Lovenox (enoxaparin sodium injection) - 3 indications

Scroll down for information on each indication:

• the prophylaxis and treatment of deep vein thrombosis; approved 1993
• the prevention of ischemic complications of unstable angina and non-Q-wave myocardial infarction; approved March of 1998
• the treatment of patients with acute ST- segment elevation myocardial infarction (STEMI); approved May of 2007

General Information

Lovenox (enoxaparin sodium) is a low molecular weight heparin (LMWH).

Lovenox is specifically indicated for the following:

• 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
  • 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
• The treatment of acute deep vein thrombosis:
  • 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
• The prophylaxis of ischemic complications of unstable angina and non–Q-wave myocardial infarction, when concurrently administered with aspirin.
• The treatment of Acute ST-Segment Elevation Myocardial Infarction Lovenox, when administered concurrently with aspirin

Lovenox is supplied as an injection for subcutaneous and intravenous administration. Scroll down to see the recommended dosage/administration for each condition.

Mechanism of Action

Lovenox (enoxaparin) is a low molecular weight heparin which has antithrombotic properties.

Side Effects

Adverse effects associated with the use of Lovenox may include, but are not limited to, the following:

• bleeding
• anemia
• thrombocytopenia
• elevation of serum aminotransferase
• diarrhea
• nausea
• ecchymosis
• fever
• edema
• peripheral edema
• dyspnea
• confusion
• injection site pain

The Lovenox drug label comes with the following Black Box Warning: 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, and other anticoagulants • A history of traumatic or repeated epidural or spinal punctures • A history of spinal deformity or spinal surgery • Optimal timing between the administration of Lovenox and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Indication 1 - the prophylaxis of deep vein thrombosis and the treatment of acute deep vein thrombosis

approved 1993

Dosage/Administration

Abdominal Surgery

• The recommended dose of Lovenox 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

Hip or Knee Replacement Surgery

• The recommended dose of Lovenox 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. A dose of Lovenox 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 Lovenox 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.

Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism

• The recommended dose of Lovenox 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 Lovenox 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 Lovenox). Continue Lovenox for a minimum of 5 days and until a therapeutic oral anticoagulant effect has been achieved.

Clinical Trial Results

Abdominal Surgery

In a double-blind, parallel group study of patients undergoing elective cancer surgery of the gastrointestinal, urological, or gynecological tract, a total of 1116 patients were enrolled in the study, and 1115 patients were treated. Lovenox 40 mg subcutaneously, administered once a day, beginning 2 hours prior to surgery and continuing for a maximum of 12 days after surgery, was comparable to heparin 5000 U every 8 hours subcutaneously in reducing the risk of DVT (54% and 61%, respectively).

Hip or Knee Replacement Surgery

In a double-blind study, Lovenox 30 mg every 12 hours subcutaneously was compared to placebo in patients with hip replacement. A total of 100 patients were randomized in the study and all patients were treated. After hemostasis was established, treatment was initiated 12 to 24 hours after surgery and was continued for 10 to 14 days after surgery. Total percentage of DVT was 5% versus 23% for Lovenox versus placebo, respectively.

A double-blind, multicenter study compared three dosing regimens of Lovenox in patients with hip replacement. A total of 572 patients were randomized in the study and 568 patients were treated. Treatment was initiated within two days after surgery and was continued for 7 to 11 days after surgery. There was no significant difference between the 30 mg every 12 hours and 40 mg once a day regimens.

In a double-blind study, Lovenox 30 mg every 12 hours subcutaneously was compared to placebo in patients undergoing knee replacement surgery. A total of 132 patients were randomized in the study and 131 patients were treated, of which 99 had total knee replacement and 32 had either unicompartmental knee replacement or tibial osteotomy. After hemostasis was established, treatment was initiated 12 to 24 hours after surgery and was continued up to 15 days after surgery. The incidence of proximal and total DVT after surgery was significantly lower for Lovenox compared to placebo.

Extended Prophylaxis of Deep Vein Thrombosis Following Hip Replacement Surgery: In a study of extended prophylaxis for patients undergoing hip replacement surgery, patients were treated, while hospitalized, with Lovenox 40 mg subcutaneously, initiated up to 12 hours prior to surgery for the prophylaxis of postoperative DVT. At the end of the peri-operative period, all patients underwent bilateral venography. In a double-blind design, those patients with no venous thromboembolic disease were randomized to a post-discharge regimen of either Lovenox 40 mg (n=90) once a day subcutaneously or to placebo (n=89) for 3 weeks. A total of 179 patients were randomized in the double-blind phase of the study and all patients were treated. In this population of patients, the incidence of DVT during extended prophylaxis was significantly lower for Lovenox compared to placebo.

In a second study, patients undergoing hip replacement surgery were treated, while hospitalized, with Lovenox 40 mg subcutaneously, initiated up to 12 hours prior to surgery. All patients were examined for clinical signs and symptoms of venous thromboembolic (VTE) disease. In a double-blind design, patients without clinical signs and symptoms of VTE disease were randomized to a post-discharge regimen of either Lovenox 40 mg (n=131) once a day subcutaneously or to placebo (n=131) for 3 weeks. A total of 262 patients were randomized in the study double-blind phase and all patients were treated. Similar to the first study the incidence of DVT during extended prophylaxis was significantly lower for Lovenox compared to placebo, with a statistically significant difference in both total DVT (Lovenox 21 [16%] versus placebo 45 [34%]) and proximal DVT (Lovenox 8 [6%] versus placebo 28 [21%].

Prophylaxis of Deep Vein Thrombosis in Medical Patients with Severely Restricted Mobility during Acute Illness

In a double blind multicenter, parallel group study, Lovenox 20 mg or 40 mg once a day subcutaneously was compared to placebo in the prophylaxis of deep vein thrombosis (DVT) in medical patients with severely restricted mobility during acute illness (defined as walking distance of <10 meters for ≤3 days). This study included patients with heart failure (NYHA Class III or IV); acute respiratory failure or complicated chronic respiratory insufficiency (not requiring ventilatory support): acute infection (excluding septic shock); or acute rheumatic disorder (acute lumbar or sciatic pain, vertebral compression [due to osteoporosis or tumor], acute arthritic episodes of the lower extremities). A total of 1102 patients were enrolled in the study, and 1073 patients were treated. Treatment continued for a maximum of 14 days (median duration 7 days). When given at a dose of 40 mg once a day subcutaneously, Lovenox significantly reduced the incidence of DVT as compared to placebo. At approximately 3 months following enrollment, the incidence of venous thromboembolism remained lower in the Lovenox 40 mg treatment group versus the placebo treatment group.

Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism

In a multicenter, parallel group study, 900 patients with acute lower extremity deep vein thrombosis (DVT) with or without pulmonary embolism (PE) were randomized to an inpatient (hospital) treatment of either (i) Lovenox 1.5 mg/kg once a day subcutaneously, (ii) Lovenox 1 mg/kg every 12 hours subcutaneously, or (iii) heparin intravenous bolus (5000 IU) followed by a continuous infusion (administered to achieve an aPTT of 55 to 85 seconds). A total of 900 patients were randomized in the study and all patients were treated. All patients also received warfarin sodium (dose adjusted according to PT to achieve an International Normalization Ratio [INR] of 2.0 to 3.0), commencing within 72 hours of initiation of Lovenox or standard heparin therapy, and continuing for 90 days. Lovenox or standard heparin therapy was administered for a minimum of 5 days and until the targeted warfarin sodium INR was achieved. Both Lovenox regimens were equivalent to standard heparin therapy in reducing the risk of recurrent venous thromboembolism (DVT and/or PE). 

Indication 2- the prevention of ischemic complications of unstable angina and non-Q-wave myocardial infarction

approved March of 1998

Dosage/Administration

The recommended dose of Lovenox is 1 mg/kg administered subcutaneously every 12 hours in conjunction with oral aspirin therapy (100 to 325 mg once daily). Treat with Lovenox for a minimum of 2 days and continue until clinical stabilization. The usual duration of treatment is 2 to 8 days.

Clinical Trial Results

In a multicenter, double-blind, parallel group study, patients who recently experienced unstable angina or non–Q-wave myocardial infarction were randomized to either Lovenox 1 mg/kg every 12 hours subcutaneously or heparin intravenous bolus (5000 U) followed by a continuous infusion (adjusted to achieve an aPTT of 55 to 85 seconds). A total of 3171 patients were enrolled in the study, and 3107 patients were treated. All patients were also treated with aspirin 100 to 325 mg per day. Treatment was initiated within 24 hours of the event and continued until clinical stabilization, revascularization procedures, or hospital discharge, with a maximal duration of 8 days of therapy. The combined incidence of the triple endpoint of death, myocardial infarction, or recurrent angina was lower for Lovenox compared with heparin therapy at 14 days after initiation of treatment. The lower incidence of the triple endpoint was sustained up to 30 days after initiation of treatment. These results were observed in an analysis of both all-randomized and all-treated patients. In a survey one year following treatment, with information available for 92% of enrolled patients, the combined incidence of death, myocardial infarction, or recurrent angina remained lower for Lovenox versus heparin (32.0% vs 35.7%). Urgent revascularization procedures were performed less frequently in the Lovenox group as compared to the heparin group, 6.3% compared to 8.2% at 30 days.

Indication 3 - the treatment of patients with acute ST- segment elevation myocardial infarction (STEMI)

approved May of 2007

Dosage/Administration

The recommended dose of Lovenox 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. 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 Lovenox between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. The usual duration of Lovenox therapy is 8 days or until hospital discharge. For patients managed with percutaneous coronary intervention (PCI), if the last Lovenox subcutaneous administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last Lovenox subcutaneous administration was given more than 8 hours before balloon inflation, administer an intravenous bolus of 0.3 mg/kg of Lovenox.

Clinical Trial Results

In a multicenter, double-blind, double-dummy, parallel-group study, patients with acute ST-segment elevation myocardial infarction (STEMI) who were to be hospitalized within 6 hours of onset and were eligible to receive fibrinolytic therapy were randomized in a 1:1 ratio to receive either Lovenox or unfractionated heparin. Study medication was initiated between 15 minutes before and 30 minutes after the initiation of fibrinolytic therapy. Unfractionated heparin was administered beginning with an intravenous bolus of 60 U/kg (maximum 4000 U) and followed with an infusion of 12 U/kg per hour (initial maximum 1000 U per hour) that was adjusted to maintain an aPTT of 1.5 to 2 times the control value. The intravenous infusion was to be given for at least 48 hours. The Lovenox dosing strategy was adjusted according to the patient’s age and renal function. For patients younger than 75 years of age, Lovenox was given as a single 30 mg intravenous bolus plus a 1 mg/kg subcutaneous dose followed by a subcutaneous injection of 1 mg/kg every 12 hours. For patients at least 75 years of age, the intravenous bolus was not given and the subcutaneous dose was reduced to 0.75 mg/kg every 12 hours. For patients with severe renal insufficiency (estimated creatinine clearance of less than 30 mL per minute), the dose was to be modified to 1 mg/kg every 24 hours. The subcutaneous injections of Lovenox were given until hospital discharge or for a maximum of eight days (whichever came first). The mean treatment duration for Lovenox was 6.6 days. The mean treatment duration of unfractionated heparin was 54 hours. When percutaneous coronary intervention was performed during study medication period, patients received antithrombotic support with blinded study drug. For patients on Lovenox, the PCI was to be performed on Lovenox (no switch) using the regimen established in previous studies, i.e. no additional dosing, if the last subcutaneous administration was less than 8 hours before balloon inflation, intravenous bolus of 0.3 mg/kg Lovenox if the last subcutaneous administration was more than 8 hours before balloon inflation. All patients were treated with aspirin for a minimum of 30 days. The primary efficacy endpoint was the composite of death from any cause or myocardial re-infarction in the first 30 days after randomization. Total follow-up was one year. The rate of the primary efficacy endpoint (death or myocardial re-infarction) was 9.9% in the Lovenox group, and 12% in the unfractionated heparin group, a 17% reduction in the relative risk.