ENOXAPARIN SODIUM 150 MG / 1ML SYRINGES, CLEXANE FORTE 150 MG / 1ML SYRINGES - patient leaflet, side effects, dosage

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

The name of your medicine is Clexane Forte 150mg/1ml Syringes (called Clexane Forte in this leaflet). Clexane Forte contains a medicine called enoxaparin sodium. This belongs to a group of medicines called Low Molecular Weight Heparins.

Clexane Forte works in two ways:

• 1) Stopping existing blood clots from getting any bigger. This helps your body to break them down and stop them causing you harm.

• 2) Stopping blood clots forming in your blood.

Clexane Forte can be used to:

• Treat blood clots that are in your blood
• Stop blood clots forming in your blood in the following situations:
• Unstable angina (where not enough blood gets to your heart)
• After an operation or long periods of bed rest due to illness
• After you have had a heart attack
• Stop blood clots forming in the tubes of your dialysis machine (used for people with kidney problems)

2. before you use clexane fortedo not have this medicine and tell your doctor if:x you are allergic (hypersensitive) to enoxaparin sodium. signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue

x You are allergic to heparin or other Low Molecular Weight Heparins such as tinzaparin or dalteparin

x You have a problem with bruising or bleeding too easily

x You are bleeding heavily

x You have an ulcer in your stomach or gut (intestine)

x You have had a stroke caused by bleeding in the brain

x You have an infection in your heart

x You are using the medicine called heparin to treat blood clots

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor, pharmacist or nurse before having Clexane Forte.

Take special care with Clexane Forte

Check with your doctor or pharmacist before having this medicine if:

a You have high blood pressure which is not controlled by medication

a You have kidney problems

a You have had a heart valve fitted

a You have ever had bruising and bleeding caused by the medicine heparin

a You have ever had a stroke

a You have ever had a stomach ulcer

a You have recently had an operation on your eyes or brain a You are a diabetic or have an illness known as ‘diabetic retinopathy’ (problems with the blood vessels in the eye caused by diabetes)

a You have any problems with your blood

a You are underweight or overweight

A You are elderly (over 65 years old) and especially if you are aged over 75 years old

If you are not sure if any of the above applies to you, talk to your doctor, pharmacist or nurse before having Clexane Forte.

Taking or using other medicines

Please tell your doctor, pharmacist or nurse if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Clexane Forte can affect the way some other medicines work. Also some medicines can affect the way Clexane Forte works.

In particular, do not take this medicine and tell your doctor if: x You are using the medicine called heparin to treat blood clots

Tell your doctor if you are taking any of the following medicines:

• Warfarin – used for thinning the blood
• Aspirin – used to stop blood clots from forming. Aspirin may also be used for pain relief and in medicines for colds and flu
• Dipyridamole, clopidogrel, or other medicines – used to stop blood clots forming
• Streptokinase, alteplase and reteplase – used to dissolve blood clots after a heart attack
• Dextran injection – used to replace blood volume
• Ibuprofen, diclofenac, ketorolac or other medicines used to treat pain and swelling in arthritis and other illnesses
• Prednisolone, dexamethasone or other steroid medicines – used to treat asthma, rheumatoid arthritis and other conditions
• Water tablets (diuretics) such as spironolactone, triamterene or amiloride. These may increase the levels of potassium in your blood when taken with Clexane Forte

Your doctor may change one of your medicines or take regular blood tests to check that taking these medicines with Clexane Forte is not causing you any harm.

Operations and anaesthetics

If you are going to have a spinal puncture or an operation where an epidural or spinal anaesthetic is used, tell your doctor that you are using Clexane Forte. Tell also your doctor if you have any problem with your spine or if you have ever had spinal surgery.

Pregnancy and breast-feeding

Talk to your doctor before you are given this medicine if you are pregnant, might become pregnant or think you may be pregnant.

You should not use this medicine if you are pregnant and have a mechanical heart valve as you may be at increased risk of developing blood clots. Your doctor should discuss this with you.

You should not breast-feed whilst using Clexane Forte. If you are planning to breast-feed, talk to your doctor, pharmacist or nurse.

3. how to use clexane fortehaving this medicine before you have clexane forte your doctor or nurse may carry out a blood test

• While you are in hospital your doctor or nurse will normally give you Clexane Forte. This is because it needs to be given as an injection
• When you go home you may need to continue to use Clexane Forte and give it to yourself (see below instructions on how to do this)
• Clexane Forte is usually given by injection underneath the skin (subcutaneous)
• Do not inject Clexane Forte into a muscle (intramuscular)

If you are not sure why you are receiving Clexane Forte or have any questions about how much Clexane Forte is being given to you, speak to your doctor, pharmacist or nurse.

How much will be given to you in hospital

• Your doctor will decide how much to give you. The amount of Clexane Forte given to you will depend on the reason it is being used
• If you have problems with your kidneys, you may be given a smaller amount of Clexane Forte

Adults including the elderly

• 1) Treating blood clots that are in your blood

• The usual dose is 1.5mg for every kilogram of your weight, each day
• Clexane Forte will usually be given for at least 5 days

• 2) Stopping blood clots forming in your blood in the following situations:

• a) Unstable angina

• The usual dose is 1mg for every kilogram of your weight, every 12 hours
• Clexane Forte will usually be given for 2 to 8 days. Your doctor will normally ask you to take aspirin as well

• b) After an operation or long periods of bed rest due to illness

The usual dose is 20mg or 40mg each day.

The dose will depend on how likely you are to develop a clot.

• If you have a low to medium risk of getting a clot, you will be given 20mg of Clexane Forte each day for 7 to 10 days. If you are going to have an operation, your first injection will usually be given 2 hours before your operation
• If you have a higher risk of getting a clot, you will be given 40mg each day for 7 to 28 days. If you are going to have an operation, your first injection will usually be given 12 hours before your operation
• If you are bedridden due to illness, you will be normally be given 40mg of Clexane Forte each day for 6 to 14 days

• c) After you have had a heart attack

Clexane can be used for two different types of heart attack called NSTEMI or STEMI. The amount of Clexane given to you will depend on your age and the kind of heart attack you have had.

• i) NSTEMI type of heart attack

• The usual amount is 1mg for every kilogram of weight, every 12 hours
• Clexane will usually be given for 2 to 8 days. Your doctor will normally ask you to take aspirin as well.

• ii) STEMI type of heart attack If you are under 75 years old

• 30mg of Clexane will be given as an injection into your vein (intravenous injection using Clexane Multidose Vial or 60, 80 or 100mg Pre-filled syringes)
• At the same time, you will also be given Clexane as an injection under your skin (subcutaneous injection). The usual dose is 1mg for every kilogram of your weight.
• Then you will be given 1mg for every kilogram of your weight every 12 hours
• The maximum amount of Clexane given for the first two injections is 100mg
• The injections will normally be given for up to 8 days

If you are aged 75 years or older

• Your doctor or nurse will give you injections of Clexane Forte under your skin (subcutaneous injection)
• The usual dose is 0.75mg for every kilogram of your weight, every 12 hours
• The maximum amount of Clexane given for the first two injections is 75mg

For patients having an operation called Percutaneous Coronary Intervention (PCI)

• Depending on when you were last given Clexane Forte, your doctor may decide to give an additional dose of Clexane before a PCI operation. This is by injection into your vein (intravenous using Clexane Multidose Vial or 60, 80 or 100mg Pre-filled Syringes).

• 3) Stopping blood clots forming in the tubes of your dialysis machine

• The usual dose is 1mg for every kilogram of your weight
• Clexane Forte is added to the tube leaving the body (arterial line) at the start of the dialysis session
• This amount is usually enough for a 4 hour session. However, your doctor may give you a further dose of 0.5 to 1mg for every kilogram of your weight if necessary

Children

This medicine should not be given to children.

How to give yourself an injection of Clexane Forte

If you are able to give Clexane Forte to yourself, your doctor or nurse will show you how to do this. Do not try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your doctor or nurse immediately.

Before injecting yourself with Clexane Forte

• Check the expiry date on the medicine. Do not use if the date has passed
• Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another syringe
• Make sure you know how much you are going to inject
• Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, oozing or is still painful. If so talk to your doctor or nurse
• Decide where you are going to inject the medicine. Change the place where you inject each time from the right to the left side of your stomach. Clexane Forte should be injected just under the skin on your stomach, but not too near the belly button or any scar tissue (at least 5cm away from these)

Ask your doctor, pharmacist or nurse for advice before taking any medicine if you are pregnant or breast-feeding.

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THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY

Clexane® Forte 120mg 150mg Pre-Filled Syringes

(enoxaparin sodium)

The following information is extracted from the SPC

Technical information for the administration of Clexane Syringes

• 1 NAME OF THE MEDICINAL PRODUCT

Clexane® Forte Syringes

• 2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Pre-filled syringes:

120 mg Injection Enoxaparin sodium 120 mg (equivalent to 12,000 IU anti-Xa activity) in 0.8 mL Water for Injections

150 mg Injection Enoxaparin sodium 150 mg (equivalent to 15,000 IU anti-Xa activity) in 1.0 mL Water for Injections

For full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless to pale yellow solution.

4.2 Posology and method of administration

Adults:

Prophylaxis of venous thromboembolism:

In patients with a low to moderate risk of venous thromboembolism the recommended dosage is 20 mg (2,000 IU) once daily by subcutaneous injection for

7 to 10 days, or until the risk of thromboembolism has diminished. In patients undergoing surgery, the initial dose should be given approximately

2 hours pre-operatively.

In patients with a higher risk, such as in orthopaedic surgery, the dosage should be 40 mg (4,000 IU) daily by subcutaneous injection with the initial dose administered approximately 12 hours before surgery.

In patients with a high-risk of venous thromboembolism who undergo abdominal or pelvic surgery for cancer and are not otherwise at risk for major bleeding complications, the recommended dosage is 40 mg (4,000 IU) once daily by subcutaneous injection for 4 weeks with the initial dose administered approximately 12 hours before surgery.

Prophylaxis of venous thromboembolism in medical patients:

The recommended dose of enoxaparin sodium is 40 mg (4,000 IU) once daily by subcutaneous injection. Treatment with enoxaparin sodium is prescribed for a minimum of 6 days and continued until the return to full ambulation, for a maximum of 14 days.

Treatment of venous thromboembolism:

Clexane should be administered subcutaneously as a single daily injection of 1.5 mg/kg (150 IU/kg). Clexane treatment is usually prescribed for at least

5 days and until adequate oral anticoagulation is established.

Dosage chart for 1.5mg/kg SC treatment of DVT, PE or both

Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

Treatment of unstable angina and non-Q-wave myocardial infarction

The recommended dose is 1mg/kg Clexane every 12 hours by subcutaneous injection, administered concurrently with oral aspirin (100 to 325mg once daily). Treatment with Clexane in these patients should be prescribed for a minimum of 2 days and continued until clinical stabilisation. The usual duration of treatment is 2 to 8 days.

Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

Treatment of acute ST-segment Elevation Myocardial Infarction

The recommended dose of enoxaparin sodium is a single IV bolus of 30mg (using the Clexane 100mg/ml Multidose Vial or 60mg, 80mg or

100mg prefilled syringes) plus a 1mg/kg SC dose followed by 1mg/kg administered SC every 12 hours (max 100mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses). For dosage in patients >75 years of age, see section 4.2 Posology and method of administration: Elderly.

(1) Not to be given for the first two doses – (maximum 100mg for the first two doses only, followed by 1mg/kg dosing for the remaining doses) Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

When administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific) enoxaparin sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive acetylsalicylic acid (ASA) as soon as they are identified as having STEMI and maintained under (75 to 325mg once daily) unless contraindicated.

The recommended duration of enoxaparin sodium treatment is 8 days or until hospital discharge, whichever comes first.

For patients managed with Percutaneous Coronary Intervention (PCI): If the last enoxaparin sodium SC administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last SC administration was given more than 8 hours before balloon inflation, an IV bolus of 0.3mg/kg of enoxaparin sodium should be administered (using the Clexane 100mg/ml Multidose Vial or 60mg, 80mg or 100mg prefilled syringes).

Prevention of extracorporeal thrombus formation during haemodialysis:

A dose equivalent to 1 mg/kg (100 IU/kg) introduced into the arterial line at the beginning of a dialysis session is usually sufficient for a 4 hour session. If fibrin rings are found, such as after a longer than normal session, a further dose of 0.5 to 1mg/kg (50 to 100 IU/kg) may be given. For patients at a high risk of haemorrhage the dose should be reduced to 0.5 mg/kg (50 IU/kg) for double vascular access or 0.75 mg/kg (75 IU/kg) for single vascular access.

Elderly:

For treatment of acute ST-segment Elevation Myocardial Infarction in elderly patients >75 years of age, do not use an initial IV bolus. Initiate dosing with 0.75mg/kg SC every 12 hours (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses).

For other indications, no dosage adjustments are necessary in the elderly, unless kidney function is impaired (see also section 4.2 Posology and method of administration: Renal impairment ; section 4.4 Special warnings and precautions for use: Haemorrhage in the elderly; Renal impairment and Monitoring ; section 5.2 Pharmacoki­netic properties).

Instructions on injecting yourself with Clexane Forte:

• 1) Wash your hands and the area that you will inject with soap and water.

Dry them.

• 2) Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going to inject. A lounge chair, recliner, or bed propped up with pillows is ideal.

• 3) Choose an area on the right or left side of your stomach. This should be at least 5 centimetres away from your belly button and out towards your sides.

Remember: Do not inject yourself within 5cm of your belly button or around existing scars or bruises. Change the place where you inject between the left and right sides of your stomach, depending on the area you were last injected.

4) Carefully pull off the needle cap from the Clexane Forte syringe. Throw away the cap. The syringe is pre-filled and ready to use.

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure the needle stays clean (sterile).

• 5) Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin.

Make sure you hold the skin fold throughout the injection.

• 6) Hold the syringe so that the needle is pointing downwards (vertically at a 90° angle). Insert the full length of the needle into the skin fold.

• 7) Press down on the plunger with your thumb. This will send the medication into the fatty tissue of the stomach. Make sure you hold the skin fold throughout the injection.

• 8) Remove the needle by pulling it straight out. A protective sleeve will automatically cover the needle. You can now let go of the skin fold.

Note: the safety system allowing release of the protective sleeve can only be activated when the syringe has been emptied by pressing the plunger all the way down.

To avoid bruising, do not rub the injection site after you have injected yourself.

• 9) Drop the used syringe with its protective sleeve into the sharps bin provided. Close the container lid tightly and place the container out of reach of children.

When the container is full, give it to your doctor or home care nurse for disposal. Do not put it in the household rubbish.

If you have too much or too little Clexane Forte

If you think that you have used too much or too little Clexane Forte, tell your doctor, nurse or pharmacist immediately, even if you have no signs of a problem. If a child accidentally injects or swallows Clexane Forte, take them to a hospital casualty department straight away.

If you forget to use Clexane Forte

If you forget to give yourself a dose, have it as soon as you remember. Do not give yourself a double dose on the same day to make up for a forgotten dose. Keeping a diary will help to make sure you do not miss a dose.

If you stop using Clexane Forte

It is important for you to keep having Clexane Forte injections until your doctor decides to stop them. If you stop, you could get a blood clot which can be very dangerous.

Blood Tests

Using Clexane Forte may affect the results of some blood tests. If you are going to have a blood test, it is important to tell your doctor you are having Clexane Forte.

4. possible side effects

Like all medicines, Clexane Forte can cause side-effects, although not everybody gets them.

Tell a nurse or doctor or go to hospital straight away if you notice any of the following side-effects:

Very common (affects more than 1 in 10 people)

• Bleeding a lot from a wound.

Common (affects 1 to 10 people in a 100)

• A painful rash of dark red spots under the skin which do not go away when you put pressure on them. You may also notice pink patches on your skin. These are more likely to appear in the area you have been injected with Clexane Forte.

Uncommon (affects 1 to 10 people in a 1,000)

• Sudden severe headache. This could be a sign of bleeding in the brain.
• A feeling of tenderness and swelling in your stomach. You may have bleeding inside your stomach.

Rare (affects less than 1 in a 1000 people)

• If you have an allergic reaction. The signs may include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.

Frequency unknown

• If you have had a spinal puncture or a spinal anaesthetic and notice tingling, numbness and muscular weakness, particularly in the lower part of your body. Also if you lose control over your bladder or bowel (so you cannot control when you go to the toilet).

Tell a nurse or doctor as soon as possible if you notice any of the following side effects:

Common (affects 1 to 10 people in a 100)

• You bruise more easily than usual. This could be because of a blood problem (thrombocytopenia).
• You have pain, swelling or irritation in the area you have been injected with Clexane Forte. This normally gets better after a few days.

Rare (affects less than 1 in a 1000 people)

• If you have a mechanical heart valve, treatment with Clexane Forte might not be sufficient to prevent blood clots. You may notice that you have difficulty breathing, tiredness or difficulty exercising, chest pain, numbness, feeling sick or loss of consciousness. This could be due to a blood clot on the heart valve

Frequency unknown

• Feeling tired, faint, dizzy, having pale skin.

These could be symptoms of anaemia

• You notice yellowing of your skin or eyes and your urine becomes darker in colour.

This could be a liver problem.

Other side effects that you should discuss with your nurse or doctor if you are concerned about them:

Very common (affects more than 1 in 10 people)

• Changes in the results of blood tests done to check how your liver is working. These usually go back to normal after you stop having Clexane Forte.

Rare (affects less than 1 in a 1000 people)

• Changes in the potassium levels in your blood. This is more likely to happen in people with kidney problems or diabetes. Your doctor will be able to check this by carrying out a blood test.

Frequency unknown

• If Clexane Forte is used for a long period of time (more than 3 months), it may increase the risk of you getting a condition called ‘osteoporosis’. This is when your bones are more likely to break.
• Headache
• Hair loss

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at:

By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store and dispose of clexane forte

• Keep out of the sight and reach of children.
• Do not use Clexane Forte after the expiry date which is stated on the syringe label and on the box. The expiry date refers to the last day of that month.
• Do not store above 25oC. Do not refrigerate or freeze.
• Store in the original container in order to protect from light.
• If your syringes become discoloured or show any signs of deterioration, return them to your pharmacist.
• Medicines should not be disposed of via wastewater or household waste. If you are using this medicine at home you will be given a container (a sharps bin) to use for disposal. Return the sharps bin or any used or unused syringes to your doctor or nurse or pharmacist for disposal. These measures will help to protect the environment.

• 6. Further information
  
  What Clexane Forte contains

• Each pre-filled syringe contains 150mg enoxaparin sodium (equivalent to 15,000 IU anti-Xa activity), in 1ml water for injection.
• The other ingredient is water for injections.

What Clexane Forte looks like and contents of the pack

Glass pre-filled syringe fitted with injection needle, rubber stopper and an automatic safety device containing a clear, colourless to pale yellow solution for injection.

Clexane Forte Syringes are supplied in packs of 10.

Manufacturer

Sanofi Winthrop Industrie,

180 rue Jean Jaures,

94702 Maisons Alfort, France.

It is procured from within the EU by MPT Pharma Ltd, Westgate Business Park, Unit 5–7 Tintagel Way, Aldridge, Walsall, WS9 8ER, UK.

Repackaged by MPT Pharma Ltd

PL:33532/0601

Leaflet dated 08th October 2015

Leaflet coded xxxxxxxxxxxxxxx

Clexane® is a registered trademark of Aventis Pharma SA.

■><------------------------------------------------------------

1) not to be given for the first two doses – (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses) Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

Children: Not recommended, as dosage not established.

Renal impairment: (See also section 4.4 Special warnings and precautions for use: Renal impairment and Monitoring ; section 5.2 Pharmacoki­netic properties).

Severe renal impairment:

A dosage adjustment is required for patients with severe renal impairment (creatinine clearance < 30 ml/min), according to the following tables, since enoxaparin sodium exposure is significantly increased in this patient population:

Dosage adjustments for therapeutic dosage range

Dosage adjustments for prophylactic dosage ranges

The recommended dosage adjustments do not apply to the haemodialysis indication.

• * The Clexane 100mg/ml Multidose Vial or Clexane 60mg, 80mg or 100mg pre-filled syringes should be used to administer the IV dose.

Moderate and mild renal impairment:

Although no dosage adjustments are recommended in patients with moderate renal impairment (creatinine clearance 30–50 ml/min) or mild renal impairment (creatinine clearance 50–80 ml/min), careful clinical monitoring is advised.

Spinal/epidural anaesthesia:

For patients receiving spinal/epidural anaesthesia see section 4.4 Special warnings and precautions for use: Spinal/epidural anaesthesia.

Hepatic impairment: In the absence of clinical studies, caution should be exercised.

Body weight :

No dosage adjustments are recommended in obesity or low body weight (see also section 4.4 Special warnings and precautions for use: Low body weight and Monitoring ; section 5.2 Pharmacoki­netic properties).

Clexane is administered by subcutaneous injection for the prevention of venous thromboembolic disease, treatment of deep vein thrombosis or for the treatment of unstable angina, non-Q-wave myocardial infarction and acute ST elevation myocardial infarction (STEMI); through the arterial line of a dialysis circuit for the prevention of thrombus formation in the extra-corporeal circulation during haemodialysis; and via intravenous (bolus) injection through an intravenous line only for the initial dose of acute STEMI indication and before PCI when needed (using the Clexane 100mg/ml Multidose Vial or 60mg, 80mg or 100mg prefilled syringes). It must not be administered by the intramuscular rou­te.

To avoid accidental needle stick after injection, the prefilled syringes are fitted with an automatic safety device.

Subcutaneous injection technique

The prefilled disposable syringe is ready for immediate use. Clexane should be administered when the patient is lying down by deep subcutaneous injection. The administration should be alternated between the left and right anterolateral or posterolateral abdominal wall. The whole length of the needle should be introduced vertically into a skin fold held between the thumb and index finger. The skin fold should not be released until the injection is complete.

Once the plunger is fully pressed down the safety device is activated automatically. This protects the used needle.

Note: The plunger has to be pressed down all the way for the safety device to be activated.

Do not rub the injection site after administration.

Intravenous (Bolus) Injection technique (for acute STEMI indication only)

For intravenous injection, either the Multidose Vial or 60mg, 80mg or 100mg prefilled syringes can be used. Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or co-administered with other medications. To avoid the possible mixture of enoxaparin sodium with all other drugs, the intravenous access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the intravenous bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.

• Initial 30mg bolus

For the initial 30mg bolus, using an enoxaparin sodium graduated prefilled syringe (60, 80 or 100mg), expel the excessive volume to retain only 30mg (0.3ml) in the syringe. The 30mg dose can then be directly injected into an injection site in the intravenous line.

• Additional bolus for PCI when last SC administration was given more than 8 hours before balloon insertion

For patients being managed with Percutaneous Coronary Intervention (PCI), an additional IV bolus of 0.3mg/kg is to be administered if last SC administration was given more than 8 hours before balloon inflation (see section 4.2 Posology and method of administration: Treatment of acute ST-segment Elevation Myocardial Infarction).

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 3mg/ml.

To obtain a 3mg/ml solution, using a 60mg enoxaparin sodium prefilled syringe, it is recommended to use a 50ml infusion bag (i.e. using either normal saline solution (0.9%) or 5% dextrose in water) as follows:

Withdraw 30ml from the infusion bag with a syringe and discard the liquid. Inject the complete contents of the 60mg enoxaparin sodium prefilled syringe into the 20ml remaining in the bag. Gently mix the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration into the intravenous line (using an appropriate injection site or port).

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume of diluted solution (ml) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare the dilution immediately before use and to discard any remaining solution immediately after use.

Volume to be injected through intravenous line after dilution is completed

6 PHARMACEUTICAL PARTICULARS

• 6.1 List of excipients

Water for Injections.

• 6.2 Incompati­bilities
  
  Subcutaneous Injection

  Clexane should not be mixed with any other injections or infusions.

Intravenous (Bolus) Injection for acute STEMI indication only

Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.

• 6.3 Shelf life

Do not use Clexane Forte after the expiry date which is stated on the syringe label and on the box. The expiry date refers to the last day of that month.

• 6.4 Special precautions for storage

Do not store above 25oC.

Do not refrigerate or freeze.

Clexane pre-filled syringes are single dose containers – discard any unused product.

• 6.5 Nature and contents of container

Glass pre-filled syringe fitted with injection needle, rubber stopper and an automatic safety device containing a clear, colourless to pale yellow solution for injection.

Clexane Forte Syringes are supplied in packs of 10.

Package Leaflet: Information for the User

Enoxaparin Sodium 150mg/1ml Syringes

Read all of this leaflet carefully before you start using this medicine

• 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. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If any of the side-effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, pharmacist or nurse.
• Enoxaparin Sodium is also available in other strengths.

• 1. What Enoxaparin Sodium is and what it is used for

• 2. Before you use Enoxaparin Sodium

• 3. How to use Enoxaparin Sodium

• 4. Possible side-effects

• 5. How to store and dispose of Enoxaparin Sodium

• 6. Further information

1. what enoxaparin sodium is and what it is used for

The name of your medicine is Enoxaparin Sodium 150mg/1ml Syringes (called Enoxaparin Sodium in this leaflet). Enoxaparin Sodium contains a medicine called enoxaparin sodium. This belongs to a group of medicines called Low Molecular Weight Heparins.

Enoxaparin Sodium works in two ways:

• 1) Stopping existing blood clots from getting any bigger. This helps your body to break them down and stop them causing you harm.

• 2) Stopping blood clots forming in your blood.

Enoxaparin Sodium can be used to:

• Treat blood clots that are in your blood
• Stop blood clots forming in your blood in the following situations:
• Unstable angina (where not enough blood gets to your heart)
• After an operation or long periods of bed rest due to illness
• After you have had a heart attack
• Stop blood clots forming in the tubes of your dialysis machine (used for people with kidney problems)

2. before you use enoxaparin sodiumdo not have this medicine and tell your doctor if:x you are allergic (hypersensitive) to enoxaparin sodium. signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue

x You are allergic to heparin or other Low Molecular Weight Heparins such as tinzaparin or dalteparin

x You have a problem with bruising or bleeding too easily

x You are bleeding heavily

x You have an ulcer in your stomach or gut (intestine)

x You have had a stroke caused by bleeding in the brain

x You have an infection in your heart

x You are using the medicine called heparin to treat blood clots

Do not take this medicine if any of the above apply to you. If you are not sure, talk to your doctor, pharmacist or nurse before having Enoxaparin Sodium.

Take special care with Enoxaparin Sodium

Check with your doctor or pharmacist before having this medicine if:

a You have high blood pressure which is not controlled by medication a You have kidney problems

a You have had a heart valve fitted

a You have ever had bruising and bleeding caused by the medicine heparin

a You have ever had a stroke

a You have ever had a stomach ulcer

a You have recently had an operation on your eyes or brain

a You are a diabetic or have an illness known as ‘diabetic retinopathy’ (problems with the blood vessels in the eye caused by diabetes)

a You have any problems with your blood

a You are underweight or overweight

A You are elderly (over 65 years old) and especially if you are aged over 75 years old

If you are not sure if any of the above applies to you, talk to your doctor, pharmacist or nurse before having Enoxaparin Sodium.

Taking or using other medicines

Please tell your doctor, pharmacist or nurse if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Enoxaparin Sodium can affect the way some other medicines work. Also some medicines can affect the way Enoxaparin Sodium works.

In particular, do not take this medicine and tell your doctor if: x You are using the medicine called heparin to treat blood clots

Tell your doctor if you are taking any of the following medicines:

• Warfarin – used for thinning the blood
• Aspirin – used to stop blood clots from forming. Aspirin may also be used for pain relief and in medicines for colds and flu
• Dipyridamole, clopidogrel, or other medicines – used to stop blood clots forming
• Streptokinase, alteplase and reteplase – used to dissolve blood clots after a heart attack
• Dextran injection – used to replace blood volume
• Ibuprofen, diclofenac, ketorolac or other medicines used to treat pain and swelling in arthritis and other illnesses
• Prednisolone, dexamethasone or other steroid medicines – used to treat asthma, rheumatoid arthritis and other conditions
• Water tablets (diuretics) such as spironolactone, triamterene or amiloride. These may increase the levels of potassium in your blood when taken with Enoxaparin Sodium

Your doctor may change one of your medicines or take regular blood tests to check that taking these medicines with Enoxaparin Sodium is not causing you any harm.

Operations and anaesthetics

If you are going to have a spinal puncture or an operation where an epidural or spinal anaesthetic is used, tell your doctor that you are using Enoxaparin Sodium. Tell also your doctor if you have any problem with your spine or if you have ever had spinal surgery.

Pregnancy and breast-feeding

Talk to your doctor before you are given this medicine if you are pregnant, might become pregnant or think you may be pregnant.

You should not use this medicine if you are pregnant and have a mechanical heart valve as you may be at increased risk of developing blood clots. Your doctor should discuss this with you.

You should not breast-feed whilst using Enoxaparin Sodium. If you are planning to breast-feed, talk to your doctor, pharmacist or nurse.

Ask your doctor, pharmacist or nurse for advice before taking any medicine if you are pregnant or breast-feeding.

K

3. how to use enoxaparin sodiumhaving this medicine before you have enoxaparin sodium your doctor or nurse may carry out a blood test

• While you are in hospital your doctor or nurse will normally give you Enoxaparin Sodium. This is because it needs to be given as an injection
• When you go home you may need to continue to use Enoxaparin Sodium and give it to yourself (see below instructions on how to do this)
• Enoxaparin Sodium is usually given by injection underneath the skin (subcutaneous)
• Do not inject Enoxaparin Sodium into a muscle (intramuscular)

If you are not sure why you are receiving Enoxaparin Sodium or have any questions about how much Enoxaparin Sodium is being given to you, speak to your doctor, pharmacist or nurse.

How much will be given to you in hospital

• Your doctor will decide how much to give you. The amount of Enoxaparin Sodium given to you will depend on the reason it is being used
• If you have problems with your kidneys, you may be given a smaller amount of Enoxaparin Sodium

Adults including the elderly

• 1) Treating blood clots that are in your blood

• The usual dose is 1.5mg for every kilogram of your weight, each day
• Enoxaparin Sodium will usually be given for at least 5 days

• 2) Stopping blood clots forming in your blood in the following situations:

• a) Unstable angina

• The usual dose is 1mg for every kilogram of your weight, every 12 hours
• Enoxaparin Sodium will usually be given for 2 to 8 days. Your doctor will normally ask you to take aspirin as well

• b) After an operation or long periods of bed rest due to illness

The usual dose is 20mg or 40mg each day.

The dose will depend on how likely you are to develop a clot.

• If you have a low to medium risk of getting a clot, you will be given 20mg of Enoxaparin Sodium each day for 7 to 10 days. If you are going to have an operation, your first injection will usually be given 2 hours before your operation
• If you have a higher risk of getting a clot, you will be given 40mg each day for 7 to 28 days. If you are going to have an operation, your first injection will usually be given 12 hours before your operation
• If you are bedridden due to illness, you will be normally be given 40mg of Enoxaparin Sodium each day for 6 to 14 days

• c) After you have had a heart attack

Enoxaparin Sodium can be used for two different types of heart attack called NSTEMI or STEMI. The amount of Enoxaparin Sodium given to you will depend on your age and the kind of heart attack you have had.

• i) NSTEMI type of heart attack

• The usual amount is 1mg for every kilogram of weight, every 12 hours
• Enoxaparin Sodium will usually be given for 2 to 8 days. Your doctor will normally ask you to take aspirin as well.

• ii) STEMI type of heart attack If you are under 75 years old

• 30mg of Enoxaparin Sodium will be given as an injection into your vein (intravenous injection using Enoxaparin Sodium Multidose Vial or 60, 80 or 100mg Pre-filled syringes)
• At the same time, you will also be given Enoxaparin Sodium as an injection under your skin (subcutaneous injection). The usual dose is 1mg for every kilogram of your weight.
• Then you will be given 1mg for every kilogram of your weight every 12 hours
• The maximum amount of Enoxaparin Sodium given for the first two injections is 100mg
• The injections will normally be given for up to 8 days

If you are aged 75 years or older

• Your doctor or nurse will give you injections of Enoxaparin Sodium under your skin (subcutaneous injection)
• The usual dose is 0.75mg for every kilogram of your weight, every 12 hours
• The maximum amount of Enoxaparin Sodium given for the first two injections is 75mg

For patients having an operation called Percutaneous Coronary Intervention (PCI)

• Depending on when you were last given Enoxaparin Sodium, your doctor may decide to give an additional dose of Enoxaparin Sodium before a PCI operation. This is by injection into your vein (intravenous using Enoxaparin Sodium Multidose Vial or 60, 80 or 100mg Pre-filled Syringes).

• 3) Stopping blood clots forming in the tubes of your dialysis machine

• The usual dose is 1mg for every kilogram of your weight
• Enoxaparin Sodium is added to the tube leaving the body (arterial line) at the start of the dialysis session
• This amount is usually enough for a 4 hour session. However, your doctor may give you a further dose of 0.5 to 1mg for every kilogram of your weight if necessary

Children

This medicine should not be given to children.

How to give yourself an injection of Enoxaparin Sodium

If you are able to give Enoxaparin Sodium to yourself, your doctor or nurse will show you how to do this. Do not try to inject yourself if you have not been trained how to do so. If you are not sure what to do, talk to your doctor or nurse immediately.

Before injecting yourself with Enoxaparin Sodium

• Check the expiry date on the medicine. Do not use if the date has passed
• Check the syringe is not damaged and the medicine in it is a clear solution. If not, use another syringe
• Make sure you know how much you are going to inject
• Check your abdomen to see if the last injection caused any redness, change in skin colour, swelling, oozing or is still painful. If so talk to your doctor or nurse
• Decide where you are going to inject the medicine. Change the place where you inject each time from the right to the left side of your stomach. Enoxaparin Sodium should be injected just under the skin on your stomach, but not too near the belly button or any scar tissue (at least 5cm away from these)

THE FOLLOWING INFORMATION IS INTENDED FOR HEALTHCARE PROFESSIONALS ONLY

Enoxaparin Sodium 120mg 150mg Pre-Filled Syringes

The following information is extracted from the SPC

Technical information for the administration of Enoxaparin Sodium Syringes

1 NAME OF THE MEDICINAL PRODUCT

Enoxaparin Sodium Syringes

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Pre-filled syringes:

120 mg Injection Enoxaparin sodium 120 mg (equivalent to 12,000 IU anti-Xa activity) in 0.8 mL Water for Injections

150 mg Injection Enoxaparin sodium 150 mg (equivalent to 15,000 IU anti-Xa activity) in 1.0 mL Water for Injections

For full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless to pale yellow solution.

4.2 Posology and method of administration

Adults:

Prophylaxis of venous thromboembolism:

In patients with a low to moderate risk of venous thromboembolism the recommended dosage is 20 mg (2,000 IU) once daily by subcutaneous injection for

7 to 10 days, or until the risk of thromboembolism has diminished. In patients undergoing surgery, the initial dose should be given approximately

2 hours pre-operatively.

In patients with a higher risk, such as in orthopaedic surgery, the dosage should be 40 mg (4,000 IU) daily by subcutaneous injection with the initial dose administered approximately 12 hours before surgery.

In patients with a high-risk of venous thromboembolism who undergo abdominal or pelvic surgery for cancer and are not otherwise at risk for major bleeding complications, the recommended dosage is 40 mg (4,000 IU) once daily by subcutaneous injection for 4 weeks with the initial dose administered approximately 12 hours before surgery.

Prophylaxis of venous thromboembolism in medical patients:

The recommended dose of enoxaparin sodium is 40 mg (4,000 IU) once daily by subcutaneous injection. Treatment with enoxaparin sodium is prescribed for a minimum of 6 days and continued until the return to full ambulation, for a maximum of 14 days.

Treatment of venous thromboembolism:

Enoxaparin Sodium should be administered subcutaneously as a single daily injection of 1.5 mg/kg (150 IU/kg). Enoxaparin Sodium treatment is usually prescribed for at least 5 days and until adequate oral anticoagulation is established.

Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

Treatment of unstable angina and non-Q-wave myocardial infarction

The recommended dose is 1mg/kg Enoxaparin Sodium every 12 hours by subcutaneous injection, administered concurrently with oral aspirin (100 to 325mg once daily). Treatment with Enoxaparin Sodium in these patients should be prescribed for a minimum of 2 days and continued until clinical stabilisation.

The usual duration of treatment is 2 to 8 days.

Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

Treatment of acute ST-segment Elevation Myocardial Infarction

The recommended dose of enoxaparin sodium is a single IV bolus of 30mg (using the Enoxaparin Sodium 100mg/ml Multidose Vial or 60mg, 80mg or 100mg prefilled syringes) plus a 1mg/kg SC dose followed by 1mg/kg administered SC every 12 hours (max 100mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses). For dosage in patients >75 years of age, see section 4.2 Posology and method of administration: Elderly.

Dosage chart for 1mg/kg SC treatment of STEMI

(1) Not to be given for the first two doses – (maximum 100mg for the first two doses only, followed by 1mg/kg dosing for the remaining doses) Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

When administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific) enoxaparin sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive acetylsalicylic acid (ASA) as soon as they are identified as having STEMI and maintained under (75 to 325mg once daily) unless contraindicated.

The recommended duration of enoxaparin sodium treatment is 8 days or until hospital discharge, whichever comes first.

For patients managed with Percutaneous Coronary Intervention (PCI): If the last enoxaparin sodium SC administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last SC administration was given more than 8 hours before balloon inflation, an IV bolus of 0.3mg/kg of enoxaparin sodium should be administered (using the Enoxaparin Sodium 100mg/ml Multidose Vial or 60mg, 80mg or 100mg prefilled syringes).

Prevention of extracorporeal thrombus formation during haemodialysis:

A dose equivalent to 1 mg/kg (100 IU/kg) introduced into the arterial line at the beginning of a dialysis session is usually sufficient for a 4 hour session. If fibrin rings are found, such as after a longer than normal session, a further dose of 0.5 to 1mg/kg (50 to 100 IU/kg) may be given. For patients at a high risk of haemorrhage the dose should be reduced to 0.5 mg/kg (50 IU/kg) for double vascular access or 0.75 mg/kg (75 IU/kg) for single vascular access.

Elderly:

For treatment of acute ST-segment Elevation Myocardial Infarction in elderly patients >75 years of age, do not use an initial IV bolus. Initiate dosing with 0.75mg/kg SC every 12 hours (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses).

For other indications, no dosage adjustments are necessary in the elderly, unless kidney function is impaired (see also section 4.2 Posology and method of administration: Renal impairment ; section 4.4 Special warnings and precautions for use: Haemorrhage in the elderly; Renal impairment and Monitoring ; section 5.2 Pharmacoki­netic properties).

Instructions on injecting yourself with Enoxaparin Sodium:

• 1) Wash your hands and the area that you will inject with soap and water.

Dry them.

• 2) Sit or lie in a comfortable position so you are relaxed. Make sure you can see the place you are going to inject. A lounge chair, recliner, or bed propped up with pillows is ideal.

• 3) Choose an area on the right or left side of your stomach. This should be at least 5 centimetres away from your belly button and out towards your sides.

Remember: Do not inject yourself within 5cm of your belly button or around existing scars or bruises. Change the place where you inject between the left and right sides of your stomach, depending on the area you were last injected.

4) Carefully pull off the needle cap from the Enoxaparin Sodium syringe. Throw away the cap. The syringe is pre-filled and ready to use.

Do not press on the plunger before injecting yourself to get rid of air bubbles. This can lead to a loss of the medicine. Once you have removed the cap, do not allow the needle to touch anything. This is to make sure the needle stays clean (sterile).

• 5) Hold the syringe in the hand you write with (like a pencil) and with your other hand, gently pinch the cleaned area of your abdomen between your forefinger and thumb to make a fold in the skin.

Make sure you hold the skin fold throughout the injection.

• 6) Hold the syringe so that the needle is pointing downwards (vertically at a 90° angle). Insert the full length of the needle into the skin fold.

• 7) Press down on the plunger with your thumb. This will send the medication into the fatty tissue of the stomach. Make sure you hold the skin fold throughout the injection.

• 8) Remove the needle by pulling it straight out. A protective sleeve will automatically cover the needle. You can now let go of the skin fold.

Note: the safety system allowing release of the protective sleeve can only be activated when the syringe has been emptied by pressing the plunger all the way down.

To avoid bruising, do not rub the injection site after you have injected yourself.

• 9) Drop the used syringe with its protective sleeve into the sharps bin provided. Close the container lid tightly and place the container out of reach of children.

When the container is full, give it to your doctor or home care nurse for disposal. Do not put it in the household rubbish.

If you have too much or too little Enoxaparin Sodium

If you think that you have used too much or too little Enoxaparin Sodium , tell your doctor, nurse or pharmacist immediately, even if you have no signs of a problem. If a child accidentally injects or swallows Enoxaparin Sodium , take them to a hospital casualty department straight away.

If you forget to use Enoxaparin Sodium

If you forget to give yourself a dose, have it as soon as you remember.

Do not give yourself a double dose on the same day to make up for a forgotten dose. Keeping a diary will help to make sure you do not miss a dose.

If you stop using Enoxaparin Sodium

It is important for you to keep having Enoxaparin Sodium injections until your doctor decides to stop them. If you stop, you could get a blood clot which can be very dangerous.

Blood Tests

Using Enoxaparin Sodium may affect the results of some blood tests. If you are going to have a blood test, it is important to tell your doctor you are having Enoxaparin Sodium.

4. possible side effects

Like all medicines, Enoxaparin Sodium can cause side-effects, although not everybody gets them.

Tell a nurse or doctor or go to hospital straight away if you notice any of the following side-effects:

Very common (affects more than 1 in 10 people)

• Bleeding a lot from a wound.

Common (affects 1 to 10 people in a 100)

• A painful rash of dark red spots under the skin which do not go away when you put pressure on them. You may also notice pink patches on your skin. These are more likely to appear in the area you have been injected with Enoxaparin Sodium.

Uncommon (affects 1 to 10 people in a 1,000)

• Sudden severe headache. This could be a sign of bleeding in the brain.
• A feeling of tenderness and swelling in your stomach. You may have bleeding inside your stomach.

Rare (affects less than 1 in a 1000 people)

• If you have an allergic reaction. The signs may include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.

Frequency unknown

• If you have had a spinal puncture or a spinal anaesthetic and notice tingling, numbness and muscular weakness, particularly in the lower part of your body. Also if you lose control over your bladder or bowel (so you cannot control when you go to the toilet).

Tell a nurse or doctor as soon as possible if you notice any of the following side effects:

Common (affects 1 to 10 people in a 100)

• You bruise more easily than usual. This could be because of a blood problem (thrombocytopenia).
• You have pain, swelling or irritation in the area you have been injected with Enoxaparin Sodium. This normally gets better after a few days.

Rare (affects less than 1 in a 1000 people)

• If you have a mechanical heart valve, treatment with Enoxaparin Sodium might not be sufficient to prevent blood clots. You may notice that you have difficulty breathing, tiredness or difficulty exercising, chest pain, numbness, feeling sick or loss of consciousness. This could be due to a blood clot on the heart valve

Frequency unknown

• Feeling tired, faint, dizzy, having pale skin.

These could be symptoms of anaemia

• You notice yellowing of your skin or eyes and your urine becomes darker in colour.

This could be a liver problem.

Other side effects that you should discuss with your nurse or doctor if you are concerned about them:

Very common (affects more than 1 in 10 people)

• Changes in the results of blood tests done to check how your liver is working. These usually go back to normal after you stop having Enoxaparin Sodium.

Rare (affects less than 1 in a 1000 people)

• Changes in the potassium levels in your blood. This is more likely to happen in people with kidney problems or diabetes. Your doctor will be able to check this by carrying out a blood test.

Frequency unknown

• If Enoxaparin Sodium is used for a long period of time (more than 3 months), it may increase the risk of you getting a condition called ‘osteoporosis’. This is when your bones are more likely to break.
• Headache
• Hair loss

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at:

By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store and dispose of enoxaparin sodium

• Keep out of the sight and reach of children.
• Do not use Enoxaparin Sodium after the expiry date which is stated on the syringe label and on the box. The expiry date refers to the last day of that month.
• Do not store above 25oC. Do not refrigerate or freeze.
• Store in the original container in order to protect from light.
• If your syringes become discoloured or show any signs of deterioration, return them to your pharmacist.
• Medicines should not be disposed of via wastewater or household waste. If you are using this medicine at home you will be given a container (a sharps bin) to use for disposal. Return the sharps bin or any used or unused syringes to your doctor or nurse or pharmacist for disposal. These measures will help to protect the environment.

• 6. Further information
  
  What Enoxaparin Sodium contains

• Each pre-filled syringe contains 150mg enoxaparin sodium (equivalent to 15,000 IU anti-Xa activity), in 1ml water for injection.
• The other ingredient is water for injections.

What Enoxaparin Sodium looks like and contents of the pack

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• 1) not to be given for the first two doses – (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses) Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe and so some of the volumes recommended in this table have been rounded up to the nearest graduation.

Children: Not recommended, as dosage not established.

Renal impairment: (See also section 4.4 Special warnings and precautions for use: Renal impairment and Monitoring ; section 5.2 Pharmacoki­netic properties).

Severe renal impairment:

A dosage adjustment is required for patients with severe renal impairment (creatinine clearance < 30 ml/min), according to the following tables, since enoxaparin sodium exposure is significantly increased in this patient population:

Dosage adjustments for therapeutic dosage range

Dosage adjustments for prophylactic dosage ranges

The recommended dosage adjustments do not apply to the haemodialysis indication.

*The Enoxaparin Sodium 100mg/ml Multidose Vial or Enoxaparin Sodium 60mg, 80mg or 100mg pre-filled syringes should be used to administer the IV dose.

Moderate and mild renal impairment:

Although no dosage adjustments are recommended in patients with moderate renal impairment (creatinine clearance 30–50 ml/min) or mild renal impairment (creatinine clearance 50–80 ml/min), careful clinical monitoring is advised.

Spinal/epidural anaesthesia:

For patients receiving spinal/epidural anaesthesia see section 4.4 Special warnings and precautions for use: Spinal/epidural anaesthesia.

Hepatic impairment: In the absence of clinical studies, caution should be exercised.

Body weight :

No dosage adjustments are recommended in obesity or low body weight (see also section 4.4 Special warnings and precautions for use: Low body weight and Monitoring ; section 5.2 Pharmacoki­netic properties).

Enoxaparin Sodium is administered by subcutaneous injection for the prevention of venous thromboembolic disease, treatment of deep vein thrombosis or for the treatment of unstable angina, non-Q-wave myocardial infarction and acute ST elevation myocardial infarction (STEMI); through the arterial line of a dialysis circuit for the prevention of thrombus formation in the extra-corporeal circulation during haemodialysis; and via intravenous (bolus) injection through an intravenous line only for the initial dose of acute STEMI indication and before PCI when needed (using the Enoxaparin Sodium 100mg/ml Multidose Vial or 60mg, 80mg or 100mg prefilled syringes). It must not be administered by the intramuscular rou­te.

To avoid accidental needle stick after injection, the prefilled syringes are fitted with an automatic safety device.

Subcutaneous injection technique

The prefilled disposable syringe is ready for immediate use. Enoxaparin Sodium should be administered when the patient is lying down by deep subcutaneous injection. The administration should be alternated between the left and right anterolateral or posterolateral abdominal wall. The whole length of the needle should be introduced vertically into a skin fold held between the thumb and index finger. The skin fold should not be released until the injection is complete.

Once the plunger is fully pressed down the safety device is activated automatically. This protects the used needle.

Note: The plunger has to be pressed down all the way for the safety device to be activated.

Do not rub the injection site after administration.

Intravenous (Bolus) Injection technique (for acute STEMI indication only)

For intravenous injection, either the Multidose Vial or 60mg, 80mg or 100mg prefilled syringes can be used. Enoxaparin sodium should be administered through an intravenous line. It should not be mixed or co-administered with other medications. To avoid the possible mixture of enoxaparin sodium with all other drugs, the intravenous access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the intravenous bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.

• Initial 30mg bolus

For the initial 30mg bolus, using an enoxaparin sodium graduated prefilled syringe (60, 80 or 100mg), expel the excessive volume to retain only 30mg (0.3ml) in the syringe. The 30mg dose can then be directly injected into an injection site in the intravenous line.

• Additional bolus for PCI when last SC administration was given more than 8 hours before balloon insertion

For patients being managed with Percutaneous Coronary Intervention (PCI), an additional IV bolus of 0.3mg/kg is to be administered if last SC administration was given more than 8 hours before balloon inflation (see section 4.2 Posology and method of administration: Treatment of acute ST-segment Elevation Myocardial Infarction).

In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 3mg/ml.

To obtain a 3mg/ml solution, using a 60mg enoxaparin sodium prefilled syringe, it is recommended to use a 50ml infusion bag (i.e. using either normal saline solution (0.9%) or 5% dextrose in water) as follows:

Withdraw 30ml from the infusion bag with a syringe and discard the liquid. Inject the complete contents of the 60mg enoxaparin sodium prefilled syringe into the 20ml remaining in the bag. Gently mix the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration into the intravenous line (using an appropriate injection site or port).

After dilution is completed, the volume to be injected can be calculated using the following formula [Volume of diluted solution (ml) = Patient weight (kg) x 0.1] or using the table below. It is recommended to prepare the dilution immediately before use and to discard any remaining solution immediately after use.

Volume to be injected through intravenous line after dilution is completed

• 6 PHARMACEUTICAL PARTICULARS

• 6.1 List of excipients

Water for Injections.

• 6.2 Incompati­bilities
  
  Subcutaneous Injection

  Enoxaparin Sodium should not be mixed with any other injections or infusions.

Intravenous (Bolus) Injection for acute STEMI indication only

Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.

• 6.3 Shelf life

Do not use Enoxaparin sodium after the expiry date which is stated on the syringe label and on the box. The expiry date refers to the last day of that month.

• 6.4 Special precautions for storage

Do not store above 25oC.

Do not refrigerate or freeze.

Enoxaparin Sodium pre-filled syringes are single dose containers – discard any unused product.

• 6.5 Nature and contents of container