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Enoxaparin (including biosimilars available in Canada): Drug information

Enoxaparin (including biosimilars available in Canada): Drug information
(For additional information see "Enoxaparin (including biosimilars available in Canada): Patient drug information" and see "Enoxaparin (including biosimilars available in Canada): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US 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.

Brand Names: US
  • Lovenox
Brand Names: Canada
  • Inclunox;
  • Inclunox HP;
  • Lovenox;
  • Lovenox HP;
  • Noromby;
  • Noromby HP;
  • Redesca;
  • Redesca HP
Pharmacologic Category
  • Anticoagulant;
  • Anticoagulant, Low Molecular Weight Heparin
Dosing: Adult

The adult dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editor: Edith A Nutescu, PharmD, MS, FCCP.

Note: One mg of enoxaparin is equal to 100 units of anti-factor 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.

Frostbite

Frostbite (adjunctive agent) (off-label use): Note: Patients should be transferred to a facility that is familiar with managing patients with frostbite. Anticoagulation may be used in conjunction with thrombolytic therapy, either concurrently (eg, heparin) or following administration of the thrombolytic, but not as monotherapy (Ref). Optimal regimens, administration routes, and doses, including the use of therapeutic or low-dose anticoagulation after thrombolytic therapy, have not been identified; refer to institutional protocols.

Example regimen:

SUBQ: 1 mg/kg every 12 hours; start after completion of thrombolytic therapy and continue for 7 to 14 days; some centers initiate anticoagulation with unfractionated heparin, then transition to enoxaparin to complete the treatment course (Ref).

Hemodialysis, intermittent, anticoagulation of circuit

Hemodialysis, intermittent, anticoagulation of circuit (off-label use):

Note: Standard dosing has not been established for intermittent hemodialysis. Recommendations provided below are examples. Refer to institutional protocols. May need to individualize dose based on patient-specific needs.

Injection into arterial line of hemodialysis circuit: 0.5 to 1 mg/kg administered once at the beginning of hemodialysis (Ref). Some experts recommend 20 to 40 mg administered once at the beginning of hemodialysis (Ref).

Ischemic heart disease

Ischemic heart disease:

Acute coronary syndromes:

Non-ST-elevation acute coronary syndromes:

SUBQ: 1 mg/kg every 12 hours in conjunction with an appropriate antiplatelet regimen; continue for the duration of hospitalization or until percutaneous coronary intervention (PCI) is performed.

ST-elevation myocardial infarction:

Note: Initial dosing is the same for patients who undergo reperfusion with fibrinolysis or PCI and for patients who do not undergo reperfusion. In patients with STEMI receiving thrombolytics, initiate enoxaparin between 15 minutes before and 30 minutes after fibrinolytic therapy. Use in conjunction with an appropriate antiplatelet regimen (Ref).

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. SUBQ: 0.75 mg/kg (maximum: 75 mg for the first 2 doses only) every 12 hours.

Duration: Therapy may be continued for up to 8 days (minimum of 48 hours when undergoing reperfusion with fibrinolysis) or until revascularization (Ref).

Percutaneous coronary intervention, adjunctive therapy (off label) (alternative agent):

Note: Consider for use as an alternative to unfractionated heparin (Ref).

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 (Ref).

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 (Ref).

If PCI occurs >12 hours after the last SUBQ dose: May use an established anticoagulation regimen (eg, unfractionated heparin, bivalirudin) (Ref).

Mechanical heart valve

Mechanical heart valve (bridging anticoagulation) (off-label use):

Note: Bridging during intervals of subtherapeutic anticoagulation should be considered for patients with mechanical mitral or tricuspid valve replacement; however, for patients with mechanical aortic valve replacement, bridging is not required unless an additional thromboembolic risk factor is present or patient has an older generation mechanical aortic valve (Ref).

SUBQ: 1 mg/kg every 12 hours; adjust dose based on anti-factor Xa monitoring (Ref). For additional information regarding anti-factor Xa monitoring, refer to the Reference Range field.

Superficial vein thrombosis, acute symptomatic

Superficial vein thrombosis, acute symptomatic (alternative agent) (off-label use):

Note: Consider as an alternative to fondaparinux for use in patients at increased risk for thromboembolism or with recurrent superficial vein thrombosis.

SUBQ: 40 mg once daily for 45 days (Ref).

Venous thromboembolism prophylaxis

Venous thromboembolism prophylaxis:

Medical patients with acute illness at moderate and high risk for venous thromboembolism:

SUBQ: 40 mg once daily; continue for length of hospital stay or until patient is fully ambulatory and risk of venous thromboembolism (VTE) has diminished (Ref). Extended prophylaxis beyond acute hospital stay is not routinely recommended (Ref); however, in high-risk COVID-19 patients who are discharged from the hospital, some experts would consider extended prophylaxis with a direct oral anticoagulant (eg, rivaroxaban) (Ref).

Bariatric surgery patients at high risk for venous thromboembolism, perioperative (off-label use):

Note: Optimal dosing strategies have not been established. Dosing regimens based on best available evidence (Ref).

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 (Ref).

Nonmajor orthopedic surgery of lower limb (alternative therapy) (off-label use):

Note: Early ambulation alone is preferred when feasible, but pharmacologic prophylaxis may be considered for patients with higher than usual risk (eg, history of VTE, limited mobility, or undergoing high-risk surgery such as Achilles tendon repair, femoral fracture, tibial plateau fracture, or ligament repair of the knee) (Ref).

SUBQ: 40 mg once daily initiated ≥6 to 10 hours after surgery; continue for the duration of immobilization (Ref).

Nonorthopedic surgery (off label):

Patients with active cancer:

SUBQ: 40 mg started 10 to 12 hours before surgery and 40 mg once daily thereafter (Ref).

or

SUBQ: 40 mg started 2 to 4 hours before surgery and 40 mg once daily thereafter (Ref).

or

SUBQ: 40 mg once daily started ~12 to 24 hours after surgery (Ref).

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

Patients without active 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 (Ref). Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days) (Ref).

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 (Ref).

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

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) (Ref).

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 (Ref). 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 (Ref). Anticoagulation should continue for up to 6 weeks postpartum, but potentially longer (Ref).

Total hip arthroplasty 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 (Ref). Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days (Ref); some experts suggest a duration at the higher end of range (eg, 30 days) (Ref).

Total knee arthroplasty:

SUBQ: 30 mg every 12 hours, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved (Ref). Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days (Ref); some experts suggest a duration at the lower end of the range (eg, 10 to 14 days) (Ref).

Trauma, moderate to high risk (off-label use):

Note: Time of initiation is a balance between the benefits of VTE prevention and risk for bleeding. In most trauma patients, initiate within 24 to 48 hours of hospital admission provided hemostasis has been achieved and risk for bleeding is low. Prophylaxis may be delayed in some subgroups, such as those with traumatic brain injury, active bleeding, coagulopathy, spinal cord injury, spine surgery, or solid organ injury, but can be started within 72 hours in most situations (Ref). For trauma that results primarily in orthopedic injury, refer to "Total hip arthroplasty or hip fracture surgery"and "Total knee arthroplasty" indications above. Practices may vary due to specific population risk of VTE and risk for bleeding; refer to institution-specific protocols. General dosing guidance is below.

Patients ≤65 years of age, ≥50 kg, and CrCl >60 mL/ minute:

Non–weight-based dosing: SUBQ: 40 mg every 12 hours; consider dose adjustment based on anti-factor Xa level, targeting a peak level of 0.2 to 0.4 units/mL or a trough level of 0.1 to 0.2 units/mL (Ref).

Weight-based dosing: SUBQ: 0.5 mg/kg every 12 hours; consider dose adjustment based on anti-factor Xa level, targeting a peak level of 0.2 to 0.4 units/mL or a trough level of 0.1 to 0.2 units/mL (Ref).

Patients >65 years of age, <50 kg, CrCl 30 to 60 mL/minute, traumatic brain injury, or spine trauma: SUBQ: 30 mg every 12 hours; consider dose adjustment based on anti-factor Xa level, targeting a peak level of 0.2 to 0.4 units/mL or a trough level of 0.1 to 0.2 units/mL (Ref).

Pregnant trauma patients:

Patients >90 kg: SUBQ: 40 mg every 12 hours; dose adjustment based on anti-factor Xa level is recommended, targeting a peak level of 0.2 to 0.4 units/mL or a trough level of 0.1 to 0.2 units/mL (Ref).

Patients ≤90 kg: SUBQ: 30 mg every 12 hours; dose adjustment based on anti-factor Xa level is recommended, targeting a peak level of 0.2 to 0.4 units/mL or a trough level of 0.1 to 0.2 units/mL (Ref).

Duration of therapy: Optimal duration of prophylaxis is unknown; prophylaxis should be continued throughout hospitalization based on patient risk factors (Ref).

Venous thromboembolism treatment

Venous thromboembolism treatment:

Note: For timing of initiating oral anticoagulant, see "Transitioning Between Anticoagulants."

Deep vein thrombosis and/or pulmonary embolism (pulmonary embolism is an off-label use): SUBQ: 1 mg/kg every 12 hours (preferred) or 1.5 mg/kg once every 24 hours.

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 venous thromboembolism: 3 months (provided the provoking risk factor is no longer present) (Ref).

Unprovoked venous thromboembolism or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of VTE recurrence and bleeding (Ref).

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

Venous thromboembolism 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 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 (Ref).

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 (Ref).

Venous thromboembolism treatment in pregnancy:

SUBQ: 1 mg/kg every 12 hours (Ref). Consider anti-factor Xa monitoring for dose adjustment (Ref). For additional information regarding anti-factor 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 (Ref). 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 (Ref). 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 (Ref).

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 (Ref).

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 (Ref).

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: Start warfarin and continue enoxaparin until INR is within therapeutic range (Ref). Note: For the treatment of VTE, overlap enoxaparin with warfarin until INR is ≥2 for at least 2 measurements taken ~24 hours apart (duration of overlap is usually 4 to 5 days) (Ref).

Transitioning from therapeutic-dose enoxaparin to a direct oral anticoagulant: Start direct oral anticoagulant (DOAC) within 2 hours prior to the next scheduled dose of enoxaparin.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: In patients with kidney impairment anti-factor Xa levels may be used to monitor anticoagulant effects.

CrCl >50 mL/minute: No dose adjustment necessary for most indications.

Venous thromboembolism prophylaxis in trauma patients, moderate to high risk (off-label use): CrCl 50 to 60 mL/minute: SUBQ: 30 mg every 12 hours; consider dose adjustment based on anti-factor Xa level, targeting a peak level of 0.2 to 0.4 units/mL or a trough level of 0.1 to 0.2 units/mL (Ref).

CrCl 30 to 50 mL/minute: No dose adjustment necessary for most indications.

Note: Bleeding risk may be increased when standard treatment doses are used (eg, treatment of venous thromboembolism) (Ref); monitor closely for evidence of bleeding. Empiric dose reduction strategies have been proposed (Ref) but lack robust evidence.

Venous thromboembolism prophylaxis in trauma patients, moderate to high risk (off-label use): SUBQ: 30 mg every 12 hours; consider dose adjustment based on anti-factor Xa level, targeting a peak level of 0.2 to 0.4 units/mL or a trough level of 0.1 to 0.2 units/mL (Ref).

CrCl <30 mL/minute:

Venous thromboembolism prophylaxis (except in trauma patients): SUBQ: 30 mg once daily. Note: The Canadian labeling recommends 20 or 30 mg once daily (based on risk/benefit assessment) for prophylaxis in abdominal or colorectal surgery or in medical patients during acute illness.

Venous thromboembolism prophylaxis in trauma patients, moderate to high risk (off-label use): Use another form of pharmacologic prophylaxis (eg, unfractionated heparin) (Ref).

Venous thromboembolism treatment: SUBQ: 1 mg/kg once daily.

ST-elevation myocardial infarction:

<75 years of age: Initial: IV: 30 mg as a single dose with the first dose of the SUBQ maintenance regimen administered at the same time as the IV bolus; maintenance: SUBQ: 1 mg/kg once daily. Note: Canadian labeling recommends a maximum dose of 100 mg for the first SUBQ dose.

≥75 years of age: Omit IV bolus; maintenance: SUBQ: 1 mg/kg once daily. Note: Canadian labeling recommends a maximum dose of 100 mg for the first SubQ dose.

Non-ST-elevation acute coronary syndromes: SUBQ: 1 mg/kg once daily.

Hemodialysis, intermittent (thrice weekly) (systemic anticoagulation): SUBQ: Not dialyzable (Klingel 2004a): Avoid use if possible, as there may be accumulation of active heparin metabolites that are undetected by anti-factor Xa assays (Ref). Serious bleeding complications have been reported with use in patients who are dialysis dependent or have severe kidney failure (Ref). Note that some retrospective studies suggest that enoxaparin may be used for deep vein thrombosis prophylaxis in dialysis patients with no increase in bleeding risk (Ref).

Peritoneal dialysis: SUBQ: Not dialyzable (Ref). Avoid use if possible. In one pharmacokinetic trial, peritoneal dialysis subjects exhibited a greater anti-factor Xa 12-hour concentration compared to healthy volunteers and hemodialysis patients.

CRRT or PIRRT (systemic anticoagulation): SUBQ: Avoid use if possible. Significant clearance unlikely (Ref). If used, monitor closely for bleeding and utilize anti-factor Xa monitoring (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Dosing: Pediatric

(For additional information see "Enoxaparin (including biosimilars available in Canada): Pediatric drug information")

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: Pediatric") (Ref); extra precaution should be taken to ensure accurate dose delivery.

Prophylaxis

Prophylaxis: Limited data available (Ref): Note: May consider titrating dose to achieve a 4 to 6 hours postdose target anti-factor Xa level of 0.1 to 0.3 units/mL (Ref):

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

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 (Ref). Once-daily dosing in pediatric patients with normal renal function is not feasible due to faster enoxaparin clearance and lower drug exposure in pediatric patients compared to adults (Ref). Duration of treatment based on thrombosis site, clinical response, and other identified risk factors; usual duration between 6 weeks and 3 months (Ref):

Initial:

Chest/AHA guidelines (Ref).

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 (Ref) are required in pediatric patients (especially in young infants or critically ill) (Ref). Some centers have used the following:

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

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

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

6 to 18 years: SUBQ: 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 (Ref); based on pharmacokinetic parameters, steady-state levels are typically reached between second and fourth dose. Studies have suggested that initial dosing and dosage titration from the Chest guidelines do not consistently result in therapeutic anti-factor Xa levels; more aggressive dosing may be necessary (Ref).

Previous Chest guidelines (Ref) suggested the following dosage adjustments to achieve the target anti-factor Xa range (Ref):

Enoxaparin Dosage Titration for Thrombosis Treatment

Anti-factor Xa

Dose Titration

Time to Repeat Anti-factor Xa Levela,c

a Based on pharmacokinetic parameters including half-life and steady-state levels.

b Trough anti-factor Xa level to ensure continued drug clearance and optimize safety; may consider checking trough anti-factor Xa levels in high-risk patients (eg, patients with changing renal function and/or increased risk of bleeding). Goal trough anti-factor Xa level not defined/reported for twice-daily dosing; trough anti-factor Xa level of 0.1 units/mL has been suggested with once-daily dosing.

c Consider more frequent anti-factor Xa monitoring based clinical scenario.

Adapted from Monagle P, Michelson AD, Bovill E, et al. Antithrombotic therapy in children. Chest. 2001;119:344S-370S; Monagle P, Chan AKC, 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-e801S. doi:10.1378/chest.11-2308; and Wiltrout K, Lissick J, Raschka M, Nickel A, Watson D. Evaluation of a pediatric enoxaparin dosing protocol and the impact on clinical outcomes. J Pediatr Pharmacol Ther. 2020;25(8):689-696. doi:10.5863/1551-6776-25.8.689.

<0.35 units/mL

Increase dose by 25%

4 to 6 hours after second dose

0.35 to 0.49 units/mL

Increase dose by 10%

4 to 6 hours after second dose

0.5 to 1 unit/mL

Keep same dosage

Next day, then 1 week later, then every 1 to 4 weeks (4 to 6 hours after dose)

1.1 to 1.5 units/mL

Decrease dose by 20%

4 to 6 hours after second dose; may consider checking trough level immediately before next dose to confirm drug clearance.b

1.6 to 2 units/mL

Hold dose for 3 hours and decrease dose by 30%

Consider checking trough level immediately before next dose to confirm drug clearanceb, then 4 to 6 hours after second dose.

>2 units/mL

Hold all doses until anti-factor Xa is 0.5 units/mL, then decrease dose by 40%

While level is ≥0.5 units/mL: 12 hours after last dose and every 12 hours until anti-factor Xa <0.5 units/mL.

Once enoxaparin restarted: 4 to 6 hours after second dose; may consider more frequent monitoring based on clinical scenario.

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific recommendations; use with caution and monitor patient closely; based on experience in adult patients, dosage adjustment suggested in some instances.

Dialysis: Enoxaparin has not been FDA approved for use in dialysis patients (pediatric or adult). Its elimination is primarily via the renal route. Serious bleeding complications have been reported with use in adult patients who are dialysis dependent or have severe renal failure. LMWH administration at fixed doses without monitoring has greater unpredictable anticoagulant effects in patients with chronic kidney disease. If used, dosages should be reduced and anti-Xa levels frequently monitored, as accumulation may occur with repeated doses. Many clinicians would not use enoxaparin in this population especially without timely anti-Xa levels.

Hemodialysis: Not dialyzable (Ref). Supplemental dose is not necessary.

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.

Dosing: Older Adult

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: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Acute coronary syndromes:

Class 1, 2, and 3 obesity (BMI ≥30 kg/m2):

ST-elevation myocardial infarction: SUBQ: After an initial single IV bolus (in patients <75 years of age) or no IV bolus (in patients ≥75 years of age), administer 1 mg/kg SUBQ every 12 hours using actual body weight; a maximum dose of 100 mg is recommended for the first 2 doses for patients <75 years of age and maximum dose of 75 mg for patients ≥75 years of age (Ref). Refer to "Dosing: Adult."

Non-ST-elevation acute coronary syndromes: SUBQ: 1 mg/kg every 12 hours using actual body weight (Ref); bleeding rates may be higher when weight exceeds 150 kg. Consider lower doses (0.7 to 1 mg/kg every 12 hours) or a dose capping strategy (eg, maximum dose: 150 mg every 12 hours) (Ref).

Venous thromboembolism treatment:

Class 1, 2, and 3 obesity (BMI ≥30 kg/m2):

SUBQ: 1 mg/kg every 12 hours (based on actual body weight); usual dosing range: 0.7 to 1 mg/kg every 12 hours (Ref). In patients with BMI ≥50 kg/m2, use the lower end of the usual dosing range; for patients with extreme BMI (~114 kg/m2), doses below the usual dosage range may be indicated (Ref); anti-factor Xa monitoring is recommended in select patients (eg, high risk of bleeding and/or ≥150 kg) (Ref).

Venous thromboembolism prophylaxis: Note: For bariatric surgery recommendations, see "Dosing: Adult: Venous thromboembolism prophylaxis, bariatric surgery, high venous thromboembolism risk."

Class 1 and 2 obesity (BMI 30 to 39 kg/m2): Use standard dosing (Ref). Refer to "Dosing: Adult" for indication-specific doses.

Class 3 obesity (BMI ≥40 kg/m2): Note: Choice of fixed dosing or weight-based dosing strategy is an area of clinical controversy; either regimen is reasonable (Ref).

SUBQ: 40 mg twice daily (Ref) or 0.5 mg/kg twice daily (based on actual body weight) (Ref). For patients with BMI >50 kg/m2, consider 60 mg twice daily (Ref) or 0.5 mg/kg twice daily (based on actual body weight) (Ref). Note: Wide variability exists in the reported dosing range and target anti-factor Xa level.

Rationale for recommendations:

Acute coronary syndromes: Data evaluating initial doses greater than 150 mg are limited. One study reported higher major bleeding rates in patients when weight was >150 kg and standard enoxaparin doses (based on actual body weight) were used compared to reduced doses (<0.95 mg/kg) (Ref). Based on this, reduced doses should be considered. Alternatively, some have recommended a dose capping strategy (Ref). Anti-factor Xa level monitoring is suggested (Ref).

Venous thromboembolism treatment: Minimal data exist for initial doses that exceed 150 mg every 12 hours, as most studies either utilized dose-capping strategies or did not include a substantial number of patients weighing >150 kg (Ref). In patients with a BMI ≥40 kg/m2, pharmacokinetic studies have demonstrated supratherapeutic anti-factor Xa levels with standard dosing (1 mg/kg every 12 hours based on actual body weight) (Ref). However, dose capping is not recommended in patients with obesity due to risk of treatment failure (Ref).

Venous thromboembolism prophylaxis: Potentially reduced absorption following SUBQ dosing in patients with obesity can result in variable exposure (Ref). In addition, due to the uncertainty of weight-based dosing metrics, dose adjustment using anti-factor Xa monitoring is recommended, where available (Ref).

Dosage Forms: US

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 Prefilled Syringe, Injection, as sodium:

Generic: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL); 80 mg/0.8 mL (0.8 mL)

Solution Prefilled Syringe, Injection, 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)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

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]

Redesca: 300 mg/3 mL (3 mL) [contains benzyl alcohol]

Solution Prefilled Syringe, Injection, as sodium:

Inclunox: 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)

Inclunox HP: 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL)

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)

Lovenox HP: 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL)

Noromby: 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)

Noromby HP: 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL)

Redesca: 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)

Redesca HP: 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL)

Administration: Adult

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 administer into bruised or scarred skin or through clothing. 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.

Administration: Pediatric

Parenteral: For SUBQ use only, do not administer IM or IV. Administer by deep SUBQ injection. In neonates, the thighs are the usual sites for injection (Ref). In adults, it is recommended to alternate between the left or right anterolateral and left or right posterolateral abdominal wall; these injection sites, in addition to the triceps, have also been suggested in children and adolescents with adequate subcutaneous tissue (Ref). Do not rub injection site after SUBQ administration as bruising may occur. When administering 30 mg or 40 mg SUBQ from a commercially prefilled syringe, do not expel the air bubble from the syringe prior to injection (in order to avoid loss of drug).

Use: Labeled Indications

Acute coronary syndromes: Unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction.

Deep vein thrombosis treatment (acute): Inpatient treatment (patients with or without pulmonary embolism [PE]) and outpatient treatment (patients without PE).

Venous thromboembolism 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: In Canada, Inclunox, Noromby, and Redesca are approved as biosimilars to Lovenox; Inclunox HP, Noromby HP, and Redesca HP are approved as biosimilars to Lovenox HP.

Use: Off-Label: Adult

Frostbite; Hemodialysis, intermittent, anticoagulation of circuit; Mechanical heart valve (bridging anticoagulation); Pulmonary embolism (acute); Superficial vein thrombosis, acute symptomatic; Venous thromboembolism prophylaxis, bariatric surgery patients at high risk for venous thromboembolism, perioperative; Venous thromboembolism prophylaxis, nonmajor orthopedic surgery of lower limb; Venous thromboembolism prophylaxis, nonorthopedic surgery and trauma

Medication Safety Issues
Sound-alike/look-alike issues:

Lovenox may be confused with Lasix, Levaquin, Levemir, Lotronex, Protonix

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

National Patient Safety Goals:

The Joint Commission (TJC) requires healthcare organizations that provide anticoagulant therapy to have approved protocols and evidence-based practice guidelines in place to reduce the risk of anticoagulant-associated patient harm. Patients receiving anticoagulants should receive individualized care through a defined process that includes medication selection, dosing (including adjustments for age, renal function, or liver function), drug-drug interactions, drug-food interactions, other applicable risk factors, monitoring, patient and family education, proper administration, reversal of anticoagulation, management of bleeding events, and perioperative management. This does not apply to routine short-term use of anticoagulants for prevention of venous thromboembolism during procedures or hospitalizations (NPSG.03.05.01).

Adverse Reactions (Significant): Considerations
Major bleeding

Enoxaparin may increase the risk of bleeding (hemorrhage), including severe and potentially fatal major hemorrhage as defined by the International Society on Thrombosis and Hemostasis (Ref). Bleeding is partially reversible with the use of protamine. Although the risk of bleeding is dependent upon many factors, at recommended doses enoxaparin does not significantly affect PT or aPTT; therefore, if monitoring, anti-factor Xa levels must be used (Ref).

Mechanism: Dose-related; related to the pharmacologic action (ie, anticoagulant; inhibition of factor Xa with less inhibition of factor IIa) (Ref).

Onset: Varied; time to onset of bleeding is unpredictable and affected by many variables. In one study, time to bleeding ranged from after the second dose to after 25 days of therapy (Ref).

Risk factors:

• Dose (Ref)

• Kidney impairment (CrCl <50 mL/minute) (Ref)

• Uncontrolled hypertension (Ref)

• Females (Ref)

• Age >75 years (Ref)

• Obesity (Ref)

• Bridging with warfarin therapy (Ref)

• Concurrent antiplatelet agents (Ref)

• Hepatic impairment (Ref)

• History of GI bleeding (Ref)

• Peptic ulcer disease (Ref)

• Anemia (Ref)

• Congenital or acquired bleeding disorders

• Hemorrhagic stroke or use shortly after brain, spinal, or ophthalmic surgery

• Thrombocytopenia or platelet defects or history of heparin-induced thrombocytopenia

• Hypertensive or diabetic retinopathy

• Patients undergoing invasive procedures

Spinal or epidural hematomas

Spinal hematoma or epidural intracranial hemorrhage may occur in patients treated with enoxaparin who are receiving neuraxial anesthesia or undergoing spinal puncture; may result in long-term or permanent paralysis. Spontaneous spinal epidural hematoma (SEH) have also been reported (Ref). Withholding enoxaparin and treating immediately with consideration for spinal cord decompression may improve symptoms but may not be able to entirely prevent or reverse neurologic sequelae (Ref).

Mechanism: SEH due to neuraxial anesthesia or spinal puncture is related to trauma in the presence of impaired hemostasis with enoxaparin (Ref). Spontaneous SEH may be due to venous rupture and hemorrhage secondary to sudden increase in thoracic and/or abdominal pressure (Ref).

Onset: SEH in patients treated with enoxaparin who received neuraxial anesthesia or spinal puncture: Rapid; several studies reported onset within 2 to 3 days after initiation (Ref). In cases of spontaneous SEH, onset of symptoms occurred within 1 dose to 1 week of enoxaparin therapy (Ref).

Risk factors:

• Use of indwelling epidural catheters (Ref)

• Concurrent administration of other drugs that affect hemostasis (eg, aspirin, nonsteroidal anti-inflammatory drugs, platelet inhibitors, other anticoagulants) (Ref)

• History of traumatic or repeated epidural or spinal punctures (Ref)

• History of spinal deformity or surgery (Ref)

• If optimal timing between administration of enoxaparin and neuraxial procedures is unknown

• Older patients (Ref)

• Females (Ref)

• Congenital coagulation deficiencies (Ref)

• Underlying vascular lesions (Ref)

• Risk factors for spontaneous SEH: Conditions causing increased intra-abdominal pressure (eg, coughing, Valsalva maneuver, weight-lifting) (Ref)

Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) and thrombosis in heparin-induced thrombocytopenia (HITT) have occurred, with some cases complicated by organ infarction, limb ischemia, and/or death. Low platelet counts from acute HIT are reversible upon enoxaparin discontinuation and initiation of appropriate interventions (Ref).

Mechanism: Immunologic. Caused by IgG antibodies binding to heparin and platelet-factor 4 (PF4) complexes, leading to platelet activation, consumption, and subsequent thrombosis (Ref).

Onset: Varied; depends on heparin exposure in the past 30 days. Usually occurs 5 to 14 days after exposure in heparin-naive patients (5 to 7 days with enoxaparin), or <1 day after repeat exposure in patients who received heparin in the past 30 days (Ref).

Risk factors:

• Duration of therapy (>5 days) (Ref)

• Patient population (surgical and trauma patients at highest risk versus medical and obstetrical patients) (Ref)

• Females (Ref)

• Dose (treatment dosing is a higher risk than prophylactic dosing) (Ref)

• Higher with unfractionated heparin compared to low-molecular weight heparin (eg, enoxaparin) (Ref)

Adverse Reactions

The following adverse reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Hematologic & oncologic: Anemia (≤16%) (table 1), hemorrhage (4% to 13%)

Enoxaparin: Adverse Reaction: Anemia

Drug (Enoxaparin)

Comparator (Heparin)

Placebo

Dose

Indication

Number of Patients (Enoxaparin)

Number of Patients (Heparin)

Number of Patients (Placebo)

Comments

3%

3%

N/A

40 mg daily

Abdominal or colorectal surgery

1,228

1,234

N/A

N/A

16%

5%

7%

40 mg daily

Hip or knee replacement surgery

288

766

115

Peri-operative period

2%

5%

7%

30 mg q12h

Hip or knee replacement surgery

1,080

766

115

N/A

<2%

5%

7%

40 mg daily

Hip or knee replacement surgery

131

766

115

Extended prophylaxis period

Enoxaparin: Adverse Reaction: Hemorrhage

Drug (Enoxaparin)

Comparator (Heparin)

Placebo

Dose

Indication

Number of Patients (Enoxaparin)

Number of Patients (Heparin)

Number of Patients (Placebo)

Comments

7%

6%

N/A

40 mg daily

Abdominal or colorectal surgery

1,128

1,234

N/A

N/A

13%

4%

3%

40 mg daily

Hip or knee replacement surgery

288

766

115

Peri-operative period

5%

4%

3%

40 mg daily

Hip or knee replacement surgery

131

766

115

Extended prophylaxis period

4%

4%

3%

30 mg q12h

Hip or knee replacement surgery

1,080

766

115

N/A

1% to 10%:

Cardiovascular: Peripheral edema (6%)

Dermatologic: Ecchymoses (3%)

Gastrointestinal: Nausea (3%)

Genitourinary: Hematuria (≤2%)

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

Enoxaparin: Adverse Reaction: Major Hemorrhage

Drug (Enoxaparin)

Comparator (Heparin)

Placebo

Dose

Indication

Number of Patients (Enoxaparin)

Number of Patients (Heparin)

Number of Patients (Placebo)

Comments

4%

3%

N/A

40 mg daily

Abdominal surgery

555

560

N/A

N/A

2%

1%

N/A

Initial 30 mg IV bolus followed by 1 mg/kg q12h SubQ

Acute ST-segment elevation myocardial infarction

10,176

10,151

N/A

N/A

4%

3%

N/A

40 mg daily

Colorectal surgery

673

674

N/A

N/A

2%

2%

N/A

1.5 mg/kg daily

Deep vein thrombosis with or without pulmonary embolism treatment

298

554

N/A

N/A

2%

2%

N/A

1 mg/kg q12h

Deep vein thrombosis with or without pulmonary embolism treatment

559

554

N/A

N/A

2%

N/A

N/A

40 mg daily

Hip replacement surgery with extended prophylaxis

288

N/A

N/A

Peri-operative period

0%

N/A

N/A

40 mg daily

Hip replacement surgery with extended prophylaxis

221

N/A

N/A

Extended prophylaxis period

4%

6%

N/A

30 mg q12h

Hip replacement surgery without extended prophylaxis

786

541

N/A

N/A

1%

1%

N/A

30 mg q12h

Knee replacement surgery without extended prophylaxis

294

225

N/A

N/A

<1%

N/A

<1%

40 mg daily

Severely restricted mobility during acute illness

360

N/A

362

N/A

1%

1%

N/A

1 mg/kg q12h

Unstable angina and non–Q-wave myocardial infarction

1,578

1,529

N/A

N/A

Enoxaparin: Adverse Reaction: Thrombocytopenia

Drug (Enoxaparin)

Comparator (Heparin)

Placebo

Dose

Indication

Number of Patients (Enoxaparin)

Number of Patients (Heparin)

Number of Patients (Placebo)

Comments

2%

N/A

N/A

N/A

Acute ST-segment elevation myocardial infarction

N/A

N/A

N/A

N/A

0.1%

0.2%

0.4%

N/A

N/A

N/A

N/A

N/A

Platelet counts <50,000/mm3

1%

1%

0.7%

N/A

N/A

N/A

N/A

N/A

Platelet counts between 100,000/mm3 and 50,000/mm3

3%

N/A

3%

40 mg daily

Severely restricted mobility during acute illness

360

N/A

362

N/A

Hepatic: Increased serum alanine aminotransferase (>3 x ULN: 6%), increased serum aspartate aminotransferase (>3 x ULN: 6%)

Local: Bleeding at injection site (3% to 5%), hematoma at injection site (9%), pain at injection site (2%)

Nervous system: Confusion (2%)

Miscellaneous: Fever (5% to 8%)

<1%:

Cardiovascular: Atrial fibrillation, cardiac failure

Respiratory: Pneumonia, pulmonary edema

Frequency not defined: Local: Bruising at injection site, erythema at injection site, irritation at injection site

Postmarketing:

Cardiovascular: Hypersensitivity angiitis, thrombosis (prosthetic value [in pregnant females; McLintock 2009] or associated with enoxaparin-induced thrombocytopenia; can cause limb ischemia or organ infarction [Singh 2020])

Dermatologic: Alopecia (Wang 2006), maculopapular rash (Kim 2003), pruritus (MacLaughlin 2002), skin necrosis (Abou Issa 2015; Coelho 2016), urticaria (Abou Issa 2015; Villanueva 2012), vesicobullous rash (Miguel-Gomez 2016; Villanueva 2012)

Endocrine & metabolic: Hyperkalemia (Scalese 2016), hyperlipidemia (very rare) (Resic 2010; Tomsu 1998), hypertriglyceridemia (Resic 2010; Tomsu 1998)

Hematologic & oncologic: Acute posthemorrhagic anemia (Bala 2017), purpuric disease (Li 2019), spinal hematoma (rare: <1%) (Heppner 2004), thrombocythemia (Meenpidiyil 2020), thrombosis in heparin-induced thrombocytopenia

Hepatic: Hepatotoxicity (hepatocellular and cholestatic; including increased serum alkaline phosphatase) (Baker 2009; Mehershahi 2020])

Hypersensitivity: Anaphylactic shock, anaphylaxis (Anders 2013; Leguisamo 2015), angioedema (Smith 2004), nonimmune anaphylaxis (MacLaughlin 2002), type IV hypersensitivity reaction (Cabanas 1998)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Ronceray 2012)

Local: Injection site reaction (including nodules, inflammation, oozing)

Nervous system: Epidural intracranial hemorrhage (rare: <1%) (Wysowski 1998), headache

Neuromuscular & skeletal: Osteoporosis (following long-term therapy) (Wawrzyska 2003)

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.

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: 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: May rarely 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: Use with extreme caution or avoid in patients with history of HIT (Warkentin 2001). 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.

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 may be required. In pediatric patients with renal impairment, more frequent monitoring is recommended (Bahabri 2021).

Special populations:

• Older adult: 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.

• 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: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 anti-factor 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 CrCl <30 mL/minute.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

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

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

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

Antithrombin: May enhance the anticoagulant effect of Heparins (Low Molecular Weight). Risk C: 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. Risk X: Avoid combination

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

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

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. Risk C: 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. Risk X: Avoid combination

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

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: 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. Risk X: Avoid combination

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

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

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

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy

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

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

Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

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

Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

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

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

Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

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

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

Nonsteroidal Anti-Inflammatory Agents: May enhance the anticoagulant effect of Enoxaparin. Management: Discontinue nonsteroidal anti-inflammatory agents (NSAIDs) prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: 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. Risk X: Avoid combination

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

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

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

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

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

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. Risk C: 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. Risk X: Avoid combination

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

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

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

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: Monitor for signs and symptoms of bleeding if these agents are combined. For the treatment of acute ischemic stroke, avoidance with anticoagulants is often recommended, see full Lexicomp or drug interaction monograph for details. Risk C: Monitor therapy

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

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

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

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

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

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

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Reproductive Considerations

Patients undergoing assisted reproduction therapy (ART) may be at increased risk for thrombosis. Venous thromboembolism prophylaxis is not routinely recommended for patients undergoing ART; however, prophylactic doses of low-molecular-weight heparin (LMWH) are recommended for patients who develop severe ovarian hyperstimulation syndrome (ACCP [Bates 2012]; ASH [Bates 2018]; SOGC [Shmorgun 2017]). In addition, prophylactic doses of LMWH are recommended in patients undergoing ART who have a positive antiphospholipid antibody test but are not diagnosed with antiphospholipid syndrome (APS), as well as patients diagnosed with obstetric APS. Therapeutic doses of LMWH are recommended in patients undergoing ART diagnosed with thrombotic APS (ACR [Sammaritano 2020]).

Pregnancy Considerations

Low-molecular-weight heparin (LMWH) does not cross the placenta (ACOG 2018).

An increased risk of fetal bleeding or teratogenic effects have not been reported (ACCP [Bates 2012]).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of LMWH may be altered; dosing adjustment may be required. Prophylactic doses of LMWH may also need modifying in pregnant patients at extremes of body weight (ACOG 2018).

The risk of venous thromboembolism (VTE) is increased in pregnant patients especially during the third trimester and first week postpartum. LMWH is recommended over unfractionated heparin for the treatment of acute VTE in pregnant patients. LMWH is also recommended over unfractionated heparin for VTE prophylaxis in pregnant patients with certain risk factors (eg, homozygous factor V Leiden, antiphospholipid antibody syndrome with ≥3 previous pregnancy losses) (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]; ESC [Regitz-Zagrosek 2018]). Consult current recommendations for appropriate use in pregnancy.

LMWH may be used prior to cesarean delivery in patients with additional risk factors for developing VTE. Risk factors may include a personal history of DVT or PE, inherited thrombophilia, or patients with class III obesity (SMFM 2020).

LMWH may also be used in pregnant patients with mechanical heart valves. When choosing therapy, fetal outcomes (ie, pregnancy loss, malformations), maternal outcomes (ie, VTE, hemorrhage), burden of therapy, and maternal preference should be considered. Patients with mechanical heart valves have an increased risk of adverse fetal and maternal outcomes (including valve thrombosis) and these risks are greater without appropriate anticoagulation. Increased monitoring of anti-factor Xa levels is required; frequent dose titration may be needed to maintain adequate therapeutic anti-factor Xa concentrations during pregnancy (consult current recommendations for details) (ACC/AHA [Otto 2021]; ESC [Regitz-Zagrosek 2018]).

LMWH is the recommended class of anticoagulants for pregnant patients hospitalized for manifestations of COVID-19, taking into consideration risk factors for bleeding, including threatened delivery. Prophylactic doses are recommended during hospitalization if there are no contraindications to use. Recommendations for or against the use of therapeutic doses are not available due to insufficient data in pregnant patients with COVID-19 without VTE. Patients prescribed antithrombotic therapy prior to a COVID-19 diagnosis should continue their therapy (NIH 2022).

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

Breastfeeding Considerations

It is not known if enoxaparin is present in breast milk.

Small amounts of another low-molecular-weight heparin (LMWH) have been detected in breast milk; however, because they have a low oral bioavailability, LMWHs are unlikely to cause adverse events in a breastfeeding infant. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. LMWH is considered compatible with breastfeeding (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]).

Monitoring Parameters

Platelet count, hemoglobin, hematocrit, fecal occult blood, signs and symptoms of bleeding, anti-factor 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-factor Xa activity is not required but has been utilized in patients with obesity and/or renal insufficiency.

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

Monitoring anti-factor 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 (ACC/AHA [Otto 2021]; ACCP [Guyatt 2012]).

Lumbar puncture/neuraxial anesthesia: In patients who are anticoagulated during or immediately following a lumbar puncture or neuraxial anesthesia (eg, 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).

Reference Range

Adults: The following therapeutic ranges for anti-factor Xa activity have been suggested but have not been validated in a controlled trial. Anti-factor Xa activity should be measured 4 to 6 hours after dosing, beginning after the third or fourth dose when steady state has been achieved (ACC/AHA [Otto 2021]; ACCP [Garcia 2012]; ACOG 2018; Nutescu 2009).

Mechanical heart valve (bridging anticoagulation):

Anti-factor Xa activity target:

Non-pregnant patients: Monitoring anti-factor Xa activity is not necessary. However, some experts recommend monitoring, if possible, and targeting a range of 0.5 to 1 units/mL (ESC/EACTS [Baumgartner 2017]).

Pregnant patients: 0.8 to 1.2 units/mL (ACC/AHA [Otto 2021]). Some experts recommend higher anti-factor Xa targets (eg, 1 to 1.2 units/mL) for mechanical mitral valves and lower targets (0.8 to 1 units/mL) for mechanical aortic valves (Nelson-Piercy 2019). Note: Target trough anti-factor Xa activity should be ≥0.6 units/mL (Goland 2014).

Venous thromboembolism treatment (pulmonary embolism and/or deep vein thrombosis):

Anti-factor Xa activity target:

Once-daily dosing: 1 to 2 units/mL; if there is concern for accumulation (eg, renal impairment) a trough measurement (target <0.5 units/mL) may be useful (ACCP [Garcia 2012]; Nutescu 2009).

Twice-daily dosing: 0.6 to 1 units/mL Note: Twice-daily dosing is recommended in pregnant patients (ACCP [Garcia 2012]; ACOG 2018).

Venous thromboembolism prophylaxis:

Pregnant patients: 0.2 to 0.6 units/mL (ACCP [Bates 2012]).

Trauma, moderate to high risk: Consider dose adjustment based on anti-factor Xa level, targeting a peak level of 0.2 to 0.4 units/mL or trough level of 0.1 to 0.2 units/mL (WTA [Ley 2020]).

Mechanism of Action

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 anti-factor Xa to anti-factor IIa activity than unfractionated heparin.

Pharmacokinetics

Onset of action: Peak effect: SubQ: Anti-factor Xa and antithrombin (anti-factor IIa): 3 to 5 hours

Duration: 40 mg dose: Anti-factor Xa activity: ~12 hours

Distribution: 4.3 L (based on anti-factor Xa activity)

Protein binding: Does not bind to heparin binding proteins

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

Bioavailability: Adults: SubQ: ~100%

Half-life elimination, plasma: 2 to 4 times longer than standard heparin, independent of dose; based on anti-factor Xa activity: 4.5 to 7 hours

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

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

Pharmacokinetics: Additional Considerations

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

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

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

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).

Pricing: US

Solution (Enoxaparin Sodium Injection)

300 mg/3 mL (per mL): $12.80 - $28.17

Solution (Lovenox Injection)

300 mg/3 mL (per mL): $25.66

Solution Prefilled Syringe (Enoxaparin Sodium Injection)

30 mg/0.3 mL (per 0.3 mL): $3.61 - $24.35

40 mg/0.4 mL (per 0.4 mL): $4.81 - $32.47

60 mg/0.6 mL (per 0.6 mL): $6.96 - $48.77

80 mg/0.8 mL (per 0.8 mL): $9.64 - $65.03

100 mg/mL (per mL): $12.05 - $81.28

120 mg/0.8 mL (per 0.8 mL): $14.64 - $97.57

150 mg/mL (per mL): $18.32 - $121.97

Solution Prefilled Syringe (Lovenox Injection)

30 mg/0.3 mL (per 0.3 mL): $7.70

40 mg/0.4 mL (per 0.4 mL): $10.25

60 mg/0.6 mL (per 0.6 mL): $15.39

80 mg/0.8 mL (per 0.8 mL): $20.51

100 mg/mL (per mL): $25.64

120 mg/0.8 mL (per 0.8 mL): $30.77

150 mg/mL (per mL): $38.46

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Bolentax (CR, DO, GT, HN, MX, NI, PA, SV);
  • Clenox (CO, PE);
  • Clexane (AE, AR, AU, BB, BE, BF, BG, BH, BJ, BM, BR, BS, CH, CI, CL, CN, CO, CR, CU, CY, CZ, DE, DO, EC, EE, ES, ET, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, IE, IL, IN, IT, JM, JO, JP, KE, KR, KW, LK, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NZ, PA, PE, PH, PK, PL, PR, PY, QA, RO, RU, SA, SC, SD, SG, SI, SK, SL, SN, SV, TH, TN, TR, TT, TW, TZ, UA, UG, UY, VE, VN, ZA, ZM, ZW);
  • Clexane Forte (IL, SG);
  • Crusia (FI, PL);
  • Cutenox (BR, IN, LK);
  • Dilutol (EC, VN);
  • Enixum (RU);
  • Enoclex (PH);
  • Enoparin (VE);
  • Enox (TR);
  • Enoxane (PH);
  • Exowin (IN);
  • Flenox (UA);
  • Grefac (IN);
  • Henoxil (CL);
  • Inhexa (PL);
  • Inhixa (AT, ES, NL);
  • Klexane (DK, FI, IS, NO, SE);
  • Lomoh-40 (PH);
  • Lomoh-60 (PH);
  • Lovenox (AT, AU, FR, ID, LB, PT);
  • Olxarin (PH);
  • Versa (BR)


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