Clexane pre-filled syringes Ref.[2796] Active ingredients: Enoxaparin

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.

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.

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 1 mg/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 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 1mg/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.

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).

(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 ranges:

Dosage adjustments for prophylactic dosage ranges:

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

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.

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. 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:

Orally administered enoxaparin is poorly absorbed and even large oral doses should not lead to any serious consequences. This may be checked by plasma assays of anti-Xa and anti-IIa activities.

Accidental overdose following parenteral administration may produce haemorrhagic complications. The anticoagulant effects can be largely neutralised by the slow intravenous injection of Protamine, but even with high doses of Protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralised (maximum about 60%). The initial dose of Protamine depends on the dose of enoxaparin given and also consideration of the maximum recommended Protamine dose (50mg). Data on Protamine dosing in humans for enoxaparin overdose is extremely limited. The available data suggest that in the first 8 hours after enoxaparin administration 1mg Protamine should neutralise the effects of 1mg of enoxaparin. Where the dose of enoxaparin has exceeded 50mg, an initial dose of 50mg Protamine would be appropriate, based on the maximum recommended single protamine dose. Decisions regarding the necessity and dose of subsequent Protamine injections should be based on clinical response rather than measurement of anti Xa or anti XIIa results. The physician should also consider that the amount of enoxaparin in the body drops to 50% after 8 hours and 33% or less after 12 hours. The dose of Protamine should be adjusted depending on the length of time since enoxaparin was administered.

36 months.

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

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

Solution for injection in Type I glass pre-filled syringes fitted with injection needle and an automatic safety device in packs of 10.

See section 4.2 Posology and method of administration.