Does Lovenox (enoxaparin) cause side effects?

Lovenox (enoxaparin) is an anticoagulant (blood thinner) used to prevent deep vein thrombosis (DVT) after abdominal surgery, or hip or knee replacement surgeries, and in patients with reduced mobility due to illness.

It is used both in and out of the hospital for treating deep vein thrombosis and pulmonary embolism. Lovenox also is used for preventing a second heart attack and related complications after a heart attack and for preventing blood clots in arterial stents.

Common side effects of Lovenox include

Serious side effects of Lovenox include

Drug interactions of Lovenox include medications such as aspirin, clopidogrel, warfarin, other anticoagulants, and nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, diclofenac, and others that increase the risk of bleeding will add to the effects of Lovenox and further increase the risk of bleeding that is associated with Lovenox.

Lovenox does not cross the placenta and shows no evidence of effects on the fetus. It often is used during pregnancy as an alternative to oral anticoagulants such as warfarin, which cannot be safely used during pregnancy.

Lovenox multiple-dose vials contain benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal "gasping syndrome" in premature neonates.

Lovenox vials preserved with benzyl alcohol should be used with caution in pregnant women and only if clearly needed because benzyl alcohol may cross the placenta.

It is unknown if Lovenox is excreted in breast milk. Since most medicines are excreted in breast milk, it is recommended that women receiving Lovenox should not breastfeed.

What are the important side effects of Lovenox (enoxaparin)?

Common side effect associated with Lovenox are:

Other possible side effects include:

  • Abnormal liver tests in the blood
  • Mild local irritation
  • pain
  • Local injection site reaction

Possible serious side effects include:

Lovenox (enoxaparin) side effects list for healthcare professionals

The following serious adverse reactions are also discussed in other sections of the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

  • During clinical development for the approved indications, 15,918 patients were exposed to Lovenox.
  • These included 1,228 for prophylaxis of deep vein thrombosis following abdominal surgery in patients at risk for thromboembolic complications, 1,368 for prophylaxis of deep vein thrombosis following hip or knee replacement surgery, 711 for prophylaxis of deep vein thrombosis in medical patients with severely restricted mobility during acute illness, 1,578 for prophylaxis of ischemic complications in unstable angina and non-Q-wave myocardial infarction, 10,176 for treatment of acute ST-elevation myocardial infarction, and 857 for treatment of deep vein thrombosis with or without pulmonary embolism.
  • Lovenox doses in the clinical trials for prophylaxis of deep vein thrombosis following abdominal or hip or knee replacement surgery or in medical patients with severely restricted mobility during acute illness ranged from 40 mg subcutaneously once daily to 30 mg subcutaneously twice daily.
  • In the clinical studies for prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction doses were 1 mg/kg every 12 hours and in the clinical studies for treatment of acute ST-segment elevation myocardial infarction Lovenox doses were a 30 mg intravenous bolus followed by 1 mg/kg every 12 hours subcutaneously.
Hemorrhage

The following rates of major bleeding events have been reported during clinical trials with Lovenox (see Tables 2 to 7).

Table 2: Major Bleeding Episodes Following Abdominal and Colorectal Surgery*

IndicationsDosing Regimen
Lovenox 40 mg daily subcutaneouslyHeparin 5000 U q8h subcutaneously
Abdominal Surgeryn=555n=560
23 (4%)16 (3%)
Colorectal Surgeryn=673n=674
28 (4%)21 (3%)
* 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.

Table 3: Major Bleeding Episodes Following Hip or Knee Replacement Surgery*

IndicationsDosing Regimen
Lovenox 40 mg daily subcutaneouslyLovenox 30 mg q12h subcutaneouslyHeparin 15,000 U/24h subcutaneously
Hip Replacement Surgery without Extended Prophylaxis†n=786
31 (4%)
n=541
32 (6%)
Hip Replacement Surgery with Extended Prophylaxis
Peri-operative Period‡n=288
4 (2%)
Extended Prophylaxis Period§n=221
0 (0%)
Knee Replacement Surgery without Extended Prophylaxis†n=294
3 (1%)
n=225
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 and intracranial hemorrhages were always considered major. In the knee replacement surgery trials, intraocular hemorrhages were also considered major hemorrhages.
† Lovenox 30 mg every 12 hours subcutaneously initiated 12 to 24 hours after surgery and continued for up to 14 days after surgery
‡ Lovenox 40 mg subcutaneously once a day initiated up to 12 hours prior to surgery and continued for up to 7 days after surgery
§ Lovenox 40 mg subcutaneously 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 postoperative 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 patients versus 1.8% of the placebo patients.

Table 4: Major Bleeding Episodes in Medical Patients with Severely Restricted Mobility During Acute Illness*

IndicationDosing Regimen
Lovenox† 20 mg daily subcutaneouslyLovenox† 40 mg daily subcutaneouslyPlacebo†
Medical Patients During Acute Illnessn=351n=360n=362
1 (<1%)3 (<1%)2 (<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.
† The rates represent major bleeding on study medication up to 24 hours after last dose.

Table 5: Major Bleeding Episodes in Deep Vein Thrombosis with or without Pulmonary Embolism Treatment*

IndicationDosing Regimen†
Lovenox 1.5 mg/kg daily subcutaneouslyLovenox 1 mg/kg q12h subcutaneouslyHeparin aPTT Adjusted Intravenous Therapy
Treatment of DVT and PEn=298n=559n=554
5 (2%)9 (2%)9 (2%)
* 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.
† 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 or standard heparin therapy and continuing for up to 90 days.

Table 6: Major Bleeding Episodes in Unstable Angina and Non-Q-Wave Myocardial Infarction

IndicationDosing Regimen
Lovenox* 1 mg/kg q12h subcutaneouslyHeparin* aPTT Adjusted Intravenous Therapy
Unstable Angina and Non-Q- Wave MI†,‡n=1578n=1529
17 (1%)18 (1%)
* The rates represent major bleeding on study medication up to 12 hours after dose.
† Aspirin therapy was administered concurrently (100 to 325 mg per day).
‡ 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.

Table 7: Major Bleeding Episodes in Acute ST-Segment Elevation Myocardial Infarction

IndicationDosing Regimen
Lovenox* Initial 30 mg intravenous bolus followed by 1 mg/kg q12h subcutaneouslyHeparin* aPTT Adjusted Intravenous Therapy
Acute ST-Segment Elevation Myocardial Infarctionn=10176n=10151
n (%)n (%)
Major bleeding (including ICH)†211 (2.1)138 (1.4)
Intracranial hemorrhages (ICH)84 (0.8)66 (0.7)
* The rates represent major bleeding (including ICH) up to 30 days
† Bleedings were considered major if the hemorrhage caused a significant clinical event associated with a hemoglobin decrease by ≥5 g/dL. ICH were always considered major.

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.

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 should be interpreted with caution.

Local Reactions

Local irritation, pain, hematoma, ecchymosis, and erythema may follow subcutaneous injection of Lovenox.

Adverse Reactions In Patients Receiving Lovenox For Prophylaxis Or Treatment Of DVT, PE

Other adverse reactions that were thought to be possibly or probably related to treatment with Lovenox, 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 group, are provided below (see Tables 8 to 11).

Table 8: Adverse Reactions Occurring at ≥2% Incidence in Lovenox-Treated Patients Undergoing Abdominal or Colorectal Surgery

Adverse ReactionDosing Regimen
Lovenox 40 mg daily subcutaneously
n=1228 %
Heparin 5000 U q8h subcutaneously
n=1234 %
SevereTotalSevereTotal
Hemorrhage<17<16
Anemia<13<13
Ecchymosis0303

Table 9: Adverse Reactions Occurring at ≥2% Incidence in Lovenox-Treated Patients Undergoing Hip or Knee Replacement Surgery

Adverse ReactionDosing Regimen
Lovenox 40 mg daily subcutaneouslyLovenox 30 mg q12h subcutaneously
n=1080 %
Heparin 15,000 U/24h subcutaneously
n=766 %
Placebo q12h subcutaneously
n=115 %
Peri-operative Period
n=288* %
Extended Prophylaxis Period
n=131† %
SevereTotalSevereTotalSevereTotalSevereTotalSevereTotal
Fever0800<15<1403
Hemorrhage<11305<141403
Nausea<13<1202
Anemia0160<2<1225<17
Edema<12<1202
Peripheral edema0600<13<1403
* Data represent Lovenox 40 mg subcutaneously once a day initiated up to 12 hours prior to surgery in 288 hip replacement surgery patients who received Lovenox peri-operatively in an unblinded fashion in one clinical trial.
† Data represent Lovenox 40 mg subcutaneously once a day given in a blinded fashion as extended prophylaxis 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.

Table 10: Adverse Reactions Occurring at ≥2% Incidence in Lovenox-Treated Medical Patients with Severely Restricted Mobility During Acute Illness

Adverse ReactionDosing Regimen
Lovenox 40 mg daily subcutaneously
n=360 %
Placebo daily subcutaneously
n=362 %
Dyspnea3.35.2
Thrombocytopenia2.82.8
Confusion2.21.1
Diarrhea2.21.7
Nausea2.51.7

Table 11: Adverse Reactions Occurring at ≥2% Incidence in Lovenox-Treated Patients Undergoing Treatment of Deep Vein Thrombosis with or without Pulmonary Embolism

Adverse ReactionDosing Regimen
Lovenox 1.5 mg/kg daily subcutaneously
n=298 %
Lovenox 1 mg/kg q12h subcutaneously
n=559 %
Heparin aPTT Adjusted Intravenous Therapy
n=544 %
SevereTotalSevereTotalSevereTotal
Injection Site Hemorrhage0503<1<1
Injection Site Pain020200
Hematuria020<1<12

Adverse Events In Lovenox-Treated Patients With Unstable Angina Or Non-Q-Wave Myocardial Infarction

Non-hemorrhagic clinical events reported to be related to Lovenox therapy occurred at an incidence of ≤1%.

Non-major hemorrhagic events, primarily injection site ecchymosis and hematomas, were more frequently reported in patients treated with subcutaneous Lovenox than in patients treated with intravenous heparin.

Serious adverse events with Lovenox 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 group are provided below (see Table 12).

Table 12: Serious Adverse Events Occurring at ≥0.5% Incidence in Lovenox-Treated Patients with Unstable Angina or Non-Q-Wave Myocardial Infarction

Adverse EventDosing Regimen
Lovenox 1 mg/kg q12h subcutaneously
n=1578 n (%)
Heparin aPTT Adjusted Intravenous Therapy
n=1529 n (%)
Atrial fibrillation11 (0.70)3 (0.20)
Heart failure15 (0.95)11 (0.72)
Lung edema11 (0.70)11 (0.72)
Pneumonia13 (0.82)9 (0.59)

Adverse Reactions In Lovenox-Treated Patients With Acute ST-Segment Elevation Myocardial Infarction

In a clinical trial in patients with acute ST-segment elevation myocardial infarction, thrombocytopenia occurred at a rate of 1.5%.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of Lovenox. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

There have been reports of epidural or spinal hematoma formation with concurrent use of Lovenox and spinal/epidural anesthesia or spinal puncture. The majority of patients had a postoperative 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.

Local reactions at the injection site (e.g. nodules, inflammation, oozing), systemic allergic reactions (e.g. pruritus, urticaria, anaphylactic/anaphylactoid reactions including shock), vesiculobullous rash, cases of hypersensitivity cutaneous vasculitis, purpura, skin necrosis (occurring at either the injection site or distant from the injection site), thrombocytosis, and thrombocytopenia with thrombosis have been reported.

Cases of hyperkalemia have been reported. Most of these reports occurred in patients who also had conditions that tend toward the development of hyperkalemia (e.g., renal dysfunction, concomitant potassium-sparing drugs, administration of potassium, hematoma in body tissues). Very rare cases of hyperlipidemia have also been reported, with one case of hyperlipidemia, with marked hypertriglyceridemia, reported in a diabetic pregnant woman; causality has not been determined.

Cases of headache, hemorrhagic anemia, eosinophilia, alopecia, hepatocellular and cholestatic liver injury have been reported.

Osteoporosis has also been reported following long-term therapy.

What drugs interact with Lovenox (enoxaparin)?

Whenever possible, agents which may enhance the risk of hemorrhage should be discontinued prior to initiation of Lovenox therapy.

These agents include medications such as:

If coadministration is essential, conduct close clinical and laboratory monitoring.

Summary

Lovenox (enoxaparin) is an anticoagulant (blood thinner) used to prevent deep vein thrombosis (DVT) after abdominal surgery, or hip or knee replacement surgeries, and in patients with reduced mobility due to illness. Common side effects of Lovenox include bleeding, fever, nausea, diarrhea, fluid retention, abnormal liver tests in the blood, and local injection site reactions (mild local irritation or pain). Lovenox does not cross the placenta and shows no evidence of effects on the fetus. It is unknown if Lovenox is excreted in breast milk.

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Medically Reviewed on 9/23/2020
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