexane Forte to direct oral anticoagulants (DOACs)
  Stop taking Clexane Forte. Start taking the direct oral anticoagulant 0 to 2 hours before the scheduled time of the next injection; then continue taking it normally.
• Switching from direct oral anticoagulants to Clexane Forte
  Stop taking the direct oral anticoagulant. Treatment with Clexane Forte may be started 12 hours after the last dose of the direct oral anticoagulant.
  Using more than the recommended dose of Clexane Forte
  If you think you have used too high or too low a dose of Clexane Forte, inform your doctor, pharmacist, or nurse immediately, even if there are no signs of any problems. In case of accidental injection or ingestion of Clexane Forte by a child, go immediately to the hospital emergency department.

Missing a dose of Clexane Forte
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 helps ensure you do not miss a dose.
Stopping treatment with Clexane Forte
It is important to continue Clexane Forte injections until your doctor advises you to stop. Stopping treatment may lead to blood clot formation, which can be very dangerous.
If you have any further questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like any medicine, this medicine can cause adverse effects, although not everyone experiences them.
Serious adverse effects
Stop using Clexane Forte and seek immediate medical advice from a doctor or nurse if you experience signs of a severe allergic reaction (such as rash, difficulty breathing or swallowing, swelling of the face, lips, tongue, mouth, throat or eyes).
If any of the following symptoms occur, stop using enoxaparin and seek immediate medical assistance:

• Red, scaly, widespread rash with lumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized pustular eruption).

Like other similar medicines used to reduce blood clotting, Clexane Forte may cause bleeding. This could potentially be life-threatening. In some cases, bleeding may not be immediately visible.
Seek immediate medical advice if:

• the patient experiences any bleeding that does not stop spontaneously
• the patient develops signs of excessive bleeding such as weakness, fatigue, paleness, dizziness with headaches, or unexplained swelling. The doctor may decide to monitor the patient more closely or change the treatment.

Seek immediate medical advice if:

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

• increased tendency to bruising more than usual. This may be due to a reduced platelet count
• pink spots on the skin. These changes are more likely at the sites where Clexane Forte injections are administered
• skin rash (urticaria)
• itchy, red skin
• bruising or pain at the injection site
• reduced number of red blood cells
• increased platelet count
• headache.

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

• sudden, severe headache – this may be a sign of intracranial bleeding
• 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 1000 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 a lump at the injection site.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Poland.
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 authorisation holder or its representative in Poland.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Clexane Forte

Do not store above 25 °C. Do not freeze.
Keep the medicine 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 this medicine if you notice a cracked syringe, solid particles in the solution, or if the solution has an abnormal colour (see "What Clexane Forte looks like and what the pack contains").
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 Clexane Forte contains

• The active substance is enoxaparin sodium.
• Each ml contains 150 mg of enoxaparin sodium, corresponding to 15,000 IU anti-Xa activity. Each 0.8 ml pre-filled syringe contains 12,000 IU (120 mg) of enoxaparin sodium. Each 1 ml pre-filled syringe contains 15,000 IU (150 mg) of enoxaparin sodium.
• The other component is: water for injections.

What Clexane Forte looks like and contents of the pack
Clexane Forte is a clear, colourless or slightly yellow solution for injection in a glass pre-filled syringe (with or without automatic safety system). Pack sizes: 2, 5, 6, 10, 20, 30, 50 pre-filled syringes and multipacks containing 3 x 10 pre-filled syringes.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France

Manufacturer
Sanofi Winthrop Industrie
180, rue Jean Jaurès
94 700 Maisons-Alfort
France
Sanofi-Aventis Private Co. Ltd
Budapest Logistics and Distribution Platform
Bdg. DC5, Campona utca 1.
Budapest, 1225
Hungary
Sanofi-Aventis GmbH
Turm A, 29. OG, Wienerbergstraße 11
1100 Vienna
Austria
Sanofi Winthrop Industrie
1051 Boulevard Industriel
76580 Le Trait
France
Sanofi-Aventis Deutschland GmbH
Industriepark Höchst-Brüningstraße 50
65926 Frankfurt am Main
Germany

For further information on this medicinal product and its names in the European Economic Area countries, please contact the representative of the Marketing Authorisation Holder in Poland:
Sanofi Sp. z o.o.
ul. Marcina Kasprzaka 6
01-211 Warsaw
tel.: +48 22 280 00 00

Other sources of information
Detailed information on this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (www.urpl.gov.pl).