Clexane

Package leaflet: Information for the patient

Clexane, 30,000 IU (300 mg)/3 ml, solution for injection
Enoxaparin sodium
Please read 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 questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not give it to others. This medicine may harm others, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Clexane is and what it is used for
2. Important information 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 a substance called enoxaparin sodium. It belongs to a group of medicines known as low molecular weight heparins (LMWH).

How Clexane works
Clexane 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 bloodstream.

What Clexane is used for
Clexane may be used to:

• Treat existing blood clots in the patient’s bloodstream.
• Prevent the formation of blood clots in the patient’s bloodstream 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
• Prevent clot formation in unstable angina (when insufficient blood is delivered to the heart muscle) or after a heart attack
• Prevent clotting in the dialysis machine tubing (used in patients with severe kidney function disorders).

2. Important information before using Clexane

The medicine contains 15 mg of benzyl alcohol per 1 ml. Benzyl alcohol may cause allergic reactions.
Do not use Clexane if:

• the patient is allergic to enoxaparin sodium or any of the other ingredients of this medicine (listed in section 6), or to 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 which caused a serious drop in the number of blood cells responsible for blood clotting (platelets) within the last 100 days.
• 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 surgery on the brain or eyes, including recent haemorrhagic stroke.
• the patient is being treated with Clexane for blood clots and a procedure is planned within the next 24 hours:
  - lumbar puncture
  - surgical procedure under spinal or epidural anaesthesia.
• the patient is a premature infant or a newborn in the first month of life – due to the risk of severe toxic effects, including breathing problems (so-called "respiratory distress syndrome"). Clexane should not be used in the above-mentioned patients. If in doubt, consult a doctor or pharmacist before starting treatment with Clexane.

Warnings and precautions
Clexane must not be substituted 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 instructions for use.
Before starting treatment with Clexane, consult a doctor or pharmacist if:

• the patient has ever had a reaction to heparin causing a significant drop in the number of blood cells responsible for blood clotting (platelets)
• the patient has a heart valve prosthesis
• the patient has endocarditis (an infection of the inner lining of the heart)
• the patient has or has had stomach ulcers
• the patient has recently had a stroke
• the patient has high blood pressure
• the patient has diabetes or diabetic eye disease (diabetic retinopathy)
• the patient has recently undergone eye or brain surgery
• the patient is elderly (over 65 years of age), particularly if over 75 years of age
• the patient has kidney disease
• the patient has liver disease
• the patient is underweight or overweight
• the patient has elevated potassium levels in the blood (this can be checked in a laboratory blood test)
• the patient is currently taking medicines that may cause bleeding (see section 2 "Clexane with other medicines")
• the patient has spinal problems or has undergone spinal surgery. If any of the above situations apply, or if the patient has any doubts, consult a doctor or pharmacist before starting treatment with Clexane.

Patients with liver or kidney disease should contact their doctor. A large amount of benzyl alcohol may accumulate in their body and cause adverse effects (so-called metabolic acidosis).
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.

Tests and monitoring
Before starting treatment with this medicine and periodically during treatment, the patient may undergo blood tests to check the number of platelets (blood cells responsible for blood clotting) and potassium levels in the blood.

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

Clexane with other medicines
Tell 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 section 3 "Changing anticoagulant therapy")
• 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 some medicines used for 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.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, 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 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.
Pregnant women or those who are breastfeeding should contact their doctor, as a large amount of benzyl alcohol may accumulate in their body and cause adverse effects (so-called metabolic acidosis).

Driving and using machines
Clexane does not affect the ability to drive or operate machinery.

Clexane in multidose vials contains benzyl alcohol

• Clexane in multidose vials contains benzyl alcohol (15 mg/ml), which is a preservative. It may cause poisoning and allergic reactions in infants and children under 3 years of age. The medicine should not be used in premature infants or newborns during the first month of life due to the risk of severe toxic effects, including breathing disorders.
• It is recommended that pregnant women use Clexane formulations that do not contain benzyl alcohol.

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

3. How to use Clexane

This medicine should always be used exactly as directed by your doctor or pharmacist. If you have any doubts,
you should consult your doctor or pharmacist.
Taking the medicine

• Clexane is usually administered to you by a doctor or nurse. This is because it needs to be given by injection.
• Clexane is usually given by subcutaneous injection.
• Clexane may be given by intravenous injection following certain types of heart attack or after surgery.
• Clexane may be injected into the dialysis tubing that carries blood away from the body (into the so-called arterial line) at the beginning of a dialysis session.
• Clexane must not be given by intramuscular injection.

Dose of medicine

• Your doctor will decide how much Clexane you should receive. The dose depends on the reason for treatment.
• If you have kidney disease, you may receive a lower dose of Clexane.

1) Treatment of blood clots in the patient

• 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 receive Clexane.

2) Prevention of blood clots during surgery or in patients with limited mobility due to illness

• The dose depends on the individual patient's risk of developing clots. You will receive Clexane at a dose of 2000 IU (20 mg) or 4000 IU (40 mg) daily.
• If you are scheduled for surgery, the first injection is usually given 2 hours or 12 hours before the procedure.
• If you have limited mobility due to illness, you usually receive Clexane at a dose of 4000 IU (40 mg) daily.
• Your doctor will decide how long you should receive Clexane.

3) Prevention of blood clots in patients with unstable angina or after myocardial infarction

• Clexane can be used in two different types of heart attack.
• The dose of Clexane will depend on the patient's age and the type of heart attack that occurred.

Non-ST-segment elevation myocardial infarction (NSTEMI):

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

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

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

ST-segment elevation myocardial infarction (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 in the first two doses is 7500 IU (75 mg).
• Your doctor will decide how long you should receive Clexane.

Patients undergoing percutaneous coronary intervention (PCI):

• Depending on when the last dose of Clexane was given, your doctor may decide to administer an additional dose of Clexane before the PCI procedure. The medicine will then be given by intravenous injection.

4) Prevention of blood clots in dialyzer tubing

• The usual dose is 100 IU (1 mg) per kilogram of body weight.
• Clexane 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-injection of Clexane
If you are able to self-administer Clexane injections, your doctor or nurse will demonstrate how to do it. Do not attempt to give yourself an injection unless you have been properly trained. If you have any doubts about how to do it, contact your doctor or nurse immediately. Correct subcutaneous injection technique (called "subcutaneous injection") may reduce pain and bruising at the injection site.
Before self-injecting Clexane

• Prepare all necessary supplies: a multi-dose vial, syringe, alcohol swab or soap and water, and a sharps container for medical waste.
• Check the expiry date on the packaging. Do not use the medicine after this date.
• Check that the vial is not damaged and that the liquid is clear. If not, use another vial.
• Confirm the correct dose to be injected.
• Examine your abdomen to check whether the previous injection caused redness, skin discoloration, swelling, oozing, or if it is still painful. If so, contact your doctor or nurse.
• Clexane should be injected just under the skin of the abdomen, but not too close to the navel or any scars (at least 5 cm away). Choose the injection site and alternate between the left and right sides of the abdomen.

Instructions for self-injection of Clexane:
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 toward the sides.

• Do not inject within 5 cm of the navel or near existing scars or bruises.
• Change injection sites alternately 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 so you are relaxed. Make sure the injection site is clearly visible. A chair, examination table, or bed with pillows for support is suitable.

Injection

1. Draw up the correct dose from the vial using the appropriate syringe. A drop may appear at the needle tip. If so, remove the drop by tapping the syringe gently with the needle pointing downward. You may now proceed with the injection.
2. Hold the syringe in the hand you write with (like a pencil). With the other hand, gently pinch the cleaned abdominal skin between your thumb and index finger to form a skin fold.

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

3. Hold the syringe with the needle pointing downward (vertically at a 90° angle). Insert the full length of the needle into the skin fold.
4. Press the plunger with your thumb to inject the medicine into the fatty tissue of the abdomen. Inject the entire contents of the syringe.
5. 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.
   Switching anticoagulant medicines

• Switching from Clexane to vitamin K antagonists (such as warfarin)
  Your doctor will recommend blood tests to monitor your INR and will inform you when to stop taking Clexane.
• Switching from vitamin K antagonists (such as warfarin) to Clexane
  Stop taking the vitamin K antagonist medicine. Your doctor will recommend a blood test to monitor your INR and will inform you when to start taking Clexane.
• Switching from Clexane to direct oral anticoagulants (DOACs)
  Stop taking Clexane. Begin taking the direct oral anticoagulant 0 to 2 hours before the scheduled time of the next injection, then continue taking it as usual.
• Switching from a direct oral anticoagulant to Clexane
  Stop taking the direct oral anticoagulant. Clexane treatment may be started 12 hours after the last dose of the direct oral anticoagulant.

Using more Clexane than recommended
If you think you have used too much or too little Clexane, contact your doctor, pharmacist, or nurse immediately, even if you do not notice any symptoms. In case of accidental injection or ingestion of Clexane by a child, go immediately to the hospital emergency department.
Missing a dose of Clexane
If you miss a dose, take it as soon as possible. Do not take a double dose to make up for a missed dose. Keeping a diary can help ensure you do not miss doses.
Stopping Clexane treatment
It is important to continue Clexane injections until your doctor tells you to stop. Stopping treatment may lead to the formation of a blood clot, which could be very dangerous.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects
Stop using Clexane and contact a doctor or nurse immediately if signs of a severe allergic reaction occur (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 help:

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

Like other similar medicines used to reduce blood clotting, Clexane may cause bleeding. This could potentially be life-threatening. In some cases, bleeding may not be immediately visible.
Contact a doctor immediately if:

• the patient experiences any bleeding that does not stop spontaneously
• the patient shows signs of excessive bleeding such as weakness, fatigue, paleness, dizziness with headaches or unexplained swelling. The doctor may decide to subject the patient to closer monitoring or change the medicine.

Contact a doctor immediately:

• if the patient experiences any signs of a blood vessel blocked by a blood clot, such as: cramping pain, redness, increased warmth or swelling in one of the lower limbs – these are symptoms of deep vein thrombosis

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

• if 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 check platelet count.

Other side 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 – this may be due to a reduced platelet count
• pink spots on the skin – these changes are more likely at the sites where Clexane injections are administered
• skin rash (urticaria)
• itchy, red skin
• bruising or pain at the injection site
• reduced number of red blood cells
• increased number of platelets
• headaches.

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

• sudden, severe headache – this may indicate bleeding into the brain
• sensation of tenderness and swelling in the stomach – this may indicate bleeding into the stomach
• 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 lips, face, throat or tongue
• increased potassium levels in blood – this is more likely in people with kidney disease or diabetes. The doctor may check this with a blood test
• increased number of eosinophils in 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 control over bladder or bowel movements (a condition in which the patient cannot control when they need to go to the toilet)
• hardening or lump at the injection site.

Reporting of side effects
If any side effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Side effects can also be reported directly to the Department for 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
Side effects can also be reported to the marketing authorisation holder or its representative in Poland.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Clexane

Do not store above 25 °C.
After opening the vial, use within 28 days.
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 this medicine if you notice a cracked vial, particles in the solution, or an abnormal solution colour (see "What Clexane looks like and contents of the pack").
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Clexane contains

• The active substance is enoxaparin sodium. Each ml contains 100 mg of enoxaparin sodium, corresponding to 10,000 IU anti-Xa activity. Each 3 ml vial contains 30,000 IU (300 mg) of enoxaparin sodium.
• The excipients are: benzyl alcohol and water for injections.

What Clexane looks like and contents of the pack
Clexane is a clear, colourless or slightly yellowish solution for injection in a glass vial.
Pack sizes: 1, 5 and 10 vials.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Sanofi Winthrop Industrie
82, Avenue Raspail
94250 Gentilly
France
Manufacturer
Sanofi-Aventis Deutschland GmbH
Brüningstraße 50 / Industriepark Höchst
65926 Frankfurt am Main
Germany
For further information about 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 Warszawa
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)