Enoxaparin STADA 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.
Although the concentrations of the various low-molecular-weight heparins are all expressed in anti-Xa international units (IU), their efficacy is not only related to their anti-Xa activity. It would be dangerous to replace one LMWH dosage regimen by another as each regimen has been validated by specific clinical studies. Particular care is therefore required and the specific instructions for use of each drug must be followed.
Spinal/epidural anesthesia in patients given prevent treatment with LMWH: There have been rare reports of spinal hematomas following administration of LMWH during spinal/epidural anesthesia, resulting in long-term or permanent paralysis.
The risk of intra-spinal hematomas appears to be higher in epidural anesthesia with a catheter than in spinal anesthesia. 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.
The occurrence of these rare events may be increased by prolonged post-operative use of epidural catheters.
To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and epidural or spinal anesthesia/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.
If pre-operative LMWH treatment is required (long term bedridden patients, trauma) and if the benefit of local/regional spinal anesthesia has been carefully weighed, patients who received a pre-operative injection of LMWH can be anesthetized provided that an interval of at least 12 hours is respected between the heparin injection and the spinal anesthesia. Close neurological monitoring is recommended due to the risk of intraspinal hematoma.
In almost all patients, prophylactic treatment with LMWH can be initiated within 6 to 8 hours after the anesthesia or removal of the catheter, under neurological monitoring.
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 <30 ml/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).
Extra caution should be exercised during co-administration with other drugs which affect hemostasis (specifically non-steroidal anti-inflammatory drugs, aspirin).
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 in structured to inform their physician immediately if they experience any of the previously mentioned signs or symptoms. If signs or symptoms of spinal haematoma are suspected, urgent diagnosis and treatment including spinal cord decompression should be initiated.
Risk of heparin-induced thrombocytopenia (HIT): 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 several years. Enoxaparin sodium is to be used with extreme caution in patients with a history (more than 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.
Solution for injection containing 6000 anti-Xa IU (60 mg) Coronary angioplasty revascularization procedure: To minimize the risk of hemorrhage during coronary angioplasty for unstable angina, non-Q-wave myocardial infarction and acute ST-segment elevation myocardial infarction, it is recommended that the advised intervals between enoxaparin injections be strictly complied with. It is important to perform hemostasis at the vascular puncture site following coronary angioplasty. If an occlusion device is used, the introducer can be removed immediately. If manual compression is performed, the introducer must be removed 6 hours after the last SC/IV injection of enoxaparin. If enoxaparin treatment is continued, the following injection must be performed at the earliest 6 to 8 hours after removal of the introducer. The puncture site must be monitored to detect any signs of bleeding or hematoma.
Prophylactic treatment in acute medical conditions: In patients with an acute infection or acute rheumatic disorder, prophylactic treatment is only justified if the disorder is associated with at least one of the following venous thromboembolic risk factors: age >75 years; cancer; history of venous thromboembolism; obesity; hormone therapy; heart failure; chronic respiratory failure.
In medical prophylaxis, there is very limited clinical experience in elderly patients over 80 years of age whose bodyweight is below 40 kg.
Use in Pregnancy: Pregnant women with Mechanical prosthetic heart valves: The use of Enoxaparin Injection for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. During a clinical study in pregnant women with mechanical prosthetic heart valves receiving 1 mg/kg enoxaparin twice daily to reduce the risk of thromboembolic events, two of eight women developed thrombosis which led to an obstructed valve with fatal outcome for both the woman and the fetus. In addition, other isolated post-marketing cases of thrombosis have been reported in pregnant women with mechanical prosthetic heart valves who received thromboembolic prophylaxis with enoxaparin. Therefore, the risk of thromboembolic events in this population might be higher (see Precautions for use: Mechanical prosthetic heart valves under Precautions).
Use in children: As no relevant data are available, use of LMWH is not recommended in children.