LOVENOX® is produced by a unique, proprietary manufacturing process that creates a biological product with specific biochemical features
To help ensure the quality and safety of LOVENOX®,
sanofi-aventis uses a consistent and highly controlled manufacturing process
- Our high standards of manufacturing, drug testing, quality controls, and audits
are used to help ensure:
- —Traceability and quality of crude heparin from
- —Verification of multiple pharmacologic and chemical characteristics (molecular weight,
- LOVENOX® is consistently tested to ensure the high quality and integrity
of its manufacturing practices, which help ensure that the product is stable and
LOVENOX® is well established with over 17 years
- Evidence-based medicine supports the use of LOVENOX®
based on Phase III clinical trial data and real-world experience1-18
- LOVENOX® has been studied in more than 72,000 patients20
- —Efficacy and safety demonstrated in the management
of patients across the spectrum of acute coronary syndrome, deep vein thrombosis
(DVT) prophylaxis in acutely ill medical patients, DVT prophylaxis in certain surgical
patients, and DVT treatment of both inpatients and outpatients1-18
- —Benefit/risk profile confirmed in registry and
outcome trials in thousands of patients21-24
- —Recommended in key guidelines worldwide and cited
for extent of clinical evidence10-12,14
- Reinforced by over 17 years of experience in clinical settings in the United States19
- —The most widely studied and prescribed LMWH25,26
- —Demonstrated efficacy and safety in a wide range
LOVENOX® — produced by a sanofi-aventis proprietary process — has
established clinical safety and efficacy data through Phase III clinical trials to support
the proven and predictable product profile.
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.
Click here for information on Sharps Medical Waste Disposal.
1. Antman EM, Morrow DA, McCabe CM, 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.
2. 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.
3. Cohen M, Demers C, Gerfinkel 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.
4. Samama MM, Cohen AT, Darmon J-Y, et al. A comparison
of enoxaparin with placebo for the prevention of venous thromboembolism in acutely
ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group.
N Eng J Med. 1999;341(11):793-800.
5. 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.
6. 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(7):932-940.
7. 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.
8. 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.
9. Bergqvist D, Eldor A, Thorlacius-Ussing O, et
al; 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.
10. 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.
11. Antman EM, Hand M, Armstrong PW, et al; 2007
Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for
the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf
of the 2004 Writing Committee. 2007 focused update of the ACC/AHA 2004 guidelines
for the management of patients with ST-elevation myocardial infarction: a report
of the American College of Cardiology/American Heart Association Task Force on Practice
Guidelines. Circulation. 2008;117(2):296-329.
12. 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):381S-453S.
13. Kearon C, Kahn SR, Agnelli G, Goldhaber S,
Raskob GE, Comerota AJ. Antithrombotic therapy for venous thromboembolic disease:
American College of Chest Physicians evidence-based clinical practice guidelines
(8th edition). Chest. 2008;133(6 suppl):454S-545S.
14. Stahl TJ, Gregorcyk SG, Hyman NH, Buie WD;
Standards Practice Task Force of The American Society of Colon and Rectal Surgeons.
Practice parameters for the prevention of venous thrombosis. Dis Colon Rectum. 2006;49(10):1477-1483.
15. Lyman GH, Khorana AA, Falanga A, et al. American
Society of Clinical Oncology guideline: recommendations for venous thromboembolism
prophylaxis and treatment in patients with cancer. J Clin Oncol. 2007;25(34):5490-5505.
16. Johanson NA, Lachiewicz PF, Lieberman JR,
et al; AAOS Physician Volunteer Work Group. American Academy of Orthopaedic Surgeons
clinical guideline on prevention of symptomatic pulmonary embolism in patients undergoing
total hip or knee arthroplasty: summary of recommendations. http://www.aaos.org/Research/guidelines/PE_guideline.pdf.
Accessed April 1, 2008.
17. ACOG Committee on Practice Bulletins—Gynecology,
American College of Obstetricians and Gynecologists. ACOG practice
bulletin no. 84: prevention of deep vein thrombosis and pulmonary embolism. Obstet
Gynecol. 2007;110(2, pt 1):429-440.
18. American Society of Regional Anesthesia and Pain Medicine.
Consensus statements: regional anesthesia in the anticoagulated patient: defining
the risks. http://www.asra.com/publications/consensus-statements-2.html. Accessed
September 26, 2006.
19. LOVENOX® (enoxaparin sodium injection) Prescribing Information.
sanofi-aventis, Bridgewater, NJ.
20. Data on file, sanofi-aventis, Bridgewater,
21. Klein W, Kraxner W, Hödl R, et al; GRACE Investigators.
Patterns of use of heparins in ACS. Correlates and hospital outcomes: the Global
Registry of Acute Coronary Events (GRACE). Thromb Haemost. 2003;90(3):519-527.
22. Goldhaber SZ, Tapson VF; DVT FREE
Steering Committee. A prospective registry of 5,451 patients with ultrasound-confirmed
deep vein thrombosis. Am J Cardiol. 2004;93(2):259-262.
23. Fitchett DH, Langer A, Armstrong PW, Tan M,
Mendelsohn A, Goodman SG; INTERACT Trial Long-Term Follow-Up Investigators.
Randomized evaluation of the 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. Long-term results of
the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment
(INTERACT) trial. Am Heart J. 2006;151(2):373-379.
24. Goodman SG, Cohen M, Bigonzi F, et al; Efficacy
and Safety of Subcutaneous Enoxaparin in Non—Q Wave Coronary Events (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.
25. IMS National Sales Perspectives, February
26. PubMed.gov: a service of the US National Library of Medicine
and the National Institutes of Health. Search clinical trials for:
ardeparin, certoparin, dalteparin, enoxaparin, nadroparin, reviparin, and tinzaparin.
PubMed.gov website. http://www.ncbi.nlm.nih.gov/pubmed. Accessed April 22, 2009.