LOVENOX® achieves and maintains therapeutic anti-Xa and IIa levels with maximum
peak activity within 3 to 5 hours. And it provides consistent and predictable anticoagulation.
The mechanism of action of LOVENOX® provides a high anti-Xa:anti-IIa
ratio, potentially increasing antithrombotic effect,6,10,25-28
100% bioavailability based on factor Xa activity,10,28
and a lower incidence of heparin-induced thrombocytopenia.27,28
LOVENOX®—pharmacodynamics
In humans, LOVENOX® given at a dose of 1.5 mg/kg subcutaneously (SC) is characterized
by a higher ratio of anti-factor Xa to anti-factor IIa activity (mean ± SD, 14.0
± 3.1; based on areas under anti-factor activity versus time curves) compared to
the ratios observed for heparin (mean ± SD, 1.22 ± 0.13). Increases of up to 1.8 times
the control values were seen in the thrombin time and the activated partial
thromboplastin time (aPTT).6
LOVENOX® at a 1 mg/kg dose (100 mg/mL concentration), administered SC every
12 hours to patients in a large clinical trial, resulted in aPTT values of 45 seconds
or less in the majority of patients (n=1607). A 30-mg IV bolus immediately followed
by a 1 mg/kg SC administration resulted in aPTT postinjection values of 50 seconds.
The average aPTT postinjection value on day 1 was about 16% higher than on day 4.6
Pharmacokinetics of LOVENOX® IV bolus and SC dosing10,29
In the Le Liboux study10,29,a
- After an initial 30-mg IV bolus followed by the
first 1-mg/kg q12h SC dose
- —LOVENOX® immediately reached therapeutic anti-Xa
levels (0.66 ± 0.23 IU/mL) and maintained a therapeutic level until the SC dose
was absorbed
- —LOVENOX® provided initial peak anti-Xa levels
of 1.16 ± 0.17 IU/mL 2 to 4 hours after treatment initiation, with an average exposure
corresponding to 84% of steady-state levels
In the PEPCI study30,b
- LOVENOX® SC provided anti-Xa levels that were within
the target range (0.6 to 1.8 IU/mL) in 98% of patients 2 to 8 hours after the last
SC dose
- An additional 0.3-mg/kg IV bolus given 8 to 12 hours
after the last SC dose maintains anti-Xa levels within target range for an additional
2 hours
Important Safety Information
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 is necessary.
Consider the benefits and risks before neuraxial intervention in patients anticoagulated
or to be anticoagulated for thromboprophylaxis.
CONTRAINDICATIONS
- 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 only)
WARNINGS AND PRECAUTIONS
- 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. An unexplained fall in hematocrit (HCT) or blood pressure
should lead to a search for a bleeding site
- 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®
ADVERSE REACTIONS
- 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 at 1-800-633-1610.
Please see full Prescribing Information, including boxed WARNING.
Prescription LOVENOX® is available in pharmacies.
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