Clexane 12,000 IU (120 mg)/0.8 ml solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

CLEXANE 12,000 IU (120 mg)/0.8 ml solution for injection in pre-filled syringe

enoxaparin sodium

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It may harm them.
• If you get any side effects, talk to your doctor or pharmacist, even if it is a side effect not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Clexane is and what it is used for

Clexane contains an active substance called enoxaparin sodium. It belongs to a group of medicines known as "low molecular weight heparin" or LMWH.

How Clexane works

Clexane works in two ways:

1. Preventing existing blood clots from getting larger. This helps your body to break them down and prevents further damage.
2. Preventing the formation of new blood clots.

What Clexane is used for

Clexane may be used:

• To treat existing blood clots
• To prevent the formation of blood clots in the following situations:
  • before and after surgery
  • when you have a short-term illness and are unable to move around for a period of time
  • if you have had a blood clot due to cancer, to prevent further clots from forming
• To prevent blood clots in cases of unstable angina (a condition in which insufficient blood reaches the heart) or after a heart attack
• To prevent blood clots in the tubes of a dialysis machine (used in people with serious kidney problems)

2. What you need to know before using Clexane

Do not use Clexane if:

• you are 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.

Signs of an allergic reaction include: rash, difficulty breathing or swallowing, swelling of the face, lips, tongue, mouth, throat or eyes.

• you have previously had a reaction to heparin that caused a severe drop in the number of blood cells involved in clotting (platelets) within the last 100 days
• you have antibodies in your blood against enoxaparin
• you are experiencing severe bleeding or have conditions with a high risk of bleeding such as:
  • stomach ulcer, recent brain or eye surgery, or cerebral hemorrhage.
• you are using Clexane to treat blood clots and are scheduled to undergo within 24 hours:
  • a lumbar or spinal puncture
  • surgery with spinal or epidural anesthesia.

Do not use Clexane if any of the conditions mentioned affect you. If you are unsure, consult your doctor or pharmacist before using Clexane.

Warnings and precautions

Clexane 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 do not have the same activity or the same instructions for use.

Consult your doctor or pharmacist before starting to use Clexane if:

• you have ever had a reaction to heparin that caused a severe decrease in the number of cells involved in blood clotting (platelets)
• you have had a heart valve implanted
• you have endocarditis (an infection of the inner lining of the heart)
• you have a history of gastric ulcer
• you have recently had a cerebral haemorrhage
• you have high blood pressure
• you have diabetes or diabetes-related blood vessel problems in the eyes (known as diabetic retinopathy)
• you have recently undergone eye or brain surgery
• you are an elderly person (over 65 years of age), and especially if you are over 75 years old
• you have kidney problems
• you have liver problems
• you have a very low body weight or are overweight
• you have high levels of potassium in your blood (which could be detected by a blood test)
• you are currently taking medicines that affect bleeding (see section 2, “Use of Clexane with other medicines”)
• you have any spinal problems or have undergone spinal surgery.

If any of the conditions mentioned above apply to you (or if you are unsure), consult your doctor or pharmacist before using Clexane.

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

Blood tests and monitoring

You may need to have a blood test before starting this medicine and while you are using it, to check the levels of cells involved in blood clotting (platelets) and the levels of potassium in your blood.

Children and adolescents

The efficacy and safety of Clexane have not been evaluated in children or adolescents.

Use of Clexane with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

• warfarin – used to reduce blood clotting
• aspirin (also known as acetylsalicylic acid or ASA), clopidogrel, or other medicines used to prevent blood clots (see section 3, “Switching anticoagulant medicines”)
• dextran injection – used as a blood substitute
• ibuprofen, diclofenac, ketorolac, and other medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) used to treat pain and inflammation in arthritis and other conditions
• prednisolone, dexamethasone, and other medicines used to treat asthma, rheumatoid arthritis, and other diseases
• medicines that increase potassium levels in blood, such as potassium salts, diuretics (medicines to remove fluid), and some medicines used to treat heart problems.

Surgery and anaesthesia

If you are scheduled to undergo a lumbar or spinal puncture, or a surgical procedure involving spinal or epidural anesthesia, inform your doctor that you are using Clexane.

Pregnancy and breastfeeding

If you are pregnant, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

If you are pregnant and have a mechanical heart valve, you may have an increased risk of blood clots. Your doctor will discuss this with you.

If you are breastfeeding or planning to breastfeed, you should consult your doctor before using this medicine.

Driving and use of machines

Clexane does not affect the ability to drive and use machines.

It is recommended that the healthcare professional record the brand name and batch number of the product you are using.

3. How to use Clexane

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

Medicine use

• Usually, your doctor or nurse will administer Clexane to you. This is because it must be given by injection.
• Clexane is generally administered by injection under the skin (subcutaneous route).
• Clexane may be administered by injection into your veins (intravenous route) after certain types of heart attacks or surgical procedures.
• Clexane may be added to the tube draining from the body (arterial line) at the beginning of a dialysis session.
• Do not administer Clexane into muscle (intramuscular route).

What dose will be given to you

• Your doctor will decide the dose of Clexane you will receive. The dose depends on the reason for which it is being used.
• If you have any kidney problems, you may be given a lower dose of Clexane.

1. Treatment of blood clot formation

• 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 will receive Clexane.

1. Prevention of blood clot formation during surgical procedures or periods of limited mobility due to illness

• The dose depends on your risk of developing a clot. You will be given 2,000 IU (20 mg) or 4,000 IU (40 mg) of Clexane per day.
• If you are undergoing surgery, the first injection is usually given 2 or 12 hours before the operation.
• If you have reduced mobility due to illness, you will usually be given 4,000 IU (40 mg) of Clexane per day.
• Your doctor will decide how long you will receive Clexane.

1. Prevention of blood clot formation in unstable angina or after a heart attack

• Clexane may be used in two different types of heart attacks.
• The dose of Clexane you receive will depend on your age and the type of heart attack you have had.

Heart attack type NSTEMI (myocardial infarction without ST-segment elevation):

• The usual dose is 100 IU (1 mg) per kilogram of body weight every 12 hours.
• Your doctor will usually also advise you to take aspirin (acetylsalicylic acid).
• Your doctor will decide how long you will receive Clexane.

Heart attack type STEMI (ST-segment elevation myocardial infarction) if under 75 years of age:

• You will receive an initial intravenous injection of 3,000 IU (30 mg) of Clexane.
• At the same time, you will receive a subcutaneous (under the skin) injection of Clexane. The usual dose is 100 IU (1 mg) per kilogram of body weight every 12 hours.
• Your doctor will usually also advise you to take aspirin (acetylsalicylic acid).
• Your doctor will decide how long you will receive Clexane.

Heart attack type STEMI if 75 years of age or older:

• The usual dose is 75 IU (0.75 mg) per kilogram of body weight every 12 hours.
• The maximum dose of Clexane administered in the first two injections is 7,500 IU (75 mg).
• Your doctor will decide how long you will receive Clexane.

For patients undergoing percutaneous coronary intervention (PCI):

• Depending on when you received your last injection of Clexane, your doctor may decide to administer an additional dose of Clexane before a PCI procedure. This would be given by intravenous injection.

1. Prevention of blood clot formation in dialysis tubing

• The usual dose is 100 IU (1 mg) per kilogram of body weight.
• Clexane is added to the tube draining from the body (arterial line) at the beginning of a dialysis session. This amount is usually sufficient for a 4-hour session. However, your doctor may administer an additional injection of 50 IU to 100 IU (0.5 to 1 mg) per kilogram of body weight if necessary.

If you are to self-inject Clexane

If you are able to self-inject Clexane, your doctor or nurse will show you how to do it. Do not attempt to self-inject unless you have been properly trained. If you are unsure what to do, consult your doctor or nurse immediately. Correct subcutaneous injection technique (known as “subcutaneous injection”) helps reduce pain and bruising at the injection site.

Before self-injecting Clexane

• Prepare what you will need: syringe, alcohol swab or soap and water, and a sharps container
• Check the medicine’s expiry date. Do not use if expired.
• Check that the syringe is undamaged and that the solution is clear. If not, use another syringe.
• Make sure you know the dose you are to inject.
• Check the area of your abdomen where the last injection was given for redness, skin discoloration, swelling, discharge, or persistent pain. If any of these occur, consult your doctor or nurse.

Instructions for self-injecting Clexane:

(Instructions for syringes without safety device)

Preparing the injection site

1. Choose an area on the right or left side of your abdomen. At least 5 cm away from the navel and toward either side.
   • Do not inject within 5 cm around your navel or near scars or bruises.
   • Alternate between the left and right sides of your abdomen depending on where you last injected.

1. Wash your hands. Clean (do not rub) the injection site with an alcohol swab or soap and water.
2. Sit or lie down in a comfortable position so you are relaxed. Ensure you can clearly see the injection site. A couch, reclining chair, or bed with pillows is ideal.

Selecting the dose

1. Carefully remove the needle cap by pulling it off. Discard the cap.
   • Before injecting, do not press the plunger to remove air bubbles. This may result in loss of medication.
   • Once the cap is removed, do not touch anything with the needle to ensure it remains clean (sterile).

1. If the amount of medicine in the syringe matches your prescribed dose, no dose adjustment is needed. You are now ready to administer the injection.
2. If the dose depends on your body weight, you may need to adjust the dose in the syringe to match the prescribed amount. In this case, expel the excess medication by holding the syringe downward (to keep the air bubble in the syringe) and expelling the excess into a container.
3. A drop may appear at the tip of the needle. If so, remove the drop before injecting by gently tapping the syringe with the needle pointing downward. You are now ready to administer the injection.

Administering the injection

1. Hold the syringe in your writing hand (like a pencil). With the other hand, gently pinch the cleaned area of your abdomen between your index finger and thumb to form a skin fold.
   • Be sure to hold this skin fold throughout the injection.
2. Hold the syringe so the needle points straight down (vertically at a 90º angle). Insert the entire needle into the skin fold.

1. Press the plunger with your thumb to deliver the medication into the fatty tissue of your abdomen. Complete the injection by using all the medicine in the syringe.
2. Remove the needle straight out from the injection site. Point the needle away from yourself and others. You may now release the skin fold.

After completion

1. To avoid bruising, do not rub the injection site after injecting.
2. Place the used syringe in a sharps container. Close the container tightly and keep it out of children’s reach. When the container is full, dispose of it as instructed by your doctor or pharmacist.

Unused medicine and all materials that have come into contact with it must be disposed of according to local regulations.

Instructions for syringes with automatic safety device type ERISTM:

Preparing the injection site

1. Choose an area on the right or left side of your abdomen. At least 5 cm away from the navel and toward either side.
   • Do not inject within 5 cm around your navel or near scars or bruises.
   • Alternate between the left and right sides of your abdomen depending on where you last injected.

1. Wash your hands. Clean (do not rub) the injection site with an alcohol swab or soap and water.
2. Sit or lie down in a comfortable position so you are relaxed. Ensure you can clearly see the injection site. A couch, reclining chair, or bed with pillows is ideal.

Selecting the dose

1. Carefully remove the needle cap by pulling it off. Discard the cap.
   • Before injecting, do not press the plunger to remove air bubbles. This may result in loss of medication.
   • Once the cap is removed, do not touch anything with the needle to ensure it remains clean (sterile).

1. If the amount of medicine in the syringe matches your prescribed dose, no dose adjustment is needed. You are now ready to administer the injection.
2. If the dose depends on your body weight, you may need to adjust the dose in the syringe to match the prescribed amount. In this case, expel the excess medication by holding the syringe downward (to keep the air bubble in the syringe) and expelling the excess into a container.
3. A drop may appear at the tip of the needle. If so, remove the drop before injecting by gently tapping the syringe with the needle pointing downward. You are now ready to administer the injection.

Administering the injection

1. Hold the syringe in your writing hand (like a pencil). With the other hand, gently pinch the cleaned area of your abdomen between your index finger and thumb to form a skin fold.
   • Be sure to hold this skin fold throughout the injection.
2. Hold the syringe so the needle points straight down (vertically at a 90º angle). Insert the entire needle into the skin fold.

1. Press the plunger with your thumb to deliver the medication into the fatty tissue of your abdomen. Complete the injection by using all the medicine in the syringe.
2. Remove the needle straight out from the injection site. A protective sheath will automatically cover the needle. You may now release the skin fold. The safety device will only release the protective sheath once the syringe is fully emptied by pressing the plunger deeply.

After completion

1. To avoid bruising, do not rub the injection site after injecting.
2. Place the used syringe in a sharps container. Close the container tightly and keep it out of children’s reach. When the container is full, dispose of it as instructed by your doctor or pharmacist.

Unused medicine and all materials that have come into contact with it must be disposed of according to local regulations.

Instructions for syringes with automatic safety device type PREVENTISTM:

Preparing the injection site

1. Choose an area on the right or left side of your abdomen. At least 5 cm away from the navel and toward either side.
   • Do not inject within 5 cm around your navel or near scars or bruises.
   • Alternate between the left and right sides of your abdomen depending on where you last injected.

1. Wash your hands. Clean (do not rub) the injection site with an alcohol swab or soap and water.
2. Sit or lie down in a comfortable position so you are relaxed. Ensure you can clearly see the injection site. A couch, reclining chair, or bed with pillows is ideal.

Selecting the dose

1. Carefully remove the needle cap by pulling it off. Discard the cap.
   • Before injecting, do not press the plunger to remove air bubbles. This may result in loss of medication.
   • Once the cap is removed, do not touch anything with the needle to ensure it remains clean (sterile).

1. If the amount of medicine in the syringe matches your prescribed dose, no dose adjustment is needed. You are now ready to administer the injection.
2. If the dose depends on your body weight, you may need to adjust the dose in the syringe to match the prescribed amount. In this case, expel the excess medication by holding the syringe downward (to keep the air bubble in the syringe) and expelling the excess into a container.
3. A drop may appear at the tip of the needle. If so, remove the drop before injecting by gently tapping the syringe with the needle pointing downward. You are now ready to administer the injection.

Administering the injection

1. Hold the syringe in your writing hand (like a pencil). With the other hand, gently pinch the cleaned area of your abdomen between your index finger and thumb to form a skin fold.
   • Be sure to hold this skin fold throughout the injection.
2. Hold the syringe so the needle points straight down (vertically at a 90º angle). Insert the entire needle into the skin fold.

1. Press the plunger with your thumb to deliver the medication into the fatty tissue of your abdomen. Complete the injection by using all the medicine in the syringe.
2. Remove the needle straight out from the injection site while keeping your finger on the plunger. Point the needle away from yourself and others, then firmly press the plunger to activate the safety mechanism. The protective sheath will automatically cover the needle. You will hear a “click” confirming activation of the safety system. You may now release the skin fold.

After completion

1. To avoid bruising, do not rub the injection site after injecting.
2. Place the used syringe in a sharps container. Close the container tightly and keep it out of children’s reach. When the container is full, dispose of it as instructed by your doctor or pharmacist.

Unused medicine and all materials that have come into contact with it must be disposed of according to local regulations.

Switching anticoagulant medicines

• Switching from Clexane to vitamin K antagonists (such as warfarin)

Your doctor will request a blood test for a parameter called INR and will tell you when to stop treatment with Clexane.

• Switching from vitamin K antagonists (such as warfarin) to Clexane

Stop using the vitamin K antagonist. Your doctor will request an INR blood test and will tell you when to start using Clexane.

• Switching from Clexane to direct oral anticoagulants

Stop using Clexane. Start taking the direct oral anticoagulant 0 to 2 hours before your next scheduled injection, then continue as usual.

• Switching from direct oral anticoagulant to Clexane

Stop taking the direct oral anticoagulant. Do not start Clexane until 12 hours after the last dose of the direct oral anticoagulant.

If you use more Clexane than you should

If you think you have used too much or too little Clexane, inform your doctor, pharmacist, or nurse immediately, even if you do not show signs of any problems. If a child accidentally injects or swallows Clexane, take them immediately to the hospital emergency department.

In case of overdose or accidental administration, consult your doctor immediately or go to the nearest hospital emergency department, bringing this leaflet with you, or call the Toxicology Information Service at 91 562 04 20, stating the medicine and the amount administered.

If you forget to use Clexane

If you forget to administer a dose, do so as soon as you remember. Do not use a double dose on the same day to make up for missed doses. To help ensure you do not miss any doses, it may be helpful to use a diary.

If you stop using Clexane

It is important that you continue receiving Clexane until your doctor decides to stop treatment. If you stop using it, a blood clot may form, which can be very dangerous.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Serious adverse effects

Stop treatment with Clexane and inform your doctor or nurse immediately if you experience any sign of a severe allergic reaction (such as rash, difficulty breathing or swallowing, swelling of the face, lips, tongue, mouth, throat or eyes).

Stop treatment with enoxaparin and inform your doctor or nurse immediately if you experience any of the following symptoms:

• a widespread red, scaly rash with lumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the beginning of treatment (acute generalized exanthematous pustulosis).

Like other similar medicines used to reduce blood clots, Clexane may cause bleeding. This could be life-threatening. In some cases, bleeding may not be obvious.

Inform your doctor immediately if:

• you have any bleeding that does not stop by itself
• you have signs of excessive bleeding (such as feeling very weak, fatigue, paleness, or dizziness with headache or unexplained swelling).

Your doctor may decide to keep you under strict monitoring or change your medication.

You must inform your doctor immediately:

• if you experience any signs of a blood vessel blockage caused by a blood clot, such as:

• cramping pain, redness, warmth, or swelling in one of your legs – these are symptoms of deep vein thrombosis

• shortness of breath, chest pain, fainting, or coughing up blood – these are symptoms of pulmonary embolism

• if you develop a painful skin rash with dark red spots under the skin that do not fade when pressed.

Your doctor may request a blood test to check your platelet count.

Other adverse effects:

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

• bleeding
• increased liver enzymes.

Common (may affect up to 1 in 10 people):

• bruising more easily than usual – this could be due to a blood disorder caused by a low platelet count
• pinkish skin patches – these occur more frequently at the site where Clexane was injected
• skin rash (wheals, hives)
• redness and itching of the skin
• bruising or pain at the injection site
• decrease in the number of red blood cells in the blood
• increase in the number of platelets in the blood
• headache.

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

• sudden severe headache – this could be a sign of bleeding in the brain
• tenderness, sensitivity to touch, and swelling of the stomach – could indicate gastrointestinal bleeding
• large, irregular red lesions on the skin, with or without blisters
• skin irritation (local irritation)
• yellowing of the skin or eyes, and darkening of urine – this could be due to a liver problem.

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

• severe allergic reaction – signs may include: skin rash, difficulty swallowing or breathing, swelling of the lips, face, throat or tongue
• increased potassium levels in blood – this is more likely in people with kidney problems or diabetes. Your doctor can check this with a blood test
• increased eosinophil count in blood – your doctor can check this with a blood test
• hair loss
• osteoporosis (a condition in which bones are more likely to fracture)
• tingling, numbness, and muscle weakness (especially in the lower part of the body) following a lumbar puncture or spinal anaesthesia
• loss of bladder or bowel control (inability to control urination or defecation)
• hardening or nodule at the injection site.

Reporting of adverse effects

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

5. Storage of Clexane

Do not store above 25°C. Do not freeze.

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

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

Do not use this medicine if you notice a crack in the syringe, particles suspended in the solution, or an abnormal colour of the solution (see "Description of the product and contents of the pack").

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their packaging at the SIGRE collection point at your pharmacy. If you are in doubt, ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Clexane

• The active substance is enoxaparin sodium.

Each ml contains 150 mg of enoxaparin sodium, equivalent to 15,000 IU anti-Xa activity.

• Each 0.8 ml pre-filled syringe contains 12,000 IU (120 mg) of enoxaparin sodium.
• The other ingredient is water for injections.

Appearance of the product and contents of the pack

Clexane is an injectable solution in a glass pre-filled syringe (with or without automatic safety device), transparent, ranging from colourless to slightly yellow.

It is available in packs of 2, 5, 6, 10, 20, 30, 50 pre-filled syringes, and in multiple packs of 3 x 10 pre-filled syringes.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

sanofi-aventis, S.A.

C/ Roselló i Porcel, 21

08016 Barcelona

Spain

Manufacturer

Sanofi Winthrop Industrie

180 rue Jean Jaurès

94700 Maisons-Alfort

France

Or

Sanofi-Aventis Private Co. Ltd

Budapest Logistics and Distribution Platform

Bdg. DC5, Campona utca1.

Budapest, 1225

Hungary

Or

Sanofi-Aventis GmbH

Turm A, 29. OG, Wienerbergstraße 11

1100 Vienna

Austria

Or

Sanofi Winthrop Industrie
1051 Boulevard Industriel
76580 Le Trait
France

Or

Sanofi-Aventis Deutschland GmbH

Industriepark Höchst-Brüningstraße 50

65926 Frankfurt am Main

Germany

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

Austria, France, Portugal: Lovenox.

Belgium, Germany, Greece, Luxembourg, Slovenia, Spain: Clexane.

Czech Republic, Hungary, Ireland, Poland, Slovakia, United Kingdom: Clexane Forte.

Italy: Clexane T.

Finland, Norway, Sweden: Klexane.

Date of latest revision of this leaflet: February 2022

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/