Enoxaparin (Lovenox)

Emergency & Prehospital

• STEMI treated with fibrinolysis: Some patients are managed medically and others get later PCI, including routine transfer for angiography. The IV bolus is timed with the fibrinolytic, then subcut for the hospital stay. Fibrinolysis with no planned invasive approach? Enoxaparin is the anticoagulant the 2025 ACC/AHA ACS guideline recommends, with fondaparinux as the alternative. Continue until revascularization or for the hospital stay, up to 8 days.
• Interfacility transfer after a dose: ACS, PE or DVT patients. Know the time and size of the last dose. They decide cath lab dosing and reversal.

ED / ICU / Transport

• NSTE-ACS (unstable angina, NSTEMI): The option to use instead of UFH when no early invasive approach is planned. Aspirin goes with it.
• Acute DVT with or without PE: Starts as inpatient treatment. DVT without PE can be treated as an outpatient. For most hospitalized PE, it is preferred over UFH.
• PCI in a patient already on enoxaparin: The IV top-up depends on how long it has been since the last subcut dose.
• Cancer-associated VTE: Preferred over UFH for initial treatment. For the next 3–6 months, a DOAC is suggested over LMWH. LMWH is still often chosen when GI or GU bleeding risk is high, when strong drug interactions are present, or when oral absorption is poor. That is a specialist decision.
• VTE in pregnancy: The preferred anticoagulant. Warfarin and DOACs are avoided.

Other Uses

• VTE prophylaxis: abdominal surgery, hip or knee replacement, and acutely ill medical patients with severely restricted mobility
• Trauma VTE prophylaxis (off-label, not an FDA-labeled indication, AAST consensus, not a trial-proven dose): the usual dose is a fixed 30 mg subcut q12h. Anti-Xa-adjusted dosing may be considered in trauma or surgical ICU patients with low bleeding risk. Draw a peak 4 hr after the 3rd dose, with a target of 0.2–0.4 IU/mL. If it is below target, increase by 10 mg and recheck 4 hr after the 3rd new dose. Several authors advise not exceeding 60 mg q12h. Weight-based dosing for BMI above 30 is acceptable in trauma. It is commonly started at 0.5 or 0.6 mg/kg, or 30 mg for 50–60 kg, 40 mg for 61–99 kg and 50 mg for over 100 kg, aiming for anti-Xa levels of 0.2–0.4 IU/mL. It is not recommended with traumatic intracranial hemorrhage. After TBI, start prophylaxis as soon as possible, generally 24–72 hr after admission, once intracranial and extracranial hemorrhage is stable and neurosurgery agrees. In renal failure, UFH three times daily is advised. The published research is mixed in quality. It is unproven that anti-Xa adjustment lowers VTE.
• Bridging around warfarin interruption: ASH strongly recommends against periprocedural LMWH bridging in VTE patients at low to moderate recurrence risk. Only selected high-risk patients get it, per specialist plan (off-label).

The adult doses below are the labeled regimens, unless a row says off-label. The trauma prophylaxis row is off-label (AAST consensus). The label has no weight-based dose for obesity outside trauma. That use follows local protocol.

Available Forms

• 100 mg/mL prefilled syringes (preservative-free): 30 mg/0.3 mL and 40 mg/0.4 mL; graduated 60 mg/0.6 mL, 80 mg/0.8 mL and 100 mg/1 mL
• 150 mg/mL graduated prefilled syringes (preservative-free): 120 mg/0.8 mL and 150 mg/1 mL
• Multiple-dose vial: 300 mg/3 mL (100 mg/mL) with benzyl alcohol 15 mg/mL; the form used for IV boluses
• Generics: the same strengths come from several manufacturers. Syringe label colors vary by maker.

Adult Dosing

Once CrCl falls under 30 mL/min, every regimen changes. See Special Populations.

Pediatric Dosing

The starting doses come from the 2012 CHEST pediatric guideline. Needs vary widely, especially in neonates, so follow pediatric hematology or institutional protocol, and check anti-Xa levels. For weight estimation, see weight-based dosing.

Preparation & Administration

• Subcut technique: patient supine; deep subcut injection into a pinched skin fold of the anterolateral or posterolateral abdominal wall, alternating sides; insert the whole needle and hold the fold throughout; do not rub afterward
• Air bubble: do not expel it from a prefilled syringe (drug is lost); for a partial dose from a graduated syringe, eject the excess until only the ordered dose remains
• IV bolus: use the multiple-dose vial and a tuberculin or similar syringe; give through an IV line flushed with 0.9% sodium chloride or D5W before and after; do not mix with other drugs
• Never IM: intramuscular injection is not allowed (hematoma)
• Site: not into bruised or scarred skin, not through clothing

Switching Anticoagulants

• To warfarin: start warfarin within 72 hr; overlap at least 5 days and until the INR is 2–3
• To or from apixaban or rivaroxaban: start the new agent when the next dose of the old one is due (rivaroxaban up to 2 hr before)
• To or from UFH: start the infusion when the next enoxaparin dose would be due, usually without a bolus; give the first enoxaparin dose when the infusion stops (heparin)
• Not interchangeable: enoxaparin, UFH and other LMWHs are not equivalent unit for unit.

Contraindications

• Active major bleeding
• Immune-mediated HIT within the past 100 days, or circulating HIT antibodies
• Hypersensitivity to enoxaparin, heparin or pork products
• Benzyl alcohol hypersensitivity (multiple-dose vial only)

Precautions

• Bleeding risk: bacterial endocarditis, congenital or acquired bleeding disorders, active GI ulcer or angiodysplasia, hemorrhagic stroke, recent brain, spine or eye surgery, uncontrolled hypertension, diabetic retinopathy, antiplatelet co-therapy
• Renal impairment: exposure climbs as CrCl falls. Dose reduction starts below 30 mL/min.
• Low body weight: fixed doses give higher exposure in women under 45 kg and men under 57 kg.
• HIT more than 100 days ago, antibodies negative: use it only after non-heparin alternatives have been considered.
• Mechanical heart valves: not well studied. Valve thrombosis has been reported, fatal cases in pregnancy included.

Hold / Reassess If

• Platelets fall below 100,000/mm³: stop enoxaparin and evaluate for HIT
• New bleeding, or unexplained fall in hematocrit or blood pressure: hold and search for a bleeding site
• Neuraxial procedure or catheter placement or removal: the delay depends on the last dose. After a low dose (30 mg once or twice daily, 40 mg daily), wait at least 12 hr. After a high dose (0.75 mg/kg or 1 mg/kg q12h, 1.5 mg/kg daily), wait at least 24 hr. On 0.75 or 1 mg/kg q12h, skipping the second daily dose lengthens the delay. If CrCl <30 mL/min, consider doubling the wait: at least 24 hr after 30 mg daily, 48 hr after 1 mg/kg daily. Anti-Xa is still detectable at these times. The delays lower the risk. They do not remove it. Next dose at least 4 hr after catheter removal. For the first dose after puncture, and before high-dose LMWH with a catheter in place, follow the current ASRA Pain Medicine guideline (fifth edition, which uses low-dose and high-dose terms) and institutional policy.
• CrCl falls below 30 mL/min: switch to the reduced regimen or consider UFH

Common

• Bleeding and anemia (major bleeding up to about 4% in the label trials)
• Injection-site pain, hematoma, ecchymosis and erythema
• Asymptomatic AST/ALT rise above 3× normal in up to about 6%
• Moderate thrombocytopenia (100,000–50,000/mm³) in about 1.3%
• Nausea, diarrhea, fever, peripheral edema

Serious / Life-Threatening

Osteoporosis has been linked to long-term therapy.

Overdose & Toxicity Management

• Signs: bleeding; anti-Xa far above range
• No bleeding: hold the next dose and recheck. The anti-Xa effect wears off over about 12 hr, and slower in renal failure.
• Bleeding: protamine 1 mg slow IV per 1 mg enoxaparin given in the past 8 hr; 0.5 mg per 1 mg if the dose was more than 8 hr ago or a second dose is needed (aPTT still prolonged 2–4 hr later); over 10 min, max 50 mg per dose; may not be needed after 12 hr
• Partial reversal only: protamine cannot neutralize more than about 60% of anti-Xa activity. So transfuse, and control the source.
• Protamine risks: it can cause severe hypotension and anaphylactoid reactions. Have resuscitation ready before you start it.

• PT and aPTT do not monitor enoxaparin: Therapeutic doses barely prolong the aPTT. A normal result does not exclude anticoagulation.
• Who gets anti-Xa: Anti-Xa monitoring is not routine in adults. ASH 2018 conditionally suggests against anti-Xa-guided LMWH dosing, including with CrCl below 30 mL/min, obesity and pregnancy. Levels are standard only in children and in pregnant women with mechanical valves, under specialist care. The FDA label differs. It allows anti-Xa monitoring in renal impairment or bleeding.

Clinically Significant Interactions

IV Compatibility

• Diluents: compatible with 0.9% sodium chloride or D5W
• Do not mix: no other drugs in the same syringe or line; flush before and after the bolus
• Verify with an institutional compatibility resource.

• Pediatrics: not FDA-approved. Specialist use, with anti-Xa titration and preservative-free syringes. See the Pediatric Dosing table.
• Neonates: infants under 2 months need higher per-kg doses. The multiple-dose vial is not for neonates or infants, because of benzyl alcohol gasping syndrome.
• Pregnancy: a retrospective cohort of 693 live births found no rise in major birth defects. Some mothers and neonates had bleeding. ASH recommends LMWH over UFH for VTE in pregnancy, given once or twice daily. Plan delivery after the treatment doses stop. As delivery nears, consider a shorter-acting anticoagulant (UFH) per the obstetric and anesthesia plan, so neuraxial anesthesia can be done. Use preservative-free syringes. With a mechanical valve, valve thrombosis has been fatal. That needs specialist care with peak and trough anti-Xa.
• Lactation: transfer into human milk is unknown, and the animal data are very limited. ASH lists LMWH as a safe option while breastfeeding.
• Older Adults: bleeding rises with age at treatment doses. At 75 or older with STEMI, skip the bolus and use 0.75 mg/kg. Check CrCl, and watch anyone under 45 kg.
• Renal Impairment: at CrCl 30–80 mL/min, no adjustment is needed, but watch for bleeding. Under 30 mL/min, use the reduced regimens below. Exposure doubled in a hemodialysis study. UFH is often chosen on dialysis or when renal function is unstable.
• Hepatic Impairment: the drug has not been studied in hepatic impairment, and no specific adjustment is established.
• Obesity / Dosing Weight: treatment doses use actual body weight, with no fixed cap (ASH). There is no consensus on prophylactic dosing for BMI above 30 outside trauma, so follow local protocol. For trauma, see Indications.
• Low Body Weight: fixed prophylactic doses raise exposure by 52% in women under 45 kg and by 27% in men under 57 kg. Watch for bleeding.
• Prior HIT: it is contraindicated within 100 days, or whenever circulating antibodies are present.

• Scope: RN and critical-care transport give subcut doses and STEMI IV boluses. Paramedic use alongside prehospital fibrinolysis (Paramedic/RN/CCT) depends on state and agency protocol.
• Storage & Stability: store at 25°C (77°F), with excursions allowed between 15–30°C (59–86°F). Keep it in the carton. Discard an opened multiple-dose vial after 28 days. Keep the vehicle within that range too.
• Carried Concentration: the 100 mg/mL and 150 mg/mL syringes look alike. Read the mg strength, and give the mg dose, not a mL volume.
• Trauma and Bleeding: in every anticoagulated trauma or head-injury patient, ask about LMWH. Record the last dose time and size, because protamine is only a partial reversal.
• Altitude / Environment: altitude has no specific effect. Vibration and poor light hide bleeding, so recheck access and sheath sites and neuro status.
• Handoff Essentials: indication, weight, CrCl, last dose (mg, route, time), fibrinolytic and antiplatelets given, sheath status, platelet trend, neuraxial catheter status.

Mechanism of Action

• It binds antithrombin through its pentasaccharide sequence. That speeds up inactivation of factor Xa and, to a lesser degree, thrombin (IIa).
• Short chains (average molecular weight about 4,500 daltons) rarely bridge antithrombin to thrombin. The result is an anti-Xa:anti-IIa ratio of about 14:1, against about 1:1 for UFH.
• It binds less to plasma proteins and cells. That gives a predictable, weight-based response without routine monitoring.
• It has no fibrinolytic activity. It stops clot extension while the body's own fibrinolysis does its work.

Pharmacokinetics

• Half-life: about 4.5 hr after a single subcut dose, and about 7 hr with repeated dosing. Renal impairment prolongs it.
• Bioavailability: about 100% after subcut dosing. Steady state comes by day 2 on once-daily dosing and about day 4 on twice-daily dosing.
• Metabolism: the liver desulfates and depolymerizes it into less active fragments.
• Elimination: the kidneys clear it. Active fragments make up about 10% of the dose, and total fragments about 40%.
• Distribution: the anti-Xa volume of distribution is about 4.3 L, mostly intravascular.

Generic Name

Enoxaparin sodium, from porcine intestinal mucosa heparin

Brand Names

Lovenox (US); generics; Clexane (international)

Pharmacologic Class

Low molecular weight heparin (LMWH); antithrombin-dependent factor Xa inhibitor

Therapeutic Class

Parenteral anticoagulant

Controlled Substance

Not controlled

ISMP High-Alert

Yes: ISMP high-alert medication (antithrombotic agents, including low molecular weight heparin)

Look-Alike / Sound-Alike

100 mg/mL vs 150 mg/mL syringes; enoxaparin vs heparin or other LMWHs (not interchangeable)

Error-Prone Abbreviations to Avoid

“SC”, “SQ” or “sub q” (write “subcut”); “q.d.” (write “daily”)