Enoxaparin Kamada | Enoxaparin Forte Kamada

/ Kamada

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 orthopedic surgery), the last injection should be administered no later than 12 hours prior to surgery and resumed 12 hours after surgery.
* For patients who undergo major orthopedic surgery an extended thromboprophylaxis up to 5 weeks is recommended.
* 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 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 hemorrhage, 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.
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.
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.
See prescribing information for full details

* 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 extra corporeal 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).

* Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins (LMWH) or to any of the excipients.
* 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.

History of HIT (>100 days)
Circulating antibodies may persist several years.
Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin- induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments are considered (e.g. danaparoid sodium or lepirudin).
Monitoring of platelet counts
In patients with cancer with a platelet count below 80 g/L, anticoagulation treatment can only be considered on a case-by-case basis and careful monitoring is recommended.
The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually appears between the 5th and the 21st day following the beginning of enoxaparin sodium treatment.
The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with cancer.
Therefore, it is recommended that the platelet counts be measured before the initiation of therapy with enoxaparin sodium and then regularly thereafter during the treatment.
If there are clinical symptoms suggestive of HIT (any new episode of arterial and/or venous thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reactions on treatment), platelet count should be measured.
In practice, if a confirmed significant decrease of the platelet count is observed (30 to 50 % of the initial value), enoxaparin sodium treatment must be immediately discontinued, and the patient switched to another non-heparin anticoagulant alternative treatment.
Haemorrhage
As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the haemorrhage should be investigated, and appropriate treatment instituted.
Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with increased potential for bleeding.
Laboratory tests
At highe doses, increases in activated partial thromboplastin time (aPTT), and activated clotting time (ACT) may occur. Increases in aPTT and ACT are not linearly correlated with increasing enoxaparin sodium antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium activity.
Spinal/Epidural anaesthesia or lumbar puncture
Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of enoxaparin sodium at therapeutic doses.
There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and spinal/epidural anaesthesia or spinal puncture procedures resulting in long term or permanent paralysis.
These events are rare with enoxaparin sodium dosage regimens 4,000 IU (40 mg) once daily or lower. The risk of these events is higher with the use of post-operative indwelling epidural catheters, with the concomitant use of additional drugs affecting haemostasis such as Non- Steroidal Anti-Inflammatory Drugs (NSAIDs), with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal surgery or spinal deformity.
Should it decide to administer anticoagulation in the context of epidural or spinal anaesthesia/analgesia or lumbar puncture, frequent monitoring must be exercised to detect any signs and symptoms of neurological impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to report immediately if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae.
Skin necrosis / cutaneous vasculitis
Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment discontinuation.
Percutaneous coronary revascularization procedures
To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure device is used, the sheath can be removed immediately. If a manual compression method is used, sheath should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma formation.
Acute infective endocarditis
Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of cerebral haemorrhage. If such use is considered absolutely necessary, the decision must be made only after a careful individual benefit risk assessment.
Elderly
No increased bleeding tendency is observed in the elderly with the prophylactic dosage ranges. Elderly patients (especially patients eighty years of age and older) may be at an increased risk for bleeding complications with the therapeutic dosage ranges. Careful clinical monitoring is advised and dose reduction might be considered in patients older than 75 years treated for STEMI.
Renal impairment
In patients with renal impairment, there is an increase in exposure of enoxaparin sodium which increases the risk of bleeding. In these patients, careful clinical monitoring is advised, and biological monitoring by anti-Xa activity measurement might be considered.
Enoxaparin sodium is not recommended for patients with end stage renal disease (creatinine clearance<15 mL/min) due to lack of data.
In patients with severe renal impairment (creatinine clearance 15-30 mL/min), since exposure of enoxaparin sodium is significantly increased, a dosage adjustment is recommended for therapeutic and prophylactic dosage ranges.
Hepatic impairment
Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased potential for bleeding. Dose adjustment based on monitoring of anti-Xa levels is unreliable in patients with liver cirrhosis and not recommended.
Low weight
An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of bleeding. Therefore, careful clinical monitoring is advised in these patients.
Obese Patients
Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in obese patients (BMI >30 kg/m2) has not been fully determined and there is no consensus for dose adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism.
Hyperkalaemia
Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, taking medicinal products known to increase potassium. Plasma potassium should be monitored regularly especially in patients at risk.
Sodium
This medical product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.
Acute generalised exanthematous pustulosis
Acute generalised exanthematous pustulosis (AGEP) has been reported with frequency not known in association with enoxaparin treatment. At the time of prescription, patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, enoxaparin should be withdrawn immediately and an alternative treatment considered (as appropriate).
See prescribing information for full details.

Very common: Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality)
Common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis, allergic reaction, headache, urticaria, pruritus, erythema, injection site haematoma, injection site pain, other injection site reaction (such as oedema, haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction).
See prescribing information for full details.

Concomitant use not recommended:
Medicinal products affecting haemostasis: It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products such as: Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including ketorolac, Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and anticoagulants.
Concomitant use with caution:
Other medicinal products affecting haemostasis such as: Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose (cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in acute coronary syndrome due to the risk of bleeding, dextran 40, systemic glucocorticoids.
Medicinal products increasing potassium levels: Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin sodium under careful clinical and laboratory monitoring.

Pregnancy:  In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third trimester of pregnancy. There is no information available concerning the first trimester.
If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before.
Lactation: It is not known whether unchanged enoxaparin is excreted in human breast milk. The oral absorption of enoxaparin sodium is unlikely. This medical product can be used during breastfeeding.

Signs and symptoms
Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin sodium will be absorbed.
Management
The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium injection, protamine administration may not be required. However, even with high doses of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%).