GHEMAXAN

Posology Prophylaxis of venous thromboembolic disease in moderate and high-risk surgical patients • Individual thromboembolic risk for patients can be estimated using a 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. 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 preferably started 12 hours before surgery. 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, 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, 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. g. mobility). The benefit is not established for treatment longer than 14 days. 5 mg/kg) or as a twice-daily injection 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. 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.

2). In the extended treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and prevention of its recurrence in patients with active cancer, physicians should carefully assess the individual thromboembolic and bleeding risks of the patient.

5 mg/kg) once daily SC injection up to 6 months. The benefit of continuous anticoagulant therapy should be reassessed after 6 months of treatment. Prevention of thrombus formation during haemodialysis The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium.

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. 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 stabilisation. 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-naïve 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. • For dosage in patients ≥ 75 years of age, see paragraph “Elderly”.

• 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. 3 mg/kg) enoxaparin sodium should be administered. Paediatric population The safety and efficacy of enoxaparin sodium in the paediatric population […]

Summary of the safety profile Enoxaparin sodium has been evaluated in more than 15,000 patients who received enoxaparin sodium in clinical trials, performed with a reference product. These included 1,776 for prophylaxis of deep vein thrombosis following orthopaedic or abdominal surgery in patients at risk for thromboembolic complications, 1,169 for prophylaxis of deep vein thrombosis in acutely ill medical patients with severely restricted mobility, 559 for treatment of DVT with or without PE, 1,578 for treatment of unstable angina and non-Q-wave myocardial infarction and 10,176 for treatment of acute STEMI.

The enoxaparin sodium regimen administered during these clinical trials varies depending on the indication. The enoxaparin sodium dose was 4,000 IU (40 mg) SC once daily for prophylaxis of deep vein thrombosis following surgery or in acutely ill medical patients with severely restricted mobility.

5 mg/kg) SC dose once a day. In the clinical studies for treatment of unstable angina and non-Q-wave myocardial infarction, doses were 100 IU/kg (1 mg/kg) SC every 12 hours and, in the clinical study for treatment of acute STEMI, the enoxaparin sodium regimen was a 3,000 IU (30 mg) IV bolus followed by 100 IU/kg (1 mg/kg) SC every 12 hours.

4 and 'Description of selected adverse reactions' below). 4). Tabulated summary list of adverse reactions Other adverse reactions observed in clinical studies and reported in post- marketing experience (* indicates reactions from post-marketing experience) are detailed below.

Frequencies are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) or not known (cannot be estimated from the available data). Within each system organ class, adverse reactions are presented in order of decreasing seriousness.

4). 27 cm Formatted: Font: 11 pt Formatted: Font: 11 pt Nervous system disorders • Common: headache* Vascular disorders • Rare: spinal haematoma* (or neuraxial haematoma). 4). Hepatobiliary disorders • Very common: hepatic enzymes increased (mainly transaminases > 3 times the upper limit of normal) • Uncommon: hepatocellular liver injury * • Rare: cholestatic liver injury* Skin and subcutaneous tissue disorders • Common: urticaria, pruritus, erythema • Uncommon: bullous dermatitis • Rare: alopecia* • Rare: cutaneous vasculitis*, skin necrosis* usually occurring at the injection site (these phenomena have usually been preceded by purpura or erythematous plaques, infiltrated and painful).

Injection site nodules* (inflammatory nodules, which were not cystic enclosure of enoxaparin). They resolve after a few days and should not cause treatment discontinuation. 5). 2% of the patients (surgical patients). Some of these cases have been fatal.

In surgical patients, haemorrhage complications were considered major: (1) if the haemorrhage caused a significant clinical event, or (2) if accompanied by haemoglobin decrease ≥ 2 g/dL or transfusion of 2 or more units of blood products.

Retroperitoneal and intracranial haemorrhages were always considered major. 5). 27 cm Formatted: Font: 11 pt Formatted: […]

4. 4). 2). • Severe renal impairment: Enoxaparin sodium is not recommended for patients with end-stage renal disease (creatinine clearance < 15 mL/min) due to lack of data in this population outside the prevention of thrombus formation in extracorporeal circulation during haemodialysis.

Dosage table for patients with severe renal impairment (creatinine clearance 15-30 mL/min): Indication Dosing regimen Prophylaxis of venous thromboembolic disease 2,000 IU (20 mg) SC once daily Treatment of DVT and PE 100 IU/kg (1 mg/kg) body weight SC once daily Extended treatment of DVT and PE in patients with active cancer 100 IU/kg (1 mg/kg) body weight SC once daily Treatment of unstable angina and NSTEMI 100 IU/kg (1 mg/kg) body weight SC once daily Treatment of acute STEMI (patients under 75 years) Treatment of acute STEMI (patients over 75 years) 1 × 3,000 IU (30 mg) IV bolus plus 100 IU/kg (1 mg/kg) body weight SC and then 100 IU/kg (1 mg/kg) body weight SC every 24 hours No IV initial bolus, 100 IU/kg (1 mg/kg) body weight SC and then 100 IU/kg (1 mg/kg) body weight SC every 24 hours The recommended dosage adjustments do not apply to the haemodialysis indication.

• Moderate and mild renal impairment: Although no dosage adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment, careful clinical monitoring is advised.

Method of administration Ghemaxan should not be administered by the intramuscular route. For the prophylaxis of venous thromboembolic disease following surgery, treatment of DVT and PE, extended treatment of DVT and PE in patients with active cancer, 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 medicinal product when using pre-filled syringes.

When the quantity of medicinal product to be injected needs adjusting 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 cases, the volume shall be rounded up to the nearest graduation.

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.

Do not rub the injection site after administration. 6). In case of self-administration, patients 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.

For IV injection, either the multidose vial or pre-filled syringe can be used. Enoxaparin sodium should be administered through an IV line. It should not be mixed or co-administered with other medicinal products. To avoid the possible mixture of enoxaparin sodium with all other medicinal products, the IV access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV bolus administration of enoxaparin sodium to clear the port of medicinal product.

9%) or 5% dextrose in water. •Initial 3,000 IU (30 mg) bolus For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the excess volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg) dose can then be directly injected into an injection site in the intravenous line.

3 mg/kg) is to be administered if last SC administration was given more than 8 hours before balloon inflation. In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the medicinal product to 300 IU/mL (3 mg/mL).

e. 9%) or 5% dextrose in water) as follows: Withdraw 30 mL from the infusion bag with a syringe and discard the liquid. Inject the complete contents of the 6,000 IU (60 mg) enoxaparin sodium pre-filled syringe into the 20 mL 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 IV line. 1] or […]

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