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Enoxaparin Sodium

Pronunciation: ee-nox-AP-a-rin SOE-dee-um
Class: Low molecular weight heparin (LMWH)

Trade Names

- Injection 30 mg per 0.3 mL
- Injection 40 mg per 0.4 mL
- Injection 60 mg per 0.6 mL
- Injection 80 mg per 0.8 mL
- Injection 100 mg/mL
- Injection 120 mg per 0.8 mL
- Injection 150 mg/mL
- Injection 300 mg per 3 mL

Lovenox HP (Canada)


Causes higher anti–factor Xa to antithrombin activities (anti-factor IIa) ratio than heparin, which may prevent thrombosis.



Bioavailability is approximately 100%. T max 3 to 5 h after subcutaneous injection.


Vd is approximately 4.3 L (for anti–factor Xa activity).


Metabolized in the liver by desulfation and/or depolymerization to low molecular weight species.


Cl is approximately 15 mL/min. Elimination half-life is 4.5 h (single dose) to 7 h (repeat dosing) (based on anti–factor Xa activity).

Special Populations

Renal Function Impairment

AUC increased 65% in patients with severe renal impairment (CrCl less than 30 mL/min).

Hepatic Function Impairment

Pharmacokinetic studies have not been conducted.


The 10-day mean AUC was about 15% higher than the mean day 1 AUC value.


Apparent clearance and maximum observed activity derived from anti–factor Xa values following subcutaneous dosing were slightly higher in men than in women.


Mean AUC of anti–Factor Xa activity is marginally higher at steady state in obese healthy patients. Anti–factor Xa exposure was found to be 52% higher in low-weight women (less than 45 kg) and 27% higher in low-weight men (less than 57 kg).

Indications and Usage

Prevention of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing hip or knee replacement surgery or abdominal surgery and in medical patients who are at risk for thromboembolic complications because of severely restricted mobility during an acute illness; in conjunction with warfarin for inpatient treatment of acute DVT with or without PE, or outpatient treatment of acute DVT without PE; prevention of ischemic complications of unstable angina and non–Q-wave MI when coadministered with aspirin; treatment of acute ST-segment elevation MI (STEMI) in patients receiving thrombolysis and being managed medically or with percutaneous coronary intervention (PCI).

Unlabeled Uses

Prevention of exercise-induced bronchorestriction; venous thromboembolism; prophylaxis in cancer patients with central venous catheters; venous thromboembolism prophylaxis in general surgery and/or gynecologic surgery.


Hypersensitivity to enoxaparin, heparin, benzyl alcohol (multidose formulation only), or pork products; active major bleeding; thrombocytopenia associated with positive in vitro test for antiplatelet antibody in the presence of enoxaparin.

Dosage and Administration

Abdominal Surgery

Subcutaneous 40 mg/day with the initial dose given 2 h prior to surgery. Usual duration of administration is 7 to 10 days; up to 12 days has been administered in clinical trials.

Acute Illness

Subcutaneous 40 mg every day for 6 to 11 days; up to 14 days has been administered in clinical trials.


IV/Subcutaneous Single IV bolus of 30 mg plus a 1 mg/kg subcutaneous dose followed by 1 mg/kg every 12 h (max, 100 mg for first 2 doses only, followed by 1 mg/kg dosing for the remaining doses). All patients identified as having STEMI should also receive aspirin 75 to 325 mg once daily unless contraindicated.

DVT/PE Treatment
Adults, Outpatient

Subcutaneous 1 mg/kg every 12 h.

Adults, Inpatient

Subcutaneous 1 mg/kg every 12 h or 1.5 mg/kg every day given at the same time each day.

Adults, Outpatient and Inpatient

Initiate warfarin therapy when appropriate (usually within 72 h of enoxaparin). Continue enoxaparin for a minimum of 5 days and until a therapeutic anticoagulant effect has been achieved. The average duration is 7 days; up to 17 days has been administered in clinical trials.

Hip or Knee Replacement Surgery

Subcutaneous 30 mg twice daily, with initial dose given within 12 to 24 h postoperatively, provided hemostasis has been established. Average duration of administration is 7 to 10 days; up to 14 days has been administered in clinical trials. For hip replacement surgery, 40 mg every day, given initially 9 to 15 h prior to surgery, may be considered; continue prophylaxis for 3 wk.

Unstable Angina/Non–Q-Wave MI

Subcutaneous 1 mg/kg every 12 h in conjunction with oral aspirin therapy (100 to 325 mg every day); usual duration of treatment is 2 to 8 days; up to 12.5 days has been administered in clinical trials.

Renal Function Impairment

Subcutaneous Dosage adjustments for patients with severe renal impairment (CrCl less than 30 mL/min) are as follows:

Prophylaxis in abdominal surgery or hip or knee replacement surgery; prophylaxis in medical patients during acute illness

Subcutaneous 30 mg once daily.

Inpatient DVT with or without PE in conjunction with warfarin; outpatient treatment of DVT without PE in conjunction with warfarin; prophylaxis of ischemic complications of unstable angina and non–Q-wave MI in conjunction with aspirin; acute STEMI in patients 75 yr of age or older in conjunction with aspirin (no initial bolus)

Subcutaneous 1 mg/kg once daily.

Acute STEMI in patients younger than 75 yr of age in conjunction with aspirin

30 mg IV bolus plus 1 mg/kg subcutaneously, followed by 1 mg/kg subcutaneously once daily.


For treatment of acute STEMI in elderly patients 75 years of age and older, do not use an initial IV bolus. Initiate dosing with 0.75 mg/kg subcutaneous every 12 h (max, 75 mg for the first 2 doses only, followed by 0.75 mg/kg dosing for the remaining doses).

General Advice

  • Enoxaparin is a clear, colorless to pale yellow solution and should be inspected visually for particulate matter and discoloration prior to administration.
  • For subcutaneous or IV bolus injection. Do not administer by IM injection.
  • With patient lying down, administer by subcutaneous injection. Alternate administration between left and right anterolateral and posterolateral abdominal wall. Introduce whole length of needle into skinfold held between thumb and forefinger; hold skinfold throughout injection.
  • Do not aspirate into syringe; do not rub site after injection. These activities may cause tissue damage and subcutaneous bleeding.
  • For IV injection, use the multidose vial. Flush IV access with saline or dextrose solution prior to and following the IV bolus of enoxaparin to clear the port of the drug.
  • Do not mix or coadminister with other injections or infusions. For IV use, enoxaparin can be mixed with saline 0.9% solution or dextrose 5% in water.


Store at 59° to 86°F. Do not store multidose vials for more than 28 days after the first use.

Drug Interactions


The risk of severe bleeding may be increased. Close clinical and laboratory monitoring (aPTT and/or anti-Xa) is indicated during coadministration of enoxaparin and antithrombin. Adjust the dose of enoxaparin accordingly. Reduced doses of enoxaparin are recommended when coadministered with antithrombin III.

Drugs that increase the risk of bleeding (eg, oral anticoagulants [eg, warfarin], platelet inhibitors [eg, dipyridamole], NSAIDs, salicylates, sulfinpyrazone, ticlopidine)

Use enoxaparin with caution because of increased risk of hemorrhagic reactions.

SSRIs (eg, fluoxetine)

The risk of severe bleeding may be increased. Carefully monitor the coagulation status of the patient and observe the patient for bleeding. Adjust therapy as needed.

Adverse Reactions


Atrial fibrillation, heart failure (1%).


Cutaneous vasculitis, purpura, skin necrosis occurring at the injection site or distant from the injection, vesiculobullous rash (postmarketing).


Nausea (3%); diarrhea (2%).


Anemia (16%); hemorrhage (13%); major bleeding (4%); thrombocytopenia (3%); thrombocytopenia with thrombosis, thrombocytosis (postmarketing).


Systemic allergic reactions including anaphylactic/anaphylactoid reactions, pruritus, and urticaria (postmarketing).

Lab Tests

Increased AST and ALT more than 3 times ULN (6%); hyperkalemia, hyperlipidemia, hypertriglyceridemia (postmarketing).


Injection-site hemorrhage (5%); ecchymosis (3%); injection-site pain (2%); erythema, hematoma, mild local irritation, pain; injection-site reactions, including inflammation, nodules, and oozing (postmarketing).


Dyspnea (3%); lung edema, pneumonia (1%).


Fever (8%); peripheral edema (6%); confusion, edema, hematuria (2%); epidural or spinal hematoma (postmarketing).



Spinal/Epidural hematomas

Risk of spinal/epidural hematoma increased in patients receiving neuraxial anesthesia or spinal puncture and who are anticoagulated with LMWH or heparinoids. Other risk factors include indwelling epidural catheters, history of repeated or traumatic epidural or spinal puncture, history of spinal deformity or spinal surgery, or concomitant use of other drugs affecting hemostasis (eg, NSAIDs, platelet inhibitors, anticoagulants). Risk of long-term or permanent paralysis.


Periodic CBCs, including platelet count, and stool occult blood tests are recommended. Anti-factor Xa may be used to monitor the anticoagulant effect in patients with significant renal impairment or in patients who develop abnormal coagulation parameters or bleeding. Monitor frequently for signs/symptoms of neurological impairment. Monitor thrombocytopenia of any degree. Observe all low-weight women (less than 45 kg), low-weight men (less than 57 kg), pregnant women, and patients with renal impairment carefully for signs and symptoms of bleeding.


Category B .




Safety and efficacy not established.


Delayed elimination and risk of bleeding possible. Use with caution. Dosage adjustment is recommended in elderly patients for the treatment of acute STEMI.

Renal Function

Delayed elimination may occur. Use with caution and adjust dosage in patients with severe renal impairment (CrCl < 30 mL/min).

Hepatic Function

Use with caution.

Special Risk Patients

Use extreme caution in patients with a history of heparin-induced thrombocytopenia; use drug with caution in patients with diabetic retinopathy, bleeding diathesis, uncontrolled arterial hypertension, or history of recent GI ulceration and hemorrhage.

Benzyl alcohol

Multiple-dose vials contain benzyl alcohol as a preservative; it has been associated with a fatal “gasping syndrome” in premature neonates.


Use with extreme caution in patients with conditions associated with increased risk of hemorrhage. Major hemorrhages, including intracranial and retroperitoneal bleeding, have been reported.

Interchangeability with heparin

Cannot be used interchangeably (unit for unit) with heparin or other LMWHs.

Low-weight patients

Use with caution in women weighing less than 45 kg and men weighing less than 57 kg.

Percutaneous coronary revascularization procedures

To minimize the risk of bleeding, adhere precisely to the recommended dosing intervals and the sheath removal recommendations.

Prosthetic heart valves

Isolated cases of prosthetic heart valve thrombosis have been reported; pregnant women with mechanical prosthetic heart valves may be at higher risk.


Use with extreme caution in patients who have a history of heparin-induced thrombocytopenia.




Patient Information

  • Inform patients who have had neuraxial anesthesia or spinal puncture, especially if they are taking concomitant NSAIDs, platelet inhibitors, or other anticoagulants, to watch for signs and symptoms of spinal or epidural hematoma, such as tingling, numbness (especially in the lower limbs), and muscular weakness, and to contact their health care provider immediately if they occur.
  • Advise patients that the use of aspirin and other NSAIDs may enhance the risk of hemorrhage.
  • Instruct patient to report any signs of bleeding or bruising; signs of thrombocytopenia (eg, a rash of dark spots under the skin); or black, bloody, or tarry stools immediately.
  • If patient has home therapy, teach patient or family member proper subcutaneous injection technique.
  • Caution patient to take safety precautions to prevent cuts and bruising (eg, use electric razor, soft toothbrush, handrails).
  • Advise patients to inform their health care providers and dentists that they are taking enoxaparin or any other product known to affect bleeding before any surgery is scheduled or before any new drug is taken.

Copyright © 2009 Wolters Kluwer Health.