WARNING: SPINAL/EPIDURAL HEMATOMA

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• Use of indwelling epidural catheters
• Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
• A history of traumatic or repeated epidural or spinal punctures
• A history of spinal deformity or spinal surgery

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

• FRAGMIN is contraindicated in patients with active major bleeding, history of heparin induced thrombocytopenia, hypersensitivity to dalteparin sodium, heparin, or pork products.
• FRAGMIN is contraindicated in patients undergoing epidural/neuraxial anesthesia as a treatment for unstable angina and non-Q-wave MI and for prolonged VTE prophylaxis due to an increased risk of bleeding associated with the dosage of FRAGMIN recommended for these indications.
• FRAGMIN, like other anticoagulants, should be used with extreme caution in patients who have an increased risk of hemorrhage; bleeding can occur at any site during therapy. An unexpected drop in hematocrit or blood pressure should lead to a search for a bleeding site.
• FRAGMIN should be used with caution in patients with bleeding diathesis, thrombocytopenia or platelet defects, severe liver or kidney insufficiency, hypertensive or diabetic retinopathy, and recent gastrointestinal bleeding.
• FRAGMIN should be used with extreme caution in patients with history of heparin-induced thrombocytopenia.

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  In FRAGMIN clinical trials supporting non-cancer indications, platelet count of <50,000/mm³ occurred in <1% of patients.

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  In FRAGMIN clinical trials supporting the extended treatment of symptomatic VTE in patients with cancer, platelet counts of <100,000/mm³ occurred in 13.6% of patients, including 6.5% who also had platelet counts less than 50,000/mm³. In the same clinical trial, thrombocytopenia was reported as an adverse event in 10.9% of patients in the FRAGMIN arm and 8.1% of patients in the oral anticoagulant arm. FRAGMIN dose was decreased or interrupted in patients whose platelet counts fell below 100,000/mm³.

• Thrombocytopenia of any degree should be monitored closely. Heparin-induced thrombocytopenia can occur with administration of FRAGMIN. The incidence of this complication is unknown at present. In clinical practice, rare cases of thrombocytopenia with thrombosis have also been observed.
• Each multiple-dose vial of FRAGMIN contains benzyl alcohol as a preservative. Benzyl alcohol has been reported to be associated with a fatal “Gasping Syndrome” in premature infants. Because benzyl alcohol may cross the placenta, use caution when administering FRAGMIN preserved with benzyl alcohol to pregnant women. If anticoagulation with FRAGMIN is needed during pregnancy, use preservative-free formulations, where possible.
• Periodic routine complete blood counts, including platelet count, blood chemistry, and stool occult blood tests are recommended during the course of treatment with FRAGMIN.
• The most commonly reported side effect is hematoma at the injection site.
• Allergic reactions (i.e., pruritus, rash, fever, injection site reaction, bulleous eruption) have occurred. A few cases of anaphylactoid reactions have been reported.
• Use FRAGMIN with care in patients receiving oral anticoagulants, platelet inhibitors, and thrombolytic agents because of increased risk of bleeding.
• FRAGMIN cannot be used interchangeably (unit for unit) with unfractionated heparin or other low molecular weight heparins.
• FRAGMIN^® Injection is not intended for intramuscular administration.
• For more information about FRAGMIN please see Full Prescribing Information