Name of the medicinal product
Clexane® Syringes 8,000 IU (80 mg)/0.8 ml solution for injection in pre-filled syringes
Qualitative and quantitative composition
Each pre-filled syringe contains enoxaparin sodium 6,000 IU anti-Xa activity (equivalent to 60 mg) in 0.6 ml water for injections.
8,000 IU (80 mg) /0.8 ml
Enoxaparin sodium is a biological substance obtained by alkaline depolymerization of heparin benzyl ester derived from porcine intestinal mucosa.
Pharmaceutical form
Solution for injection in pre-filled syringes.
Clear, colourless to yellowish solution, pH-value 5.5-7.5.
Therapeutic indications
Clexane Syringes is indicated in adults for:
• Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular those undergoing orthopaedic or general surgery including cancer surgery.
• Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at increased risk of venous thromboembolism.
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require thrombolytic therapy or surgery.
• Prevention of thrombus formation in extracorporeal circulation during haemodialysis.
• Acute coronary syndrome:
- Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), in combination with oral acetylsalicylic acid.
- Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be managed medically or with subsequent percutaneous coronary intervention (PCI).
Posology and method of administration
Posology
Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients
Individual thromboembolic risk for patients can be estimated using validated risk stratification model.
• In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 2,000 IU (20 mg) once daily by subcutaneous (SC) injection. Preoperative initiation (2 hours before surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.
In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the patient no longer has significantly reduced mobility.
• In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily given by SC injection preferably started 12 hours before surgery. If there is a need for earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 12 hours prior to surgery and resumed 12 hours after surgery.
o For patients who undergo major orthopaedic surgery an extended thromboprophylaxis up to 5 weeks is recommended.
o For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or pelvic surgery for cancer an extended thromboprophylaxis up to 4 weeks is recommended.
Prophylaxis of venous thromboembolism in medical patients
The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection.
Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status (e.g. mobility). The benefit is not established for a treatment longer than 14 days.
Treatment of DVT and PE
Enoxaparin sodium can be administered SC either as a once daily injection of 150 IU/kg (1.5 mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg).
The regimen should be selected by the physician based on an individual assessment including evaluation of the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis.
Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy should be initiated when appropriate.
Prevention of thrombus formation during haemodialysis
The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium.
For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.
During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg (0.5 to 1 mg/kg) may be given.
No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during haemodialysis sessions.
Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI
• For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 100 IU/kg (1 mg/kg) every 12 hours by SC injection administered in combination with antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical stabilization. The usual duration of treatment is 2 to 8 days.
Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325 mg/day long-term regardless of treatment strategy.
• For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) SC dose followed by 100 IU/kg (1 mg/kg) administered SC every 12 hours (maximum 10,000 IU (100 mg) for each of the first two SC doses). Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg to 325 mg once daily) should be administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. 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.
o For patients managed with PCI, if the last dose of enoxaparin sodium SC 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 30 IU/kg (0.3 mg/kg) enoxaparin sodium should be administered.
Method of administration
Clexane Syringes should not be administered by the intramuscular route.
For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by SC injection.
• For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a SC injection.
• For the prevention of thrombus formation in the extracorporeal circulation during haemodialysis, it is administered through the arterial line of a dialysis circuit.
The pre-filled disposable syringe is ready for immediate use.
• SC injection technique:
Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by deep SC injection.
Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using pre-filled syringes. When the quantity of drug to be injected requires to be adjusted based on the patient's body weight, use the graduated pre-filled syringes to reach the required volume by discarding the excess before injection. Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe, and in such case the volume shall be rounded up to the nearest graduation.
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 gently held between the thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the injection site after administration.
The safety system is triggered at the end of the injection.
In case of self-administration, patient should be advised to follow instructions provided in the patient information leaflet included in the pack of this medicine.
• IV (bolus) injection (for acute STEMI indication only):
For acute STEMI, treatment is to be initiated with a single IV bolus injection immediately followed by a SC injection.
Contraindications
Enoxaparin sodium is contraindicated in patients with:
• Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins;
• History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies;
• Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities;
• Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for treatment in the previous 24 hours.
