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Enoxaparin Sodium

Pronunciation

Class: Heparins
CAS Number: 9005-49-6
Brands: Lovenox

Warning(s)

Special Alerts:

[Posted 11/06/2013] ISSUE: The U.S. Food and Drug Administration (FDA) is recommending that health care professionals carefully consider the timing of spinal catheter placement and removal in patients taking anticoagulant drugs, such as enoxaparin, and delay dosing of anticoagulant medications for some time interval after catheter removal to decrease the risk of spinal column bleeding and subsequent paralysis after spinal injections, including epidural procedures and lumbar punctures. These new timing recommendations, which can decrease the risk of epidural or spinal hematoma, will be added to the labels of anticoagulant drugs known as low molecular weight heparins, including Lovenox and generic enoxaparin products and similar products.

BACKGROUND: Epidural or spinal hematomas are a known risk of enoxaparin in the setting of spinal procedures and are already described in the Boxed Warning and the Warnings and Precautions sections of the labels for Lovenox and generic enoxaparin products. However, these serious adverse events continue to occur (see Data Summary). To address this safety concern, FDA worked with the manufacturer of Lovenox, Sanofi-Aventis, to further evaluate this risk and to update the Warnings and Precautions section of the Lovenox label with these additional timing recommendations. The labels for generic enoxaparin products will also be revised accordingly, as will those of other low molecular weight heparin-type products.

It is important to note that all anticoagulants carry the risk of causing spinal bleeding when used in conjunction with epidural/spinal anesthesia or spinal puncture. We are continuing to evaluate the safety of other anticoagulants to determine if additional label changes are needed.

RECOMMENDATION: Health care professionals and institutions involved in performing spinal/epidural anesthesia or spinal punctures should determine, as part of a preprocedure checklist, whether a patient is receiving anticoagulants and identify the appropriate timing of enoxaparin dosing in relation to catheter placement or removal. To reduce the potential risk of bleeding, consider both the dose and the elimination half-life of the anticoagulant:

  • For enoxaparin, placement or removal of a spinal catheter should be delayed for at least 12 hours after administration of prophylactic doses such as those used for prevention of deep vein thrombosis. Longer delays (24 hours) are appropriate to consider for patients receiving higher therapeutic doses of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily).

  • A postprocedure dose of enoxaparin should usually be given no sooner than 4 hours after catheter removal.

  • In all cases, a benefit-risk assessment should consider both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors.

For more information visit the FDA website at: and .

Warning(s)

  • Spinal/Epidural Hematoma Risk
  • Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of low molecular weight heparins (LMWHs) or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture.1 26 142

  • Risk increased by use of indwelling epidural catheters or by concomitant use of drugs affecting hemostasis (e.g., NSAIAs, platelet inhibitors, other anticoagulants).1 26 142 143

  • Risk also increased by history of traumatic or repeated epidural or spinal puncture spinal deformity, or spinal surgery.1 26

  • Monitor frequently for signs and symptoms of neurologic impairment and treat urgently if neurologic compromise noted.1 26 142 143

  • Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for thromboprophylaxis with anticoagulants.1 26 (See Hematologic Effects under Cautions.)

Introduction

Anticoagulant; an LMWH.1 2 3 4

Uses for Enoxaparin Sodium

Thromboprophylaxis in General/Abdominal Surgery

Prevention of postoperative DVT and 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 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 Hip-Replacement, Knee-Replacement, or Hip-Fracture Surgery

Prevention of postoperative DVT and 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 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 and 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

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Treatment of Acute DVT and 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 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, 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

Treatment of Superficial Vein Thrombosis

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

Unstable Angina and Non-ST Segment Elevation MI (NSTEMI)

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

Initiate anticoagulant therapy as soon as possible after hospital admission.991

In patients undergoing an invasive management strategy, the American College of Cardiology (ACC), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend use of enoxaparin, heparin, bivalirudin, or fondaparinux for anticoagulant therapy.991

In patients undergoing a conservative management strategy, recommended anticoagulants include an LMWH, heparin, or fondaparinux; fondaparinux is preferred in patients with increased risk of bleeding.991

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

Acute Ischemic Complications Following ST-Segment Elevation MI (STEMI)

Used for the treatment of patients with acute STEMI receiving thrombolysis and being managed medically or with PCI.106 150 994

Some experts state use of an LMWH also may be reasonable in patients with STEMI who are not receiving thrombolytic therapy, provided no contraindications to anticoagulation exist.106

Experts recommend use of an LMWH in combination with thrombolytic therapy and/or antiplatelet agents (e.g., aspirin, P2Y12 receptor antagonist, GP IIb/IIIa-receptor inhibitor) during and after successful coronary artery reperfusion for the prevention of ischemic complications of acute STEMI (e.g., death, reinfarction, stroke).106

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.106 129 130 131 132 133

LMWHs may be preferred over heparin in patients with acute STEMI who have preserved renal function (Scr ≤2.5 mg/dL in men or ≤2 mg/dL in women).106

Also used for prevention of systemic embolism following acute STEMI in high-risk patients (e.g., patients with large or anterior MI, atrial fibrillation, previous embolus, documented left ventricular thrombus, cardiogenic shock).106

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

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

LMWH prophylaxis 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, andfor prevention and treatment of systemic embolism associated with mechanical heart valves.138 996 1012 (See Prevention and Treatment 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

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/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

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 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

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 (bridging anticoagulation) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves who require temporary interruption of warfarin therapy during 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 Sodium 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 ST-segment elevation MI, administer as single-dose direct IV injection followed by sub-Q administration.1 Initial direct IV injection also used in selected patients with unstable angina or non-ST-segment elevation MI.136

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 World Health Organization (WHO) First International Low Molecular Weight Heparin Reference Standard.1

Adults

Prevention of DVT and 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: 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

Unstable Angina and NSTEMI
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

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

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

Acute Ischemic Complications of PCI
IV

Patients who have not received prior anticoagulant therapy: 0.5–0.75 mg/kg by direct (bolus) IV injection.994

Patients in whom sub-Q enoxaparin has been initiated prior to PCI (“upstream”): If last sub-Q dose of enoxaparin sodium was administered ≥8 hours before PCI or only 1 prior sub-Q dose given, administer an additional 0.3-mg/kg dose by direct IV injection during PCI.1 994

Prevention and Treatment 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 Dosage adjustment suggested to maintain manufacturer-recommended peak anti-factor Xa concentration 4 hours after dosing.1012 Resume usual long-term anticoagulation postpartum.1012 (See Pregnant Women with Prosthetic Heart Valves under Cautions.)

ACCP and other clinicians suggest administering LMWHs twice daily in pregnant women, at least initially, because of altered pharmacokinetics of these drugs in such women.996 1012

Consider use of a shorter-acting anticoagulant as delivery approaches.1 (See Boxed Warning.) 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

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 (Clcr 50–80 mL/minute) or moderate (Clcr 30–50 mL/minute) renal impairment.1

Adjust dosage for patients with severe renal impairment (Clcr <30 mL/minute).1 1000

DVT and PE
Thromboprophylaxis in General/Abdominal Surgery
Sub-Q

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

Thromboprophylaxis in Hip- or Knee-Replacement Surgery
Sub-Q

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

Thromboprophylaxis in Medical Conditions Associated with Thromboembolism
Sub-Q

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

Treatment of DVT with or without PE
Sub-Q

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

Unstable Angina and NSTEMI
Sub-Q

In patients with severe renal impairment (Clcr <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 (Clcr <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 (Clcr <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 ST-segment elevation MI unless renal function is impaired.1

ST-Segment Elevation MI

Patients ≥75 years of age: 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

Cautions for Enoxaparin Sodium

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

Hematologic Effects

Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of LMWHs and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.1 Frequent monitoring for signs of neurologic impairment recommended.1 (See Boxed Warning.)

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

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 blood pressure occurs.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

Cases of heparin-induced thrombocytopenia with thrombosis reported, including complications such as organ infarction, limb ischemia, or death.1 Use with extreme caution in patients with a history of heparin-induced thrombocytopenia.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 IIa activities, dosage units, and dosage.1 (See Dosage under Dosage and Administration.)

Pregnant Women with Prosthetic Heart Valves

Valve thrombosis that resulted in death and/or required surgical intervention reported during prophylaxis in pregnant women with mechanical prosthetic heart valves.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.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 Sodium

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

Drug

Interaction

Comments

Anticoagulants

Increased risk of bleeding1

No pharmacokinetic interaction noted with concomitant administration of thrombolytic agents1

If possible, discontinue other anticoagulants prior to initiating enoxaparin1

If concomitant use is essential, careful clinical and laboratory monitoring advised1

Aspirin

Increased risk of bleeding1

If possible, discontinue aspirin prior to initiating enoxaparin1

If concomitant use is essential, careful clinical and laboratory monitoring advised1

NSAIAs (e.g., ketorolac tromethamine)

Increased risk of bleeding1

If possible, discontinue NSAIAs prior to initiating enoxaparin1

If concomitant use is essential, careful clinical and laboratory monitoring advised1

Dipyridamole

Increased risk of bleeding1

If possible, discontinue dipyridamole prior to initiating enoxaparin1

If concomitant use is essential, careful clinical and laboratory monitoring advised1

Salicylates

Increased risk of bleeding1

If possible, discontinue salicylates prior to initiating enoxaparin1

If concomitant use is essential, careful clinical and laboratory monitoring advised1

Sulfinpyrazone

Increased risk of bleeding1

If possible, discontinue sulfinpyrazone prior to initiating enoxaparin1

If concomitant use is essential, careful clinical and laboratory monitoring advised1

Enoxaparin Sodium 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 IIa) 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 (Clcr <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

Compatible

Sodium chloride 0.9%

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 reporting any unexplained bleeding or bruising to clinicians.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.

Enoxaparin Sodium (Porcine)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

10 mg/0.1 mL (30, 40, 60, 80, and 100 mg)

Lovenox (available as prefilled disposable syringes)

Sanofi-Aventis

15 mg/0.1 mL (120 and 150 mg)

Lovenox (available as disposable prefilled syringes)

Sanofi-Aventis

300 mg/3 mL

Lovenox

Sanofi-Aventis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Enoxaparin Sodium 100MG/ML Solution (SANDOZ): 1/$79.99 or 3/$208.97

Enoxaparin Sodium 120MG/0.8ML Solution (SANDOZ): 1/$95.99 or 2/$259.98

Enoxaparin Sodium 150MG/ML Solution (SANDOZ): 1/$119.99 or 3/$337.99

Enoxaparin Sodium 30MG/0.3ML Solution (SANDOZ): 0/$23.99 or 1/$65.97

Enoxaparin Sodium 40MG/0.4ML Solution (SANDOZ): 0/$32.99 or 1/$80.97

Enoxaparin Sodium 60MG/0.6ML Solution (SANDOZ): 1/$46.99 or 2/$127.97

Enoxaparin Sodium 80MG/0.8ML Solution (SANDOZ): 1/$63.99 or 2/$174.96

Lovenox 100MG/ML Solution (SANOFI-AVENTIS U.S.): 10/$815.98 or 20/$1,575.96

Lovenox 150MG/ML Solution (SANOFI-AVENTIS U.S.): 10/$1,250.00 or 20/$2,399.99

Lovenox 30MG/0.3ML Solution (SANOFI-AVENTIS U.S.): 3/$259.99 or 9/$735.97

Lovenox 40MG/0.4ML Solution (SANOFI-AVENTIS U.S.): 4/$354.23 or 12/$1,038.32

Lovenox 80MG/0.8ML Solution (SANOFI-AVENTIS U.S.): 8/$649.98 or 16/$1,285.94

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 5, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Sanofi-Aventis US. Lovenox (enoxaparin sodium) injection prescribing information. Bridgewater, NJ; 2011 Apr.

2. Buckley MM, Sorkin EM. Enoxaparin: A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders. Drugs. 1992; 44:465-97. [PubMed 1382939]

3. Turpie A. Enoxaparin prophylaxis in elective hip surgery. Acta Chir Scand Suppl. 1990; 556:103-107. [PubMed 1963014]

4. Fareed J, Walenga JM, Lassen M et al. Pharmacologic profile of a low molecular weight heparin (enoxaparin): experimental and clinical validation of the prophylactic antithrombotic effects. Acta Chir Scand Suppl. 1990; 556:75-90. [PubMed 1963021]

5. Hirsh J. From unfractionated heparins to low molecular weight heparins. Acta Chir Scand Suppl. 1990; 556:42-50. [PubMed 1705072]

6. Planes A, Vochelle N, Fagola M et al. Once-daily dosing of enoxaparin (a low molecular weight heparin) in prevention of deep-vein thrombosis after total hip replacement. Acta Chir Scand Suppl. 1990; 556:108-15. [PubMed 1963015]

7. Planes A, Vochelle N, Mazas F et al. Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost. 1988; 60:407-10. [PubMed 2853459]

8. Levine MN, Hirsh J, Gent M et al. Prevention of deep-vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med. 1991; 114:545- 51. [IDIS 279488] [PubMed 1848054]

9. Haas S, Flosbach CW. Prevention of post-operative thromboembolism in general surgery with enoxaparin: preliminary findings. Acta Chir Scand Suppl. 1990; 556:96-102. [PubMed 1963023]

10. Spiro TE, Enoxaparin Clinical Trial Group. A randomized trial of enoxaparin administered post operatively for the prevention of deep-vein thrombosis following elective hip replacement surgery. Thromb Haemost. 1991; 65:927.

11. Griffiths MC, ed. USAN 1993: USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1992:238-9.

12. Bara L, Samama M. Pharmacokinetics of low molecular weight heparins. Acta Chir Scand Suppl. 1990; 556:57- 61. [PubMed 1963018]

13. Fareed J, Walenga JM, Hoppensteadt D et al. Biochemical and pharmacologic inequivalence of low molecular weight heparins. Ann N Y Acad Sci. 1989; 556:333-53. [PubMed 2544128]

14. Hoppensteadt D, Racanelli A, Walenga JM et al. Comparative antithrombotic and hemorrhagic effects of dermatan sulfate, heparan sulfate, and heparin. Semin Thromb Hemost. 1989; 15:378-85. [PubMed 2530633]

15. Fareed J, Walenga JM, Hoppensteadt D et al. Chemical and biological heterogeneity in low molecular weight heparins: implications for clinical use and standardization. Semin Thromb Hemost. 1989; 15:440-63. [PubMed 2554505]

16. Fareed J, Walenga JM, Williamson K et al. Studies on the antithrombotic effects and pharmacokinetics of heparin fractions and fragments. Semin Thromb Hemost. 1985; 11:56-74. [PubMed 3883500]

17. Rhône-Poulenc Rorer, Collegeville, PA: Personal communication.

18. Spiro TE, Colwell CW, Trowbridge AA for the Enoxaparin Clinical Trial Group. A clinical trial comparing the efficacy and safety of enoxaparin, a low molecular weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement surgery.

19. Imperiale TF, Speroff T. A meta-anlysis of methods to prevent venous thromboembolism following total hip replacement. JAMA. 1994; 271:1780-5. [IDIS 330661] [PubMed 7515115]

20. Ledere JR, Geerts WH, Desjardins L et al. Prevention of deep-vein thrombosis after major knee surgery—a randomized, double-blind trial comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb Haemost. 1992; 67:417-23. [PubMed 1321509]

21. Spiro TE, Colwell CW, Bona RD et al et al. Enoxaparin versus unfractionated heparin for prevention of venous thromboembolic disease after elective knee replacement surgery. Chest. 1994; 106(Suppl 2):48S.

22. Noble S, Peters DH, Goa KL. Enoxaparin: a reappraisal of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disease. Drugs. 1995; 49:388-410. [PubMed 7774513]

24. Heit JA, Berkowitz SD, Bona R et al. Efficacy and safety of low molecular weight heparin (ardeparin sodium) compared to warfarin for the prevention of venous thromboembolism after total knee replacement surgery: a double-blind, dose-ranging study. Thromb Haemost. 1997; 77:32-8. [IDIS 380054] [PubMed 9031445]

25. Hull R, Raskob G, Pineo G et al. A comparison of subcutaneous low-molecular weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med. 1993; 329:1370-6. [IDIS 322164] [PubMed 8413432]

26. Lumpkin MM. Dear health care professional letter regarding reports of epidural or spinal hematomas with concurrent use of low molecular weight heparins or heparinoids and spinal/epidural anesthesia or spinal puncture. Rockville, MD: US Food and Drug Administration; 1997 Dec 15.

27. ENOXACAN Study Group. Efficacy of enoxaparin versus unfractionated heparin for prevention of deep-vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg. 1997; 84:1099-103. [PubMed 9278651]

28. Dolovich LR, Ginsberg JS, Douketis JD et al. A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism. Arch Intern Med. 2000; 160:181-8. [IDIS 442244] [PubMed 10647756]

29. Levine M, Gent M, Hirsch J et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996; 334:677-81. [IDIS 361075] [PubMed 8594425]

32. Pharmacia & Upjohn, Inc. Fragmin (dalteparin sodium injection) prescribing information. Kalamazoo, MI; 1999 May.

33. Francis CW, Pelligrini VD, Totterman S et al. Prevention of deep-vein thrombosis after total hip arthroplasty: comparison of warfarin and dalteparin. J Bone Joint Surg Am. 1997; 79:1365-72. [PubMed 9314399]

34. Spiro TE, Johnson GJ, Christie MJ et al. Efficacy and safety of enoxaparin to prevent deep-vein thrombosis after hip replacement therapy. Ann Intern Med. 1994; 121:81-9. [IDIS 332861] [PubMed 8017740]

35. Planes A, Vochelle N, Darmon JY et al. Efficacy and safety of postdischarge administration of enoxaparin in the prevention of deep venous thrombosis after total hip replacement: a prospective randomised double-blind placebo-controlled trial. Drugs. 1996; 52(Suppl 7):47-54. [PubMed 9042560]

36. Bergqvist D, Benoni G, Bjorgell O et al. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996; 335:696-700. [IDIS 371704] [PubMed 8703168]

37. Horlocker TT, Heit JA. Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for reginal anesthetic management. Anesth Analg. 1997; 85:874-85. [IDIS 395935] [PubMed 9322474]

38. Davidson BL. Out-of-hospital prophylaxis with low-molecular-weight heparin in hip surgery: the Swedish study. Chest. 1998; 114(Suppl 2): 130S-2S.

40. Eikelboom JW, Anand SA, Malmberg K et al. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet. 2000; 355:1936-42. [IDIS 448634] [PubMed 10859038]

41. Cohen M, Demers C, Gurfinkel EP et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997; 337:447-52. [IDIS 389816] [PubMed 9250846]

42. Antman EM, McCabe CH, Gurfinkel EP et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 11B trial. Circulation. 1999; 100:1593-601. [IDIS 437219] [PubMed 10517729]

43. Antman EM, Cohen M, Radley D et al. Asessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction: TIMI 11B-ESSENCE meta-analysis. Circulation. 1999; 100:1602-8. [IDIS 437220] [PubMed 10517730]

44. Armstrong PW. Pursuing progress in acute coronary syndromes. Circulation. 1999; 100:1586-9. [IDIS 437218] [PubMed 10517727]

45. Hull RD, Pineo GF, Francis C et al. Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthoplasty patients: a double-blind, randomized comparison. Arch Intern Med. 2000; 160:2199-207. [IDIS 450825] [PubMed 10904464]

46. Eriksson BI, Kalebo P, Anthymyr BA et al. Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement. Comparions of low-molecular-weight heparin and unfractionated heparin. J Bone Joint Surg Am. 1991; 73:484-93. [PubMed 2013587]

47. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From and

48. Antman EM, Fox KM for the International Cardiology Forum. Guidelines for the diagnosis and management of unstable angina and non-Q-wave myocardial infarction: proposed revisions. Am Heart J; 2000;139:461-75.

49. Wallentin L. New trials of LMW heparins-light and heavy weight as good on short but what about longer distances? Eur Heart J. 1999; 20:1522-24.

50. Agency for Health Care Policy and Research. Diagnosing and managing unstable angina. 1994. (AHCPR publication no. 94-0603)

51. Cairns JA, Theroux P, Lewis D et al. Antithrombotic agents in coronary artery disease. Chest. 1998; 114(Suppl 5):611S-33S. [IDIS 416745] [PubMed 9822067]

52. Kaul S, Shah PK. Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin? J Am Coll Cardiol. 2000; 35:1699-702.

53. Klein W, Buchwald A, Hillis SE et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: Fragmin in Unstable Coronary Artery Disease Study (FRISC). Circulation. 1997; 96:61-8. [IDIS 389986] [PubMed 9236418]

54. Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet. 1996; 347:561-8. [IDIS 361634] [PubMed 8596317]

55. LeClerc JR, Geerts WH, Desjardins L et al. Prevention of venous thromboembolism after knee arthroplasty: a randomized, double-blind trial comparing enoxaparin with warfarin. Ann Intern Med. 1996; 124:619-26. [IDIS 362226] [PubMed 8607589]

56. RD Heparin Arthroplasty Group. RD Heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty. J Bone Joint Surg Am. 1994; 76:1174-85. [PubMed 8056798]

58. Gould MK, Dembitzer AD, Doyle RL et al. Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep-vein thombosis: a meta-analysis of randomized, controlled trials. Ann Intern Med. 1999; 130:800-9. [IDIS 424536] [PubMed 10366369]

64. Bonow RO, Carabello B, de Leon AC et al. ACC/AHA guidelines for the management of patients with valvular heart disease. J Am Coll Cardiol. 1998; 32:1486-588. [IDIS 417155] [PubMed 9809971]

66. Mcleod RS,, Geerts WH, Sniderman KW et al. Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery. Results of the Canadian colorectal DVT prophylaxis trials: a randomized, double-blind trial. Ann Surg. 2001; 233: 438-44. [IDIS 460439] [PubMed 11224634]

67. Samama MM,, Cohen AT, Darmon JY et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med. 1999; 341: 793-800. [IDIS 432450] [PubMed 10477777]

68. Kramer A, Gurevitch J et al. Low-molecular weight heparin for prosthetic heart valves: treatment failure. Ann Thorac Surg. 2000; 69:264-6. [IDIS 442009] [PubMed 10654529]

69. Rowan JA,, McCowan LM, Raudkivi PJ et al. Enoxaparin treatment in women with mechanical heart valves during pregnancy. Am J Obstet Gynecol. 2001; 185:633-7. [IDIS 470956] [PubMed 11568791]

70. Oles D,, Berryessa R, Campbell K et al. Emergency redo mitral valve replacement in a 27-year-old pregnant female with a clotted prosthetic mitral valve, preoperative fetal demise and postoperative ventricular assist device: a case report. Perfusion. 2001; 16:159-64. [PubMed 11334200]

71. Sanofi-Aventis US. Personal communication

72. Cohen M, Bigonzi F et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one year results of the ESSENCE study. Efficacy and safety of subcutaneous enoxaparin in non-Q wave events. J Am Coll Cardiol. 2000; 36:693-8. [IDIS 452608] [PubMed 10987586]

76. Yeghiazarians Y, Braunstein JB, Askari A. Unstable angina pectoris. N Engl J Med. 2000; 342:101-14. [IDIS 438645] [PubMed 10631280]

77. Yusuf S, Zhao F, Mehta SR et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345:494-502. [IDIS 468367] [PubMed 11519503]

78. Ridker P, Goldhaber SZ, Danielson E et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med [serial online]. 2003; 348. Available at . Accessed February 24, 2003.

79. Schafer AI. Warfarin for venous thromboembolism—walking the dosing tightrope. N Engl J Med [serial online]. 2003; 348. Editorial. Available at . Accessed February 24, 2003.

80. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12:10-1.

81. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8. (IDIS 175725) [IDIS 175725] [PubMed 6889041]

82. American College of Obstetricians and Gynecologists. ACOG Committee Opinion: safety of lovenox in pregnancy. Obstet Gynecol. 2002;100:845-6.

83. Ginsberg JS, Chan WS, Bates SM et al. Anticoagulation of pregnant women with mechanical heart valves. Arch Intern Med. 2003; 163:694-8. [IDIS 495610] [PubMed 12639202]

84. Vitale N, De Feo M, Cotrufo M. Anticoagulation for prosthetic heart valves during pregnancy: the importance of warfarin daily dose. Eur J Cardiothorac Surg. 2002; 22:656-7. Letter [PubMed 12297198]

85. Leyh RT, Fischer S, Ruhparwar A et al. Anticoagulant therapy in pregnant women with mechanical heart valves. Arch Gynecol Obstet. 2003; 268:1-4 [PubMed 12673466]

86. Srivastava AK, Gupta AK, Singh AV et al. Effect of oral anticoagulant during pregnancy with prosthetic heart valve. Asian Cardiovasc Thorac Ann. 2002; 10:306-9 [PubMed 12538273]

87. Mahesh B, Evans S, Bryan AJ. Failure of low molecular-weight heparin in the prevention of prosthetic mitral valve thrombosis during pregnancy: case report and a review of options for anticoagulation. J Heart Valve Dis. 2002; 11:745-50 [PubMed 12358414]

88. Leyh RG, Fischer S, Ruhparwar A et al. Anticoagulation for prosthetic heart valves during pregnancy: is low-molecular-weight heparin an alternative? Eur J Cardiothorac Surg. 2002; 21:577-9

89. Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000; 160:191-6 [IDIS 442245] [PubMed 10647757]

90. Berndt N, Khan I, Gallo R. A complication in anticoagulation using low-molecular weight heparin in a patient with a mechanical valve prosthesis. A case report. J Heart Valve Dis. 2000; 9:844-6 [PubMed 11128796]

91. Elkayam U. Pregnancy through a prosthetic heart valve. J Am Coll Cardiol. 1999; 33:1642-5. Editorial [IDIS 428085] [PubMed 10334436]

92. Meschengieser SS, Fondevila CG, Santarelli MT et al. Anticoagulation in pregnant women with mechanical heart valve prostheses. Heart. 1999; 82:23-6 [IDIS 433596] [PubMed 10377303]

93. Rowan JA, McCowan LM, Raudkivi PJ et al. Enoxaparin treatment in women with mechanical heart valves during pregnancy. Am J Obstet Gynecol. 2001; 185:633-7 [IDIS 470956] [PubMed 11568791]

94. Elkayam UR. Anticoagulation in pregnant women with prosthetic heart valves: a double jeopardy. J Am Coll Cardiol. 1996; 27:1704-6. Editorial [IDIS 368182] [PubMed 8636557]

95. Salazar E, Izaguirre R, Verdejo J et al. Failure of adjusted doses of subcutaneous heparin to prevent thromboembolic phenomena in pregnant patients with mechanical cardiac valve prostheses. J Am Coll Cardiol. 1996; 27:1698-703 [IDIS 368181] [PubMed 8636556]

96. Nelson-Piercy C, Letsky EA, de Swiet M. Low-molecular-weight heparin for obstetric thromboprophylaxis: experience of sixty-nine pregnancies in sixty-one women at high risk. Am J Obstet Gynecol. 1997; 176:1062-8

97. Schneider DM, Von Tempelhoff G-F, Heilmann L. Retrospective evaluation of the safety and efficacy of low-molecular-weight heparin as thromboprophylaxis during pregnancy. Am J Obstet Gynecol 1997; 177:1567-8. Letter [IDIS 399184] [PubMed 9423786]

98. Arnaout MS, Kazma H, Khalil A et al. Is there a safe anticoagulation protocol for pregnant women with prosthetic valves? Clin Exp Obstet Gynecol. 1998; 25:101-4

99. Vitale N, De Feo M, De Santo LS et al. Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol. 1999; 33:1637-41 [IDIS 428084] [PubMed 10334435]

100. Aventis. Lovenox (enoxaparin sodium) injection prescribing information. Bridgewater, NJ; 2001 Jul.

101. American College of Obstetricians and Gynecologists, Washington, DC. Personal communication.

106. Antman EM, Anbe DT, Armstrong PW et al. ACC/AHA guidelines for the management of patients with ST-elevation acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). 2004. From and .

109. Adams H, Adams R, Del Zoppo G et al. Guidelines for the early management of patients with ischemic stroke: 2005 guidelines update. A scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke. 2005; 36:916-21. [PubMed 15800252]

110. Adams H, Adams R, Brott T et al. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke. 2003; 34:1056-83. [PubMed 12677087]

115. Fox KA, Poole-Wilson PA, Henderson RA. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet. 2002; 360:743-51. [IDIS 486061] [PubMed 12241831]

116. Husted SE, Wallentin L, Lagerqvist B et al. Benefits of extended treatment with dalteparin in patients with unstable coronary artery disease eligible for revascularization. Eur Heart J. 2002; 23:1213-8. [PubMed 12127923]

117. Goodman S. Enoxaparin and glycoprotein IIb/IIIa inhibition in non-ST-segment-elevation acute coronary syndrome: insights for the INTERACT trial. Am Heart J. 2005; 149:S73-80. [IDIS 534818] [PubMed 16124951]

119. James S, amrstrong P, Califf R et al. Safety and efficacy of abciximab combined with dalteparin in the treatment of acute coronary syndromes. Eur Heart J. 2002; 23:1538-45. [PubMed 12242074]

120. Goodman SG, Fitchett D, Armstrong P et al. Randomized evaluation of the safety and efficacy of enoxaparin versus unfarctionated heparin in high-risk patients with non-ST-sgement elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor eptifibatide. Circulation. 2003; 107:238-44. [IDIS 492843] [PubMed 12538422]

121. Collet JP, Montalescot G, Golmard JL et al. Subcutaneous enoxaparin with early invasive stragety in patients with acute coronary syndromes. Am Heart J. 2004; 147:655-61. [IDIS 516969] [PubMed 15077081]

122. Eikelboom JW, Hankey GJ. Low molecular weight heparins and heparinoids. Med J Aust. 2002; 177:379-83. [IDIS 489898] [PubMed 12358583]

124. Bhatt DL, Roe MT, Peterson ED et al. Utilization of early invasive management strategies for high-risk patients with non–ST-segment elevation acute coronary syndromes. Results from the CRUSADE Quality Improvement Initiative. JAMA. 2004; 292:2096-2104. [IDIS 523736] [PubMed 15523070]

125. Gluckman TJ, Sachdev M, Schulman SP et al. A simplified approach to the management of non–ST-segment elevation acute coronary syndromes. JAMA. 2005; 293:349-357. [IDIS 527032] [PubMed 15657328]

126. Cannon CP, Weintraub WS, Demopoulos LA et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med. 2001; 344:1879–87.

127. Braunwald E. Application of current guidelines to the management of unstable angina and non-ST-elevation myocardial infarction. Circulation. 2003; 108[Suppl III]:III-28-37.

128. Hirsh J, Bauer KA, Donati MB et al. Parenteral anticoagulants: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008; 133:141S-159S. [PubMed 18574264]

129. Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001; 358:605-13. [PubMed 11530146]

130. Wallentin L, Goldstein P, Armstrong PW et al. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation. 2003; 108:135-42. [IDIS 505211] [PubMed 12847070]

131. Ross AM, Molhoek P, Lundergan C et al et al. Randomized comparison of enoxaparin, a lowmolecular- weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II). Circulation. 2001; 104:648-52. [IDIS 468365] [PubMed 11489769]

132. Wallentin L, Bergstrand L, Dellborg M et al. Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study. Eur Heart J. 2003; 24:897-908. [PubMed 12714021]

133. Baird SH, Menown IB, Mcbride SJ et al. Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. Eur Heart J. 2002; 23:627-32. [PubMed 11969277]

135. Lansky AJ, Hochman JS, Ward PA et al. Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professional from the American Heart Association. Circulation. 2005; 111:940-3. [PubMed 15687113]

136. Mahaffey KW, Ferguson JJ, Califf RM et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA. 2004; 292:45-54. [PubMed 15238590]

138. Sacco RL, Adams R, Albers G et al. Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke. Stroke. 2006; 37:577-617. [PubMed 16432246]

142. Wysowski DK, Talarico L, Bacsanyi J et al. Spinal and epidural hematoma and low-molecular-weight heparin. N Engl J Med. 1998; 338:1774. [IDIS 406829] [PubMed 9625640]

143. Weitz JI. Low molecular weight heparins. N Engl J Med. 1998; 338:687-8. [IDIS 400562] [PubMed 9490390]

146. Wallentin L, Lagerqvist B, Husted S et al. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. Lancet. 2000; 356:9-16. [IDIS 450847] [PubMed 10892758]

150. Sanofi-Aventis. Lovenox (enoxaparin sodium) injection prescribing information. Bridgewater, NJ; 2011 Apr.

991. Anderson JL, Adams CD, Antman EM et al. 2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011; 123:e426-579.

994. Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011; 58:e44-122. [PubMed 22070834]

996. Bonow RO, Carabello BA, Chatterjee K et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008; 118:e523-661.

999. Fuster V, Rydén LE, Cannom DS et al. 2011 ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2011; 123:e269-367.

1000. Holbrook A, Schulman S, Witt DM et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e152S-84S. [PubMed 22315259]

1001. Kahn SR, Lim W, Dunn AS et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e195S-226S.

1002. Gould MK, Garcia DA, Wren SM et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e227S-77S. [PubMed 22315263]

1003. Falck-Ytter Y, Francis CW, Johanson NA et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e278S-325S. [PubMed 22315265]

1004. Douketis JD, Spyropoulos AC, Spencer FA et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e326S-50S.

1005. Kearon C, Akl EA, Comerota AJ et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e419S-94S. [PubMed 22315268]

1006. Linkins LA, Dans AL, Moores LK et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e495S-530S.

1007. You JJ, Singer DE, Howard PA et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e531S-75S. [PubMed 22315271]

1008. Whitlock RP, Sun JC, Fremes SE et al. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e576S-600S. [PubMed 22315272]

1009. Lansberg MG, O'Donnell MJ, Khatri P et al. Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e601S-36S. [PubMed 22315273]

1012. Bates SM, Greer IA, Middeldorp S et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e691S-736S. [PubMed 22315276]

1013. Monagle P, Chan AK, Goldenberg NA et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e737S-801S. [PubMed 22315277]

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists, Inc; 2007: 616.

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