Enoxaparin

Usage

Enoxaparin is prescribed for the prevention and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and acute coronary syndromes (ACS) such as unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI). It is also used for DVT prophylaxis in surgical settings (e.g. abdominal, hip, or knee replacement surgery) and in medically ill patients with restricted mobility. It belongs to the pharmacological classification of anticoagulants, specifically low molecular weight heparins (LMWHs).

Enoxaparin’s mechanism of action involves potentiating the activity of antithrombin III. This leads to the inactivation of clotting factor Xa and, to a lesser extent, factor IIa (thrombin), ultimately preventing the formation of fibrin clots.

Alternate Names

Enoxaparin sodium is the generic name. A commonly known brand name is Lovenox.

How It Works

Pharmacodynamics: Enoxaparin primarily exerts its anticoagulant effect by binding to antithrombin III. This complex then inactivates factor Xa, a key enzyme in the coagulation cascade. It has a lesser effect on factor IIa (thrombin).

Pharmacokinetics: Enoxaparin is administered subcutaneously (SC) or intravenously (IV). SC administration has high bioavailability (approximately 90%). Peak anti-Xa activity is reached in 3-5 hours after SC injection. It has a half-life of 4-6 hours after repeated dosing. Enoxaparin is primarily eliminated through renal excretion, with some hepatic metabolism.

Mode of Action: Enoxaparin binds to antithrombin III, causing a conformational change that accelerates its inhibitory action on factor Xa. The enoxaparin-antithrombin III complex neutralizes factor Xa, preventing further steps in the coagulation cascade that lead to thrombin formation and fibrin clot development.

Receptor Binding/Enzyme Inhibition: Enoxaparin’s primary mechanism is through antithrombin-mediated serine protease inhibition of factor Xa.

Elimination Pathways: Predominantly renal excretion, with some hepatic metabolism. Dose adjustments are needed in patients with severe renal impairment.

Dosage

Standard Dosage

Adults:

• DVT Prophylaxis (Surgical): 40 mg SC once daily, starting 2 hours before abdominal surgery; 30 mg SC every 12 hours, initiated 12-24 hours postoperatively for hip or knee replacement surgery (for hip replacement, 40 mg SC daily initiated preoperatively is an option). Duration typically 7-10 days, may be extended.
• DVT Prophylaxis (Medical): 40 mg SC once daily until risk is reduced (6-11 days).
• DVT/PE Treatment: 1 mg/kg SC every 12 hours OR 1.5 mg/kg SC once daily, in conjunction with warfarin. Continue for at least 5 days and until therapeutic INR is reached.
• ACS (unstable angina, NSTEMI): 1 mg/kg SC every 12 hours along with aspirin. Duration: 2-8 days.
• STEMI: Complex dosing based on age and fibrinolytic use (see below).

Children: Dosing is weight-based and must be determined by a doctor. Pediatric considerations include a higher risk of bleeding.

Special Cases:

• Elderly Patients (STEMI): For those over 75, no initial IV bolus; 0.75 mg/kg SC every 12 hours (not to exceed 75 mg/dose for first two doses).
• Renal Impairment: Significant dose reductions are required in severe renal impairment (CrCl < 30 mL/min). See specific examples in “Dosage Adjustments” section.
• Hepatic Dysfunction: Use with caution due to increased bleeding risk. Close monitoring is required.
• Comorbid Conditions: Adjustments may be needed based on concomitant medications, bleeding risk factors (e.g. active cancer), and other conditions.

Clinical Use Cases

• Surgical Procedures: Doses as described above for prophylaxis.
• ICU Use: Prophylactic dosing; adjust based on renal function, weight, and anti-Xa levels.
• Acute Coronary Syndromes: Dosages detailed above.

Dosage Adjustments

• Severe Renal Impairment (CrCl <30 mL/min):
  • DVT Prophylaxis (Surgical/Medical): 30 mg SC once daily.
  • DVT Treatment: 1 mg/kg SC once daily.
  • ACS/NSTEMI: 1 mg/kg SC once daily.
  • STEMI (<75 years): 30 mg IV bolus + 1 mg/kg SC, then 1 mg/kg SC daily.
  • STEMI (>75 years): 1 mg/kg SC daily.

Side Effects

Common Side Effects:

• Bleeding (e.g., bruising, bleeding gums, prolonged bleeding from cuts)
• Injection site reactions (pain, redness, swelling)
• Anemia
• Nausea
• Fever

Rare but Serious Side Effects:

• Hemorrhage (internal bleeding)
• Thrombocytopenia (low platelet count)
• Spinal or epidural hematoma (with neuraxial anesthesia)
• Allergic reactions (including anaphylaxis)

Long-Term Effects: Osteoporosis (with prolonged high doses)

Adverse Drug Reactions (ADR): Hemorrhage, Thrombocytopenia, Heparin-induced thrombocytopenia (HIT).

Contraindications

• Active major bleeding
• History of heparin-induced thrombocytopenia (HIT)
• Hypersensitivity to enoxaparin, heparin, or pork products
• Severe renal impairment (CrCl < 30 mL/min) in some cases (prophylaxis may still be used)

Drug Interactions

• Anticoagulants (e.g., warfarin): Increased bleeding risk
• Antiplatelets (e.g., aspirin, clopidogrel): Increased bleeding risk
• NSAIDs: Increased bleeding risk

Pregnancy and Breastfeeding

Enoxaparin is generally considered safe during pregnancy and breastfeeding. It does not cross the placenta and is not found in breast milk in significant amounts. However, the benefits and risks should be carefully assessed by a doctor.

Drug Profile Summary

• Mechanism of Action: Potentiates antithrombin III, inhibiting factor Xa and, to a lesser degree, factor IIa.
• Side Effects: Bleeding, injection site reactions, anemia. Rarely: hemorrhage, thrombocytopenia, spinal hematoma.
• Contraindications: Active bleeding, HIT history, hypersensitivity.
• Drug Interactions: Anticoagulants, antiplatelets, NSAIDs.
• Pregnancy & Breastfeeding: Generally safe, but individual assessment is needed.
• Dosage: See detailed section above.
• Monitoring Parameters: Complete blood count (CBC), including platelets; anti-Xa levels in specific situations (renal impairment, obesity, pregnancy).

Popular Combinations

• Aspirin (for ACS)
• Warfarin (for initial DVT/PE treatment)

Precautions

• Assess bleeding risk before initiating therapy.
• Monitor for signs and symptoms of bleeding.
• Dose adjustment in renal impairment.
• Caution in hepatic impairment.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for enoxaparin?

A: Dosage varies depending on indication, patient characteristics (age, weight, renal function), and clinical context. See the detailed “Dosage” section above.

Q2: How is enoxaparin administered?

A: Subcutaneously (SC) into the abdominal wall. For specific situations (e.g., STEMI), it can be given intravenously (IV).

Q3: What are the major side effects of enoxaparin?

A: Bleeding is the most common side effect. Serious but rare side effects include hemorrhage and thrombocytopenia.

Q4: What are the contraindications for using enoxaparin?

A: Active major bleeding, history of HIT, and hypersensitivity to enoxaparin or heparin.

Q5: Can enoxaparin be used during pregnancy?

A: Yes, it is generally considered safe during pregnancy, but should be used under careful medical supervision.

Q6: How should enoxaparin dosage be adjusted for patients with renal impairment?

A: Dosage reduction is essential in severe renal impairment (CrCl <30ml/min). See details in “Dosage Adjustments.”

Q7: What monitoring is recommended for patients on enoxaparin?

A: Regular CBC, including platelet counts, is recommended. Anti-Xa level monitoring may be needed in select populations (obesity, renal impairment, pregnancy).

Q8: When should enoxaparin be discontinued before surgery?

A: The timing of discontinuation depends on the type of surgery and the patient’s bleeding risk. Guidelines generally recommend discontinuing at least 12-24 hours before surgery.

Q9: What is the difference between enoxaparin and unfractionated heparin?

A: Enoxaparin is a LMWH with a more predictable anticoagulant response and longer half-life than unfractionated heparin, allowing for fixed dosing and less frequent administration. It preferentially inhibits factor Xa. Unfractionated heparin requires more monitoring (aPTT).

Q10: What should be done in case of a suspected enoxaparin overdose?

A: Protamine sulfate can be administered as an antidote to partially reverse the anticoagulant effects of enoxaparin. Supportive measures should also be implemented as necessary.