1. U.S. Food and Drug Administration. FDA news release: FDA approves first generic enoxaparin sodium injection to prevent DVT. FDA website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm220092.htm?sms_ss=email. Accessed July 23, 2010.
2. IMS National Sales Perspectives, February 2009.
3. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007
guidelines for the management of patients with unstable angina/non–ST-elevation
myocardial infarction—executive summary: a report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Writing Committee to Revise
the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation
Myocardial Infarction): developed in collaboration with the American College of
Emergency Physicians, American College of Physicians, Society of Academic Emergency
Medicine, Society for Cardiovascular Angiography and Interventions, and Society
of Thoracic Surgeons. J Am Coll Cardiol. 2007;50(7):652-726.
4. U.S. Department of Health and Human Services. The Surgeon
General’s call to action to prevent deep vein thrombosis and pulmonary embolism:
2008. Office of the Surgeon General website. http://www.surgeongeneral.gov/topics/deepvein/calltoaction/call-to-action-on-dvt-2008.pdf.
September 15, 2008. Accessed October 20, 2008.
5. Rosamond W, Flegal K, Friday G, et al; American Heart
Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease
and stroke statistics—2007 update: a report from the American Heart Association
Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115(5):e69-e171.
6. LOVENOX® (enoxaparin sodium injection) Prescribing Information.
sanofi-aventis, Bridgewater, NJ.
7. Alikhan R, Cohen AT, Combe S, et al. Prevention of venous
thromboembolism in medical patients with enoxaparin: a subgroup analysis of the
MEDENOX study. Blood Coagul Fibrinolysis. 2003;14(4):341-346.
8. IMS In-hospital Sales, October 1995–September 2007.
9. Samama MM, Cohen AT, Darmon J-Y, et al; Prophylaxis in
Medical Patients with Enoxaparin Study Group. A comparison of enoxaparin with placebo
for the prevention of venous thromboembolism in acutely ill medical patients. N
Engl J Med. 1999;341(11):793-800.
10. Data on file, sanofi-aventis, Bridgewater, NJ.
11. Colwell CW Jr, Collis DK, Paulson R, et al. Comparison
of enoxaparin and warfarin for the prevention of venous thromboembolic disease after
total hip arthroplasty: evaluation during hospitalization and three months after
discharge. J Bone Joint Surg Am. 1999;81-A(7):932-940.
12. Fitzgerald RH Jr, Spiro TE, Trowbridge AA, et al; Enoxaparin
Clinical Trial Group. Prevention of venous thromboembolic disease following primary
total knee arthroplasty: a randomized, multicenter, open-label, parallel-group comparison
of enoxaparin and warfarin. J Bone Joint Surg Am. 2001;83-A(6):900-906.
13. Bergqvist D, Benoni G, Björgell O, et al. Low-molecular-weight
heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip
replacement. N Engl J Med. 1996;335(10):696-700.
14. ENOXACAN Study Group. Efficacy and safety of enoxaparin
versus unfractionated heparin for prevention of deep vein thrombosis in elective
cancer surgery: a double-blind randomized multicentre trial with venographic assessment.
Br J Surg. 1997;84(8):1099-1103.
15. Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight
heparin administered primarily at home with unfractionated heparin administered
in the hospital for proximal deep-vein thrombosis. N Engl J Med. 1996;334(11):677-681.
16. Merli G, Spiro TE, Olsson C-G, et al; Enoxaparin Clinical
Trial Group. Subcutaneous enoxaparin once or twice daily compared with intravenous
unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern
17. Antman EM, Morrow DA, McCabe CH, et al; ExTRACT-TIMI
25 Investigators. Enoxaparin versus unfractionated heparin with fibrinolysis for
ST-elevation myocardial infarction. N Engl J Med. 2006;354(14):1477-1488.
18. Antman EM, Morrow DA, McCabe CH, et al; ExTRACT-TIMI
25 Investigators. Enoxaparin versus unfractionated heparin as antithrombin therapy
in patients receiving fibrinolysis for ST-elevation myocardial infarction: design
and rationale for the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial
Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI
25). Am Heart J. 2005;149(2):217-226.
19. Cohen M, Demers C, Gurfinkel EP, et al; Efficacy and
Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events Study Group. A comparison
of low-molecular-weight heparin with unfractionated heparin for unstable coronary
artery disease. N Engl J Med. 1997;337(7):447-452.
20. Goodman SG, Cohen M, Bigonzi F, et al; Efficacy and
Safety of Subcutaneous Enoxaparin in Non–Q Wave Coronary (ESSENCE) Study Group.
Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated
heparin for unstable coronary artery disease: one-year results of the ESSENCE study.
J Am Coll Cardiol. 2000;36(3):693-698.
21. Spencer FA, Lessard D, Emery C, Reed G, Goldberg RJ.
Venous thromboembolism in the outpatient setting. Arch Intern Med. 2007;167(14):1471-1475.
22. de Jong JD, Westert GP, Lagoe R, Groenewegen PP. Variation
in hospital length of stay: do physicians adapt their length of stay decisions to
what is usual in the hospital where they work? Health Serv Res. 2006;41(2):374-394.
23. Basse L, Thorbøl JE, Løssl K, Kehlet H. Colonic surgery
with accelerated rehabilitation or conventional care. Dis Colon Rectum.
24. Anderson FA Jr, Hirsh J, White K, Fitzgerald RH Jr.
Temporal trends in prevention of venous thromboembolism following primary total
hip or knee arthroplasty 1996–2001: findings from the hip and knee registry. Chest.
25. Fuster V, Alexander RW, O’Rourke RA, eds. Hurst’s The
Heart. 10th ed. New York, NY: McGraw-Hill Medical Publishing Division;
26. Lee S, Gibson CM. Enoxaparin in acute coronary syndromes.
Expert Rev Cardiovasc Ther. 2007;5(3):387-399.
27. Weitz JI. Low-molecular-weight heparins. N Engl J Med.
28. Warkentin TE, Roberts RS, Hirsh J, Kelton JG. An improved
definition of immune heparin-induced thrombocytopenia in postoperative orthopedic
patients. Arch Intern Med. 2003;163(20):2518-2524.
29. Le Liboux A, Sanderink G-J, Grosjean P, et al. Enoxaparin
pharmacokinetics and pharmacodynamics after intravenous bolus administration alone
and at initiation of a subcutaneous dosing regimen [abstract 1106-129]. J Am Coll
Cardiol. 2000;35(suppl 1):373A-374A.
30. Martin JL, Fry ETA, Sanderink G-J, et al. Reliable anticoagulation
with enoxaparin in patients undergoing percutaneous coronary intervention: the Pharmacokinetics
of Enoxaparin in PCI (PEPCI) study. Catheter Cardiovasc Interv. 2004;61(2):163-170.
31. Turpie AGG, Levine MN, Hirsh J, et al. A randomized
controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein
thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986;315(15):925-929.
32. Leclerc JR, , Geerts WH, Desjardins L, et al. Prevention
of deep vein thrombosis after major knee surgery—a randomized, double-blind trial
comparing a low molecular weight heparin fragment (enoxaparin) to placebo. Thromb
33. Goodman SG, Fitchett D, Armstrong PW, Tan M, Langer
A; Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment
(INTERACT) Trial Investigators. Randomized evaluation of the safety and efficacy
of enoxaparin versus unfractionated heparin in high-risk patients with non–ST-segment
elevation acute coronary syndromes receiving the glycoprotein IIb/IIIa inhibitor
eptifibatide. Circulation. 2003;107(2):238-244.
34. The SYNERGY Trial Investigators. Enoxaparin vs unfractionated
heparin in high-risk patients with non–ST-segment elevation acute coronary syndromes
managed with an intended early invasive strategy: primary results of the SYNERGY
randomized trial. JAMA. 2004;292(1):45-54.
35. Hylek EM, Regan S, Henault LE, et al. Challenges to the
effective use of unfractionated heparin in the hospitalized management of acute
thrombosis. Arch Intern Med. 2003;163(5):621-627.
36. The Joint Commission. Accreditation Program: Hospitals. Chapter: National Patient Safety Goals. http://www.jointcommission.org/NR/rdonlyres/31666E86-E7F4-423E-9BE8-F05BD1CB0AA8/0/HAP_NPSG.pdf. Accessed November 28, 2008.
37. Skinner N, Moran P. Case Management Adherence Guidelines:
Deep vein thrombosis (DVT). http://www.cmsa.org/portals/0/pdf/CMAG_DVT.pdf. Accessed November 28, 2008.
38. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of
venous thromboembolism: American College of Chest Physicians evidence-based clinical
practice guidelines (8th edition). Chest. 2008;133(6 suppl):331S-453S.
39. Gerotziafas GT, Samama MM. Prophylaxis of venous thromboembolism
in medical patients.Curr Opin Pulm Med. 2004;10(5):356-365.
40. Heit JA, Cohen AT, Anderson FA; VTE Impact Assessment Group.
Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism
(VTE) events in the US. Poster 68. Presented at: 47th Annual Meeting and Exposition
of the American Society of Hematology; December 10-13, 2005; Atlanta, GA.
41. Murin S, Romano PS, White RH. Comparison of outcomes
after hospitalization for deep venous thrombosis or pulmonary embolism. Thromb Haemost.
42. Centers for Medicare & Medicaid Services and Agency for Healthcare
Research and Quality. Hospital CAHPS® (HCAHPS®) Fact Sheet. CMS
December 1, 2005. Accessed May 14, 2008.
43. Amin A, Stemkowski S, Lin J, Yang G. Thromboprophylaxis
rates in US medical centers: success or failure? J Thromb Haemost.
Important Safety Information for LOVENOX®
WARNING: SPINAL/EPIDURAL HEMATOMA
Epidural or spinal hematomas may occur in patients who are anticoagulated with low
molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia
or undergoing spinal puncture. These hematomas may result in long-term or permanent
paralysis. Consider these risks when scheduling patients for spinal procedures.
Factors that can increase the risk of developing epidural or spinal hematomas in
these patients include:
- Use of indwelling epidural catheters
- Concomitant use of other drugs that affect hemostasis, such as non-steroidal
anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants
- A history of traumatic or repeated epidural or spinal punctures
- A history of spinal deformity or spinal surgery
Monitor patients frequently for signs and symptoms of neurological impairment. If
neurological compromise is noted, urgent treatment
Consider the benefits and risks before neuraxial intervention in patients anticoagulated
or to be anticoagulated for thromboprophylaxis.
WARNINGS AND PRECAUTIONS
- LOVENOX® (enoxaparin sodium injection) is contraindicated in patients
with active major bleeding; thrombocytopenia with a positive in vitro test
for anti-platelet antibody in the presence of enoxaparin sodium; known hypersensitivity
to enoxaparin sodium, heparin, pork products, or benzyl alcohol (multi-dose formulation
- LOVENOX® should be used with extreme caution in conditions with increased
risk of hemorrhage. Major hemorrhages including retroperitoneal and intracranial
bleeding have been reported. Some of these cases have been fatal. Bleeding can occur
at any site during LOVENOX® therapy.
fall in hematocrit (HCT) or blood pressure should lead to a search for a bleeding
- For percutaneous coronary revascularization procedures, obtain hemostasis
at the puncture site before sheath removal and observe the site for signs of bleeding
or hematoma formation
- In the STEMI population, the rates of major hemorrhages (defined as requiring
5 or more units of blood for transfusion, or 15% drop in HCT or clinically overt
bleeding, including intracranial hemorrhage [ICH]) at 30 days were 2.1% in the LOVENOX®
group and 1.4% in the unfractionated heparin (UFH) group. The rates of ICH at 30
days were 0.8% in the LOVENOX® group and 0.7% in the UFH group. The 30-day rate
of the composite endpoint of death, myocardial infarction, or ICH (a measure of
net clinical benefit) was significantly lower in the LOVENOX® group (10.1%)
compared to the UFH group (12.2%)
- LOVENOX® should be used with caution in patients with bleeding diathesis,
uncontrolled arterial hypertension or a history of recent gastrointestinal ulceration,
diabetic retinopathy, renal dysfunction, or hemorrhage
- Thrombocytopenia can occur with LOVENOX®. In patients with a history of
heparin-induced thrombocytopenia (HIT), LOVENOX® should be used with extreme
caution. Thrombocytopenia of any degree should be monitored closely. If the platelet
count falls below 100,000/mm3, LOVENOX® should be discontinued. Cases
of HIT have been observed in clinical practice
- LOVENOX® cannot be used interchangeably with other branded LMWH or UFH,
as they differ in their manufacturing process, molecular weight distribution, anti-Xa
and anti-IIa activities, units, and dosages
- Pregnant women with mechanical prosthetic heart valves and their fetuses may
be at increased risk for thromboembolism. Frequent monitoring of anti-Factor Xa
levels and adjusting of dosage may be needed
- LOVENOX® multiple-dose vials contain benzyl alcohol and should be used
with caution in pregnant women and only if clearly needed due to the risk of fatal
"gasping syndrome" in premature neonates
- Periodic complete blood counts, including platelet count, and stool occult
blood tests are recommended during the course of treatment with LOVENOX®
- Most common adverse reactions (>1%) were bleeding, anemia, thrombocytopenia,
elevation of serum aminotransferase, diarrhea, and nausea
For more information, contact your local sanofi-aventis U.S. Representative or call
sanofi-aventis U.S. Medical Information Services
Please see full Prescribing Information, including boxed WARNING.
Prescription LOVENOX® is available in pharmacies.
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