A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Lovenox Side Effects, and Drug Interactions - Enoxaparin
Lovenox Side Effects, and Drug Interactions - Enoxaparin
SIDE EFFECTS
Hemorrhage
The incidence of major hemorrhagic complications during Lovenox
Injection treatment has been low.
The following rates of major bleeding events have been reported
during clinical trials with Lovenox Injection.
|
Major Bleeding Episodes Following Abdominal andColorectal
Surgery1
|
| |
Dosing Regimen
|
| |
Lovenox Inj.
|
Heparin
|
|
Indications
|
40 mg q.d. SC
|
5000 U q8h SC
|
|
Abdominal Surgery
|
n = 555
|
n = 560
|
| |
23 (4%)
|
16 (3%)
|
|
Colorectal Surgery
|
n = 673
|
n = 674
|
| |
28 (4%)
|
21 (3%)
|
|
1 Bleeding complications were considered major:
(1) if the hemorrhage caused a significant clinical event, or (2) if accompanied
by a hemoglobin decrease > 2 g/dL or transfusion of 2 or more
units of blood products. Retroperitoneal, intraocular, and intracranial
hemorrhages were always considered major.
|
|
Major Bleeding Episodes Following Hip or Knee Replacement
Surgery1
|
| |
Dosing Regimen
|
| |
Lovenox Inj.
|
Lovenox Inj.
|
Heparin
|
|
Indications
|
40 mg q.d. SC
|
30 mg q12h SC
|
15,000 U/24h SC
|
|
Hip Replacement Surgery Without Extended Prophylaxis2
|
|
n = 786
|
n = 541
|
| |
31 (4%)
|
32 (6%)
|
|
Hip Replacement Surgery With Extended Prophylaxis
|
|
Peri-operativePeriod3
|
n = 288
|
|
|
| |
4 (2%)
|
|
|
|
Extended Prophylaxis Period4
|
n = 221
|
|
|
| |
0 (0%)
|
|
|
|
Knee Replacement Surgery Without Extended Prophylaxis2
|
|
n = 294
|
n = 225
|
| |
3 (1%)
|
3 (1%)
|
|
1 Bleeding complications were considered major:
(1) if the hemorrhage caused a significant clinical event, or (2) if accompanied
by a hemoglobin decrease = 2 g/dL or transfusion of 2 or more units of
blood products. Retroperitoneal and intracranial hemorrhages were always
considered major. In the knee replacement surgery trials, intraocular
hemorrhages were also considered major hemorrhages.
|
|
2 Lovenox Injection 30 mg every 12 hours SC
initiated 12 to 24 hours after surgery and continued for up to 14 days
after surgery.
|
|
3 Lovenox Injection 40 mg SC once a day initiated
up to 12 hours prior to surgery and continued for up to 7 days after surgery.
|
|
4 Lovenox Injection 40 mg SC once a day for
up to 21 days after discharge.
|
NOTE: At no time point were the 40 mg once a day pre-operative
and the 30 mg every 12 hours post-operative hip replacement surgery prophylactic
regimens compared in clinical trials.
Injection site hematomas during the extended prophylaxis period
after hip replacement surgery occurred in 9% of the Lovenox Injection patients
versus 1.8% of the placebo patients.
|
Major Bleeding Episodes in Medical Patients With Severely
Restricted Mobility During Acute Illness1
|
| |
Dosing Regimen
|
| |
Lovenox Inj.2
|
Lovenox Inj.2
|
Placebo2
|
|
Indications
|
20 mg q.d. SC
|
40 mg q.d. SC
|
|
|
Medical Patients During
|
n = 351
|
n = 360
|
n = 362
|
|
Acute Illness
|
1 (<1%)
|
3 (<1%)
|
2 (<1%)
|
|
1 Bleeding complications were considered major:
(1) if the hemorrhage caused a significant clinical event, (2) if the
hemorrhage caused a decrease in hemoglobin of > 2 g/dL or transfusion
of 2 or more units of blood products. Retroperitoneal and intracranial
hemorrhages were always considered major although none were reported during
the trial.
|
|
2 The rates represent major bleeding on study
medication up to 24 hours after last dose.
|
|
Major Bleeding Episodes in Unstable Angina and Non-Q-Wave
Myocardial Infarction
|
| |
Dosing Regimen
|
| |
Lovenox Inj.1
|
Heparin1
|
| |
1 mg/kg q12h SC
|
aPTT Adjusted
|
|
Indication
|
|
i.v. Therapy
|
|
Unstable Angina and
|
n = 1578
|
n = 1529
|
|
Non-Q-Wave MI2,3
|
17 (1%)
|
18 (1%)
|
|
1 The rates represent major bleeding on study
medication up to 12 hours after dose.
|
|
2 Aspirin therapy was administered concurrently
(100 to 325 mg per day).
|
|
3 Bleeding complications were considered major:
(1) if the hemorrhage caused a significant clinical event, or (2) if accompanied
by a hemoglobin decrease by >3 g/dL or transfusion of 2 or more
units of blood products. Intraocular, retroperitoneal, and intracranial
hemorrhages were always considered major.
|
|
Major Bleeding Episodes in Deep Vein Thrombosis With
or Without Pulmonary Embolism Treatment 1
|
| |
Dosing Regimen2
|
| |
Lovenox Inj.
|
Lovenox Inj.
|
Heparin
|
| |
1.5 mg/kg q.d. SC
|
1 mg/kg q12h SC
|
aPTT Adjusted
|
|
Indication
|
|
|
i.v. Therapy
|
|
Treatment of DVT and PE
|
n = 298
|
n = 559
|
n = 554
|
| |
5 (2%)
|
9 (2%)
|
9 (2%)
|
|
1 Bleeding complications were considered major:
(1) if the hemorrhage caused a significant clinical event, or (2) if accompanied
by a hemoglobin decrease = 2 g/dL or transfusion of 2 or more units of
blood products. Retroperitoneal, intraocular, and intracranial hemorrhages
were always considered major.
|
|
2 All patients also received warfarin sodium
(dose-adjusted according to PT to achieve an INR of 2.0 to
|
|
3.0) commencing within 72 hours of Lovenox Injection
or standard heparin therapy and continuing for up to 90 days.
|
Thrombocytopenia
see WARNINGS: Thrombocytopenia.
Elevations of Serum Aminotransferases
Asymptomatic increases in aspartate (AST [SGOT]) and alanine
(ALT [SGPT]) aminotransferase levels greater than three times the upper limit
of normal of the laboratory reference range have been reported in up to 6.1%
and 5.9% of patients, respectively, during treatment with Lovenox Injection.
Similar significant increases in aminotransferase levels have also been observed
in patients and healthy volunteers treated with heparin and other low molecular
weight heparins. Such elevations are fully reversible and are rarely associated
with increases in bilirubin. Since aminotransferase determinations are important
in the differential diagnosis of myocardial infarction, liver disease, and pulmonary
emboli, elevations that might be caused by drugs like Lovenox Injection should
be interpreted with caution.
Local Reactions
Mild local irritation, pain, hematoma, ecchymosis, and erythema
may follow SC injection of Lovenox Injection.
Other
Other adverse effects that were thought to be possibly or probably
related to treatment with Lovenox Injection, heparin, or placebo in clinical
trials with patients undergoing hip or knee replacement surgery, abdominal or
colorectal surgery, or treatment for DVT and that occurred at a rate of at least
2% in the Lovenox Injection group, are provided below.
|
Adverse Events Occurring at >2% Incidence
inLovenox Injection Treated Patients1 Undergoing Abdominal
or Colorectal Surgery
|
| |
Dosing Regimen
|
| |
Lovenox Inj.
|
Heparin
|
| |
40 mg q.d. SC
|
5000 U q8h SC
|
| |
n = 1228
|
n = 1234
|
|
Adverse Event
|
Severe
|
Total
|
Severe
|
Total
|
|
Hemorrhage
|
<1%
|
7%
|
<1%
|
6%
|
|
Anemia
|
<1%
|
3%
|
<1%
|
3%
|
|
Ecchymosis
|
0%
|
3%
|
0%
|
3%
|
|
1 Excluding unrelated adverse events.
|
|
Adverse Events Occurring at>2% Incidence
inLovenox Injection Treated Patients1 Undergoing Hip
or Knee Replacement Surgery
|
| |
Dosing Regimen
|
|
|
Lovenox Inj. 40 mg q.d. SC
|
Lovenox Inj. 30 mg q12h SC
|
Heparin 15,000 U/24h SC
|
Placebo q12h SC
|
|
|
Peri-operative Period
|
Extended Prophylaxis Period
|
|
|
|
| |
n = 288 2
|
n = 131 3
|
n = 1080
|
n = 766
|
n = 115
|
|
Adverse Event
|
Severe Total
|
Severe Total
|
Severe Total
|
Severe Total
|
Severe Total
|
|
Fever
|
0%
|
8%
|
0%
|
0%
|
<1%
|
5%
|
<1%
|
4%
|
0%
|
3%
|
|
Hemorrhage
|
<1%
|
13%
|
0%
|
5%
|
<1%
|
4%
|
1%
|
4%
|
0%
|
3%
|
|
Nausea
|
|
|
|
|
<1%
|
3%
|
<1%
|
2%
|
0%
|
2%
|
|
Anemia
|
0%
|
16%
|
0%
|
<2%
|
<1%
|
2%
|
2%
|
5%
|
<1%
|
7%
|
|
Edema
|
|
|
|
|
<1%
|
2%
|
<1%
|
2%
|
0%
|
2%
|
|
Peripheral edema
|
0%
|
6%
|
0%
|
0%
|
<1%
|
3%
|
<1%
|
4%
|
0%
|
3%
|
|
1 Excluding unrelated adverse events.
|
|
2 Data represents Lovenox Injection 40 mg
SC once a day initiated up to 12 hours prior to surgery in 288 hip replacement
surgery patients who received Lovenox Injection peri-operatively in an
unblinded fashion in one clinical trial.
|
|
3 Data represents Lovenox Injection 40 mg
SC once a day given in a blinded fashion as extended prophy-laxis at the
end of the peri-operative period in 131 of the original 288 hip replacement
surgery patients for up to 21 days in one clinical trial.
|
|
Adverse Events Occurring at>2% Incidence
inLovenox Injection Treated Medical Patients1 With Severely
Restricted Mobility During Acute Illness
|
| |
Dosing Regimen
|
| |
Lovenox Inj.
|
Placebo
|
| |
40 mg q.d. SC
|
q.d. SC
|
| |
n = 360
|
n = 362
|
|
Adverse Event
|
%
|
%
|
|
Dyspnea
|
3.3
|
5.2
|
|
Thrombocytopenia
|
2.8
|
2.8
|
|
Confusion
|
2.2
|
1.1
|
|
Diarrhea
|
2.2
|
1.7
|
|
Nausea
|
2.5
|
1.7
|
|
1Excluding unrelated and unlikely adverse
events.
|
Adverse Events inLovenox Injection Treated Patients With
Unstable Angina or Non-Q-Wave Myocardial Infarction: Non-hemorrhagic clinical
events reported to be related to Lovenox Injection therapy occurred at an incidence
of <1%.
Non-major hemorrhagic episodes, primarily injection site ecchymoses
and hematomas, were more frequently reported in patients treated with SC Lovenox
Injection than in patients treated with i.v. heparin.
Serious adverse events with Lovenox Injection or heparin in
a clinical trial in patients with unstable angina or non-Q-wave myocardial infarction
that occurred at a rate of at least 0.5% in the Lovenox Injection group, are
provided below (irrespective of relationship to drug therapy).
|
Serious Adverse Events Occurring at >0.5% Incidence
in Lovenox InjectionTreated Patients With Unstable Angina or Non-Q-Wave
Myocardial Infarction
|
| |
Dosing Regimen
|
| |
Lovenox Inj.
|
Heparin
|
| |
1 mg/kg q12h SC
|
aPTT Adjusted
|
| |
|
i.v. Therapy
|
| |
n = 1578
|
n = 1529
|
|
Adverse Event
|
n (%)
|
n (%)
|
|
Atrial fibrillation
|
11 (0.70)
|
3 (0.20)
|
|
Heart failure
|
15 (0.95)
|
11 (0.72)
|
|
Lung edema
|
11 (0.70)
|
11 (0.72)
|
|
Pneumonia
|
13 (0.82)
|
9 (0.59)
|
|
Adverse Events Occurring at>2% Incidence
in Lovenox Injection Treated Patients1 Undergoing Treatment
of Deep Vein Thrombosis With or Without Pulmonary Embolism
|
| |
Dosing Regimen
|
|
|
Lovenox Inj. 1.5 mg/kg q.d. SC
|
Lovenox Inj. 1 mg/kg q12h SC
|
Heparin aPTT Adjusted i.v. Therapy
|
| |
n = 298
|
n = 559
|
n = 544
|
|
Adverse Event
|
Severe
|
Total
|
Severe
|
Total
|
Severe
|
Total
|
|
Injection Site Hemorrhage
|
0%
|
5%
|
0%
|
3%
|
<1%
|
<1%
|
|
Injection Site Pain
|
0%
|
2%
|
0%
|
2%
|
0%
|
0%
|
|
Hematuria
|
0%
|
2%
|
0%
|
<1%
|
<1%
|
2%
|
|
1 Excluding unrelated adverse events.
|
Ongoing Safety Surveillance
Since 1993, there have been over 80 reports of epidural or
spinal hematoma formation with concurrent use of Lovenox Injection and spinal/epidural
anesthesia or spinal puncture. The majority of patients had a post-operative
indwelling epidural catheter placed for analgesia or received additional drugs
affecting hemostasis such as NSAIDs. Many of the epidural or spinal hematomas
caused neurologic injury, including long-term or permanent paralysis. Because
these events were reported voluntarily from a population of unknown size, estimates
of frequency cannot be made.
Other Ongoing Safety Surveillance Reports
local reactions at the injection site (i.e., skin necrosis,
nodules, inflammation, oozing), systemic allergic reactions (i.e., pruritus,
urticaria, anaphylactoid reactions), vesiculobullous rash, rare cases
of hypersensitivity cutaneous vasculitis, purpura, thrombocytosis, and thrombocytopenia
with thrombosis (see WARNINGS, Thrombocytopenia).
Very rare cases of hyperlipidemia have been reported, with one case of hyperlipidemia,
with marked hypertriglyceridemia, reported in a diabetic pregnant woman; causality
has not been determined.
DRUG INTERACTIONS
Unless really needed, agents which may enhance the risk of
hemorrhage should be discontinued prior to initiation of Lovenox Injection therapy.
These agents include medications such as: anticoagulants, platelet inhibitors
including acetyl-salicylic acid, salicylates, NSAIDs (including ketorolac tromethamine),
dipyridamole, or sulfinpyrazone. If co-administration is essential, conduct
close clinical and laboratory monitoring (see PRECAUTIONS:
Laboratory Tests).
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