Marquette General Health System
Pharmacy and Therapeutics Committee
Medication Guideline
Drug Classification: 20:12.04.16 Anticoagulants/Heparins
Agent:
Formulary
X
Enoxaparin (Lovenox®)
Dalteparin (Fragmin®)
Tinzaparin (Innohep®)
Nonformulary
Restricted
Nonstock
X
X
X
X
Pharmacy and Therapeutics Committee-approved Indications for Inpatient Use:
Prophylaxis of venous thromboembolism (VTE) including:
o Deep vein thrombosis (DVT) in patients who are at risk for thromboembolic complications undergoing
abdominal surgery, hip or knee replacement surgery, or medical patients with severely restricted mobility
during acute illness.
o Ischemic complications of unstable angina and non-Q wave myocardial infarction (MI).
Treatment of the following conditions:
o DVT in patients with or without pulmonary embolism (PE).
o Treatment of acute ST-segment elevation myocardial infarction (STEMI) managed medically or with
subsequent percutaneous coronary intervention (PCI).
Note: In patients with suspected/presumed heparin-induced thrombocytopenia (HIT) or in patients with a recent history of HIT,
enoxaparin should not be utilized. Consider alternative anticoagulants including fondaparinux or the direct thrombin inhibitors
(argatroban, bivalirudin).
Dosage and Administration:
Table 1 depicts specific dosing recommendations based on actual body weight. All patients should be monitored
for signs and symptoms of bleeding. Unless otherwise indicated, enoxaparin should be administered by deep
subcutaneous (SC) injection. Administration should be alternated between the left and right anterolateral and left
and right posterolateral abdominal wall.
Bridging recommendations during initiation of warfarin therapy:
The following are recommendations from the 2012 CHEST guidelines.
discontinue therapeutic enoxaparin once the INR value reaches:
2.5 for mechanical heart valves in mitral and aortic position
1.5 for orthopedic surgery patients
2.0 for all other patient populations
Document created: 09/11.
Revised: 07/13.
Cross Reference: Anticoagulation Monitoring and Safety (100-228).
In general, it is recommended to
Marquette General Health System
Marquette General Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
Marquette General Health System
Pharmacy and Therapeutics Committee
Medication Guideline
Table 1: Enoxaparin Dosing Recommendations.
Dosing*
Indication
Prophylaxis
VTE
Abdominal surgery: 40 mg every 24 hours
Knee replacement surgery: 30 mg every 12 hours
Hip replacement surgery: 30 mg every 12 hours or 40 mg every 24 hours
Medical patients with severely restricted mobility: 40 mg every 24 hours
Trauma: 30 mg every 12 hour
Pediatric patients < 2 months: initial dose of 0.75 mg/kg every 12 hours
Pediatric patients > 2 months: initial dose of 0.5 mg/kg every 12 hours
Dosage adjustment for special patient populations:
Renal impairment (CrCl <30 mL/minute): 30 mg every 24 hours
Moderate to severe obesity (>130% IBW; TBW >150 kg; or BMI >50 kg/m2): 40 mg every 12 hours‡
Pregnancy: 30 mg every 12 hours or 40 mg every 24 hours
Usual dose: 1 mg/kg every 12 hours
Non-ST-segment elevation
acute coronary syndrome
Undergoing PCI: If the last dose of enoxaparin was given < 8 h prior to PCI, no additional anticoagulant therapy
is needed. If the last dose of enoxaparin was given 8 to 12 hours before PCI, a 0.3 mg/kg bolus of IV
enoxaparin at the time of PCI should be administered
Dosage adjustment for special patient populations:
Renal impairment (CrCl <30 mL/minute): 1 mg/kg every 24 hours
Treatment
Usual dose:
1mg/kg every 12 hours (with warfarin)† OR 1.5 mg/kg every 24 hours (with warfarin)†
Pediatric patients < 2 months: 1.5 mg/kg every 12 hours
Pediatric patients > 2 months: 1 mg/kg every 12 hours
DVT with/without PE
Dosage adjustment for special patient populations:
Renal impairment (CrCl <30 mL/minute): 1 mg/kg every 24 hours
Alternative dosing in renal impairment:
CrCl 30-60 mL/minute: Normal dosing on day 1 followed by 0.8 mg/kg/dose every 12 hours
CrCl <30 mL/minute: 1 mg/kg/dose on day 1 followed by 0.65 mg/kg/dose every 12 hours
Note: In patients with acute DVT and severe renal failure, heparin is the recommended anticoagulant.
Morbid Obesity: (>150 kg or BMI>50 kg/m2): 1mg/kg every 12 hours; adjust dose based on anti-Xa levels.
Note: Unfractionated heparin (weight-based IV infusion) is the recommended anticoagulant in patients weighing
greater than 150 kg or with a BMI >50 kg/m2.
STEMI
Pregnancy: 1 mg/kg every 12 hours
Patients <75 years of age with preserved renal function (serum creatinine levels 2.5 mg/dL in males and 2
mg/dL in females): Single 30 mg IV bolus dose plus a 1 mg/kg SC dose followed by 1 mg/kg every 12 hours
(maximum dose of 100 mg for the first 2 doses only, followed by 1 mg/kg).
Renal impairment: Single 30 mg IV bolus plus a 1 mg/kg SC dose followed by 1 mg/kg SC every 24 hours.
Patients >75 years of age with preserved renal function: 0.75 mg/kg SC every 12 hours (maximum of 75 mg
for the first 2 doses only followed by 0.75 mg/kg)
Renal impairment: 1 mg/kg SC every 24 hours
*Round doses to the nearest 10 mg for patients weighing 50 kg or more and to the nearest 5 mg for patients weighing less than 50 kg.
†
Initiate warfarin therapy, if warranted, within 72 hours and continue enoxaparin until INR is within goal range.
‡
Dose increase if the preferred regimen based on medical condition is 30 mg every 12 hours.
Monitoring/Outcomes:
Baseline laboratory: hematocrit, platelet count, serum creatinine
Signs and symptoms of DVT, bleeding/bruising, low blood pressure, tachycardia, neurological impairment
Laboratory: complete blood count, stool occult blood test, potassium levels, renal function, anti-Xa levels, liver
function tests.
Document created: 09/11.
Revised: 07/13.
Cross Reference: Anticoagulation Monitoring and Safety (100-228).
Marquette General Health System
Marquette General Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
Marquette General Health System
Pharmacy and Therapeutics Committee
Medication Guideline
Anti-Xa Monitoring
Routine monitoring of anti-Xa levels with enoxaparin is not required; however, monitoring in specific patient
populations receiving enoxaparin for treatment purposes, such as those with renal impairment, obese or pregnant,
may be necessary to ensure therapeutic anti-Xa activity. The most adequate anti-Xa range for enoxaparin
prophylaxis remains to be defined and is not recommended to be monitored at this time.
o A therapeutic peak anti-Xa level with twice daily dosing for treatment purposes is 0.5-1 unit/ml; with once
daily dosing anti-Xa activity should be between 1-2 units/ml.
o Peak anti-Xa activity should be obtained starting on day two in the special patient populations listed above.
o Peak anti-Xa activity should also be considered in patients with hemorrhage or following any dosage
adjustment.
o If accumulation is suspected, trough anti-Xa levels (drawn prior to next dose) may be obtained. The target
trough anti-Xa level is <0.5 units/ml.
Table 2: Enoxaparin Dose Adjustments Based on Peak Anti-Xa Levels*
Peak Anti- Xa Level
Recommended Dosage Adjustment
Next Anti-Xa Level
<0.35 units/mL
Increase dose by 25%
Peak level 4 hours after next dose
0.35-0.49 units/mL
Increase dose by 10%
Peak level 4 hours after next dose
0.5-1 units/mL
No change
Next day, then 1 week later, then monthly (4 hours after
dose)
1.1-1.5 units/mL
Decrease dose by 20%
Peak level 4 hours after next dose
1.6-2 units/mL
Hold dose for 3 hours and decrease dose by 30%
Trough level prior to next dose, then peak level 4 hours
after next dose
Hold all doses until anti-Xa level is 0.5 units/mL, then
decrease dose by 40%
*Adjustments for twice daily dosing.
>2 units/mL
Trough level prior to next scheduled dose and every 12
hours thereafter until anti-Xa level <0.5 units/mL
Anti-Xa Neutralization:
There is no proven method for neutralizing enoxaparin. Protamine sulfate only partially (~60%) neutralizes the antiXa activity of enoxaparin. Unless an immediate effect is needed, discontinuation of enoxaparin is generally
sufficient. If an immediate effect is needed, protamine sulfate may be given to attempt reversal of the anticoagulant
effect. If enoxaparin was given within 8 hours, protamine sulfate should be administered in a dose of 1 mg per 1
mg enoxaparin (i.e. 80 mg protamine for 80 mg of enoxaparin). If bleeding continues a dose of protamine 0.5 mg
per 1 mg of enoxaparin may be administered. Smaller doses of protamine can be given if the time since
enoxaparin administration was longer than 8 hours. Protamine should be administered by slow intravenous push at
a rate of 5 mg per minute to prevent hypotension.
Drug-Drug Interactions:
The effects of the following drug-drug interactions with enoxaparin are considered to be potentially life-threatening
or capable of causing permanent damage:
Heparin
Argatroban or Bivalirudin or Dabigatran
Fondaparinux
Neuraxial anesthesia/spinal puncture
Document created: 09/11.
Revised: 07/13.
Cross Reference: Anticoagulation Monitoring and Safety (100-228).
Marquette General Health System
Marquette General Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.
Marquette General Health System
Pharmacy and Therapeutics Committee
Medication Guideline
Interruption of Anticoagulant Therapy For Invasive Procedures:
The risk of thromboembolism versus bleeding risk should be evaluated for all patients receiving enoxaparin and
undergoing an invasive procedure. Refer to the 2008 Chest guidelines, the perioperative management of
antithrombotic therapy, for a complete discussion on risk stratification for thromboembolism and procedures
associated with a high bleeding risk.
Preoperative management
Administer the last dose of therapeutic enoxaparin 24 hours before surgery or procedure, for the last preoperative
dose of therapeutic dose enoxaparin approximately half the total daily dose should be administered.
Postoperative management
Minor surgical or other invasive procedure
Therapeutic-dose enoxaparin may be resumed approximately 24 hours after the procedure when there is adequate
hemostasis.
Major surgery of a high bleeding risk
Delay the initiation of therapeutic-dose enoxaparin for 48 to 72 hours post surgery when hemostatsis is secured.
Special Handling Procedures:
Anticoagulants/heparins are not considered hazardous drugs.
Anticoagulants/heparins are considered high-alert drugs.
References:
Enoxaparin (Lovenox®) [package insert]. Bridgewater, NJ: Sanofi-Aventis;2009.
Hirsh J, Baue KA, Donat MB, et al. Prevention of venous thromboembolism. Chest 2008;133;381S-453S.
Goodman SG, Menon V, Cannon CP, et al. Acute ST-segment elevation myocardial infarction. Chest 2008;133;708S-775S.
Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants. Chest 2008;133;141S-159S.
Harrington RA, Becker RC, Cannon CP, et al. Antithrombotic therapy for non-ST-segment elevation acute coronary
syndromes. Chest 2008;133:670S-707S.
Kearon C, Kahn SR, Agnelli G, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 2008;133:454S545S.
Douketis JD, Berger PB, Dun AS, et al. The perioperative management of antithrombotic therapy. Chest 2008;133:299S339S.
Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic
therapy. Regional Anesthesia and Pain Medicine 2010;35(1):64-101.
Duhl AJ, Paidas MJ, Ural SH, et al. Antithrombotic therapy and pregnancy: consensus report and recommendations for
prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. Am J Obstet Gynecol
2007;197:457e1-e21.
Monagle P, Michelson AD, Bovill E, et al. Antithrombotic therapy in children. Chest 2001;119:344S-370S.
Hulot JS, Montalescot G, Lechat P, et al. Dosing strategy in patients with renal failure receiving enoxaparin for the treatment
of non-ST-segment elevation acute coronary syndrome. Clin Pharmacol Ther. 2005;77:542-52.
Kruse MW, Lee JJ. Retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment. Am
Heart J. 2004;148:582-9.
Collet JP, Montalescot G, Choussat R, et al. Enoxaparin in unstable angina patients with renal failure. Int J Cardiol.
2001;80:81-2.
Document created: 09/11.
Revised: 07/13.
Cross Reference: Anticoagulation Monitoring and Safety (100-228).
Marquette General Health System
Marquette General Hospital
Marquette, MI 49855
This is a confidential professional/peer review and quality assessment document of Marquette General Health System of Marquette, MI. It is
protected from disclosure pursuant to the provisions of MCL 333.20175, MCL 333.21513, MCL 21515, MCL 331.531, MCL 331.533, MCL
330.1143a, and other state and federal laws. Unauthorized disclosure or duplication is absolutely prohibited.