0.3 ML enoxaparin sodium 100 MG/ML Prefilled Syringe [Lovenox]

INDICATIONS AND USAGE Enoxaparin sodium injection, USP is a low molecular weight heparin (LMWH) indicated for: • Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip replacement surgery, knee replacement surgery, or medical patients with severely restricted mobility during acute illness ( 1.1 ) • Inpatient treatment of acute DVT with or without pulmonary embolism ( 1.2 ) • Outpatient treatment of acute DVT without pulmonary embolism ( 1.2 ) • Prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction (MI) ( 1.3 ) • Treatment of acute ST-segment elevation myocardial infarction (STEMI) managed medically or with subsequent percutaneous coronary intervention (PCI) ( 1.4 ) 1.1 Prophylaxis of Deep Vein Thrombosis Enoxaparin sodium injection, USP is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE): • in patients undergoing abdominal surgery who are at risk for thromboembolic complications [see Clinical Studies ( 14.1 ) ] • in patients undergoing hip replacement surgery, during and following hospitalization • in patients undergoing knee replacement surgery • in medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness 1.2 Treatment of Acute Deep Vein Thrombosis Enoxaparin sodium injection, USP is indicated for: • the inpatient treatment of acute deep vein thrombosis with or without pulmonary embolism, when administered in conjunction with warfarin sodium • the outpatient treatment of acute deep vein thrombosis without pulmonary embolism, when administered in conjunction with warfarin sodium 1.3 Prophylaxis of Ischemic Complications of Unstable Angina and Non-Q-Wave Myocardial Infarction Enoxaparin sodium injection, USP is indicated for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. 1.4 Treatment of Acute ST-Segment Elevation Myocardial Infarction Enoxaparin sodium injection, USP, when administered concurrently with aspirin, has been shown to reduce the rate of the combined endpoint of recurrent myocardial infarction or death in patients with acute ST-segment elevation myocardial infarction (STEMI) receiving thrombolysis and being managed medically or with percutaneous coronary intervention (PCI).

DOSAGE AND ADMINISTRATION See full prescribing information for dosing and administration information. ( 2 ) 2.1 Pretreatment Evaluation Evaluate all patients for a bleeding disorder before starting enoxaparin sodium treatment, unless treatment is urgently needed. 2.2 Adult Dosage Abdominal Surgery The recommended dose of enoxaparin sodium is 40 mg by subcutaneous injection once a day (with the initial dose given 2 hours prior to surgery) in patients undergoing abdominal surgery who are at risk for thromboembolic complications. The usual duration of administration is 7 to 10 days [see Clinical Studies (14.1) ]. Hip or Knee Replacement Surgery The recommended dose of enoxaparin sodium is 30 mg every 12 hours administered by subcutaneous injection in patients undergoing hip or knee replacement surgery. Administer the initial dose 12 to 24 hours after surgery, provided that hemostasis has been established. The usual duration of administration is 7 to 10 days [see Clinical Studies (14.2) ]. A dose of enoxaparin sodium of 40 mg once a day subcutaneously may be considered for hip replacement surgery for up to 3 weeks. Administer the initial dose 12 (±3) hours prior to surgery. Medical Patients during Acute Illness The recommended dose of enoxaparin sodium is 40 mg once a day administered by subcutaneous injection for medical patients at risk for thromboembolic complications due to severely restricted mobility during acute illness. The usual duration of administration is 6 to 11 days [see Clinical Studies (14.3) ]. Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism The recommended dose of enoxaparin sodium injection is 1 mg/kg every 12 hours administered subcutaneously in patients with acute deep vein thrombosis without pulmonary embolism, who can be treated at home in an outpatient setting. The recommended dose of enoxaparin sodium injection is 1 mg/kg every 12 hours administered subcutaneously or 1.5 mg/kg once a day administered subcutaneously at the same time every day for inpatient (hospital) treatment of patients with acute deep vein thrombosis with pulmonary embolism or patients with acute deep vein thrombosis without pulmonary embolism (who are not candidates for outpatient treatment). In both outpatient and inpatient (hospital) treatments, initiate warfarin sodium therapy when appropriate (usually within 72 hours of enoxaparin sodium injection). Continue enoxaparin sodium injection for a minimum of 5 days and until a therapeutic oral anticoagulant effect has been achieved (International Normalization Ratio 2 to 3). The average duration of administration is 7 days[see Clinical Studies (14.4) ]. Unstable Angina and Non-Q-Wave Myocardial Infarction The recommended dose of enoxaparin sodium injection is 1 mg/kg administered subcutaneously every 12 hours in conjunction with oral aspirin therapy (100 to 325 mg once daily) in patients with unstable angina or non–Q-wave myocardial infarction. Treat with enoxaparin sodium injection for a minimum of 2 days and continue until clinical stabilization. The usual duration of treatment is 2 to 8 days [see Warnings and Precautions (5.2) and Clinical Studies (14.5) ]. Treatment of Acute ST-Segment Elevation Myocardial Infarction The recommended dose of enoxaparin sodium injection is a single intravenous bolus of 30 mg plus a 1 mg/kg subcutaneous dose followed by 1 mg/kg administered subcutaneously every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses) in patients with acute ST-segment elevation myocardial infarction. Reduce the dosage in patients ≥75 years of age [see Dosage and Administration (2.4)]. Unless contraindicated, administer aspirin to all patients as soon as they are identified as having STEMI and continue dosing with 75 to 325 mg once daily. When administered in conjunction with a thrombolytic (fibrin specific or non–fibrin specific), administer enoxaparin sodium injection between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. The usual duration of enoxaparin sodium injection therapy is 8 days or until hospital discharge. For patients managed with percutaneous coronary intervention (PCI), if the last enoxaparin sodium injection subcutaneous administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last enoxaparin sodium injection subcutaneous administration was given more than 8 hours before balloon inflation, administer an intravenous bolus of 0.3 mg/kg of enoxaparin sodium injection [see Warnings and Precautions (5.2) ]. 2.3 Dose Reduction for Patients with Severe Renal Impairment The recommended prophylaxis and treatment dosage regimens for patients with severe renal impairment (creatinine clearance <30 mL/min) are described in Table 1 [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ] . Table 1: Dosage Regimens for Patients with Severe Renal Impairment (creatinine clearance <30 mL/minute) Indication Dosage Regimen Prophylaxis in abdominal surgery 30 mg administered subcutaneously once daily Prophylaxis in hip or knee replacement surgery 30 mg administered subcutaneously once daily Prophylaxis in medical patients during acute illness 30 mg administered subcutaneously once daily Inpatient treatment of acute deep vein thrombosis with or without pulmonary embolism, when administered in conjunction with warfarin sodium 1 mg/kg administered subcutaneously once daily Outpatient treatment of acute deep vein thrombosis without pulmonary embolism, when administered in conjunction with warfarin sodium 1 mg/kg administered subcutaneously once daily Prophylaxis of ischemic complications of unstable angina and non – Q-wave myocardial infarction, when concurrently administered with aspirin 1 mg/kg administered subcutaneously once daily Treatment of acute ST-segment elevation myocardial infarction in patients <75 years of age, when administered in conjunction with aspirin 30 mg single intravenous bolus plus a 1 mg/kg subcutaneous dose followed by 1 mg/kg administered subcutaneously once daily. Treatment of acute ST-segment elevation myocardial infarction in geriatric patients ≥75 years of age, when administered in conjunction with aspirin 1 mg/kg administered subcutaneously once daily (no initial bolus) Although no dose adjustment is recommended in patients with creatinine clearance 30 to 50 mL/min and creatinine clearance 50 to 80 mL/min, observe these patients for signs and symptoms of bleeding. 2.4 Recommended Dosage for Geriatric Patients with Acute ST-Segment Elevation Myocardial Infarction For treatment of acute ST-segment elevation myocardial infarction in geriatric patients ≥75 years of age, do not use an initial intravenous bolus . Initiate dosing with 0.75 mg/kg subcutaneously every 12 hours (maximum 75 mg for the first two doses only, followed by 0.75 mg/kg dosing for the remaining doses) [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3) ] . No dose adjustment is necessary for other indications in geriatric patients unless kidney function is impaired [see Dosage and Administration (2.2) ] . 2.5 Administration Do not administer enoxaparin sodium injection by intramuscular injection. Administer enoxaparin sodium by subcutaneous injection only. Enoxaparin sodium injection is a clear, colorless to pale yellow sterile solution, and as with other parenteral drug products, should be inspected visually for particulate matter and discoloration prior to administration. Patients may self-inject by the subcutaneous route of administration only after their physicians determine that it is appropriate and with medical follow-up, as necessary. Provide proper training in subcutaneous injection technique before allowing self-injection (with or without the assistance of an injection device). Subcutaneous Injection Technique • Position patients in a supine position for enoxaparin sodium administration by deep subcutaneous inject

WARNINGS AND PRECAUTIONS Increased risk of hemorrhage: Monitor for signs of bleeding ( 5.1 , 5.2 , 5.3 ) Risk of Heparin-Induced Thrombocytopenia with or without Thrombosis ( 5.4 ) Thrombocytopenia: Monitor platelet count closely ( 5.5 ) Interchangeability with other heparins: Do not exchange with heparin or other LMWHs ( 5.6 ) Increased Risk of Thrombosis in Pregnant women with Mechanical Prosthetic Heart Valves: women and their fetuses may be at increased risk. Monitor more frequently and adjust dosage as needed. ( 5.7 ) 5.1 Increased Risk of Hemorrhage Cases of epidural or spinal hemorrhage and subsequent hematomas have been reported with the use of enoxaparin sodium and epidural or spinal anesthesia/analgesia or spinal puncture procedures, resulting in long-term or permanent paralysis. The risk of these events is higher with the use of postoperative 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 enoxaparin sodium and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of enoxaparin [see Clinical Pharmacology (12.3) ] . Placement or removal of an epidural catheter or lumbar puncture 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 (30 mg once or twice daily or 40 mg once daily) of enoxaparin sodium 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 sodium. Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial hematoma 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 sodium 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 sodium (30 mg once daily) and at least 48 hours for the higher dose (1 mg/kg/day) [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 enoxaparin sodium with extreme caution in conditions with increased risk of hemorrhage, such as bacterial endocarditis, congenital or acquired bleeding disorders, active ulcerative and angiodysplastic gastrointestinal disease, hemorrhagic stroke, or shortly after brain, spinal, or ophthalmological surgery, or in patients treated concomitantly with platelet inhibitors. Major hemorrhages including retroperitoneal and intracranial bleeding have been reported. Some of these cases have been fatal. Bleeding can occur at any site during therapy with enoxaparin sodium. An unexplained fall in hematocrit or blood pressure should lead to a search for a bleeding site. 5.2 Increased Risk of Bleeding following Percutaneous Coronary Revascularization 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 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 intravenous/subcutaneous 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 [see Dosage and Administration (2.1) ] . 5.3 Increased Risk of Bleeding in Patients with Concomitant Medical Conditions Enoxaparin sodium should be used with care in patients with a bleeding diathesis, uncontrolled arterial hypertension or a history of recent gastrointestinal ulceration, diabetic retinopathy, renal dysfunction and hemorrhage. 5.4 Risk of Heparin-Induced Thrombocytopenia with or Without Thrombosis Enoxaparin sodium may cause heparin-induced thrombocytopenia (HIT) or heparin-induced thrombocytopenia (HIT) with thrombosis (HITTS). HITTS may lead to organ infarction, limb ischemia, or death. Monitor thrombocytopenia of any degree closely. 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 [see Contraindications (4) ] . Circulating antibodies may persist for several years. Only use enoxaparin sodium in patients with a history of HIT if more than 100 days have elapsed since the prior HIT episode and no circulating antibodies are present. Because HIT may still occur in these circumstances, 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. 5.5 Thrombocytopenia Thrombocytopenia can occur with the administration of enoxaparin sodium. Moderate thrombocytopenia (platelet counts between 100,000/mm 3 and 50,000/mm 3 ) occurred at a rate of 1.3% in patients given enoxaparin sodium, 1.2% in patients given heparin, and 0.7% in patients given placebo in clinical trials. Platelet counts less than 50,000/mm 3 occurred at a rate of 0.1% in patients given enoxaparin sodium, in 0.2% of patients given heparin, and 0.4% of patients given placebo in the same trials. Thrombocytopenia of any degree should be monitored closely. If the platelet count falls below 100,000/mm 3 , enoxaparin sodium should be discontinued. 5.6 Interchangeability with Other Heparins Enoxaparin sodium cannot be used interchangeably (unit for unit) with heparin or other low molecular weight heparins as they differ in manufacturing process, molecular weight distribution, anti-Xa and anti-IIa activities, units, and dosage. Each of these medicines has its own instructions for use. 5.7 Increased Risk of Thrombosis in Pregnant Women with Mechanical Prosthetic Heart Valves Use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves may result in value thrombosis. In a clinical study of pregnant women with mechanical prosthetic heart valves given enoxaparin (1 mg/kg twice daily) to

CONTRAINDICATIONS Enoxaparin Sodium Injection is contraindicated in patients with: Active major bleeding History of immune-mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies [ see Warnings and Precautions ( 5.4 ) ] Known hypersensitivity to enoxaparin sodium (e.g., pruritus, urticaria, anaphylactic/ anaphylactoid reactions) [ see Adverse Reactions ( 6.2 ) ] Known hypersensitivity to heparin or pork products Known hypersensitivity to benzyl alcohol (which is in only the multiple-dose formulation of Enoxaparin Sodium Injection [ see Warnings and Precautions (5.8) ] • Active major bleeding ( 4 ) • History of heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies ( 4 ) • Hypersensitivity to enoxaparin sodium ( 4 ) • Hypersensitivity to heparin or pork products ( 4 ) • Hypersensitivity to benzyl alcohol (for multiple-dose formulation only) ( 4 )

Mechanism of Action Enoxaparin is a low molecular weight heparin, which has antithrombotic properties.