Class: Heparins
- Low molecular weight Heparins
- LMWHs
CAS Number: 9005-49-6

Medically reviewed by Drugs.com. Last updated on Oct 13, 2020.

• Uses
• Dosage
• Cautions
• Interactions
• Pharmacokinetics
• Patient advice
• Preparations

Introduction

Anticoagulant; an LMWH.^{1 2 3 4}

Uses for Enoxaparin

Thromboprophylaxis in General/Abdominal Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing general/abdominal surgery who are at risk for thromboembolic complications.¹

The American College of Chest Physicians (ACCP) recommends pharmacologic (e.g., LMWH) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding.¹⁰⁰² In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.¹⁰⁰²

If pharmacologic prophylaxis is used in patients undergoing general surgery, ACCP states that an LMWH or low-dose heparin (“heparin” referring throughout this monograph to unfractionated heparin) is preferred.¹⁰⁰²

Because risk of venous thromboembolism is particularly high in patients undergoing abdominal or pelvic surgery for cancer, extended (4 weeks) prophylaxis with an LMWH is recommended in such patients.¹⁰⁰²

ACCP states that the recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.¹⁰⁰²

Thromboprophylaxis in Hip-Replacement, Knee-Replacement, or Hip-Fracture Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing hip-replacement surgery.^{1 2 3 5 6 7 20 21 22 27 34 35 36 37 38 1003}

Prevention of DVT and/or PE in patients undergoing knee-replacement surgery.^{1 20 22 1003}

Also has been used for thromboprophylaxis in patients undergoing hip-fracture surgery†.¹⁰⁰³

ACCP recommends routine thromboprophylaxis (with a pharmacologic and/or mechanical method) in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery†.¹⁰⁰³

Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose heparin, warfarin, aspirin) recommended by ACCP for pharmacologic prophylaxis during major orthopedic surgery.¹⁰⁰³ When selecting an appropriate thromboprophylaxis regimen, consider factors such as efficacy, safety, logistics, and compliance.¹⁰⁰³

Medical Conditions Predisposing to Thromboembolism

Prevention of DVT, which may lead to PE, in patients with severely restricted mobility during acute illness.^{1 2 3 5 6 7 20 21 22 27 34 35 36 37 1001}

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.¹⁰⁰¹

ACCP recommends anticoagulant prophylaxis (e.g., LMWH) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding.¹⁰⁰¹ Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or hospital discharge, whichever comes first.¹⁰⁰¹

Use of LMWHs also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.¹⁰⁰¹

Risk of venous thromboembolism is particularly high in patients with cancer.¹⁰⁰¹ Use of LMWH prophylaxis suggested by ACCP in cancer outpatients with solid tumors who have additional risk factors for thromboembolism, provided risk of bleeding is low.¹⁰⁰¹

Treatment and Secondary Prevention of Acute DVT and/or PE

Inpatient treatment of acute DVT with or without PE when administered in conjunction with warfarin.^{1 28 1005}

Outpatient treatment of acute DVT without PE when administered in conjunction with warfarin.^{1 28 1005}

Recommended by ACCP as an appropriate choice of anticoagulant for initial treatment of acute proximal DVT and/or PE.¹⁰⁰⁵

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment.¹⁰⁰⁵ IV heparin also may be preferred over LMWH in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.¹⁰⁰⁵

For long-term anticoagulant therapy (secondary prevention), warfarin generally preferred in patients without cancer; however, in patients with cancer, ACCP suggests use of an LMWH because of a possible reduced response to warfarin in such patients.¹⁰⁰⁵

Continue anticoagulant therapy for at least 3 months, and possibly longer depending on individual clinical situation.¹⁰⁰⁵

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Reduction in the risk of acute cardiac ischemic events (death, MI) in patients with NSTE ACS (unstable angina or non-ST-segment-elevation MI [NSTEMI]) when administered concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blocking agents [β-blockers], clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors).^{1 40 41 42 43 48 53 146 991 1100}

Initial parenteral anticoagulants with established efficacy in patients with NSTE ACS include enoxaparin, heparin, bivalirudin (only in patients managed with an early invasive strategy), and fondaparinux.¹¹⁰⁰

Also used in patients with NSTE ACS undergoing PCI to prevent thrombus formation during the procedure.⁹⁹⁴

ST-Segment-Elevation MI (STEMI)

Used as adjunctive therapy for the management of acute STEMI in patients receiving thrombolysis and being managed medically or with PCI.^{1 162 164 165 527 994}

ACCF and AHA state that patients with STEMI undergoing thrombolytic therapy should receive an anticoagulant (e.g., heparin, enoxaparin, fondaparinux) for ≥48 hours, and preferably for the duration of the index hospitalization, up to 8 days or until revascularization is performed.⁵²⁷ Enoxaparin is preferred over heparin if extended anticoagulation (>48 hours) is necessary.⁵²⁷

Adjunctive use of an LMWH in patients with acute STEMI associated with improvement in short-term clinical outcomes (e.g., death, reinfarction, recurrent ischemia) with generally similar rates of bleeding complications compared with adjunctive heparin or placebo.^{129 130 131 132 133}

Also used in patients with STEMI undergoing PCI to prevent thrombus formation during the procedure.^{1 994} There is less experience with enoxaparin in the setting of primary PCI†.⁵²⁷

Treatment of Superficial Vein Thrombosis

LMWHs also have been used for treatment of spontaneous superficial vein thrombosis (superficial thrombophlebitis)†; ACCP suggests use of prophylactic dosages for 45 days in patients with superficial vein thrombosis of ≥5 cm in length.¹⁰⁰⁵

Thromboprophylaxis in Cardiac Surgery

Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that an LMWH may be considered for thromboprophylaxis in cardiac surgery patients† with a complicated postoperative course.¹⁰⁰²

Thromboprophylaxis in Thoracic Surgery

Pharmacologic thromboprophylaxis (e.g., LMWH) recommended by ACCP in patients undergoing thoracic surgery† who are at high risk of venous thromboembolism, provided risk of bleeding is low.¹⁰⁰²

Thromboprophylaxis in Neurosurgery

LMWHs have been used for prevention of venous thromboembolism in patients undergoing craniotomy†; however, benefits of such prophylaxis may be outweighed by possible increased risk of intracranial hemorrhage.¹⁰⁰² ACCP states that LMWH prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.¹⁰⁰²

Thromboprophylaxis with LMWHs also may be considered in high-risk patients undergoing spinal surgery† (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.¹⁰⁰²

Thromboprophylaxis in Trauma

May be used for thromboprophylaxis in patients with major trauma†.¹⁰⁰² For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests use of both a pharmacologic and mechanical method of prophylaxis, unless contraindications exist.¹⁰⁰²

Treatment of Renal Vein Thrombosis

Although use of anticoagulant therapy for renal vein thrombosis† (most common cause of spontaneous venous thromboembolism in neonates) is controversial, LMWHs are suggested by ACCP as a possible treatment option in selected neonates.¹⁰¹³

Thromboprophylaxis in Acute Ischemic Stroke

Heparin anticoagulants (i.e., LMWH or heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke†; those with additional risk factors for venous thromboembolism are more likely to benefit from such prophylaxis.¹⁰⁰⁹

ACCP suggests thromboprophylaxis with an LMWH, sub-Q heparin, or intermittent pneumatic compression in patients with acute ischemic stroke† and restricted mobility; LMWH is preferred over heparin.¹⁰⁰⁹

Prophylactic-dose heparin (heparin or an LMWH) usually initiated within 48 hours of onset of stroke and continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.¹⁰⁰⁹

LMWHs also recommended by ACCP as an option for initial management of acute arterial ischemic stroke in children† until dissection and embolic causes have been excluded.¹⁰¹³ If arterial ischemic stroke is associated with dissection or a cardioembolic origin, continued anticoagulant therapy suggested.¹⁰¹³

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy†, ACCP recommends ongoing antithrombotic therapy (e.g., with an LMWH) for 3 months.¹⁰¹³

LMWHs may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source†.¹⁰¹³

Thromboembolism During Pregnancy

Used during pregnancy for prevention and treatment of venous thromboembolism†, and for prevention and treatment of systemic embolism associated with mechanical heart valves.^{138 996 1012} (See Treatment and Prevention of Thromboembolism During Pregnancy under Dosage and Administration.)

Also has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibody (APLA) syndrome†.¹⁰¹²

LMWHs (rather than heparin or warfarin) are recommended by ACCP for prevention and treatment of thromboembolism during pregnancy†.¹⁰¹²

In pregnant women with an acute venous thromboembolic event†, ACCP recommends an LMWH for initial treatment and secondary prevention throughout the remainder of the pregnancy.¹⁰¹² To prevent recurrence of postpartum anticoagulation (for ≥6 weeks and for a total duration of ≥3 months) is suggested.¹⁰¹²

In general, thromboprophylaxis (e.g., with an LMWH) is suggested during the antepartum period only in pregnant women who have a history of thromboembolism† and are considered to be at moderate to high risk of recurrent events (e.g., those with a single episode of unprovoked venous thromboembolism, pregnancy- or estrogen-related venous thromboembolism, history of multiple unprovoked events).¹⁰¹²

Postpartum thromboprophylaxis† for 6 weeks is suggested in all pregnant women with a prior venous thromboembolic event; an LMWH (in prophylactic or intermediate dosages) or warfarin (INR 2–3) may be used for such prophylaxis.¹⁰¹²

Hereditary thrombophilias substantially increase risk of pregnancy-related venous thromboembolism; a family history of venous thromboembolism further increases risk.¹⁰¹² ACCP suggests antepartum and postpartum prophylaxis with an LMWH in some pregnant women with high-risk hereditary thrombophilias (e.g., homozygous genetic mutations for factor V Leiden or prothrombin G20210A) who have not experienced a prior venous thromboembolic event, but have a family history of thromboembolism†.¹⁰¹²

An LMWH has been used in combination with low-dose aspirin for prevention of pregnancy loss in women with antiphospholipid antibodies (APLA) syndrome and recurrent (3 or more) pregnancy loss†.^{138 1012}

Discontinue LMWH therapy ≥24 hours prior to induction of labor or cesarean section (or expected time of neuraxial anesthesia) to avoid an unwanted anticoagulant effect on fetus.¹⁰¹²

Cardioversion of Atrial Fibrillation/Flutter

LMWHs have been used for prevention of stroke and systemic embolism in patients with atrial fibrillation or atrial flutter undergoing electrical or pharmacologic cardioversion†.^{999 1007}

As an alternative to prolonged anticoagulation (e.g., usually with warfarin) prior to cardioversion in patients with atrial fibrillation lasting >48 hours or of unknown duration, LMWHs (in therapeutic dosages) may be used at the time of transesophageal echocardiography (TEE), followed by cardioversion within 24 hours if no thrombus is detected.^{999 1007}

In patients with atrial fibrillation of short duration (e.g., ≤48 hours), LMWHs (in therapeutic dosages) may be used at presentation, followed by immediate cardioversion.¹⁰⁰⁷

In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of a parenteral anticoagulant (in therapeutic dosages) prior to cardioversion, if possible; however, such anticoagulant therapy must not delay any emergency intervention.^{999 1007}

After successful cardioversion to sinus rhythm, all patients should receive therapeutic anticoagulation for ≥4 weeks.^{999 1007}

Thromboprophylaxis in Patients with Prosthetic Heart Valves

Used during conversion to maintenance therapy with warfarin to reduce the incidence of thromboembolism in patients with prosthetic mechanical heart valves†.^{64 83 87 90 93 97 98 1008}

ACCP suggests bridging anticoagulation (an LMWH in either prophylactic or therapeutic dosages or IV heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve in patients without bleeding risk, until an adequate response to warfarin is obtained.¹⁰⁰⁸

Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., those undergoing major surgery).¹⁰⁰⁴

Has been used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves†.^{138 1012} (See Thromboembolism During Pregnancy under Uses.)

Venous Thromboembolism in Pediatric Patients

An LMWH has been used for treatment and secondary prevention of venous thromboembolism in pediatric patients†; venous thromboembolism usually occurs secondary to an identifiable risk factor (e.g., presence of central venous access device) in such patients.¹⁰¹³

Recommendations regarding use of antithrombotic therapy in children generally based on extrapolation from adult guidelines.¹⁰¹³

ACCP recommends an LMWH or heparin for both initial and ongoing treatment of venous thromboembolism in children.¹⁰¹³ Potential advantages of an LMWH over heparin include reduced need for monitoring, lack of drug or dietary interactions, reduced risk of heparin-induced thrombocytopenia (HIT), and possible reduced risk of osteoporosis.¹⁰¹³

In children with central venous catheter-related thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation is suggested prior to removal.¹⁰¹³ If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.¹⁰¹³

Treatment of Cerebral Venous Sinus Thrombosis

May be used for the treatment of acute cerebral venous sinus (sinovenous) thrombosis† in adults.¹⁰⁰⁹ Once patient is stable, may convert to coumarin anticoagulant therapy.^{138 1009}

Reasonable to use full-dose LMWH rather than heparin for treatment of acute cerebral venous sinus thrombosis during pregnancy.¹⁰¹⁷ Prophylaxis with an LMWH during pregnancy and the postpartum period is reasonable in women with history of cerebral venous sinus thrombosis.¹⁰¹⁷

Recommended by ACCP as an option for initial and follow-up anticoagulation in children with cerebral venous sinus thrombosis† without substantial intracranial hemorrhage.¹⁰¹³ Also has been suggested for use in children with substantial hemorrhage.¹⁰¹³

LMWHs also suggested by ACCP as a treatment option for neonates with cerebral sinovenous thrombosis†.¹⁰¹³

Perioperative Antithrombotic Prophylaxis

ACCP suggests use of an LMWH or IV heparin during temporary interruption of warfarin therapy (bridging anticoagulation†) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves undergoing surgery or other invasive procedures; use and type of bridging anticoagulation depend on patient's risk of developing thromboembolism without warfarin therapy.¹⁰⁰⁴

In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.¹⁰⁰⁴

Enoxaparin Dosage and Administration

General

• Since routine coagulation parameters such as PT or aPTT are insensitive for monitoring enoxaparin activity, routine monitoring of coagulation parameters generally not required.¹

• Monitoring of anti-factor Xa levels may be helpful in high-risk groups, such as pregnant patients, patients with renal impairment, patients at extremes of weight, or if abnormal coagulation parameters or bleeding occurs during treatment.^{1 128 135}

• If an LMWH is used for anticoagulation in children, ACCP suggests that dosage be adjusted to a target anti-factor Xa level of 0.5–1 units/mL based on a sample taken 4–6 hours, or 0.5–0.8 units/mL based on a sample taken 2–6 hours, following sub-Q administration.¹⁰¹³

• In patients with unstable angina or NSTEMI, adhere precisely to intervals recommended between doses to minimize the risk of bleeding.¹ If a closure device is used, may remove sheath immediately after PCI.¹ Otherwise, if a manual compression method is used, remove vascular access sheath 6 hours following the last dose of enoxaparin sodium.¹ If continuing enoxaparin sodium therapy, administer the next scheduled dose no sooner than 6–8 hours after sheath removal.¹ Observe procedure site for signs of bleeding or hematoma formation.¹

Administration

Administer by deep sub-Q injection for most indications; do not give IM.¹

In patients with acute STEMI, administer as single-dose direct IV (“bolus”) injection followed by sub-Q administration.^{1 162} Direct IV injection† also used in selected patients with unstable angina or NSTEMI undergoing PCI.^{136 994}

When using multiple-dose vials, withdraw the dose using a tuberculin or equivalent syringe.¹

Do not mix enoxaparin with other injections or infusions.¹

IV Administration

May be administered by direct IV injection into an IV line.¹ Use multiple-dose vial for IV administration.¹

To avoid mixing IV enoxaparin with other drugs, flush IV line with a sufficient amount of 0.9% sodium chloride injection or 5% dextrose injection prior to and following IV administration of enoxaparin.¹

Sub-Q Administration

Patient should be supine during administration.^{1 17}

To avoid loss of drug when using the 30- or 40-mg prefilled syringes, do not expel air from syringe prior to injection.¹

Inject drug sub-Q into the left and right anterolateral and left and right posterolateral abdominal wall.¹

Insert the entire length of the needle into a skin fold created by the thumb and forefinger; hold the skin fold until the needle is withdrawn.¹

Alternate injection sites frequently.¹

To minimize bruising, do not massage injection sites after injection.¹

Dosage

Available as enoxaparin sodium; dosage expressed in terms of the salt.¹⁰⁰

Dosages for enoxaparin sodium or other LMWHs and heparin cannot be used interchangeably on a unit-for-unit (or mg-for-mg) basis.¹

Available as enoxaparin sodium.¹ Enoxaparin sodium has an approximate anti-factor Xa activity of 100 units/mg using the WHO First International Low Molecular Weight Heparin Reference Standard.¹

Adults

Prevention of DVT and/or PE

General/Abdominal Surgery

Sub-Q

40 mg once daily initiated 2 hours prior to surgery.¹

Usual duration of therapy is 7–10 days, although up to 12 days of treatment has been well tolerated in clinical trials.^{1 71}

Extended prophylaxis (for up to 4 weeks) recommended by ACCP in patients undergoing abdominal or pelvic surgery for cancer.¹⁰⁰²

Hip-Replacement Surgery

Sub-Q

30 mg every 12 hours initiated 12–24 hours after surgery, provided hemostasis has been established.¹

Alternatively, may consider dosage of 40 mg once daily, initiated approximately 12 hours before surgery.¹

Because of risk of bleeding, ACCP recommends that LMWHs be initiated at least 12 hours preoperatively or at least 12 hours postoperatively in patients undergoing major orthopedic surgery.¹⁰⁰³

Continue prophylaxis throughout the postoperative period, generally for 7–10 days, until risk of DVT has diminished; manufacturer states that up to 14 days of thromboprophylaxis was well tolerated in clinical trials.¹

Following the initial phase of thromboprophylaxis during the acute postoperative period, manufacturer recommends continued prophylaxis with 40 mg once daily for 3 weeks.¹⁵⁰

ACCP recommends a minimum of 10–14 days of thromboprophylaxis, and suggests extending prophylaxis for up to 35 days on an outpatient basis.¹⁰⁰³

Knee-Replacement Surgery

Sub-Q

30 mg every 12 hours initiated 12–24 hours after surgery, provided hemostasis has been established.¹

Because of risk of bleeding, ACCP recommends that LMWHs be initiated at least 12 hours preoperatively or 12 hours postoperatively in patients undergoing major orthopedic surgery.¹⁰⁰³

Continue prophylaxis throughout the postoperative period, generally for 7–10 days, until risk of DVT has diminished; manufacturer states that up to 14 days of thromboprophylaxis was well tolerated in clinical trials.¹

ACCP recommends a minimum of 10–14 days of thromboprophylaxis, and suggests extending prophylaxis for up to 35 days on an outpatient basis.¹⁰⁰³

Medical Conditions Predisposing to Thromboembolism

Sub-Q

Acute illness with severely restricted mobility (e.g., cancer, heart failure, severe lung disease, patients confined to bedrest): 40 mg once daily.¹ Usual duration of therapy is 6–11 days; well tolerated for up to 14 days in clinical trials.¹

ACCP suggests against the use of extended thromboprophylaxis beyond the period of patient immobilization or acute hospital stay in acutely ill medical patients.¹⁰⁰¹

Treatment of DVT with or without PE

Sub-Q

Outpatient treatment at home in patients without PE: 1 mg/kg every 12 hours.^{1 29}

Inpatient (hospital) treatment in patients with or without PE (who are not candidates for outpatient treatment): 1 mg/kg every 12 hours or 1.5 mg/kg once daily at the same time every day.¹

Average duration of therapy is 7 days, although up to 17 days of treatment has been well tolerated in clinical trials.¹

Initiate concurrent warfarin therapy when appropriate, usually within 72 hours of enoxaparin injection.¹ ACCP recommends initiating warfarin on the first treatment day and overlapping therapy with warfarin and enoxaparin for ≥5 days and until the INR is at least 2 for ≥24 hours.¹⁰⁰⁵

NSTE ACS

Sub-Q

1 mg/kg every 12 hours in conjunction with aspirin therapy (100–325 mg once daily).¹

Initiate as soon as possible after hospital admission.⁹⁹¹ Administer for a minimum of 2 days and continue until clinical stabilization.^{1 41 42}

Usual duration of treatment is 2–8 days, although up to 12.5 days of treatment has been well tolerated in clinical trials.^{1 41 42}

Patients undergoing PCI who have not received prior anticoagulant therapy: ACCF/AHA/SCAI state that it is reasonable to administer enoxaparin sodium (e.g., 0.5–0.75 mg/kg by direct IV injection) at the time of PCI†.⁹⁹⁴

Patients in whom sub-Q enoxaparin has been initiated prior to PCI (“upstream”): ACCF/AHA/SCAI state that an additional 0.3-mg/kg dose of enoxaparin sodium should be given by direct IV injection at the time of PCI if fewer than 2 prior therapeutic (e.g., 1 mg/kg) sub-Q doses of enoxaparin sodium have been given or if the last sub-Q dose of the drug was administered 8–12 hours before PCI†.⁹⁹⁴

To minimize the possibility of bleeding associated with vascular (e.g., vascular access sheath) instrumentation (e.g., PCI), adhere strictly to dosage intervals and observe precautions in removing vascular access sheath.¹ Administer next dose of enoxaparin sodium no sooner than 6–8 hours after removal of vascular access sheath;¹ ACCF/AHA/SCAI suggest removal of femoral sheath when ACT falls to <150–180 seconds or aPTT falls to <50 seconds.⁹⁹⁴ Monitor vascular access sites carefully for signs of bleeding or hematoma formation after removal of vascular sheath and during enoxaparin treatment.¹

STEMI

IV, then Sub-Q

Initial dose in patients <75 years of age: 30 mg by direct IV injection. Follow with 1 mg/kg sub-Q every 12 hours (maximum 100 mg per dose for each of the first 2 sub-Q doses, then 1 mg/kg per dose thereafter);¹ give first sub-Q dose immediately after direct IV dose.¹ (See Geriatric Patients under Dosage and Administration for dosing recommendations in patients ≥75 years of age.)

When used with thrombolytic therapy, initiate enoxaparin therapy 15 minutes before to 30 minutes after initiation of thrombolytic therapy.¹

Manufacturer states optimal duration not known but likely to be >8 days; enoxaparin therapy was continued for 8 days or until hospital discharge in clinical trials.¹

Use in conjunction with aspirin therapy (75–325 mg once daily) unless contraindicated.¹

Patients undergoing PCI: If last sub-Q dose of enoxaparin sodium was administered ≥8 hours before PCI, manufacturer recommends an additional 0.3-mg/kg dose by direct IV injection during PCI.^{1 166 167}

To minimize the possibility of bleeding associated with vascular (e.g., vascular access sheath) instrumentation (e.g., PCI), adhere strictly to dosage intervals and observe precautions in removing vascular access sheath.¹ Administer next dose of enoxaparin sodium no sooner than 6–8 hours after removal of vascular access sheath.¹ ACCF/AHA/SCAI suggest removal of femoral sheath after PCI when ACT falls to <150–180 seconds or aPTT falls to <50 seconds.⁹⁹⁴ Monitor vascular access sites carefully for signs of bleeding or hematoma formation after removal of vascular sheath and during enoxaparin treatment.¹

Treatment and Prevention of Thromboembolism During Pregnancy†

Sub-Q

Treatment of acute venous thromboembolism: 1 mg/kg every 12 hours for the remainder of pregnancy; continue anticoagulation for ≥6 weeks postpartum (minimum total duration of 3 months).¹⁰¹²

Postpartum prophylaxis in pregnant women with a prior venous thromboembolic event: Prophylactic (40 mg once daily) or intermediate (40 mg every 12 hours) dosage suggested.¹⁰¹²

Pregnant women receiving long-term coumarin anticoagulation (e.g., warfarin): An LMWH may be used throughout pregnancy in a weight-adjusted dosage (e.g., enoxaparin sodium 1 mg/kg every 12 hours) or 75% of a weight-adjusted dosage; resume long-term anticoagulation postpartum.¹⁰¹²

Primary prevention of venous thromboembolism in pregnant women with high-risk thrombophilias: Prophylactic (40 mg once daily) or intermediate (40 mg every 12 hours) dosage suggested.¹⁰¹²

Pregnant women with APLA syndrome: Antepartum administration of an LMWH in prophylactic dosages recommended by ACCP; combine with low-dose aspirin (75–100 mg daily).¹⁰¹²

Pregnant women with mechanical heart valves: ACCP recommends an LMWH throughout pregnancy or, alternatively, an LMWH until 13th week of pregnancy, substituting warfarin until close to delivery, then resuming LMWH therapy.¹⁰¹² Twice-daily administration recommended because of altered pharmacokinetics in pregnant women, with adjustment of enoxaparin sodium dosage to maintain anti-factor Xa levels of 0.7–1.2 units/mL 4 hours after dosing.⁹⁹⁶ Resume usual long-term anticoagulation postpartum.¹⁰¹² (See Patients with Mechanical Heart Valves under Cautions.)

Consider use of a shorter-acting anticoagulant as delivery approaches.¹ To avoid an unwanted anticoagulant effect on the fetus during delivery, discontinue LMWH ≥24 hours prior to induction of labor or cesarean section.¹⁰¹²

Cardioversion of Atrial Fibrillation/Flutter†

Sub-Q

For prevention of stroke and systemic embolism in patients undergoing cardioversion for atrial fibrillation or atrial flutter†, use of full venous thromboembolism treatment dosages recommended.¹⁰⁰⁷

Perioperative Antithrombotic Prophylaxis†

Sub-Q

For bridging anticoagulation during temporary interruption of warfarin therapy in patients undergoing surgery or other invasive procedures, ACCP generally recommends therapeutic dosages of a LMWH (e.g., enoxaparin sodium 1 mg/kg twice daily or 1.5 mg/kg once daily).¹⁰⁰⁴

Special Populations

Hepatic Impairment

No special population dosage recommendations at this time.¹

Renal Impairment

Use with caution in renally impaired patients.^{1 3 128} No dosage adjustments necessary in patients with mild (Cl_cr 50–80 mL/minute) or moderate (Cl_cr 30–50 mL/minute) renal impairment.¹

Adjust dosage for patients with severe renal impairment (Cl_cr <30 mL/minute).^{1 1000}

DVT and/or PE

Thromboprophylaxis in General/Abdominal Surgery

Sub-Q

In patients with severe renal impairment (Cl_cr <30 mL/minute), 30 mg once daily.¹

Thromboprophylaxis in Hip- or Knee-Replacement Surgery

Sub-Q

In patients with severe renal impairment (Cl_cr <30 mL/minute), 30 mg once daily.¹

Thromboprophylaxis in Medical Conditions Associated with Thromboembolism

Sub-Q

In patients with severe renal impairment (Cl_cr <30 mL/minute), 30 mg once daily.¹

Treatment of DVT with or without PE

Sub-Q

In patients with severe renal impairment (Cl_cr <30 mL/minute), 1 mg/kg once daily in conjunction with warfarin therapy.¹

NSTE ACS

Sub-Q

In patients with severe renal impairment (Cl_cr <30 mL/minute), 1 mg/kg once daily with concurrent aspirin therapy (100–325 mg once daily).¹

STEMI

IV and Sub-Q

In patients with severe renal impairment (Cl_cr <30 mL/minute) who are <75 years of age: 30 mg as a single direct IV dose, followed by 1 mg/kg sub-Q once daily (not to exceed 100 mg per dose for the first 2 sub-Q doses) with concurrent aspirin therapy (75–325 mg daily).¹

Sub-Q

In patients with severe renal impairment (Cl_cr <30 mL/minute) who are ≥75 years of age: 1 mg/kg once daily (not to exceed 75 mg per dose for the first 2 doses) (no initial direct IV dose) with concurrent aspirin therapy (75–325 mg daily).¹

Geriatric Patients

Use with caution; careful attention to dosing intervals and concomitant medications (particularly antiplatelet drugs) advised.¹

Manufacturer states that no dosage adjustment necessary in geriatric patients for uses other than STEMI unless renal function is impaired.¹

Patients ≥75 years of age with STEMI: 0.75 mg/kg sub-Q every 12 hours (maximum dose 75 mg for each of the first 2 doses only, then 0.75 mg/kg per dose thereafter); do not administer an initial direct IV dose.¹ Give in conjunction with aspirin therapy unless contraindicated.^{1 71}

Low-Weight Patients

Carefully monitor for signs and symptoms of bleeding in patients with low body weight (women <45 kg or men <57 kg).^{1 71}

Obese Patients

Safety and efficacy of thromboprophylactic doses in patients with body mass index (BMI) >30 kg/m² not established; closely monitor for signs and symptoms of thromboembolism in such patients.¹

Cautions for Enoxaparin

Contraindications

• Active major bleeding.¹

• Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of the drug.¹

• Known hypersensitivity to enoxaparin sodium (e.g., pruritus, urticaria, anaphylactic/anaphylactoid reactions), heparin, pork products, benzyl alcohol, or any ingredient in the formulation.¹

Warnings/Precautions

Spinal/Epidural Hematomas

Epidural or spinal hematoma reported with concurrent use of anticoagulants (e.g., LMWHs, heparinoids) and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.^{1 161 163} Such hematomas have resulted in neurologic injury, including long-term or permanent paralysis.^{1 161} (See Boxed Warning.)

Prior to performing a spinal or epidural procedure, determine whether a patient is receiving anticoagulants.¹⁶¹

Carefully consider the timing of spinal catheter placement and removal in relation to anticoagulant use, considering both dosage and pharmacokinetic properties (e.g., elimination half-life) of the anticoagulant.^{1 161}

Insertion or removal of catheter is best performed when the anticoagulant effect of enoxaparin is minimal (e.g., at least 12 hours after a low dose [30 mg once or twice daily or 40 mg once daily] or at least 24 hours after a high dose [0.75 mg/kg twice daily, 1 mg/kg twice daily, or 1.5 mg/kg once daily]).^{1 161} In patients receiving a twice-daily treatment dosage (0.75 or 1 mg/kg twice daily), omit second dose to allow for a longer delay between doses.¹ Consider doubling these recommended time delays in patients with renal impairment.¹

Consider delaying subsequent dose of enoxaparin for at least 4 hours after catheter removal based on patient's risk of bleeding versus thrombosis.^{1 161}

Frequently monitor for signs of neurologic impairment (e.g., midline back pain, numbness or weakness in lower limbs, bowel or bladder dysfunction).¹ If spinal hematoma suspected, diagnose and treat immediately; consider spinal cord decompression even though it may not prevent or reverse neurologic sequelae.¹

Other Warnings Related to Hemorrhage

As with other anticoagulants, bleeding may occur at any site during therapy.¹ Major (sometimes fatal) hemorrhages, including retroperitoneal and intracranial bleeding, have been reported.¹ Search for bleeding site if an unexplained decrease in hematocrit or BP occurs.¹

Use with extreme caution in patients with an increased risk of hemorrhage.¹ Such patients include those with bacterial endocarditis; congenital or acquired bleeding disorders; active ulceration and angiodysplastic GI disease; hemorrhagic stroke; or recent brain, spinal, or ophthalmologic surgery.¹ Increased risk for hemorrhage in patients treated concomitantly with platelet inhibitors.¹

Use with caution in patients with bleeding diathesis, uncontrolled arterial hypertension, or a history of recent GI ulceration, diabetic retinopathy, renal dysfunction, or hemorrhage.¹

Periodic CBCs, including platelet counts, and stool occult blood tests recommended.¹ If abnormal coagulation parameters or bleeding occurs, may use anti-factor Xa levels to monitor anticoagulant effects of enoxaparin.¹

Carefully monitor patients with low body weight or renal impairment for signs and symptoms of bleeding.¹

Women treated with an LMWH with or without a GP IIb/IIIa-receptor inhibitor prior to PCI appear to experience more bleeding complications than do men.¹³⁵

If enoxaparin overdosage occurs, protamine sulfate may be administered.¹ Because fatal reactions resembling anaphylaxis have been reported with protamine sulfate administration, use only when resuscitation techniques and treatment for anaphylactic shock are readily available.¹

To minimize risk of bleeding during percutaneous revascularization procedures, adhere precisely to recommended dosing intervals.¹ Ensure hemostasis at puncture site after PCI; observe for signs of bleeding or hematoma formation.¹ If arterial closure device used, may remove sheath immediately; if manual compression used, remove sheath 6 hours after last dose of enoxaparin.¹ Administer next scheduled dose no sooner than 6–8 hours after sheath removal.¹

Thrombocytopenia

Cases of HIT with thrombosis reported, including complications such as organ infarction, limb ischemia, or death.¹ Use with extreme caution in patients with a history of HIT.¹ Monitor thrombocytopenia of any degree closely.¹ If platelet count falls to <100,000/mm³, discontinue enoxaparin.¹

Interchangeability with Other Heparins

Cannot use enoxaparin sodium interchangeably with other LMWHs or heparin sodium because of differences in manufacturing process, molecular weight distribution, anti-factor Xa and anti-factor II_a activities, dosage units, and dosage.¹ (See Dosage under Dosage and Administration.)

Patients with Mechanical Prosthetic Heart Valves

Valve thrombosis that resulted in death and/or required surgical intervention reported during prophylaxis in some patients with mechanical prosthetic heart valves, including pregnant women.^{1 68 69 70 71 82 83 85 87 90} Women with mechanical prosthetic heart valves are at higher risk for thromboembolism during pregnancy.^{1 85} If enoxaparin is used in pregnant women with mechanical prosthetic heart valves, monitor peak and trough anti-factor Xa concentrations frequently and adjust dosage if necessary to maintain anti-factor Xa levels of 0.7–1.2 units/mL 4 hours after dosing.^{1 71 82 83 93}

Specific Populations

Pregnancy

Category B.¹ Because benzyl alcohol may cross the placenta, enoxaparin in multiple-dose vials containing benzyl alcohol should be used with caution and only if clearly needed in pregnant women.¹

Maternal and neonatal hemorrhage has occurred; potentially fatal.¹ Monitor pregnant women carefully for evidence of bleeding or excessive anticoagulation.¹ As delivery approaches, consider use of a shorter-acting anticoagulant.¹ (See Boxed Warning.)

Lactation

Not known whether enoxaparin is distributed into breast milk.¹ Discontinue nursing or the drug.¹ ACCP recommends that LMWHs be continued in nursing women who are already receiving such therapy.¹⁰¹²

Pediatric Use

Safety and efficacy not established.^{1 17}

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) has been associated with toxicity in neonates;^{1 80 81} each mL of enoxaparin sodium injection in multiple-dose vials contains 15 mg of benzyl alcohol as a preservative.¹

Geriatric Use

Use with caution.¹ No substantial differences in efficacy relative to younger adults.¹ Possible increased risk of bleeding complications.¹ Pay careful attention to dosing intervals and concomitant medications (especially antiplatelet medications).¹ Consider monitoring (i.e., with anti-factor Xa assay) geriatric patients with low body weight (<45 kg) and those predisposed to decreased renal function.¹

Renal Impairment

Use with caution; carefully monitor for manifestations of bleeding.¹ Monitor anti-factor Xa concentrations in patients with appreciable renal impairment.¹ Hyperkalemia reported in patients with renal failure receiving enoxaparin.¹

Decreased clearance.¹ Dosage adjustments necessary in patients with severe renal impairment. ^{1 128} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Elevated serum AST, ALT concentrations, hemorrhage (including at injection site), anemia, fever, peripheral edema.¹

Interactions for Enoxaparin

Drugs Affecting Hemostasis

Potential pharmacodynamic interaction with concomitant use of anticoagulants, platelet-aggregation inhibitors, or other drugs affecting hemostasis (increased risk of bleeding complications).¹ Use with caution.¹

Specific Drugs

Enoxaparin Pharmacokinetics

Absorption

Bioavailability

Mean absolute bioavailability of approximately 100% (based on anti-factor Xa activity) when given sub-Q in healthy individuals.¹

Onset

Maximum anti-factor Xa and antithrombin (anti-factor II_a) activities occur 3–5 hours after administration.¹

Direct IV injection of 30 mg immediately followed by 1 mg/kg dose sub-Q resulted in postinjection aPTT of 50 seconds.¹

Duration

Substantial anti-factor Xa activity persists in plasma for about 12 hours following administration (40 mg once daily).¹

Average aPTT prolongation on day 1 about 16% higher than on day 4.¹

Distribution

Extent

About 4.3 L (based on anti-factor Xa activity).¹

Enoxaparin does not appear to cross the placenta; not known whether the drug is distributed into milk.¹

Elimination

Metabolism

Metabolized, principally in the liver via desulfation and/or depolymerization, to less active metabolites.¹

Elimination Route

40% of dose is excreted in urine.¹

Half-life

4.5 hours after single sub-Q dose, approximately 7 hours after multiple dosing (based on anti-factor Xa activity).¹

Special Populations

Clearance reduced in patients with renal impairment.¹ In patients with severe renal impairment (Cl_cr <30 mL/minute), anti-factor Xa exposure (represented by AUC) was increased by approximately 65%.¹

Possible delayed elimination and increased exposure in geriatric patients.^{1 3}

Stability

Storage

Parenteral

Solution for Injection

25°C (may be exposed to 15–30°C).¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Actions

• Has less effect than heparin on thrombin at a given level of anti-factor Xa activity.^{1 2 17}

• Prolongs some global clotting function tests (i.e., thrombin time, activated partial thromboplastin time [aPTT]) by up to 1.8 times the control value.¹ At a recommended dosage in a large clinical trial, the aPTT was ≤45 seconds in most treated patients.¹

Advice to Patients

• Importance of advising patients who have had neuraxial anesthesia or spinal puncture to monitor for manifestations of spinal or epidural hematoma (e.g., tingling or numbness in lower limbs, muscle weakness), particularly if they are receiving concomitant NSAIAs, platelet-aggregation inhibitors (e.g., clopidogrel), or other anticoagulants; importance of immediately contacting a clinician if any of these symptoms occur.¹

• If therapy is to continue after hospital discharge, importance of instructing patient on proper injection technique of enoxaparin.¹

• Importance of informing patients that they may bruise and/or bleed more easily and that a longer than normal time may be required to stop bleeding when taking enoxaparin.¹ Importance of patients reporting any unusual bleeding, bruising, or signs of thrombocytopenia (e.g., dark red spots under skin) to clinician.¹

• Importance of patients informing clinicians (including dentists) that they are receiving enoxaparin therapy before scheduling any invasive procedures.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Medical Disclaimer