Enorin

Approved Medical Uses:

A. Prophylaxis of Deep Vein Thrombosis (DVT):

• In patients undergoing:
• Abdominal surgery
• Hip replacement surgery
• Knee replacement surgery
• In acutely ill medical patients with restricted mobility at risk of thromboembolism

B. Treatment of Deep Vein Thrombosis (DVT), With or Without Pulmonary Embolism (PE):

• Suitable for inpatient or outpatient treatment when oral anticoagulation is not appropriate initially.

C. Unstable Angina and Non-ST-Elevation Myocardial Infarction (NSTEMI):

• To prevent ischemic complications, in combination with aspirin.

D. ST-Elevation Myocardial Infarction (STEMI):

• For acute treatment, with or without fibrinolytic therapy, especially in conjunction with aspirin.

E. Anticoagulation During Hemodialysis:

• To prevent clot formation in the extracorporeal circuit.

Important Off-Label Uses:

• Bridging Therapy:
  Used when temporarily stopping warfarin or other oral anticoagulants (e.g., perioperative settings).
• Thromboprophylaxis in Pregnancy:
  Especially in women with thrombophilia or previous thromboembolism.
• Venous Thromboembolism (VTE) in Cancer Patients:
  Preferred over oral anticoagulants in active malignancy.
• COVID-19-Associated Coagulopathy:
  For thromboprophylaxis in hospitalized COVID-19 patients at risk of clotting complications.

Route:

• Subcutaneous (SC) injection for most indications
• Intravenous (IV) bolus for STEMI (initial dose only)

Adult Dosage:

• DVT Prophylaxis (General Surgery):
  40 mg SC once daily, starting 2 hours before surgery
• DVT Prophylaxis (Orthopedic Surgery):
  30 mg SC every 12 hours starting 12–24 hours post-surgery, or 40 mg SC once daily
• DVT Prophylaxis (Medical Patients):
  40 mg SC once daily for 6–14 days
• DVT Treatment (With or Without PE):
• 1 mg/kg SC every 12 hours
• Alternatively, 1.5 mg/kg SC once daily (for patients without high-risk PE)
• Unstable Angina/NSTEMI:
  1 mg/kg SC every 12 hours + aspirin (75–325 mg daily)
• STEMI:
• <75 years: 30 mg IV bolus + 1 mg/kg SC, then 1 mg/kg SC every 12 hours
• ≥75 years: 0.75 mg/kg SC every 12 hours (no IV bolus)

Pediatric Dosage:

• Not routinely recommended
• Off-label individualized dosing may be guided by anti-Xa monitoring

Renal Impairment (CrCl <30 mL/min):

• Prophylaxis: 30 mg SC once daily
• Treatment: 1 mg/kg SC once daily

Hepatic Impairment:

• Use with caution; no definitive dose adjustment due to limited data

Elderly Patients:

• Use with caution; adjust dose based on renal function

Duration of Use:

• 7–10 days for prophylaxis; extended use (up to 35 days) for high-risk orthopedic or medical patients

Enoxaparin Sodium is a low molecular weight heparin (LMWH) that works by inhibiting coagulation factors Xa and IIa (thrombin) via activation of antithrombin III. Its greater specificity for factor Xa results in suppression of thrombin generation, preventing the formation and propagation of clots. The anti-Xa to anti-IIa activity ratio is approximately 3:1. Unlike unfractionated heparin, Enoxaparin offers more stable pharmacokinetics, longer half-life, and reduced risk of heparin-induced thrombocytopenia (HIT), allowing for fixed dosing without routine laboratory monitoring in most patients.

• Absorption:
  Rapid and nearly complete absorption after SC injection; bioavailability ≈ 90%
• Distribution:
  Volume of distribution: 4–5 L
  Does not cross the placenta in significant amounts
• Metabolism:
  Partially metabolized in the liver by desulfation and depolymerization
• Excretion:
  Primarily renal (40% unchanged); rest as inactive metabolites
  Elimination half-life:
• ~4.5 hours (single dose)
• Up to 7 hours (repeated dosing)
• Time to Peak Plasma Levels:
  3–5 hours after SC injection (anti-Xa activity)
• Onset of Action:
  Within 3–5 hours
• Terminal Half-Life in Renal Impairment:
  Prolonged; requires dosing adjustments

• Pregnancy:
• FDA Pregnancy Category B
• Does not cross the placenta in significant amounts
• Considered safe and effective for thromboprophylaxis in pregnancy
• Preferred over warfarin in pregnant women
• Lactation:
• Enoxaparin is not significantly excreted into human milk
• No adverse effects expected in breastfed infants
• Can be used safely while breastfeeding
• Caution:
  Monitor platelet count and renal function in pregnant women

• Primary Class: Anticoagulant
• Subclass: Low Molecular Weight Heparin (LMWH)

• Known hypersensitivity to Enoxaparin, heparin, or pork-derived substances
• Active major bleeding
• History of heparin-induced thrombocytopenia (HIT)
• Severe, uncontrolled hypertension
• Acute bacterial endocarditis
• Concurrent spinal or epidural anesthesia in patients receiving Enoxaparin (risk of spinal hematoma)

• Spinal/Epidural Hematoma Risk:
  May lead to permanent paralysis; avoid concurrent neuraxial anesthesia unless essential precautions are met
• Bleeding Risk:
  Use with caution in patients with bleeding disorders, recent surgery, or active peptic ulcer
• HIT Risk:
  Monitor platelet count; discontinue immediately if HIT is suspected
• Renal Impairment:
  Increased risk of accumulation and bleeding; dose adjustment necessary
• Elderly Patients:
  Higher bleeding risk; monitor closely
• Body Weight Extremes (Obesity or Underweight):
  Consider monitoring anti-Xa levels in extremes of body weight
• Long-Term Use:
  Monitor bone density due to risk of osteoporosis with prolonged use

Common Adverse Effects (≥1%):

• Hematologic:
• Mild bleeding (bruising, epistaxis, gum bleeding)
• Anemia
• Thrombocytopenia
• Injection Site:
• Pain
• Bruising
• Erythema
• Gastrointestinal:
• Nausea
• Vomiting
• Diarrhea

Serious/Rare Adverse Effects:

• Heparin-induced thrombocytopenia (HIT)
• Severe bleeding (e.g., intracranial, gastrointestinal)
• Spinal or epidural hematoma
• Skin necrosis
• Elevated liver enzymes
• Osteopenia/osteoporosis (long-term use)

Onset:

• Most side effects occur within the first few days of therapy
• Bleeding risk is dose- and renal function-dependent

Major Interactions:

• Antiplatelet agents (e.g., aspirin, clopidogrel):
  Increased bleeding risk
• NSAIDs (e.g., ibuprofen, diclofenac):
  Additive bleeding risk
• Oral Anticoagulants (e.g., warfarin, DOACs):
  Overlapping therapy increases risk unless specifically indicated for bridging
• SSRIs and SNRIs:
  Possible enhanced bleeding risk via platelet inhibition

CYP450 Enzyme Interaction:

• Enoxaparin is not metabolized by CYP450 enzymes, minimizing hepatic interactions

Food and Alcohol Interactions:

• Alcohol increases bleeding risk
• No major food interactions reported

• COVID-19 Guidelines:
  Enoxaparin recommended for hospitalized patients with COVID-19 at risk of thromboembolic events
• Extended Thromboprophylaxis:
  Guidelines recommend up to 35 days post-orthopedic surgery in high-risk patients
• Monitoring Recommendations:
  Anti-Xa level monitoring advised in special populations (e.g., pregnancy, renal failure, obesity)
• FDA & EMA Safety Alerts:
  Warnings updated regarding risk of spinal/epidural hematoma

• Storage Temperature:
  Store at 20°C to 25°C (68°F to 77°F)
  Permitted excursions: 15°C to 30°C
• Protection Requirements:
• Protect from light
• Keep away from moisture
• Do not freeze
• Handling Instructions:
• Do not expel air bubble before injection
• Do not use if solution is cloudy or contains particles
• Reconstitution:
  Not applicable (available as prefilled syringes or multi-dose vials)