Clexane Warnings

General: Low Molecular Weight Heparins should not be used interchangeably since they differ in their manufacturing process, molecular weights, specific anti-Xa activities, units and dosage. 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.
Spinal/Epidural Anesthesia: There have been cases of neuraxial haematomas reported with the concurrent use of enoxaparin sodium and spinal/epidural anaesthesia resulting in long term or permanent paralysis). These events are rare with enoxaparin sodium dosage regimens 40 mg once daily or lower. The risk is greater with higher enoxaparin sodium dosage regimen, use of post-operative indwelling catheters or the concomitant use of additional drugs affecting haemostasis such as NSAIDs (see Interactions). The risk also appears to be increased by traumatic or repeated neuraxial 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 anaesthesia/analgesia, the pharmacokinetic profile of the drug should be considered (see Pharmacology: Pharmacokinetics under Actions).
Placement and removal of the catheter is best performed when the anticoagulant effect of enoxaparin is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known.
Placement or removal of a catheter should be delayed for at least 12 hours after administration of lower doses (20 mg once daily, 30 mg once or twice daily or 40 mg once daily) of enoxaparin, and at least 24 hours after the administration of higher doses (0.75 mg/kg twice daily, 1 mg/kg twice daily, or 1.5 mg/kg once daily) of enoxaparin. Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial haematoma will be avoided. Patients receiving the 0.75 mg/kg twice-daily dose or the 1 mg/kg twice-daily dose should not receive the second enoxaparin dose in the twice-daily regimen to allow a longer delay before catheter placement or removal. Likewise, although a specific recommendation for timing of a subsequent enoxaparin dose after catheter removal cannot be made, consider delaying this next dose for at least four hours, based on a benefit-risk assessment considering both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors. For patients with creatinine clearance <30ml/minute, additional considerations are necessary because elimination of enoxaparin is more prolonged; consider doubling the timing of removal of a catheter, at least 24 hours for the lower prescribed dose of enoxaparin (30 mg once daily) and at least 48 hours for the higher dose (1 mg/kg/day).
Should the physician decide to administer anticoagulation in the context of epidural/spinal anesthesia 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. Patients should be instructed to inform their physician immediately if they experience any of the above signs or symptoms. If signs or symptoms of spinal haematoma are suspected, urgent diagnosis and treatment including spinal cord decompression should be initiated.
Heparin-induced thrombocytopenia: Enoxaparin sodium is to be used with extreme caution in patients with a history of heparin-induced thrombocytopenia with or without thrombosis. The risk of heparin-induced thrombocytopenia may persist several years. If a history of heparin-induced thrombocytopenia is suspected, in vitro platelet aggregation tests have limited predictive value. The decision to use enoxaparin sodium in such a case must be made only in consultation with an expert in the field.
Percutaneous coronary revascularisation procedures: To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable angina, non-Q-wave myocardial infarction and acute ST-segment elevation myocardial infarction, adhere precisely to the intervals recommended between Enoxaparin sodium (Clexane) 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.
Pregnant women with mechanical prosthetic heart valves: The use of Enoxaparin sodium (Clexane) Injection 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 (1 mg/kg bid) to reduce the risk of thrombo-embolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal and fetal death. There have been isolated postmarketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving enoxaparin for thromboprophylaxis. Pregnant women with mechanical prosthetic heart valves may be at higher risk for thrombo-embolism (see Precautions).
Laboratory tests: At doses used for prophylaxis of venous thrombo-embolism, 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 aPTT (activated partial thromboplastin time), and ACT (activated clotting time) 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.