Enoxaparin: Indication, Dosage, Side Effect, Precaution

Generic Medicine Info Patient Medicine Information

This information is not country-specific. Please refer to the Indonesia prescribing information.

Generic Medicine Info

Indications and Dosage

Intravenous, Subcutaneous
Acute ST segment elevation myocardial infarction

Adult: Initially, 3,000 international units (30 mg) via IV bolus and 100 international units/kg (1 mg/kg) via SC inj given at the same time, followed by 100 international units/kg (1 mg/kg) 12 hourly via SC inj for 8 days or until hospital discharge, whichever comes 1st. Max dose for each of the 1st 2 SC doses: 10,000 international units (100 mg). Administer appropriate antiplatelet therapy (e.g. aspirin) concomitantly unless contraindicated. In patients receiving thrombolytics, administer enoxaparin between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. For patients managed with percutaneous coronary intervention (PCI): Give an additional 30 international units/kg (0.3 mg/kg) via IV bolus if the last SC inj was given >8 hours before balloon inflation.
Elderly: ≥75 years Initially, 75 international units/kg (0.75 mg/kg) 12 hourly via SC inj with Max of 7,500 international units (75 mg) for each of the 1st 2 doses. Do not administer initial IV bolus dose.

Parenteral
Prophylaxis of clotting in the extracorporeal circulation during haemodialysis

Adult: 100 international units/kg (1 mg/kg) introduced into the arterial line of the circuit at the start of the dialysis session. Patients with high risk of haemorrhage: Reduce to 50 international units/kg (0.5 mg/kg) for double vascular access or 75 international units/kg (0.75 mg/kg) for single vascular access. If fibrin rings are found (e.g. after longer than normal session), an additional dose of 50-100 international units/kg (0.5-1 mg/kg) may be given.

Subcutaneous
Deep vein thrombosis, Pulmonary embolism

Adult: 100 international units/kg (1 mg/kg) bid for an average period of 10 days. In uncomplicated patients with low risk of VTE recurrence: 150 international units/kg (1.5 mg/kg) once daily. Initiate oral anticoagulant therapy when appropriate.

Subcutaneous
Prophylaxis of venous thromboembolism during surgical procedures

Adult: Moderate risk of VTE: 2,000 international units (20 mg) once daily for 7-10 days regardless of recovery status (e.g. mobility); with the 1st dose given 2 hours before surgery. High risk of VTE (e.g. orthopaedic surgery): 4,000 international units (40 mg) once daily with the 1st dose preferably given 12 hours before surgery. Treatment duration: Up to 4 weeks (abdominal or pelvic surgery for cancer) or up to 5 weeks (major orthopaedic surgery). Alternative regimen for hip or knee replacement surgery: 3,000 international units (30 mg) bid, starting within 12-24 hours after surgery provided that haemostasis has been established; for hip replacement surgery, may continue treatment with 4,000 international units (40 mg) once daily for a further 3 weeks. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).

Subcutaneous
Non-ST segment elevation myocardial infarction, Unstable angina

Adult: In combination with antiplatelet therapy (e.g. aspirin): 100 international units/kg (1 mg/kg) 12 hourly. Continue until clinical stabilisation. Usual treatment duration: 2-8 days.

Subcutaneous
Prophylaxis of venous thromboembolism in medical patients

Adult: In patients with acute illness (e.g. acute heart failure, respiratory insufficiency, severe infections, rheumatic disease) and reduced mobility at increased risk of VTE: 4,000 international units (40 mg) once daily for at least 6-14 days regardless of recovery status (e.g. mobility).

Special Patient Group

Deep vein thrombosis; Pulmonary embolism:
Patients with active cancer: For extended treatment and prevention of recurrence: 100 international units/kg (1 mg/kg) bid via SC inj for 5-10 days, then 150 international units/kg (1.5 mg/kg) once daily via SC inj for up to 6 months.

Renal Impairment

Prophylaxis of venous thromboembolism during surgical procedures and in medical patients:

CrCl (mL/min)	Dosage
15-30	2,000 international units (20 mg) once daily via SC inj.

Deep vein thrombosis; Pulmonary embolism; Unstable angina; Non-ST segment elevation myocardial infarction:

CrCl (mL/min)	Dosage
15-30	100 international units/kg (1 mg/kg) once daily via SC inj.

Acute ST segment elevation myocardial infarction:

CrCl (mL/min)	Dosage
15-30	<75 years Initially, 3,000 international units (30 mg) via IV bolus and 100 international units/kg (1 mg/kg) via SC inj given at the same time, followed by 100 international units/kg (1 mg/kg) 24 hourly via SC inj; ≥75 years Initially, 100 international units/kg (1 mg/kg) via SC inj, followed by 100 international units/kg (1 mg/kg) 24 hourly via SC inj.

Contraindications

Hypersensitivity to enoxaparin, heparin or its derivatives, or other LMWHs. History of immune-mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in presence of circulating antibodies; active clinically significant bleeding, recent haemorrhagic stroke, gastrointestinal ulcer, recent brain, spinal, or ophthalmic surgery.

Special Precautions

Patient with history (>100 days) of HIT without circulating antibodies; cancer with platelet count <80 g/L, increased potential for bleeding (e.g. congenital or acquired bleeding disorders, history of peptic ulcer, angiodysplastic gastrointestinal disease, recent ischaemic stroke, recent diabetic retinopathy, acute infective endocarditis, severe arterial hypertension); low body weight (women <45 kg, men <57 kg), risk factors for hyperkalaemia (e.g. diabetes mellitus, haematoma in body tissues, pre-existing metabolic acidosis), prosthetic heart valves (particularly pregnant women). Patient undergoing elective surgery/procedure. Use in the setting of epidural or spinal anaesthesia/analgesia or lumbar puncture. Not for use interchangeably (unit for unit) with heparin or other LMWHs. Obese patients. Renal (including ESRD) and hepatic impairment. Elderly (particularly ≥75 years of age). Pregnancy and lactation.

Adverse Reactions

Significant: Neuraxial haematomas resulting in long-term or permanent paralysis (in patients concurrently receiving spinal/epidural anaesthesia or undergoing spinal puncture procedures); bleeding, skin necrosis, cutaneous vasculitis; prosthetic heart valve thrombosis (in patients with mechanical prosthetic heart valves treated for thromboprophylaxis), acute generalised exanthematous pustulosis. Rarely, hyperkalaemia.
Blood and lymphatic system disorders: Haemorrhagic anaemia, thrombocytosis.
Gastrointestinal disorders: Nausea.
General disorders and administration site conditions: Inj site reactions (e.g. haematoma, pain, oedema, haemorrhage, inflammation, mass), fever.
Immune system disorders: Allergic reaction.
Investigations: Increased hepatic enzymes (mainly transaminases >3 times the ULN).
Metabolism and nutrition disorders: Peripheral oedema.
Nervous system disorders: Headache.
Psychiatric disorders: Confusion.
Skin and subcutaneous tissue disorders: Pruritus, urticaria, erythema, ecchymoses.
Potentially Fatal: Major haemorrhage (e.g. retroperitoneal, intracranial, or intraocular bleeding), HIT with or without thrombosis.

Pregnancy Category (US FDA)

IV/Parenteral/SC: B

Monitoring Parameters

Obtain CBC including platelet count, faecal occult blood, anti-factor Xa levels (as clinically appropriate); serum creatinine at baseline and during treatment. Monitor patient weight before treatment and periodically thereafter. Assess for signs and symptoms of bleeding; thromboembolism (particularly in obese patients).

Overdosage

Symptoms: Haemorrhagic complications. Management: If enoxaparin was administered in the previous 8 hours, 1 mg of protamine may be used to neutralise the effect of 100 international units (1 mg) of enoxaparin. If more than 8 hours have passed or if a 2nd dose of protamine is required, an infusion of 0.5 mg of protamine per 100 international units (1 mg) of enoxaparin may be given. Administer the 2nd infusion of 0.5 mg protamine if the aPTT measured 2-4 hours after the initial infusion remains prolonged. If at least 12 hours have passed since the last enoxaparin inj, protamine use may not be necessary.

Drug Interactions

Increased risk of bleeding with anticoagulants or platelet aggregation inhibitors (e.g. aspirin, clopidogrel, ticlopidine, glycoprotein IIb/IIIa antagonists, NSAIDs).

Lab Interference

May cause false elevation of free triiodothyronine and free thyrotropin levels when assays involving prolonged incubation periods are used.

Action

Description:
Mechanism of Action: Enoxaparin is a low molecular weight heparin (LMWH) with anticoagulant properties. It has minimal effect on the activated partial thromboplastin time (aPTT) and has high anti-factor Xa activity. Its anticoagulant effects are mediated through antithrombin III resulting in antithrombotic activities.
Onset: Anti-factor Xa and anti-factor IIa (antithrombin): 3-5 hours (peak effect; SC inj).
Duration: Anti-factor Xa: Approx 12 hours (40 mg dose).
Pharmacokinetics:
Absorption: Rapidly and almost completely absorbed following SC inj. Bioavailability: Approx 100% (SC).
Distribution: Volume of distribution: 4.3 L.
Metabolism: Metabolised in the liver via desulfation and/or depolymerisation to lower molecular weight species with lesser biological potency.
Excretion: Via urine (40%; approx 10% as active fragments). Elimination half-life: Approx 4.5-7 hours (based on anti-factor Xa activity).

Storage

Store between 20-25°C. Do not freeze. Opened multi-dose vials: Stable for 28 days at 25°C.

MIMS Class

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

ATC Classification

B01AB05 - enoxaparin ; Belongs to the class of heparin group. Used in the treatment of thrombosis.

References

Anon. Enoxaparin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/02/2023.

Buckingham R (ed). Enoxaparin Sodium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2023.

Clexane Multidose Vial 30,000 IU (300 mg)/3 mL Solution for Injection (Aventis Pharma Limited Trading as Sanofi). MHRA. https://products.mhra.gov.uk. Accessed 06/02/2023.

Enoxaparin Sandoz 2,000 IU (20 mg)/0.2 mL, 4,000 IU (40 mg)/0.4 mL, and 6,000 IU (60 mg)/0.6 mL Solution for Injection in Pre-filled Syringe (Novartis Corporation [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/02/2023.

Enoxaparin Sodium Injection (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/02/2023.

Inhixa 12,000 IU (120 mg)/0.8 mL Solution for Injection in Pre-filled Syringe (Techdow Pharma Netherlands B.V.). MHRA. https://products.mhra.gov.uk. Accessed 06/02/2023.

Joint Formulary Committee. Enoxaparin Sodium. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2023.

Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. Clexane and Clexane Forte Pre-filled Syringes, Ready to Use data sheet 20 June 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 17/03/2023.

Disclaimer: This information is independently developed by MIMS based on Enoxaparin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2024 MIMS. All rights reserved. Powered by MIMS.com