Spinal or epidural hemorrhage and subsequent hematomas can occur with the associated use of low molecular weight heparins or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture. 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 NSAIDs, with traumatic or repeated epidural or spinal puncture, or in patients with a history of spinal surgery or spinal deformity [see Boxed Warning, Adverse Reactions (6.2), and Drug Interactions (7)].

To reduce the potential risk of bleeding associated with the concurrent use of FRAGMIN and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of FRAGMIN [see Clinical Pharmacology (12.3)].

Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of FRAGMIN is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. No additional hemostasis-altering medications should be administered due to the additive effects.

Patients on preoperative FRAGMIN thromboprophylaxis can be assumed to have altered coagulation. The first postoperative FRAGMIN thromboprophylaxis dose (2,500 units) should be administered 6 hours to 8 hours postoperatively. The second postoperative dose (2,500 units or 5,000 units) should occur no sooner than 24 hours after the first dose. Placement or removal of a catheter should be delayed for at least 12 hours after administration of 2,500 units once daily of FRAGMIN, at least 15 hours after the administration of 5,000 units once daily of FRAGMIN, and at least 24 hours after the administration of higher doses (200 units/kg once daily, 120 units/kg twice daily) of FRAGMIN. Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial hematoma will be avoided.

Although a specific recommendation for timing of a subsequent FRAGMIN dose after catheter removal cannot be made, consider delaying this next dose for at least 4 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 FRAGMIN may be more prolonged; consider doubling the timing of removal of a catheter, at least 24 hours for the lower prescribed dose of FRAGMIN (2,500 units or 5,000 units once daily) and at least 48 hours for the higher dose (200 units/kg once daily, 120 units/kg twice daily) [see Clinical Pharmacology (12.3)].

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 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.

Use FRAGMIN with extreme caution in patients who have an increased risk of hemorrhage, such as those with severe uncontrolled hypertension, bacterial endocarditis, congenital or acquired bleeding disorders, active ulceration and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal or ophthalmological surgery. FRAGMIN may enhance the risk of bleeding in patients with thrombocytopenia or platelet defects; severe liver or kidney insufficiency, hypertensive or diabetic retinopathy, and recent gastrointestinal bleeding. Bleeding can occur at any site during therapy with FRAGMIN.