Package Insert: Information for the User

CLEXANE 8,000 IU (80 mg)/0.8 ml Injectable Solution in Pre-filled Syringe

enoxaparin sodium

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

1. What is Clexane and what it is used for

2. What you need to know before starting to use Clexane

3. How to use Clexane

4. Possible adverse effects

5. Storage of Clexane

6. Contents of the pack and additional information

Clexanecontains an active ingredient called enoxaparin sodium. It belongs to a group of medications called “low molecular weight heparin” or LMWH.

How Clexane works

Clexaneacts in two ways:

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

What is Clexane used for

Clexanecan be used for:

• Treating blood clots
• Preventing blood clots from forming in the following situations:
• • before and after surgery
  • when you have a short-term illness and cannot move for some time
  • if you have had a blood clot due to cancer, to prevent more clots from forming.
• Preventing blood clots from forming when you have unstable angina (a condition where not enough blood reaches the heart) or after a heart attack
• Preventing blood clots from forming in the tubes of the dialysis apparatus (used in people with severe kidney problems).

Do not use Clexaneif:

• you are allergic to:
• • enoxaparin sodium or any of the other components of this medication (listed in section 6)
  • heparin or other low molecular weight heparins such as nadroparin, tinzaparin, or dalteparin.

The signs of an allergic reaction include: rash, difficulty breathing or swallowing, facial swelling, lip, tongue, mouth, throat, or eye swelling.

• you have had a reaction to heparin that caused a severe decrease in the number of cells that participate in blood clotting (platelets) in the last 100 days
• you have antibodies against enoxaparin in your blood
• you are bleeding heavily or have a high risk of bleeding due to:
• • stomach ulcer, recent brain or eye surgery, or cerebral hemorrhage.
• you are usingClexaneto treat blood clots, and will have in 24 hours:
• • lumbar puncture or spinal tap
  • surgery with spinal or epidural anesthesia.

Do not useClexaneif any of the above conditions apply. If you are unsure, consult your doctor or pharmacist before usingClexane.

Warnings and precautions

Clexaneshould not be exchanged 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 instructions for use.

Consult your doctor or pharmacist before starting to useClexaneif:

• you have had a reaction to heparin that caused a severe decrease in the number of cells that participate in blood clotting (platelets)
• you have had a heart valve implanted
• you have endocarditis (a heart infection)
• you have a history of stomach ulcers
• you have recently had a cerebral hemorrhage
• you have high blood pressure
• you have diabetes or eye blood vessel problems caused by diabetes (diabetic retinopathy)
• you have recently had eye or brain surgery
• you are an elderly person (over 65 years old) and especially if you are over 75 years old
• you have kidney problems
• you have liver problems
• you are underweight or overweight
• you have high potassium levels in your blood (which could be checked with a blood test)
• you are currently using medications that affect bleeding (see section 2, “UsingClexanewith other medications”)
• you have any problems with your spine or have had spinal surgery.

If any of the above conditions apply (or you are unsure), consult your doctor or pharmacist before usingClexane.

For patients receiving doses above 210 mg/day, this medication contains more than 24 mg of sodium (main component of table salt/cooking salt) in each dose. This is equivalent to 1.2% of the maximum daily sodium intake recommended for an adult.

Analysis and controls

You may need to have a blood test before starting to use this medication, and while you are using it; this is to check the level of cells that participate in blood clotting (platelets) and the levels of potassium in your blood.

Children and adolescents

The efficacy and safety ofClexanehave not been evaluated in children or adolescents.

UsingClexanewith other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

• warfarin – used to reduce blood clotting
• aspirin (also known as acetylsalicylic acid or AAS), clopidogrel, or other medications used to interrupt blood clot formation (see section 3, “Changing anticoagulant medication”)
• intravenous dextran – used as a blood substitute
• ibuprofen, diclofenac, ketorolac, and other medications known as nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain and inflammation in arthritis and other diseases
• prednisolone, dexamethasone, and other medications used to treat asthma, rheumatoid arthritis, and other diseases
• medications that increase potassium levels in the blood such as potassium salts, diuretics, and some medications used to treat heart problems.

Surgeries and anesthesia

Inform your doctor that you are usingClexaneif you are going to have a lumbar puncture or spinal tap, or are going to undergo surgery where spinal or epidural anesthesia will be used.

Pregnancy and breastfeeding

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

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

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

Driving and operating machinery

Clexanedoes not affect your ability to drive and operate machinery.

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

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Medication use

• Your doctor or nurse will normally administer Clexane to you. This is because it needs to be administered by injection.
• Clexane is usually administered by subcutaneous injection.
• Clexane can be administered by intravenous injection after certain types of heart attacks or surgical operations.
• Clexane can be added to the tube that comes out of the body (arterial line) at the beginning of a dialysis session.
• Do not administer Clexane by intramuscular injection.

How much will be administered

• Your doctor will decide how much Clexane will be administered to you. The amount will depend on the reason it is being used.
• If you have any kidney problems, you may be administered a smaller amount of Clexane.

1. Treatment of blood clot formation
   • The usual dose is 150 UI (1.5 mg) per kilogram of body weight once a day or 100 UI (1 mg) per kilogram of body weight twice a day.
   • Your doctor will decide how long you will receive Clexane.

1. Prevention of blood clot formation during surgical operations or periods of limited mobility due to illness
   • The dose will depend on the likelihood that you will develop a clot. You will be administered 2,000 UI (20 mg) or 4,000 UI (40 mg) of Clexane per day.
   • If you are to undergo surgery, you will usually be administered the first injection 2 or 12 hours before the operation.
   • If you have limited mobility due to illness, you will usually be administered 4,000 UI (40 mg) of Clexane per day.
   • Your doctor will decide how long you will receive Clexane.

1. Prevention of blood clot formation when you have unstable angina or after a heart attack

• Clexane can be used in two different types of heart attacks.
• The amount of Clexane that will be administered to you will depend on your age and the type of heart attack you have had.

Non-ST-elevation myocardial infarction (NSTEMI):

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

ST-elevation myocardial infarction (STEMI) if you are under 75 years:

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

ST-elevation myocardial infarction (STEMI) if you are 75 years or older:

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

For patients undergoing percutaneous coronary intervention (PCI):

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

1. Prevention of blood clot formation in dialysis equipment

• The usual dose is 100 UI (1 mg) per kilogram of body weight.
• Clexane is added to the tube that comes out of 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 perform a new injection of 50 UI to 100 UI (0.5 to 1 mg) per kilogram of body weight if necessary.

Self-administration of Clexane

If you can administer Clexane yourself, your doctor or nurse will show you how to do it. Do not attempt to administer it yourself if you have not been shown how to do it. If you are unsure what to do, consult your doctor or nurse immediately. If the injection is performed correctly under the skin (which is called a subcutaneous injection), this will help reduce pain and hematoma at the injection site.

Before self-administering Clexane

• Prepare what you will need: syringe, cotton swab with alcohol or soap and water, and sharp object container
• Check the expiration date of the medication. If it has expired, do not use it.
• Check that the syringe is not damaged and that the medication solution is transparent. If not, use another syringe.
• Make sure you know the amount to be injected.
• Check in the area of your abdomen if the last injection caused redness, skin color change, swelling, pus, or pain that still persists. If this occurred, consult your doctor or nurse.

Instructions for self-administering Clexane:

(Instructions for syringes without safety device)

Preparation of the injection site

1. Choose a site on the right or left side of your abdomen. At least 5 cm from the navel and towards either side.
   • Do not inject within 5 cm of the navel or around it if there are scars or hematomas.
   • To inject, alternate the left and right sides of your abdomen, depending on where the last injection was administered.

1. Wash your hands. Clean (do not rub) the area where the injection will be administered with a cotton swab with alcohol or soap and water.
2. Sit or lie down in a comfortable position so that you are relaxed. Make sure you can see the area where the injection will be administered. It is best to do this in a recliner, a reclining chair, or a bed with pillows.

Selection of the dose

1. Carefully remove the cap from the syringe needle by pulling it. Dispose of the cap.
   • Do not press the plunger to remove air bubbles before injecting. This can result in a loss of medication.
   • Once you have removed the cap, do not touch anything with the needle. This will ensure that the needle remains clean (sterile).

1. When the amount of medication in the syringe matches the dose prescribed, there is no need to adjust the dose. You are now ready to administer the injection.
2. When the dose depends on your body weight, you may need to adjust the dose in the syringe to match the prescribed dose. In this case, you can dispose of the excess medication by keeping the syringe pointing downwards (to keep the air bubble in the syringe) and expelling the excess into a container.
3. A drop may appear at the end of the needle. If this happens, you need to remove the drop before administering the injection by gently tapping the syringe with the needle pointing downwards. You are now ready to administer the injection.

Administration of the injection

1. Hold the syringe with the hand that writes (like a pencil). With the other hand, gently pinch the area you cleaned on your abdomen, between your index finger and thumb, to form a fold in the skin.
   • Make sure to hold this fold of skin in place while the injection is administered.
2. Hold the syringe so that the needle points straight down (vertically at a 90-degree angle). Insert the entire needle into the fold of skin.

1. Press the plunger with your thumb. This will administer the medication into the fatty tissue of your abdomen. Complete the injection using all the medication in the syringe.
2. Remove the needle from the injection site by pulling it straight out. Point the needle away from yourself and others. You can now release the fold of skin.

When you have finished

The disposal of unused medication and all materials that have come into contact with it will be done in accordance with local regulations.

Instructions for syringes with automatic safety device type ERISTM:

Preparation of the injection site

1. Choose a site on the right or left side of your abdomen. At least 5 cm from the navel and towards either side.
   • Do not inject within 5 cm of the navel or around it if there are scars or hematomas.
   • To inject, alternate the left and right sides of your abdomen, depending on where the last injection was administered.

1. Wash your hands. Clean (do not rub) the area where the injection will be administered with a cotton swab with alcohol or soap and water.
2. Sit or lie down in a comfortable position so that you are relaxed. Make sure you can see the area where the injection will be administered. It is best to do this in a recliner, a reclining chair, or a bed with pillows.

Selection of the dose

1. Carefully remove the cap from the syringe needle by pulling it. Dispose of the cap.
   • Do not press the plunger to remove air bubbles before injecting. This can result in a loss of medication.
   • Once you have removed the cap, do not touch anything with the needle. This will ensure that the needle remains clean (sterile).

1. When the amount of medication in the syringe matches the dose prescribed, there is no need to adjust the dose. You are now ready to administer the injection.
2. When the dose depends on your body weight, you may need to adjust the dose in the syringe to match the prescribed dose. In this case, you can dispose of the excess medication by keeping the syringe pointing downwards (to keep the air bubble in the syringe) and expelling the excess into a container.
3. A drop may appear at the end of the needle. If this happens, you need to remove the drop before administering the injection by gently tapping the syringe with the needle pointing downwards. You are now ready to administer the injection.

Administration of the injection

1. Hold the syringe with the hand that writes (like a pencil). With the other hand, gently pinch the area you cleaned on your abdomen, between your index finger and thumb, to form a fold in the skin.
   • Make sure to hold this fold of skin in place while the injection is administered.
2. Hold the syringe so that the needle points straight down (vertically at a 90-degree angle). Insert the entire needle into the fold of skin.

1. Press the plunger with your thumb. This will administer the medication into the fatty tissue of your abdomen. Complete the injection using all the medication in the syringe.
2. Remove the needle from the injection site by pulling it straight out. A protective cover will automatically cover the needle. You can now release the fold of skin. The safety device will only release the protective cover when the syringe is empty, by pressing the plunger deeply.

When you have finished

The disposal of unused medication and all materials that have come into contact with it will be done in accordance with local regulations.

Instructions for syringes with automatic safety device type PREVENTISTM:

Preparation of the injection site

1. Choose a site on the right or left side of your abdomen. At least 5 cm from the navel and towards either side.
   • Do not inject within 5 cm of the navel or around it if there are scars or hematomas.
   • To inject, alternate the left and right sides of your abdomen, depending on where the last injection was administered.

1. Wash your hands. Clean (do not rub) the area where the injection will be administered with a cotton swab with alcohol or soap and water.
2. Sit or lie down in a comfortable position so that you are relaxed. Make sure you can see the area where the injection will be administered. It is best to do this in a recliner, a reclining chair, or a bed with pillows.

Selection of the dose

1. Carefully remove the cap from the syringe needle by pulling it. Dispose of the cap.
   • Do not press the plunger to remove air bubbles before injecting. This can result in a loss of medication.
   • Once you have removed the cap, do not touch anything with the needle. This will ensure that the needle remains clean (sterile).

1. When the amount of medication in the syringe matches the dose prescribed, there is no need to adjust the dose. You are now ready to administer the injection.
2. When the dose depends on your body weight, you may need to adjust the dose in the syringe to match the prescribed dose. In this case, you can dispose of the excess medication by keeping the syringe pointing downwards (to keep the air bubble in the syringe) and expelling the excess into a container.
3. A drop may appear at the end of the needle. If this happens, you need to remove the drop before administering the injection by gently tapping the syringe with the needle pointing downwards. You are now ready to administer the injection.

Administration of the injection

1. Hold the syringe with the hand that writes (like a pencil). With the other hand, gently pinch the area you cleaned on your abdomen, between your index finger and thumb, to form a fold in the skin.
   • Make sure to hold this fold of skin in place while the injection is administered.
2. Hold the syringe so that the needle points straight down (vertically at a 90-degree angle). Insert the entire needle into the fold of skin.

1. Press the plunger with your thumb. This will administer the medication into the fatty tissue of your abdomen. Complete the injection using all the medication in the syringe.
2. Remove the needle from the injection site by pulling it straight out while keeping your finger on the plunger. Point the needle away from yourself and others, and press the plunger firmly to activate the safety device. A protective cover will automatically cover the needle. You will hear a "click" that confirms the activation of the safety device. You can now release the fold of skin.

When you have finished

The disposal of unused medication and all materials that have come into contact with it will be done in accordance with local regulations.

Change of anticoagulant medication

• Change from Clexane to medications that reduce blood clotting called vitamin K antagonists (such as warfarin)

Your doctor will request that you have a blood test to determine a parameter called INR and will tell you when to stop taking Clexane.

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

Stop using the vitamin K antagonist. Your doctor will request that you have a blood test to determine a parameter called INR and will tell you when to start taking Clexane.

• Change from Clexane to direct oral anticoagulants

Stop using Clexane. Start taking the direct oral anticoagulant from 0 to 2 hours before the time when you would have had the next injection, and then continue as usual.

• Change from direct oral anticoagulants to Clexane

Stop taking the direct oral anticoagulant. Do not start taking Clexane until 12 hours have passed since 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 any signs of a problem. If a child accidentally injects or swallows Clexane, take them immediately to the emergency department of a hospital.

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, phone 91 562 04 20, indicating the medication and the amount administered.

If you forget to use Clexane

If you forget to administer a dose, do it as soon as you remember. Do not use a double dose on the same day to compensate for the missed doses. To ensure that you do not forget any doses, it may be helpful to use a calendar.

If you interrupt Clexane treatment

It is essential that you continue to receive 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 other questions about the use of this medication, ask your doctor or pharmacist or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Severe side effects

Stop taking Clexaneand inform your doctor or nurse immediatelyif you experience any signs of severe allergic reaction (such as rash, difficulty breathing or swallowing, swelling of the face, lips, tongue, mouth, throat, or eyes).

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

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

Like other medicines similar to reduce blood clots, Clexanemay cause bleeding. This could put your life at risk. In some cases, the bleeding may not be apparent.

Inform your doctor immediately if:

• you have any bleeding that does not stop on its own
• 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 close observation or change your medication.

You must inform your doctor immediately:

• if you experience any signs of a blood clot blocking a blood vessel, such as:

• cramp-like pain, redness, heat, or swelling in one of your legs – which are symptoms of deep vein thrombosis
• difficulty breathing, chest pain, fainting, or coughing up blood – which are symptoms of pulmonary embolism

• if you have painful skin rash with dark red spots under the skin that do not disappear when pressed.

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

Other side effects:

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

• bleeding
• increase in liver enzymes.

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

• if you develop bruises more frequently than usual - this could be due to a blood problem caused by low platelet count
• pink patches on the skin - appear more frequently in the area where Clexane has been injected
• skin rash (hives, urticaria)
• redness and itching of the skin
• bruise or pain at the injection site
• decrease in red blood cells in the blood
• increase in platelets in the blood
• headache.

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

• severe sudden headache - this could be a sign of brain hemorrhage
• sensation of tenderness and swelling of the stomach - could be indicative of gastric hemorrhage
• large, irregular red skin lesions with or without blisters
• skin irritation (local irritation)
• yellowing of the skin or eyes, and darkening of urine color - could be due to liver problems.

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

• severe allergic reaction - symptoms of this reaction may include: skin rash, difficulty breathing or swallowing, swelling of the lips, face, throat, or tongue
• increase in potassium in the blood - this is more likely to occur in people with kidney problems or diabetes. Your doctor will be able to check it by performing a blood test
• increase in eosinophils in the blood - your doctor will be able to check it by performing a blood test
• hair loss
• osteoporosis (a disease in which the bones may be more likely to break)
• tingling, numbness, and weakness in the muscles (especially in the lower part of the body) when you have had a lumbar puncture or spinal anesthesia
• loss of bladder or bowel control (so you cannot control your needs)
• hardening or nodule at the injection site.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not use this medication if you observe a crack in the syringe, particles in suspension in the solution, or an abnormal color of the solution (see “Product Appearance and Packaging Contents”).

Medications should not be disposed of through drains or in the trash.Deposit the containers and medications you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Clexane Composition

• The active ingredient is enoxaparin sodium
• Each ml contains 100 mg of enoxaparin sodium, equivalent to 10,000 UI of anti-Xa activity

Each pre-filled syringe with 0.8 ml contains 8,000 UI (80 mg) of enoxaparin sodium

• The other component is water for injection

Product Appearance and Packaging Contents

Clexane is a transparent, colorless to yellowish injectable solution in a pre-filled glass syringe (with or without an automatic safety device),

It is available in packs of 2, 5, 6, 10, 12, 20, 24, 30, 50, 100 pre-filled syringes, and in multiple packs of 3 x 10, 9 x 10, 100 x 10, and 200 x 10 pre-filled syringes.

Only some pack sizes may be marketed.

Marketing Authorization Holder

sanofi-aventis, S.A.

C/ Roselló i Porcel, 21

08016 Barcelona

Spain

Responsible for Manufacturing

Sanofi Winthrop Industrie

Boulevard Industriel

76580 Le Trait,

France

Or

Sanofi Winthrop Industrie

180 rue Jean Jaurès

94700 Maisons-Alfort

France

Or

Chinoin Pharmaceutical and Chemical Works Private Co. Ltd

Csanyikvölgy site

Miskolc, Csanyikvölgy

H-3510

Hungary

Or

Sanofi-Aventis GmbH

Turm A, 29.OG, Wienerbergstraße 11

1100 Vienna

Austria

Or

Sanofi-Aventis Private Co. Ltd

Budapest Logistics and Distribution Platform

Bdg. DC5, Campona utca1.

Budapest, 1225

Hungary

Or

Sanofi-Aventis Deutschland GmbH

Industriepark Höchst-Brüningstraße 50

65926 Frankfurt am Main

Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria, France, Portugal: Lovenox.

Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Germany, Greece, Hungary, Ireland, Italy, Latvia, Luxembourg, Malta, Poland, Romania, Slovakia, Slovenia, Spain, United Kingdom: Clexane.

Italy: Clexane T.

Finland, Iceland, Norway, Sweden: Klexane.

Last review date of this leaflet:February 2022

Other sources of information

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/