Enoxar Special Precautions

2000 IU/0.2 mL and 6000 IU/0.6 mL soln for inj: General: Enoxaparin should not be mixed with other injections for infusion.
Enoxaparin should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension, or a history of recent gastrointestinal ulceration, diabetic retinopathy, and hemorrhage.
Enoxaparin should be used with care in elderly patients who may show delayed elimination of Enoxaparin.
If thromboembolic events occur despite Enoxaparin prophylaxis, appropriate therapy should be initiated.
4000 IU/0.4 mL soln for inj: General: Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs. These medicinal products differ in their manufacturing process, molecular weights, specific anti-Xa and anti-IIa activities, units, dosage and clinical efficacy and safety. This results in differences in pharmacokinetics and associated biological activities (e.g., anti-thrombin activity, and platelet interactions). Special attention and compliance with the instructions for use specific to each proprietary medicinal product are therefore required.
History of HIT (>100 days): The use of enoxaparin sodium in patients with a history of immune-mediated HIT within the past 100 days or in the presence of circulating antibodies is contraindicated. Circulating antibodies may persist for 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: The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually appears between the 5 and the 21-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), the platelet count should be measured. Patients must be aware that these symptoms may occur and if so, that they should inform their primary care physician.
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.
Hemorrhage: As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the hemorrhage 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, such as: impaired hemostasis, history of peptic ulcer, recent ischemic stroke, severe arterial hypertension, recent diabetic retinopathy, neuro- or ophthalmologic surgery, concomitant use of medications affecting hemostasis.
Laboratory tests: At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of fibrinogen to platelets.
At higher 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 anesthesia or lumbar puncture: Spinal/epidural anesthesia or lumbar puncture must not be performed within 24 hours of administration of enoxaparin sodium at therapeutic doses.
There have been cases of neuraxial hematomas reported with the concurrent use of enoxaparin sodium and spinal/epidural anesthesia 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 hemostasis 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.
To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of enoxaparin sodium. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of enoxaparin sodium is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. For patients with creatinine clearance [15-30 mL/minute], additional considerations are necessary because elimination of enoxaparin sodium is more prolonged.
Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/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 previously mentioned 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 hemostasis 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 hemorrhage. If such use is considered absolutely necessary, the decision must be made only after a careful individual benefit risk assessment.
Mechanical prosthetic heart valves: The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in patients with mechanical prosthetic heart valves who have received enoxaparin sodium for thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal and fetal death.
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.
Hyperkalemia: Heparins can suppress adrenal secretion of aldosterone leading to hyperkalemia, 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.
Traceability: LMWHs are biological medicinal products. In order to improve the LMWH traceability, it is recommended that health care professionals record the trade name and batch number of the administered product in the patient file.
Sodium: For patients receiving doses higher than 210 mg/day, this medicine contains more than 24 mg sodium in each dose. This is equivalent to 1.2% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
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 this population outside the prevention of thrombus formation in extracorporeal circulation during hemodialysis.
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.
No dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mL/min) and mild (creatinine clearance 50-80 mL/min) renal impairment.
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.
Use in Pregnancy & Lactation: Pregnant women with mechanical prosthetic heart valves: The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. In a clinical study of pregnant women with mechanical prosthetic heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg) twice daily) to reduce the risk of thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal and fetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism.
Use in the 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.