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Enoxaparin

Medically reviewed by Drugs.com. Last updated on Dec 20, 2018.

Pronunciation

(ee noks a PA rin)

Index Terms

  • Enoxaparin Sodium

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as sodium:

Lovenox: 300 mg/3 mL (3 mL) [contains benzyl alcohol, pork (porcine) protein]

Generic: 300 mg/3 mL (3 mL)

Solution, Subcutaneous, as sodium:

Generic: 80 mg/0.8 mL (0.8 mL)

Solution, Subcutaneous, as sodium [preservative free]:

Lovenox: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL); 60 mg/0.6 mL (0.6 mL); 80 mg/0.8 mL (0.8 mL); 100 mg/mL (1 mL); 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL) [contains pork (porcine) protein]

Generic: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL); 60 mg/0.6 mL (0.6 mL); 80 mg/0.8 mL (0.8 mL); 100 mg/mL (1 mL); 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL)

Brand Names: U.S.

  • Lovenox

Pharmacologic Category

  • Anticoagulant
  • Anticoagulant, Low Molecular Weight Heparin

Pharmacology

Standard heparin consists of components with molecular weights ranging from 4000 to 30,000 daltons with a mean of 16,000 daltons. Heparin acts as an anticoagulant by enhancing the inhibition rate of clotting proteases by antithrombin III impairing normal hemostasis and inhibition of factor Xa. Low molecular weight heparins have a small effect on the activated partial thromboplastin time and strongly inhibit factor Xa. Enoxaparin is derived from porcine heparin that undergoes benzylation followed by alkaline depolymerization. The average molecular weight of enoxaparin is 4500 daltons which is distributed as (≤20%) 2000 daltons (≥68%) 2000 to 8000 daltons, and (≤18%) >8000 daltons. Enoxaparin has a higher ratio of antifactor Xa to antifactor IIa activity than unfractionated heparin.

Distribution

4.3 L (based on antifactor Xa activity)

Metabolism

Hepatic, via desulfation and depolymerization to lower molecular weight molecules with very low biological activity

Excretion

Urine (40% of dose as active and inactive fragments; 10% as active fragments; 8% to 20% of antifactor Xa activity is recovered within 24 hours)

Clearance: Decreased by 30% in patients with CrCl <30 mL/minute

Onset of Action

Peak effect: SubQ: Antifactor Xa and antithrombin (antifactor IIa): 3 to 5 hours

Duration of Action

40 mg dose: Antifactor Xa activity: ~12 hours

Half-Life Elimination

Plasma: 2 to 4 times longer than standard heparin, independent of dose; based on anti-Xa activity: 4.5 to 7 hours

Protein Binding

Does not bind to heparin binding proteins

Special Populations: Renal Function Impairment

AUC increased 65% in patients with severe renal impairment (CrCl <30 mL/minute).

Special Populations: Elderly

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

Special Populations: Gender

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

Special Populations Note

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

Use: Labeled Indications

Acute coronary syndromes: Unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarction (STEMI)

VTE prophylaxis: Following hip or knee replacement surgery, abdominal surgery, or in medical patients with severely restricted mobility during acute illness who are at risk for thromboembolic complications. Note: Patients at risk of thromboembolic complications who undergo abdominal surgery include those with one or more of the following risk factors: age >40 years, obesity, general anesthesia lasting >30 minutes, malignancy, history of DVT or PE.

DVT treatment (acute): Inpatient treatment (patients with or without PE) and outpatient treatment (patients without PE). Note: In patients with VTE (ie, DVT or PE) and without cancer, oral anticoagulants are preferred over low-molecular-weight heparin (LMWH) (unless LMWH is used as initial parenteral anticoagulation prior to dabigatran, edoxaban, or while initiating warfarin). In patients with VTE (ie, DVT or PE) and cancer, ACCP recommends LMWH over oral anticoagulants for initial and long-term treatment (ACCP [Kearon 2012]; ACCP [Kearon 2016]).

Off Label Uses

Acute symptomatic superficial vein thrombosis (lower extremity; ≥5 cm in length)

Data from a randomized, double-blind, placebo-controlled trial support the use of enoxaparin in the treatment of this condition [Décousus 2003].

Based on the American College of Chest Physicians (ACCP) guidelines on antithrombotic therapy for VTE disease, enoxaparin is effective and recommended for use in patients with acute symptomatic superficial vein thrombosis (≥5 cm in length) of the legs.

Mechanical heart valve (bridging anticoagulation)

Based on the 2017 American Heart Association/American College of Cardiology (AHA/ACC) focused update of the 2014 guideline for the management of patients with valvular heart disease, a low-molecular-weight heparin (LMWH) (eg, enoxaparin) is reasonable to decrease the risk of thrombotic events in patients who require temporary interruption of oral anticoagulation and have a mechanical mitral heart valve, mechanical aortic heart valve plus additional risk factors for thromboembolism (eg, atrial fibrillation, previous thromboembolism, left ventricular dysfunction, or hypercoagulable condition), or older-generation mechanical valves (ball-cage or tilting disc); or in pregnant patients with a mechanical prosthetic heart valve only if anti-Xa levels can be monitored.

Pulmonary embolism (acute)

Based on the 2016 American College of Chest Physicians (ACCP) guidelines for antithrombotic therapy for VTE disease, LMWH (eg, enoxaparin) is an effective and recommended treatment option for acute pulmonary embolism (PE). However, in patients without cancer, oral anticoagulants are preferred over LMWH (unless LMWH is used as initial parenteral anticoagulation prior to dabigatran, edoxaban, or while initiating warfarin). Note: In patients with venous thromboembolism (VTE) (ie, deep vein thrombosis [DVT] or PE) and cancer, ACCP recommends LMWH over oral anticoagulants for initial and long-term treatment.

Venous thromboembolism prophylaxis in patients undergoing bariatric surgery (high VTE risk)

Data from one prospective, open-label, nonrandomized trial in patients undergoing Roux-en-Y gastric bypass (RYGB) demonstrated that a BMI-stratified, extended enoxaparin dosing regimen provided effective VTE prophylaxis [Borkgren-Okonek 2008]. In a prior nonrandomized, open-label trial in patients undergoing primary RYGB or revisional bariatric surgery, the use of enoxaparin was feasible and associated with a low incidence of postoperative VTE complications [Scholten 2002]. Additional trials may be necessary to further define the role of enoxaparin in the prevention of VTE with bariatric surgery.

The 2013 American Association of Clinical Endocrinologists/Obesity Society/American Association of Metabolic and Bariatric Surgery (AACE/TOS/ASMBS) bariatric surgery guidelines recommend early ambulation along with both sequential compression devices and subcutaneous LMWH or unfractionated heparin administered within 24 hours after surgery, with consideration of extended prophylaxis for those at high risk for VTE (eg, history of DVT).

Contraindications

Known hypersensitivity to enoxaparin (eg, pruritus, urticaria, anaphylactic/anaphylactoid reactions), heparin, pork products, or any component of the formulation (including benzyl alcohol in multiple-dose vials); history of immune mediated heparin-induced thrombocytopenia (HIT) in the past 100 days or in the presence of circulating antibodies; active major bleeding

Canadian labeling: Additional contraindications (not in US labeling): Use of multiple-dose vials in newborns or premature neonates; acute or subacute bacterial endocarditis; major blood clotting disorders; active gastric or duodenal ulcer; hemorrhagic cerebrovascular accident (except if there are systemic emboli); severe uncontrolled hypertension; diabetic or hemorrhagic retinopathy; other conditions or diseases involving an increased risk of hemorrhage; injuries to and operations on the brain, spinal cord, eyes, and ears; spinal/epidural anesthesia when repeated dosing of enoxaparin (1 mg/kg every 12 hours or 1.5 mg/kg daily) is required, due to increased risk of bleeding.

Dosing: Adult

Note: One mg of enoxaparin is equal to 100 units of anti-Xa activity (World Health Organization First International Low Molecular Weight Heparin Reference Standard). Weight-based doses (eg, 1 mg/kg) are commonly rounded to the nearest 10 mg; also see institution-specific rounding protocols, if available. Most available prefilled syringes are graduated in 10 mg increments.

Acute symptomatic superficial vein thrombosis (lower extremity; ≥5 cm in length) (off-label use): SubQ: 40 mg once daily for 45 days (ACCP [Kearon 2012]; Décousus 2003). Note: Risk of recurrence is high if anticoagulation is discontinued earlier than 45 days. Monitor d-dimer at baseline and again at 45 days; if d-dimer remains elevated, a longer course may be necessary (Scovell 2018).

Ischemic heart disease:

Acute coronary syndromes:

Non-ST elevation acute coronary syndromes: SubQ: 1 mg/kg every 12 hours in conjunction with recommended antiplatelet therapy; continue for the duration of hospitalization or until percutaneous coronary intervention (PCI) is performed. Note: Some experts suggest that enoxaparin, although comparable in efficacy to unfractionated heparin (UFH), does not have a role in patients undergoing an invasive approach due to an increased risk of bleeding; UFH or bivalirudin is preferred (Cutlip 2018b; Ferguson 2004).

ST elevation myocardial infarction (STEMI): Note: Although the manufacturer's labeling includes the use of enoxaparin for patients with STEMI undergoing primary PCI, heparin or bivalirudin is preferred. Initial dosing is the same for patients who undergo reperfusion with fibrinolysis or PCI and for patients who do not undergo reperfusion. Therapy may be continued for up to 8 days (minimum of 48 hours when undergoing reperfusion with fibrinolysis) or until revascularization. Unless contraindicated, all patients should receive aspirin and a P2Y12 inhibitor (ACCF/AHA [O'Gara 2013]). In patients with STEMI receiving thrombolytics, initiate enoxaparin between 15 minutes before and 30 minutes after fibrinolytic therapy.

Patients <75 years of age: Single IV bolus of 30 mg plus 1 mg/kg (maximum: 100 mg for the first 2 doses only) SubQ every 12 hours. The first SubQ dose should be administered with the IV bolus.

Patients ≥75 years of age: Note: No IV bolus is administered in this population. SubQ: 0.75 mg/kg (maximum: 75 mg for the first 2 doses only) every 12 hours.

PCI, adjunctive therapy (off-label):

If patient undergoing PCI has been treated with multiple doses of enoxaparin and PCI occurs within 8 hours after the last SubQ enoxaparin dose: No additional enoxaparin is needed (ACCF/AHA/SCAI [Levine 2011]).

If PCI occurs 8 to 12 hours after the last SubQ enoxaparin dose in a patient treated with multiple doses of enoxaparin or the patient received only 1 therapeutic SubQ dose (eg, 1 mg/kg): Administer a single IV dose of 0.3 mg/kg (ACCF/AHA/SCAI [Levine 2011]).

If PCI occurs >12 hours after the last SubQ dose: May use an established anticoagulation regimen (eg, full-dose UFH or bivalirudin) (ACCF/AHA/SCAI [Levine 2011]).

Note: Not generally initiated in patients undergoing elective PCI and not preferred in patients undergoing PCI for acute coronary syndromes (Cutlip 2018a; Lincoff 2018).

Mechanical heart valve (bridging anticoagulation) (off-label use): Note: Bridging during periprocedural intervals of subtherapeutic anticoagulation may be considered if there is an additional thromboembolic risk factor, such as atrial fibrillation, left ventricular systolic dysfunction, older-generation mechanical valves, or mechanical mitral or tricuspid valve replacement. Individuals with aortic valve replacement but without additional risk factors for thrombosis (other than the mechanical valve) may not require bridging (AHA/ACC [Nishimura 2017]). It is also reasonable to use enoxaparin for this indication during pregnancy, especially during the first trimester (AHA/ACC [Nishimura 2014]; Nelson-Piercy 2018).

SubQ: 1 mg/kg every 12 hours; adjust dose based on anti-Xa monitoring (ACCP [Douketis 2012]). For additional information regarding anti-Xa monitoring, refer to the Reference Range field.

VTE prophylaxis: Note: For patients assessed to be at the highest risk (eg, Caprini score >8, stroke, active cancer, multiple risk factors), many experts combine pharmacologic methods with mechanical methods or increase the dose frequency to twice daily (eg, 30 or 40 mg twice daily). Increasing the dose should always be balanced against the risk of bleeding (Malhotra 2018; Pai 2018a; Pai 2018b).

Bariatric surgery, high VTE risk (off-label use): Note: Optimal dosing strategies have not been established. Dosing regimens based on best available evidence (Birkmeyer 2012; Borkgren-Okonek 2008; Scholten 2002).

BMI ≤50 kg/m2: SubQ: 40 mg every 12 hours initiated at least 2 hours before surgery

BMI >50 kg/m2: SubQ: 60 mg every 12 hours initiated at least 2 hours before surgery

Note: Optimal duration of prophylaxis is unknown, but is usually continued until hospital discharge and may be extended for up to 6 weeks postoperatively depending upon VTE risk. There is no consensus on indications for extended prophylaxis following bariatric surgery (Lim 2018).

Hospitalized medical patients with acute illness at moderate and high risk for VTE (including patients with active cancer):SubQ: 40 mg once daily; continue for length of hospital stay or until patient is fully ambulatory and risk of VTE has diminished (ACCP [Kahn 2012]; ASCO [Lyman 2013]; ASCO [Lyman 2015]). Note: Extended prophylaxis beyond acute hospital stay is not routinely recommended (ACCP [Kahn 2012]; Sharma 2012).

Major nonorthopedic surgery (patients with active cancer) (off-label): Note: Regimens vary and include the following:

SubQ: 40 mg started 10 to 12 hours before surgery and 40 mg once daily thereafter (ASCO [Lyman 2013])

or

SubQ: 20 mg started 2 to 4 hours before surgery and 40 mg once daily thereafter (ASCO [Lyman 2013])

or

SubQ: 40 mg once daily started ~12 to 24 hours after surgery (Bauer 2019; Pai 2018a)

Note: The optimal duration of prophylaxis has not been established. It is usually given for a minimum of 7 to 10 days (ASCO [Lyman 2013]; ASCO [Lyman 2015]). Extending for up to 4 weeks may be reasonable in those undergoing major abdominal or pelvic surgery (ASCO [Lyman 2013]; ASCO [Lyman 2015]).

Nonorthopedic surgery (patients without cancer): Note: For patients with moderate and high risk of VTE and low risk of bleeding: SubQ: 40 mg once daily, with initial dose given at least 2 hours before abdominal surgery or ~12 hours before other nonorthopedic surgery. Alternatively, may postpone pharmacologic prophylaxis until after surgery (eg, high bleeding risk) when it is safe to initiate (Pai 2018a). If hemostasis is difficult to achieve postoperatively, hold prophylaxis until it is safe to reinitiate. Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days) (ACCP [Gould 2012]; Pai 2018a).

Pregnancy (off-label): Note: For patients at moderate and high VTE risk during antepartum and postpartum periods. Dose intensity is individualized based on risks of thrombosis and bleeding complications.

Prophylactic dose: SubQ: 40 mg once every 24 hours (ACOG 2018)

Intermediate dose: SubQ: 40 mg every 12 hours (ACOG 2018); however, some experts use an alternative intermediate regimen of 40 mg SubQ once daily, increasing as pregnancy progresses to 1 mg/kg once daily (Bauer 2018b; Malhotra 2018).

Adjusted dose (therapeutic): SubQ: 1 mg/kg every 12 hours; reserved for patients at the highest risk (eg, history of recurrent thrombosis or severe thrombophilia) (ACCP [Bates 2012]; ACOG 2018)

Note: Anticoagulation management prior to delivery is individualized. Options include replacing with UFH at ~36 to 37 weeks' gestation or extending to 38 to 39 weeks' gestation in patients at very low risk of delivery while on enoxaparin (Bauer 2018b). In such patients, discontinue enoxaparin ≥12 hours before delivery (for prophylactic doses) or ≥24 hours before delivery (for higher doses), particularly if neuraxial anesthesia is planned; may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred (ACOG 2018). Anticoagulation should continue for up to 6 weeks postpartum in high-risk women (ACCP [Bates 2012]).

Total hip arthroplasty (THA) or hip fracture surgery: SubQ: 40 mg once daily or 30 mg every 12 hours, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved (ACCP [Falck-Ytter 2012]; Eriksson 2001; Pai 2018b). Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days. Prophylaxis can be extended beyond the minimum 10 to 14 days for up to 35 days; may discontinue earlier if fully ambulatory (ACCP [Falck-Ytter 2012]; Bergqvist 1996; Eikelboom 2001; Pai 2018b; Sobieraj 2012); some experts suggest a duration at the higher end of range (eg, 30 days) for THA (Pai 2018b).

Total knee arthroplasty (TKA): SubQ: 30 mg every 12 hours, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved (ACCP [Falck-Ytter 2012]; Pai 2018b). Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days. Prophylaxis can be extended beyond the minimum 10 to 14 days for up to 35 days; may discontinue earlier if fully ambulatory (ACCP [Falck-Ytter 2012]; Eikelboom 2001; Pai 2018b); some experts suggest a duration at the lower end of the range (eg, 10 to 14 days) for TKA (Pai 2018b).

VTE treatment: Note: For timing of initiating oral anticoagulant, see Transitioning between anticoagulants. For patients with active cancer, see VTE treatment in patients with active cancer.

DVT and/or PE (PE is an off-label use): Inpatient treatment: SubQ: 1 mg/kg every 12 hours (preferred) or 1.5 mg/kg once every 24 hours. Note: In select low-risk patients, may consider outpatient treatment using 1 mg/kg every 12 hours for the remainder of the course after first dose administered in hospital or urgent care center (ACCP [Kearon 2016]; Aujesky 2011; Erkens 2010).

Duration of therapeutic anticoagulation (first episode, general recommendations): Optimal duration of therapy is unknown and depends on many factors, such as whether provoking events were present, patient risk factors for recurrence and bleeding, and individual preference.

Provoked VTE: 3 months (provided the provoking risk factor is no longer present) (ACCP [Kearon 2016])

Unprovoked PE or DVT (proximal or isolated distal): ≥3 months depending on risk of VTE recurrence and bleeding (ACCP [Kearon 2012]; ACCP [Kearon 2016]; ISTH [Baglin 2012]).

Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals.

VTE treatment in patients with active cancer:

Months 1 to 6: SubQ: Initial: 1 mg/kg every 12 hours or 1.5 mg/kg once daily for 5 to 10 days followed by long-term anticoagulation for a total duration of 3 to 6 months. Note: Twice-daily dosing may be more efficacious than once-daily dosing based on post hoc data (ASCO [Lyman 2013]; ASCO [Lyman 2015]; Bauer 2018a).

Maintenance beyond 6 months: ACCP and ASCO guidelines for VTE prophylaxis/treatment recommend considering continuing anticoagulation beyond 6 months in select patients due to the persistent high risk of recurrence in those with active cancer; consider risk versus benefit of bleeding and recurrence (ACCP [Kearon 2012]; ACCP [Kearon 2016]; ASCO [Lyman 2013]; ASCO [Lyman 2015]).

VTE treatment in pregnancy: SubQ: 1 mg/kg every 12 hours (ACCP [Bates 2012]); ACOG 2018). Some experts suggest anti-Xa monitoring for dose adjustment (ACCP [Bates 2012]). For additional information regarding anti-Xa monitoring, refer to the Reference Range field.

Note: Anticoagulation management prior to delivery is individualized. Options include replacing with UFH at ~36 to 37 weeks' gestation or extending to 38 to 39 weeks' gestation in patients at very low risk of delivery while on enoxaparin (Bauer 2018b). In such patients, discontinue enoxaparin ≥24 hours before delivery, particularly if neuraxial anesthesia is planned; may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred (ACOG 2018). Optimal duration of anticoagulation is unknown. In general, total duration (antepartum plus postpartum) should be at least 3 to 6 months with at least 6 weeks postpartum (ACOG 2018; Malhotra 2018).

Transitioning between anticoagulants: Note: This provides general guidance on transitioning between anticoagulants; also refer to local protocol for additional detail:

Transitioning from another anticoagulant to enoxaparin:

Transitioning from therapeutic IV UFH infusion to therapeutic-dose enoxaparin: Discontinue UFH and begin enoxaparin within 1 hour. Note: If aPTT is not in therapeutic range at the time UFH is discontinued, consult local protocol (Nutescu 2007).

Transitioning from enoxaparin to another anticoagulant:

Transitioning from therapeutic-dose enoxaparin to therapeutic IV UFH infusion: Start IV UFH (rate based on indication) 1 to 2 hours before the next dose of enoxaparin would have been due. Note: Omit IV UFH loading dose (Nutescu 2007).

Transitioning from prophylactic enoxaparin to therapeutic IV UFH: UFH should be started without delay. A UFH bolus/loading dose may be used if indicated.

Transitioning from therapeutic-dose enoxaparin to warfarin for VTE treatment: Start warfarin on the first or second treatment day and overlap with enoxaparin until INR is ≥2 for at least 2 measurements ~24 hours apart (duration of overlap is usually 4 to 5 days) (ACCP [Ageno 2012]; Hull 2018).

Transitioning from therapeutic-dose enoxaparin to warfarin for nonvalvular atrial fibrillation: In patients not at high risk of immediate thromboembolism, warfarin is usually started without parenteral anticoagulant (ie, no bridging). In patients at high risk of immediate thromboembolism, overlapping with enoxaparin until INR is within therapeutic range (bridging) may be considered (ACCP [You 2012]).

Transitioning from therapeutic-dose enoxaparin to a direct oral anticoagulant (DOAC): Note: In treatment of VTE, some DOACs (dabigatran, edoxaban) require 5 days of parenteral anticoagulation prior to transitioning.

General transition recommendation: Start DOAC within 2 hours prior to the next scheduled dose of enoxaparin.

VTE initial treatment transition (alternative recommendation): For acute VTE, some experts start DOAC within 6 to 12 hours after the last dose of a twice-daily LMWH regimen or within 12 to 24 hours after a once-daily LMWH regimen (Hull 2018).

Dosing: Geriatric

SubQ: Refer to adult dosing. Increased incidence of bleeding with doses of 1.5 mg/kg/day or 1 mg/kg every 12 hours; injection-associated bleeding and serious adverse reactions are also increased in elderly patients. Careful attention should be paid to elderly patients, particularly those <45 kg. Note: Dosage alteration/adjustment may be required.

Dosing: Pediatric

Note: Enoxaparin has ~100 anti-factor Xa units/mg enoxaparin (World Health Organization First International Low Molecular Weight Heparin Reference Standard). In order to improve accurate measurement and avoid dilution of enoxaparin pediatric enoxaparin doses, the following methods have reported at some centers: Dose rounding to the nearest whole mg (down or up, as appropriate) and administering with ≤100 unit insulin syringe (see Preparation for Administration) (Bauman 2009a; Bauman 2009b); extra precaution should be taken to ensure accurate dose delivery.

Prophylaxis: Limited data available (Giglia 2013; Monagle 2012):

Infants 1 to <2 months: SubQ: 0.75 mg/kg/dose every 12 hours

Infants ≥2 months, Children, and Adolescents: SubQ: 0.5 mg/kg/dose every 12 hours

Thrombosis; treatment: Note: Preliminary data from 213 pediatric patients evaluating 1,061 anti-factor Xa levels suggests that pediatric dose titration in patients <2 years of age may be affected by assay methodology (Greene 2014); SubQ:

Initial:

Chest/AHA guidelines (Giglia 2013; Monagle 2012)

Infants 1 to <2 months: SubQ: 1.5 mg/kg/dose every 12 hours

Infants ≥2 months, Children, and Adolescents: SubQ: 1 mg/kg/dose every 12 hours

Alternate dosing: Some data suggest that initial doses higher than those recommended in the Chest guidelines (Monagle 2012) are required in pediatric patients (especially in young infants or critically ill) (Bauman 2009; Malowany 2007; Malowany 2008; Schloemer 2014). Some centers have used the following:

1 to <3 months: 1.8 mg/kg/dose every 12 hours

3 to 12 months: 1.5 mg/kg/dose every 12 hours

1 to 5 years: 1.2 mg/kg/dose every 12 hours

6 to 18 years: 1.1 mg/kg/dose every 12 hours

Dosing adjustment, thrombosis treatment: Titrate dose to achieve a 4 to 6 hours postdose target anti-factor Xa level of 0.5 to 1 units/mL (Monagle 2012); duration of treatment based on thrombosis site, clinical response, and other identified risk factors; usual duration between 6 weeks and 3 months (Monagle 2012). A prospective study of 177 courses of enoxaparin in pediatric patients (146 treatment courses) reported considerable variation in maintenance dosage requirements (Dix 2000).

Previous CHEST guidelines (Molinari 2011; Monagle 2001; Monagle 2008) suggested the following dosage adjustments to achieve the target anti-factor Xa range (Duplaga 2001).

Enoxaparin Dosage Titration

Antifactor Xa

Dose Titration

Time to Repeat Antifactor Xa Level

Modified from Monagle P, Michelson AD, Bovill E, et al. Antithrombotic therapy in children. Chest. 2001;119:344S-370S

<0.35 units/mL

Increase dose by 25%

4 h after next dose

0.35-0.49 units/mL

Increase dose by 10%

4 h after next dose

0.5-1 unit/mL

Keep same dosage

Next day, then 1 wk later, then monthly

(4 h after dose)

1.1-1.5 units/mL

Decrease dose by 20%

Before next dose

1.6-2 units/mL

Hold dose for 3 h

and decrease dose by 30%

Before next dose,

then 4 h after next dose

>2 units/mL

Hold all doses until

antifactor Xa is 0.5 units/mL,

then decrease dose by 40%

Before next dose and

every 12 h until

antifactor Xa <0.5 units/mL

Table has been converted to the following text.

Enoxaparin Dosage Titration

Antifactor Xa <0.35 units/mL:

Increase dose by 25%; repeat antifactor Xa level 4 hours after next dose

Antifactor Xa 0.35 to 0.49 units/mL:

Increase dose by 10%; repeat antifactor Xa level 4 hours after next dose

Antifactor Xa 0.5 to 1 unit/mL:

Keep same dosage; repeat antifactor Xa level next day, then 1 week later, then monthly (4 hours after dose)

Antifactor Xa 1.1 to 1.5 units/mL:

Decrease dose by 20%; repeat antifactor Xa level before next dose

Antifactor Xa 1.6 to 2 units/mL:

Hold dose for 3 hours and decrease dose by 30%; repeat antifactor Xa level before next dose, then 4 hours after next dose

Antifactor Xa >2 units/mL:

Hold all doses until antifactor Xa is 0.5 units/mL, then decrease dose by 40%; repeat antifactor Xa level before next dose and every 12 hours until antifactor Xa <0.5 units/mL

Modified from Monagle P, Michelson AD, Bovill E, et al. Antithrombotic therapy in children. Chest. 2001;119:344S-370S

Dosing: Obesity

Note: Specific dosing recommendations may not be available for all indications. For bariatric surgery, see Dosing: Adult: VTE prophylaxis, bariatric surgery, high VTE risk.

ST elevation myocardial infarction (STEMI): Use weight-based dosing; a maximum dose of 100 mg is recommended for the first 2 doses (Nutescu 2009).

Unstable angina or non-ST elevation myocardial infarction (NSTEMI) (also referred to as non-ST elevation acute coronary syndromes [NSTE-ACS]): Use actual body weight to calculate dose; a fixed upper-dose limit is not recommended (Nutescu 2009).

VTE prophylaxis: Note: The following recommendations may be applied to all indications for VTE prophylaxis except Bariatric Surgery, which already states specific dosing based on BMI and Pregnancy, which requires individualized dosing based on thromboembolic risk.

BMI 30 to 39 kg/m2: Use standard prophylaxis dosing.

BMI ≥40 kg/m2: Increase standard prophylaxis dose by 30% (Nutescu 2009); however, the ideal dose is unknown.

VTE treatment: Use actual body weight to calculate dose. A fixed upper-dose limit is not recommended; however, increased monitoring and dosage adjustment based on anti-Xa levels may be considered. Use of twice-daily dosing preferred (Nutescu 2009).

Administration

Note: Enoxaparin is available in 100 mg/mL and 150 mg/mL concentrations.

SubQ: Administer by deep SubQ injection alternating between the left or right anterolateral and left or right posterolateral abdominal wall. Do not mix with other infusions or injections. In order to minimize bruising, do not rub injection site. To avoid loss of drug from the 30 mg and 40 mg prefilled syringes, do not expel the air bubble from the syringe prior to injection.

IV: STEMI and PCI only: The US labeling recommends using the multiple-dose vial to prepare IV doses. The Canadian labeling recommends either the multiple-dose vial or a prefilled syringe. Do not mix or coadminister with other medications; may be administered with NS or D5W. Flush IV access site with a sufficient amount of NS or D5W prior to and following IV bolus administration. When used prior to percutaneous coronary intervention or as part of treatment for ST-elevation myocardial infarction (STEMI), a single dose may be administered IV except when the patient is ≥75 years of age and is experiencing STEMI then only administer by SubQ injection.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze. Do not store multiple-dose vials for >28 days after first use.

Drug Interactions

5-Aminosalicylic Acid Derivatives: May enhance the adverse/toxic effect of Heparins (Low Molecular Weight). Specifically, the risk for bleeding/bruising may be increased. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Aliskiren: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Aliskiren. Monitor therapy

Angiotensin II Receptor Blockers: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy

Antithrombin: May enhance the anticoagulant effect of Heparins (Low Molecular Weight). Monitor therapy

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Consider therapy modification

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination

Eplerenone: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Eplerenone. Monitor therapy

Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification

Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Consider therapy modification

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Palifermin: Heparins (Low Molecular Weight) may increase the serum concentration of Palifermin. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Pentoxifylline: May enhance the anticoagulant effect of Heparins (Low Molecular Weight). Monitor therapy

Potassium Salts: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium Salts. Monitor therapy

Potassium-Sparing Diuretics: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. Monitor therapy

Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination

Adverse Reactions

As with all anticoagulants, bleeding is the major adverse effect of enoxaparin. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables. At the recommended doses, single injections of enoxaparin do not significantly influence platelet aggregation or affect global clotting time (ie, PT or aPTT).

>10%: Hematologic & oncologic: Anemia (≤16%), hemorrhage (4% to 13%)

1% to 10%:

Cardiovascular: Peripheral edema (6%)

Central nervous system: Confusion (2%)

Gastrointestinal: Nausea (3%)

Hematologic & oncologic: Major hemorrhage (<1% to 4%; includes cases of intracranial [up to 0.8%], retroperitoneal, or intraocular hemorrhage; incidence varies with indication/population), ecchymoses (3%), thrombocytopenia (1% to 2%)

Hepatic: Increased serum ALT (>3 x ULN: 6%), increased serum AST (>3 x ULN: 6%)

Local: Hematoma at injection site (9%), bleeding at injection site (3% to 5%), pain at injection site (2%)

Renal: Hematuria (≤2%)

Miscellaneous: Fever (≤8%)

<1%, postmarketing, and/or case reports: Acute posthemorrhagic anemia, alopecia, anaphylactoid reaction, anaphylaxis, atrial fibrillation, bruising at injection site, eosinophilia, epidural hematoma (spinal; after neuroaxial anesthesia or spinal puncture; risk may be increased with indwelling epidural catheter or concomitant use of other drugs affecting hemostasis), erythema at injection site, headache, hepatic injury (hepatocellular and cholestatic), hyperkalemia, hyperlipidemia (very rare), hypersensitivity angiitis, hypersensitivity reaction, hypertriglyceridemia, injection site reactions (including nodules, inflammation, oozing), irritation at injection site, osteoporosis (following long-term therapy), pneumonia, pruritus, pulmonary edema, purpura, shock, skin necrosis, thrombocythemia, thrombosis in heparin-induced thrombocytopenia, thrombosis (prosthetic value [in pregnant females] or associated with enoxaparin-induced thrombocytopenia; can cause limb ischemia or organ infarction), urticaria, vesicobullous rash

ALERT: U.S. Boxed Warning

Spinal/Epidural hematoma:

Epidural or spinal hematomas may occur in patients who are anticoagulated with LMWHs or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures.

Factors that can increase the risk of developing epidural or spinal hematomas in these patients include use of indwelling epidural catheters; concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, and other anticoagulants; a history of traumatic or repeated epidural or spinal punctures; and a history of spinal deformity or spinal surgery. Optimal timing between the administration of enoxaparin and neuraxial procedures is not known.

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary.

Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: Monitor patient closely for signs or symptoms of bleeding. Certain patients are at increased risk of bleeding. Risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; severe uncontrolled hypertension; hemorrhagic stroke; or use shortly after brain, spinal, or ophthalmic surgery; in patients treated concomitantly with platelet inhibitors; recent GI bleeding or ulceration; renal dysfunction and hemorrhage; thrombocytopenia or platelet defects or history of heparin-induced thrombocytopenia; severe liver disease; hypertensive or diabetic retinopathy; or in patients undergoing invasive procedures. Discontinue if bleeding occurs. Protamine may be considered as a partial reversal agent in overdose situations (consult Protamine monograph for dosing recommendations). To minimize risk of bleeding following PCI, achieve hemostasis at the puncture site after PCI. If a closure device is used, sheath can be removed immediately. If manual compression is used, remove sheath 6 hours after the last IV/SubQ dose of enoxaparin. Do not administer further doses until 6 to 8 hours after sheath removal; observe for signs of bleeding/hematoma formation.

• Hyperkalemia: Monitor for hyperkalemia; can cause hyperkalemia possibly by suppressing aldosterone production. Most commonly occurs in patients with risk factors for the development of hyperkalemia (eg, renal dysfunction, concomitant use of potassium-sparing diuretics or potassium supplements, hematoma in body tissues).

.• Thrombocytopenia: Thrombocytopenia can occur. Cases of HIT and heparin-induced thrombocytopenia with thrombosis (HITTS), some complicated by organ infarction, limb ischemia, or death, have been observed; monitor platelet count closely. Use with extreme caution or avoid in patients with history of HIT (Warkentin 2001); use is contraindicated in patients with a history of immune-mediated HIT within the past 100 days or in the presence of circulating antibodies. In patients with a history of HIT, use only if >100 days have elapsed since the prior HIT episode and no circulating antibodies are present (HIT may still occur in these patients; assess risk vs benefit and use only after non-heparin alternative treatments are considered). Discontinue therapy and consider alternative treatment if platelets are <100,000/mm3 and/or thrombosis develops. Use caution in patients with congenital or drug-induced thrombocytopenia or platelet defects.

Disease-related concerns:

• Prosthetic heart valves: Cannot be recommended for long-term thromboprophylaxis in patients with prosthetic heart valves (especially pregnant women) due to insufficient evidence.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment needed if CrCl <30 mL/minute.

Special populations:

• Elderly: Use with caution in the elderly; delayed elimination may occur. Dosage alteration/adjustment may be required (eg, omission of IV bolus in acute STEMI in patients ≥75 years of age).

• Low weight patients: Risk of bleeding may be increased in women <45 kg and in men <57 kg.

• Obesity: Safety and efficacy of prophylactic dosing of enoxaparin has not been established in patients who are obese (>30 kg/m2) nor is there a consensus regarding dosage adjustments; monitor closely for signs/symptoms of thromboembolism. Anti-Xa levels are increased to appropriate levels when enoxaparin is dosed on actual body weight in obese patients weighing up to 144 kg (Sanderink 2002). Monitoring of anti-Xa levels 4 hours after the dose may be warranted. The American College of Chest Physicians Practice Guidelines suggest consulting with a pharmacist regarding dosing in bariatric surgery patients and other obese patients who may require higher doses of LMWH (ACCP [Gould 2012]).

• Surgical patients: In patients receiving bridging anticoagulation with therapeutic dose enoxaparin, the American College of Chest Physicians suggests that the last preoperative dose of enoxaparin be administered ~24 hours prior to surgery (ACCP [Douketis 2012]).

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and should not be used in pregnant women. In neonates, large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”); the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Other warnings/precautions:

• Administration: Do not administer intramuscularly.

• Conversion to other products: Not to be used interchangeably (unit for unit) with heparin or any other low molecular weight heparins.

• Neuraxial anesthesia: [US Boxed Warning]: Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include use of indwelling epidural catheters; concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants; a history of traumatic or repeated epidural or spinal punctures; and a history of spinal deformity or spinal surgery. Optimal timing between the administration of enoxaparin and neuraxial procedures is not known. Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis. Delay placement or removal of catheter for at least 12 hours after administration of low-dose enoxaparin (eg, 30 to 60 mg/day) and at least 24 hours after high-dose enoxaparin (eg, 0.75 to 1 mg/kg twice daily or 1.5 mg/kg once daily); risk of neuraxial hematoma may still exist since antifactor Xa levels are still detectable at these time points. Patients receiving twice daily high-dose enoxaparin should have the second dose withheld to allow a longer time period prior to catheter placement or removal. Upon removal of catheter, consider withholding enoxaparin for at least 4 hours. Consider doubling these times in patients with creatinine clearance <30 mL/minute. If anticoagulation is administered during or immediately following diagnostic lumbar puncture, epidural anesthesia/analgesia, or spinal anesthesia/analgesia monitor frequently for signs and symptoms of neurological impairment (midline back pain, sensory and motor deficits, bowel and/or bladder dysfunction). If spinal hematoma is suspected, diagnose and treat immediately; spinal cord decompression may be considered although it may not prevent or reverse neurological sequelae.

Monitoring Parameters

Platelet count, hemoglobin, hematocrit, fecal occult blood, signs and symptoms of bleeding, anti-Xa levels (as appropriate), and serum creatinine at baseline and during therapy; monitoring of PT and/or aPTT is not necessary. Routine monitoring of anti-Xa activity is not required but has been utilized in patients with obesity and/or renal insufficiency.

For patients > 144 kg, if anti-Xa monitoring is available, adjusting dose based on anti-Xa activity is recommended; if anti-Xa monitoring is unavailable, reduce dose if bleeding occurs (Garcia 2012; Nutescu 2009). Monitor obese patients closely for signs/symptoms of thromboembolism.

Monitoring anti-Xa activity is recommended in pregnant women receiving therapeutic doses of enoxaparin or when receiving enoxaparin for the prevention of thromboembolism with mechanical heart valves (ACCP [Guyatt 2012]).

Pregnancy Considerations

Low molecular weight heparin (LMWH) does not cross the placenta; increased risks of fetal bleeding or teratogenic effects have not been reported (Bates 2012).

LMWH is recommended over unfractionated heparin for the treatment of acute VTE in pregnant women. LMWH is also recommended over unfractionated heparin for VTE prophylaxis in pregnant women with certain risk factors (eg, homozygous factor V Leiden, antiphospholipid antibody syndrome with ≥3 previous pregnancy losses). Prophylaxis is not routinely recommended for women undergoing assisted reproduction therapy; however, LMWH therapy is recommended for women who develop severe ovarian hyperstimulation syndrome. For women undergoing cesarean section and who have additional risk factors for developing VTE, the prophylactic use of LMWH may be considered (Bates 2012). Consult current recommendations for appropriate use in pregnant women.

LMWH may also be used in women with mechanical heart valves (consult current guidelines for details) (Bates 2012; Nishimura 2014). Women who require long-term anticoagulation with warfarin and who are considering pregnancy, LMWH substitution should be done prior to conception when possible. When choosing therapy, fetal outcomes (ie, pregnancy loss, malformations), maternal outcomes (ie, VTE, hemorrhage), burden of therapy, and maternal preference should be considered (Bates 2012). Monitoring antifactor Xa levels is recommended (Bates 2012; Nishimura 2014).

Multiple-dose vials contain benzyl alcohol (avoid in pregnant women due to association with gasping syndrome in premature infants); use of preservative-free formulations is recommended.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, injection site irritation, or diarrhea. Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), angina, shortness of breath, skin discoloration, swelling of arms or legs, back pain, numbness or tingling feeling, muscle weakness, paralysis, urinary incontinence, fecal incontinence, dizziness, passing out, confusion, severe headache, or severe loss of strength (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

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