Skip to content
Disclaimer to the On-line Edition
This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.

ENOXAPARIN


Indication

  • the treatment of thrombotic disease, deep vein thrombosis (DVT), and pulmonary embolisms(PE)1

Pharmacology

  • enoxaparin is a low molecular weight heparin (LMWH) fragment that possesses anticoagulant action2
  • commercially available LMWHs have molecular weights that vary from 4,000 to 6,000 (regular heparin consists of a mixture of molecules whose molecular weights range from 5,000 to 30,000)8
  • enoxaparin (as well as other LMWHs) catalyses the inactivation of Factor Xa by antithrombin III

    Schematic to illustrate the role of enoxaparin in the inactivation of Factor Xa by Antithrombin III

    http://www.med.monash.edu.au/biochem/thcme/blood.html

  • weakly metabolized in the liver by desulfation and depolymerization4
  • cleared by the kidneys (small amounts of the drug are eliminated in the intact or slightly degraded form)4
  • peak plasma anti-Xa levels appear 3 to 5 hours after the SC injection of enoxaparin4,11

Side Effects

  • major bleeds occurred in 4% of 173 children (1 day of age to 18 years old). These bleeds consisted of: gastrointestinal bleeds, intracranial bleeds, and thigh haematomas (at Insuflon injection sites)5
  • minor bleeding (at the Insuflon injection site, oozing from central venous line (CVL), gastric tubes and abscess sites) occurred in 17% of patients receiving enoxaparin therapy5
  • liver: caused asymptomatic elevations of liver enzymes in 6% of adult patients6
  • hypersensitivity: thrombocytopenia, skin rash, and anaphylactoid reactions are rare but occur with all LMWH6 (not reported in neonates)

Monitoring and Laboratory Tests:

  • platelets, occult blood and anti-Xa activity; the monitoring of PT and/or PTT is not necessary11

Enoxaparin Dosage Titration

Antifactor Xa

Dose Titration

Time to Repeat Antifactor Xa Level

<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
(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

Precautions:

  • avoid IM injections and arterial punctures during anticoagulation9

Dose

  • usual initial dose:
    • term neonates : 1.7 mg/kg q12h(14)
    • preterm neonates : 2 mg/kg q12h(14)

  • enoxaparin has a 96 hour automatic stop order (ASO) and must be reordered every 96 hours unless the order specifies a duration of treatment
  • adjust dose according to anti-factor Xa levels taken 4 to 6 hours after SC dose (sample collection should be done at the mid-interval between doses; 0.45 mL of blood is the minimum volume required in a DIC screen tube; notify lab prior to obtaining sample)
  • it is suggested that the anti-factor Xa level be drawn on day 1 and/or day 2, and after a therapeutic level is achieved, weekly monitoring is normally sufficient 9
  • therapeutic range of anti-factor Xa level : 0.5 - 1.0 units / mL
  • enoxaparin (LOVENOX ©) has 110 anti-factor Xa units / mg
  • must be administered subcutaneously (SC)
  • use an indwelling SC catheter (Insuflon catheter) to minimize injections--refer to Insuflon policy
  • after the drug has been administered, flush the Insuflon catheter with 0.02mL of 0.9% NaCl to account for the dead space
  • replacement of the Insuflon catheter is recommended every 3 to 4 days; the catheter must not remain in place for greater than 7 days
  • enoxaparin cannot be used interchangeably (unit for unit) with unfractionated heparin or other LMWHs as the actions, molecular weight distributions, units, and doses differ6

Supplied

For doses less than 5mg:

  • if the dose is less than 5mg, then the dose is rounded to the nearest 0.5mgand supplied by Pharmacy in a 30unit Insulin syringe (each gradient of 1unit is equal to 1mg of enoxaparin)

For doses equal to or greater than 5mg:

  • for doses greater than, or equal to, 5mg and up to 10mg, the dose will be rounded to the nearest mg and will be supplied in syringes as the undiluted, preservative free product (5mg / 0.05mL)

Procedure for Enoxaparin Dosing, Plasma Heparin Assay (Hepa) and Preparation of Dosage Form

Purpose:
To coordinate the Plasma Heparin Assay (Hepa), subsequent dosing and preparation of final dilution.

Summary of Procedure :

  1. Enoxaparin should be dosed at standard times (0200 and 1400). Blood for the plasma heparin assay (Hepa) should be taken at 4 hours after the administration of the 0200 dose only.
  2. The nurse who collects the blood sample should call the Special Hematology Lab and leave a Voice Mail indicating that a sample of blood for the plasma heparin assay (Hepa) is on its way . This will ensure prioritization of the sample when the laboratory staff come in at 0700 and is a critical part of this coordinated plan.
  3. The blood sample will go on the first transport to the Special Hematology Lab at 0700. It will usually arrive by 0900.
  4. The plasma heparin assay (Hepa) result should be available by 1100 for AM NICU Rounds.
  5. A new Enoxaparin order, if required, should be sent to Pharmacy by 1300.
  6. If a new dose is ordered it will be prepared by Pharmacy and sent to the the NICU before 1400.
  7. The Special Hematology Lab is open 0700-1700 during the week. A Paediatric Hematologist must authorize the plasma heparin assay (Hepa) on the weekend, since a technician is available only "On-Call".

Antidote for enoxaparin overdose:

GUIDELINES FOR ADMINISTRATION OF PROTAMINE SULPHATE
  • in instances of enoxaparin overdose the anti-factor Xa activity of enoxaparin can be partially neutralized with protamine sulphate
  • an order should be written for a vial of protamine sulfate to be kept at the bedside
  • IV protamine sulfate 1% (10 mg / mL) should be administered over at least 10 minutes (by an MD or CNS/NP) or it may be diluted further in a dextrose or saline fluid and administered as a slow IV infusion over 30 minutes by an RN10
  • the dose of protamine sulphate should be identical to the dose of enoxaparin6 (1 mg of protamine sulphate to neutralize 1 mg of enoxaparin) if given within 3 to 4 hours of the last enoxaparin dose; if the elapsed time since the last enoxaparin dose is greater than 4 hours, the protamine dose should be reduced to compensate for the half-life of enoxaparin - contact pharmacy for discussion of dose.
  • anaphylaxis has been reported with protamine sulphate
  • hypotension, bradycardia and flushing are caused by rapid IV injection


References

  1. Massicote P, Adams M, Marzinotto V, et al: Low molecular weight heparin in pediatric patients with thrombotic disease: A dose finding study. J Pediatr 1996;128 :313-318.
  2. AHFS Drug Information, McEvoy GK (ed), American Society of Hospital Pharmacists, 1998.
  3. Principles of Pharmacology, Munson P (ed), Chapman and Hall, 1995.
  4. Anon: "Lovenox"(R), Product Monograph, Rhône-Poulene Roner, Montreal, Quebec.
  5. Dix D, Andrew M, Marzinotto V, et al: The use of low molecular weight heparin in pediatric patients: A prospective cohort study. J Pediatr 2000; 128:439-445.
  6. Compendium of Pharmaceuticals and Specialties, Wellbanks L et al (eds) Canadian Pharmacists Association, 2000.
  7. Mewborn AL, Kessler JM, Joyner KA: Compatibility and activity of enoxaparin sodium in 0.9% sodium chloride injection for 48 hours. Am J Health-Syst Pharm 1996; :167-169.
  8. Hirsh J and Levine MN : Low molecular weight heparins. Blood 1992; 79 : 1-17.
  9. Andrew M and de Weber G : Pediatric Thromboembolism and Stroke Protocols, BC Decker Inc, Hamilton, 1997.
  10. Phelps SJ and Hak EB : Guidelines for Administration of Intravenous Medications to Pediatric Patients, American Society of Health System Pharmacists, 1996.
  11. Lacy CF, Armstrong LL, Goldman MP and Lance LL : Drug Information Handbook, American Pharmaceutical Association, 8th Edition, 2000-2001.
  12. Hanas R : Insuflon ® Guide - the management of subcutaneous indwelling catheters for insulin injections, Department of Pediatrics, Uddevalla, Sweden.
  13. The Hospital for Sick Children Nursing Procedure Manual : Injecting subcutaneous medication via an Insuflon ®, September 1995.
  14. Janet I Malowany, David C Knoppert, Anthony KC Chan, Dion Pepelassis, David SC Lee. Enoxaparin use in the neonatal intensive care unit (NICU) : experience over 8 years. Pharmacotherapy (In Press).
  15. Charland SC et al. Activity of enoxaparin sodium in tuberculin syringes for 10 days. Amer J Health - Syst Pharm 1998;55. 1296-8.
  16. Dager WF et al. Anti-Xa stability of diluted enoxaparin for use in pediatrics. Ann Pharmacother 2004;38:569-73.

New : January 2001
Updated: August 2010
Heather Teetzel, summer Pharmacy student 2000, contributed to this monograph.


Last Uploaded: Thursday, 26-May-2011 00:53:35 EDT
About Us Patients, Families & Visitors For Health Professionals Careers Research & Training Ways to Give
LHSC Maps & Directions Programs & Services Media Room Contact Us For Our Employees Privacy Statement Terms & Conditions