Enoxaparin

Mechanism of Action

LMWH; antithrombotic that inhibits factor Xa by increasing inhibition rate of clotting proteases that are activated by antithrombin III

Generally does not increase PT or PTT

Absorption

Bioavailability: 92%

Onset: 3-5 hr (peak effect)

Duration: 12 hr (40 mg)

AUC: 14.26 hr·U/mL

Distribution

Vd: 4.3 L

Metabolism

Metabolized by liver via desulfation and/or depolymerization to lower molecular weight species

Elimination

Half-life: 4.5 hr (single dose based on anti-Xa activity); 7 hr (repeated dosing)

Total body clearance: 26 mL/min

Excretion: Urine (40%)

GENERIC AVAILABLE: Yes

Common side effect associated with Lovenox are:

• Bleeding
• Fever
• Nausea
• Diarrhea
• Fluid retention

Other possible side effects include:

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

Possible serious side effects include:

• Liver damage
• A reduction in blood platelets
• Red blood cells (anemia)
• Major bleeding
• Hematoma
• Ecchymosis
• Erythema
• Atrial fibrillation
• Heart failure
• Pulmonary edema
• Hypersensitivity reactions
• Pneumonia
• Osteoporosis
• Skin necrosis
• Increased potassium levels
• Anemia
• Prosthetic heart valve thrombosis

Lovenox is administered by injection under the skin (subcutaneous) or intravenously.

• Preventing deep vein thrombosis after abdominal surgery: 40 mg subcutaneous injection once daily.
• Preventing deep vein thrombosis after knee replacement: 30 mg subcutaneous injection every 12 hours.
• Preventing deep vein thrombosis after hip replacement: 30 mg every 12 hours or 40 mg once daily by subcutaneous injection.
• Preventing deep vein thrombosis in ill patients with limited mobility: 40 mg subcutaneous injection once daily.
• Treatment of deep vein thrombosis or pulmonary embolism: 1 mg/kg every 12 hours or 1.5 mg/kg once daily by subcutaneous injection.
• Outpatient treatment of deep vein thrombosis: 1 mg/kg subcutaneous injection every 12 hours.
• Treatment of severe heart attacks (ST elevation myocardial infarction or STEMI): For patients under the age of 75, 30 mg intravenously plus 1 mg/kg subcutaneously followed by 1 mg/kg every 12 hours (maximum of 100 mg for each of the first two subcutaneous doses only). For patients over age 75, 0.75 mg/kg subcutaneously every 12 hours (maximum of 75 mg for each of the first two subcutaneous doses only). All patients should receive aspirin. Doses should be reduced in patients with impaired kidney function.
• Treatment of chest pain (unstable angina) or mild heart attack (non-Q-wave myocardial infarction): 1 mg/kg subcutaneously every 12 hours with aspirin.
• For coronary artery stent procedures (percutaneous coronary intervention or PCI): Patients should receive 0.3 mg/kg during stent placement if the last dose of Lovenox was administered more than 8 hours before the procedure.

• Lovenox is available in pre-filled syringes containing 30, 40, 60, 80, 100, 120, and 150 mg.
• Multiple dose vial: 300 mg

All Lovenox products should be stored at room temperature, between 15 and 30 C (59 and 86 F).

Common Side Effects of Lovenox

Among the most common possible side effects of Lovenox are excessive bleeding and bruising. Use caution when using sharp instruments such as razors, and avoid situations in which you can be cut, injured, or bruised.

Severe Side Effects of Lovenox

There are many possibly severe side effects of Lovenox. If any of these occur, call your doctor right away.

• Paralysis
• Tarry, black, or red stools
• Dark brown or red urine
• Bruising
• Chest discomfort
• Any unusual bleeding — such as from the nose, mouth, wounds, or under the skin
• Low back pain
• Pain on urination
• Hands or feet swelling
• Coughing up of blood or ''coffee ground'' material
• Fever
• Seizures
• Dizziness or lightheadedness

Rare Side Effects of Lovenox

Many other side effects of Lovenox are rare. These include:

• Back pain
• Sensations of burning, tickling
• Pain in the chest
• Severe fatigue
• Fainting
• Fast, irregular heartbeat
• Rash or hives
• Weight gain
• Cough, chills

Lovenox can interact with numerous medications. As a precaution, tell your doctor if you are taking any other prescription, non-prescription, over-the-counter (OTC), illegal and recreational drugs, herbal remedies, nutritional and dietary supplements while on Lovenox.

It is important to avoid taking medicines that can increase a risk of bleeding while you are taking Lovenox. Drugs that should be avoided include:

• Aspirin
• Ibuprofen (Motrin, Advil)
• Apixaban (Eliquis)
• Dabigatran etexilate (Pradaxa)
• Naproxen (Aleve, Naprosyn, others)
• Tinzaparin (Innohep)

Sometimes, a medicine that is usually not recommended to be taken with Lovenox may be required. In that case, your doctor may have to change the dose of one or both medicines or change how often you take them.

Enoxaparin is a prescription medication used:

• to prevent blood clots in hospital patients who are on bed rest
• to prevent blood clots in hospital patients who are about to have abdominal (stomach), hip, or knee surgery
• in the hospital along with aspirin to prevent complications of chest pain (angina) and heart attack
• in the hospital along with warfarin (Coumadin) to prevent blood clots in the legs with or without a blockage of a lung artery (pulmonary embolism)
• at home along with warfarin (Coumadin) to prevent blood clots in the legs without a blockage of a lung artery (pulmonary embolism)

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• anticoagulants, or blood thinners, such as heparin
• platelet inhibitors, such as clopidogrel (Plavix)
• acetylsalicylic acids, such as aspirin (Ecotrin)
• salicylates, such as Pepto-Bismol
• non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Advil) and naproxen (Aleve)
• ketorolac tromethamine (Toradol)
• dipyridamole (Persantine)
• sulfinpyrazone (Anturane)

This is not a complete list of enoxaparin drug interactions. Ask your doctor or pharmacist for more information.

• Store enoxaparin at room temperature.
• Keep this and all medicines out of the reach of children.

You should not use this medicine if you have active bleeding, or a low level of platelets in your blood after testing positive for a certain antibody while using enoxaparin.

Enoxaparin can cause a very serious blood clot around your spinal cord if you undergo a spinal tap or receive spinal anesthesia (epidural), especially if you have a genetic spinal defect, a history of spinal surgery or repeated spinal taps, or if you are using other drugs that can affect blood clotting, including blood thinners or NSAIDs (ibuprofen, Advil, Aleve, and others). This type of blood clot can lead to long-term or permanent paralysis.

Get emergency medical help if you have symptoms of a spinal cord blood clot such as back pain, numbness or muscle weakness in your lower body, or loss of bladder or bowel control.

• It is used to thin the blood so that clots will not form.
• It is used to treat blood clots.
• It is used to lower the number of heart attacks in patients who have unstable angina or mild heart attacks.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Feeling very tired or weak.
• Dizziness or passing out.
• Feeling confused.
• Very bad headache.

• Enoxaparin Sodium

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as sodium:

Lovenox: 300 mg/3 mL (3 mL) [contains benzyl alcohol, pork (porcine) protein]

Generic: 300 mg/3 mL (3 mL)

Solution, Subcutaneous, as sodium [preservative free]:

Lovenox: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL); 60 mg/0.6 mL (0.6 mL); 80 mg/0.8 mL (0.8 mL); 100 mg/mL (1 mL); 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL) [contains pork (porcine) protein]

Generic: 30 mg/0.3 mL (0.3 mL); 40 mg/0.4 mL (0.4 mL); 60 mg/0.6 mL (0.6 mL); 80 mg/0.8 mL (0.8 mL); 100 mg/mL (1 mL); 120 mg/0.8 mL (0.8 mL); 150 mg/mL (1 mL)

AUC increased 65% in patients with severe renal impairment (CrCl <30 mL/minute).

Apparent clearance and maximum observed activity derived from anti–factor Xa values following subcutaneous dosing were slightly higher in men than in women.

Hypersensitivity to enoxaparin, heparin, pork products, or any component of the formulation (including benzyl alcohol in multiple-dose vials); thrombocytopenia associated with a positive in vitro test for antiplatelet antibodies in the presence of enoxaparin; active major bleeding

Canadian labeling: Additional contraindications (not in U.S. labeling): Use of multiple-dose vials in newborns or premature neonates; history of confirmed or suspected immunologically-mediated heparin-induced thrombocytopenia; acute or subacute bacterial endocarditis; major blood clotting disorders; active gastric or duodenal ulcer; hemorrhagic cerebrovascular accident (except if there are systemic emboli); severe uncontrolled hypertension; diabetic or hemorrhagic retinopathy; other conditions or diseases involving an increased risk of hemorrhage; injuries to and operations on the brain, spinal cord, eyes, and ears; spinal/epidural anesthesia when repeated dosing of enoxaparin (1 mg/kg every 12 hours or 1.5 mg/kg daily) is required, due to increased risk of bleeding.

Note: Use of enoxaparin in patients with current heparin-induced thrombocytopenia (HIT) or HIT with thrombosis is not recommended and considered contraindicated due to high cross-reactivity to heparin-platelet factor-4 antibody (Guyatt [ACCP], 2012; Warkentin, 1999).

CrCl ≥30 mL/minute: No specific adjustment recommended (per manufacturer); monitor closely for bleeding.

CrCl <30 mL/minute:

DVT prophylaxis in abdominal surgery, hip replacement, knee replacement, or in medical patients during acute illness: SubQ: 30 mg once daily. Note: The Canadian labeling recommends 20 to 30 mg once daily (based on risk/benefit assessment) for prophylaxis in abdominal or colorectal surgery or in medical patients during acute illness.

DVT treatment: SubQ: 1 mg/kg once daily

STEMI:

<75 years: Initial: IV: 30 mg as a single dose with the first dose of the SubQ maintenance regimen administered at the same time as the IV bolus; Maintenance: SubQ: 1 mg/kg once daily. Note: Canadian labeling recommends a maximum dose of 100 mg for the first SubQ dose.

≥75 years of age: Omit IV bolus; Maintenance: SubQ: 1 mg/kg once daily. Note: Canadian labeling recommends a maximum dose of 100 mg for the first SubQ dose.

Unstable angina, NSTEMI: SubQ: 1 mg/kg once daily

Dialysis: Enoxaparin has not been FDA approved for use in dialysis patients. Its elimination is primarily via the renal route. Serious bleeding complications have been reported with use in patients who are dialysis dependent or have severe renal failure. LMWH administration at fixed doses without monitoring has greater unpredictable anticoagulant effects in patients with chronic kidney disease. If used, dosages should be reduced and anti-Xa levels frequently monitored, as accumulation may occur with repeated doses. Many clinicians would not use enoxaparin in this population especially without timely anti-Xa levels.

Hemodialysis: Not dialyzable (NCS/SCCM [Frontera 2016]). Supplemental dose is not necessary.

Peritoneal dialysis: Significant drug removal is unlikely based on physiochemical characteristics.

Commonly reported side effects of enoxaparin include: anemia and hemorrhage. Other side effects include: fever. See below for a comprehensive list of adverse effects.

Applies to enoxaparin: injectable solution

General

The most common adverse reactions were bleeding, anemia, thrombocytopenia, elevation of serum aminotransferase, diarrhea, and nausea.[Ref]

Cardiovascular

Common (1% to 10%): Major hemorrhage
Uncommon (0.1% to 1%): Atrial fibrillation, heart failure
Frequency not reported: Hemorrhage
Postmarketing reports: Shock, valve thrombosis in patients with prosthetic heart valves[Ref]

Hematologic

Common (1% to 10%): Thrombocytopenia, anemia, platelet counts between 100,000 and 50,000/mm3
Uncommon (0.1% to 1%): Platelet counts less than 50,000/mm3
Frequency not reported: Thrombocytosis
Postmarketing reports: Hemorrhagic anemia, platelet count increased, eosinophilia[Ref]

Hepatic

Common (1% to 10%): ALT increased asymptomatically, AST increased asymptomatically
Frequency not reported: Hepatic enzymes increased
Postmarketing reports: Hepatocellular liver injury, cholestatic liver injury[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, diarrhea
Uncommon (0.1% to 1%): Retroperitoneal hemorrhage[Ref]

Local

Common (1% to 10%): Injection site hematoma, injection site pain, other injection site reaction
Uncommon (0.1% to 1%): Local irritation, injection site skin necrosis
Postmarketing reports: Injection site nodules[Ref]

Dermatologic

Common (1% to 10%): Urticaria, pruritus, erythema
Uncommon (0.1% to 1%): Bullous dermatitis
Postmarketing reports: Cutaneous vasculitis, skin necrosis, alopecia[Ref]

Metabolic

Common (1% to 10%): Peripheral edema, edema
Rare (less than 0.1%): Hyperkalemia
Postmarketing reports: Hyperlipidemia, hypertriglyceridemia[Ref]

Immunologic

Common (1% to 10%): Allergic reaction
Rare (0.01% to 0.1%): Anaphylactic/anaphylactoid reaction
Very rare (less than 0.01%): Immuno-allergic thrombocytopenia
Postmarketing reports: Immuno-allergic thrombocytopenia with thrombosis[Ref]

Respiratory

Common (1% to 10%): Dyspnea
Uncommon (0.1% to 1%): Lung edema, pneumonia[Ref]

Genitourinary

Uncommon (0.1% to 1%): Hematuria[Ref]

Psychiatric

Common (1% to 10%): Confusion[Ref]

Other

Common (1% to 10%): Fever[Ref]

Nervous system

Uncommon (0.1% to 1%): Intracranial hemorrhage
Postmarketing reports: Headache, spinal hematoma[Ref]

Musculoskeletal

Postmarketing reports: Osteoporosis following treatment longer than 3 months[Ref]

Some side effects of enoxaparin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Unstable Angina and Non Q Wave Myocardial Infarction:
1 mg/kg subcutaneously every 12 hours in conjunction with oral aspirin therapy (100 to 325 mg once a day)

Duration of therapy: At least 2 days and until clinical stabilization. Usual duration is 2 to 8 days; up to 12.5 days has been well tolerated in clinical trials.

Use: Prophylaxis of ischemic complications of unstable angina and non Q wave myocardial infarction, when concurrently administered with aspirin.

Acute ST-Segment Elevation Myocardial Infarction (STEMI):
30 mg IV bolus once plus 1 mg/kg subcutaneously once followed by 1 mg/kg subcutaneously every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg for the remaining doses)

Duration of therapy: Optimal duration is unknown, but it is likely to be longer than 8 days.

Comments:
-When given in conjunction with a thrombolytic, enoxaparin should be given between 15 minutes prior and 30 minutes after the start of fibrinolytic treatment.
-All patients should be given oral aspirin therapy (75 to 325 mg once a day unless contraindicated).
-For patients managed by percutaneous coronary intervention (PCI), if the last subcutaneous dose of enoxaparin was less than 8 hours before balloon inflation, no additional dosing is required. If the last subcutaneous dose was given more than 8 hours before balloon inflation, an IV bolus of 0.3 mg/kg should be given.

Use: Prophylaxis of recurrent myocardial infarction or death in patients with acute STEMI receiving thrombolysis and being managed medically or with PCI, when concurrently administered with aspirin.

Data not available

• When injecting subcutaneously, ensure the whole length of the needle is introduced to a skin fold held between the thumb and forefinger. There is no need to expel the bubble from the syringe before injecting. Avoid rubbing the injection site after injecting to minimize bruising.
• Call emergency services immediately if you have any symptoms of thromboembolism (blood clots), such as shortness of breath, pain in the legs, or confusion. People with excess body weight are more at risk of thromboembolism.
• Report any tingling, numbness, or weakness to your doctor, particularly if you have had a spinal puncture or spinal or epidural anesthesia.
• Enoxaparin reduces the ability of your blood to clot, so small cuts may take longer to stop bleeding than normal, and you may bruise more easily. Report any unusual bleeding, bruising or rashes to your doctor.
• Tell all health professionals, including your dentist, that you are administering/being administered enoxaparin.

Due to its relatively large molecular weight, this drug is not expected to undergo excretion into breast milk or to be absorbed from breast milk by the infant.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: This drug has been used without apparent harmful effects in the nursing infant.

LactMed Record Number

104

Last Revision Date

20170411

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