Enoxaparin parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
All formulations of enoxaparin.
Drugs List
Therapeutic Indications
Uses
Haemodialysis - prevention of clotting in extracorporeal circulation
Non ST elevation myocardial infarction: Adjunctive treatment
ST-segment elevation myocardial infarction: treatment
Treatment of venous thromboembolic disease with DVT or pulmonary embolism
Unstable angina: Adjunctive treatment
Venous thromboembolism in cancer patients: prophylaxis and treatment
Venous thromboembolism in medical patients: prophylaxis
Venous thromboembolism in surgical patients: prophylaxis
Unlicensed Uses
Thrombotic events in children: Prophylaxis
Thrombotic events in children: Treatment
Treatment of VTE in pregnancy
Dosage
Adults
Prophylaxis of venous thromboembolism (VTE) in surgical patients
Patients with moderate risk of VTE
20mg (2000units) subcutaneously once daily, for seven to ten days or until risk of thromboembolism has diminished.
In patients undergoing surgery the initial dose should be given 2 hours pre-operatively.
Patients with high risk of VTE
40mg (4000units) subcutaneously once daily. Initial dose should be given 12 hours pre-operatively.
Patients undergoing major orthopaedic surgery should receive an extended thromboprophylaxis of up to five weeks.
Patients undergoing abdominal or pelvic surgery for cancer should receive an extended thromboprophylaxis of up to four weeks.
Prophylaxis of VTE in medical patients with acute illness and reduced mobility
40mg (4000units) subcutaneously once daily. Treatment continued for a minimum of six days and until the return to full ambulation, for a maximum of fourteen days.
Extended treatment and prophylaxis of recurrence of venous thromboembolism (VTE) in cancer patients
1mg/kg (100units/kg) subcutaneously twice daily for 5 to 10 days, followed by 1.5mg/kg (150units/kg) by subcutaneous injection once daily for up to 6 months.
Treatment of venous thromboembolism in uncomplicated patients with low risk of VTE recurrence
1.5mg/kg (150units/kg) subcutaneously once daily. Continue for on average ten days and until oral anticoagulation is established.
Treatment of venous thromboembolism in all other patients
1mg/kg (100units/kg) subcutaneously twice daily. Continue for on average ten days. Initiate oral anticoagulant when appropriate.
Prevention of extracorporeal thrombus formation during haemodialysis
1mg/kg (100units/kg) is introduced into the arterial line at the beginning of dialysis. This dose is normally sufficient for a 4 hour session.
If fibrin rings are found, such as after a longer than normal session, a further dose of 500micrograms/kg to 1mg/kg (50units/kg to 100units/kg) may be given.
For patients at a high risk of haemorrhage, the dose should be reduced to 500micrograms/kg (50units/kg) for double vascular access or 750micrograms/kg (75units/kg) for single vascular access.
Treatment of unstable angina and non-ST segment elevation myocardial infarction (NSTEMI)
1mg/kg (100units/kg) subcutaneously every 12 hours, administered concurrently with antiplatelet therapy, for minimum of two days and continued until clinical stabilisation.
Usual duration of treatment is two to eight days.
Treatment of acute ST segment elevation myocardial infarction (STEMI)
Initial dose: a single IV bolus of 30mg (3000units), plus a single 1mg/kg (100units/kg) dose subcutaneously.
Maintenance dose: 1mg/kg (100units/kg) subcutaneously every 12 hours (maximum of 100mg (10,000units) - for the first two subcutaneous doses only).
When administered in conjunction with a thrombolytic, enoxaparin sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy.
The recommended duration of enoxaparin sodium treatment is eight days or until hospital discharge, whichever comes first.
For patients managed with percutaneous coronary intervention (PCI): If the last enoxaparin sodium subcutaneous administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last subcutaneous administration was given more than 8 hours before balloon inflation, an IV bolus of 300micrograms/kg (30units/kg) of enoxaparin sodium should be administered.
Treatment of venous thromboembolism in pregnancy (unlicensed) (based on early pregnancy bodyweight)
Bodyweight under 50kg: 40mg (4000units) subcutaneously twice daily.
Bodyweight 50kg to 69kg: 60mg (6000units) subcutaneously twice daily.
Bodyweight 70kg to 89kg: 80mg (8000units) subcutaneously twice daily.
Bodyweight 90kg and over: 100mg (10,000units) subcutaneously twice daily.
Elderly
Acute STEMI in patients aged 75 years and above
750micrograms/kg (75units/kg) subcutaneously every 12 hours (maximum 75mg (7500units) for the first two doses only. Initial IV bolus must not be used. Then 750micrograms/kg (75units/kg) subcutaneous dosing for the remaining doses).
For all other indications (See Dosage; Adult).
Children
Prophylaxis of thrombotic episodes (unlicensed)
Children aged 2 months to 18 years
500micrograms/kg (50units/kg) subcutaneously twice daily, maximum 40mg (4000units) daily.
Children aged 1 to 2 months
750micrograms/kg (75units/kg) subcutaneously twice daily.
Treatment of thrombotic episodes (unlicensed)
Children aged 2 months to 18 years
1mg/kg (100units/kg) subcutaneously twice daily.
Children aged 1 to 2 months
1.5mg/kg (150units/kg) subcutaneously twice daily.
Treatment of venous thromboembolism in pregnancy (unlicensed) (based on early pregnancy bodyweight)
Children aged 12 to 18 years
Bodyweight under 50kg: 40mg (4000units) subcutaneously twice daily.
Bodyweight 50kg to 69kg: 60mg (6000units) subcutaneously twice daily.
Bodyweight 70kg to 89kg: 80mg (8000units) subcutaneously twice daily.
Bodyweight 90kg and over: 100mg (10,000units) subcutaneously twice daily.
Neonates
Prophylaxis of thrombotic episodes (unlicensed)
750micrograms/kg (75units/kg) subcutaneously twice daily.
Treatment of thrombotic episodes (unlicensed)
1.5mg/kg (150units/kg) to 2mg/kg (200units/kg) subcutaneously twice daily.
The multidose vial of enoxaparin sodium contains benzyl alcohol and should not be given to neonates.
Patients with Renal Impairment
Severe renal impairment (creatinine clearance 15 to 30ml/minute)
Adjust dose as follows: (The recommended dosage adjustments do not apply to the haemodialysis indication.)
Prophylactic Dosage Ranges
Reduce standard dosing of 40mg (4000units) by subcutaneous injection once daily to 20mg (2000units) by subcutaneous injection once daily.
No dosage adjustment is necessary in the case of a standard dose of 20mg (2000units) by subcutaneous injection once daily.
Therapeutic Dosage Ranges
Reduce standard dosing 1mg/kg (100units/kg) by subcutaneous injection twice daily to 1mg/kg (100units/kg) by subcutaneous injection once daily.
Reduce standard dosing 1.5mg/kg (150units/kg) by subcutaneous injection once daily to 1mg/kg (100units/kg) by subcutaneous injection once daily.
Reduce 30mg (3000units) single IV bolus plus a 1mg/kg (100units/kg) subcutaneous dose followed by 1mg/kg (100units/kg) twice daily to 30mg (3000units) single IV bolus plus a 1mg/kg (100units/kg) subcutaneous dose followed by 1mg/kg (100units/kg) once daily.
For elderly patients aged 75 years or older (for STEMI only)
Reduce 750micrograms/kg (75units/kg) subcutaneous twice daily without initial bolus to 1mg/kg (100units/kg) subcutaneous once daily without initial bolus.
Additional Dosage Information
Additional IV bolus for PCI when last subcutaneous administration was given more than 8 hours before balloon insertion
For patients being managed with PCI, an additional bolus of 300micrograms/kg (30units/kg) is to be administered if the last subcutaneous administration was given more than 8 hours before balloon inflation. In order to assure accuracy of the small volume to be injected it is recommended to dilute the drug to 3mg/ml (300units/ml).
Administration
Enoxaparin is administered by subcutaneous injection for the prevention of venous thromboembolic disease, treatment of deep vein thrombosis, PE and for the treatment of unstable angina, NSTEMI and acute STEMI. It can also be administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the extra-corporeal circulation during haemodialysis, and via intravenous (bolus) injection through an intravenous line only for the initial dose of acute STEMI indication and before PCI when needed.
It must not be given by any other route.
Contraindications
Haemorrhage
Hypersensitivity to benzyl alcohol
Locoregional anaesthesia when receiving LMWH treatment
Predisposition to haemorrhage
Acute bacterial endocarditis
Arteriovenous malformation
Central nervous system surgery
Creatinine clearance<15ml/min-unless for thrombosis prophylaxis in dialysis
History of HIT within 100 days or presence of circulating antibodies
Neoplasm with increased bleeding risk
Prosthetic heart valve with pregnancy
Recent ocular surgery
Thrombocytopenia
Precautions and Warnings
Children under 18 years
Elderly
Lumbar puncture
Obese patients with a BMI greater than 30kg/m2
Percutaneous coronary intervention
Recent surgery
Spinal/epidural anaesthesia
Weight below 45kg in females
Weight below 57kg in males
Diabetes mellitus
Diabetic retinopathy
Hepatic impairment
History of HIT over 100 days ago without circulating antibodies
History of peptic ulcer
Hyperkalaemia
Impaired haemostasis
Metabolic acidosis
Platelet count below 80x10 to the power of 9/L- if treating cancer patients
Pregnancy
Prosthetic heart valve
Recent ischaemic cerebrovascular accident
Renal impairment
Severe hypertension
Reduce dose in patients with creatinine clearance below 30ml/min
Not all available brands are licensed for all age groups
Some presentations may contain benzyl alcohol
Different brands of this product are not interchangeable
Different low molecular weight heparins may not be equivalent
Record name and batch number of administered product
Increased risk of spinal haematoma with post-op insitu epidural catheter
Monitor platelets before starting and during treatment
Monitor anti-Factor Xa levels in patients at risk of bleeding
Monitor elderly receiving therapeutic doses
Monitor low body weight patients (females <45kg and males <57kg)
Monitor neurological function in patients under anaesthesia
Monitor plasma potassium in patients at risk of hyperkalaemia
Monitor potential bleeding sites
Monitor renal function in patients with renal impairment
Adrenal suppression may occur leading to hyperkalaemia
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report back pain immediately
Advise patient to report bladder dysfunction immediately
Advise patient to report bowel dysfunction immediately
Advise patient to report numbness/weakness in the lower limbs immediately
Advise patient to seek medical advice if severe skin reaction occurs
Discontinue if platelet count is significantly reduced
Discontinue if vasculitis occurs
May affect results of some laboratory tests
Discontinue if severe skin reaction occurs
Discontinue if skin necrosis at injection site occurs
Advise patient not to take NSAIDs unless advised by clinician
Injection site bleeding may occur and should be investigated and treated appropriately.
As with other anticoagulants, there have been rare cases of intraspinal haematomas reported with the concurrent use of enoxaparin and spinal/epidural anaesthesia or spinal puncture, resulting in long term or permanent paralysis. These events are rare with enoxaparin sodium dosage regimens 40mg (4000units) once daily or lower. The risk is greater with the use of post operative indwelling catheters or the concomitant use of additional drugs affecting haemostasis such as NSAIDs. The risk also appears to be increased by traumatic or repeated neuraxial puncture or in patients with a history of spinal surgery or spinal deformity.
Placement or removal of a spinal catheter should be delayed for 12 hours after administration of prophylactic doses of enoxaparin sodium, whereas patients receiving higher doses of enoxaparin sodium (1.5mg/kg (150units/kg) once daily) will require longer delays (24 hours). In severe renal impairment (creatinine clearance 15 to 30ml/minute), when enoxaparin is used in treatment doses, consider doubling the timing of puncture/catheter placement or removal to at least 48 hours. The subsequent enoxaparin sodium dose should be given no sooner than 4 hours after catheter removal.
To reduce the potential risk of bleeding associated with the concurrent use of enoxaparin sodium and epidural anaesthesia/analgesia or spinal puncture, the pharmacokinetic profile of the drug should be considered. Placement and removal of the epidural catheter or lumbar puncture is best performed when the anticoagulation effect of enoxaparin is low.
Obese patients are at greater risk of thromboembolism and should be observed carefully for thromboembolism. The safety and efficacy of prophylactic doses in BMI greater than 30kg/square metre have not be determined.
To minimise the risk of bleeding following percutaneous coronary revascularisation procedures during the treatment of unstable angina, NSTEMI or acute STEMI, adhere precisely to the intervals recommended between enoxaparin sodium doses. It is important to achieve homeostasis at the puncture site after PCI. If a closure device is used, the sheath can be removed immediately. If a manual compression method is used, the sheath should be removed 6 hours after the last IV/ subcutaneous enoxaparin sodium injection. If the treatment is continued, the next scheduled dose should be given no sooner than 6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or haematoma formation.
For some patients with pulmonary embolism (e.g. those with severe haemodynamic instability) alternative treatment such as thrombolysis or surgery may be indicated.
The multi dose vials contain benzyl alcohol and should not be used in neonates and may result in fatality. Benzyl alcohol may cause toxic reactions and anaphylactoid reactions in children under 3 years old.
At higher doses of enoxaparin sodium, increases in APTT (activated partial thromboplastin time) and ACT (activated clotting time) may occur. Increases in APTT & ACT are not linearly correlated with increasing enoxaparin sodium antithrombotic activity and therefore are unsuitable and unreliable for monitoring enoxaparin sodium activity.
Enoxaparin should not be used in patients with major intraspinal or intracerebral vascular abnormalities.
Physicians should carefully assess the thromboembolic and bleeding risks in patients with active cancer, during the extended treatment of deep vein thrombosis and pulmonary embolism and prevention of its recurrence.
In cancer patients with a platelet count below 80g/L, treatment can only be considered on a case-by-case basis with careful monitoring throughout treatment.
Pregnancy and Lactation
Pregnancy
Use enoxaparin with caution during pregnancy. Enoxaparin is contraindicated in pregnant women with prosthetic heart valves.
The manufacturer advises caution if enoxaparin is used during pregnancy. Animal studies have not shown any evidence of foetotoxicity or teratogenicity. At the time of writing there is limited published information regarding the use of enoxaparin during pregnancy. Potential risks are unknown.
Lactation
Enoxaparin is considered safe for use during breastfeeding.
The manufacturer states enoxaparin may be used safely when breastfeeding. The presence of enoxaparin in human breast milk is unknown but due to its large molecular weight, transfer is not expected.
Side Effects
Acute generalised exanthematous pustulosis
Allergic reaction
Alopecia
Anaphylactic reaction
Anaphylactoid reaction
Bullous dermatoses
Cholestatic liver changes
Cutaneous vasculitis
Eosinophilia
Epistaxis
Erythema
Gastrointestinal bleeding
Haematoma
Haematoma (injection site)
Haematuria
Haemorrhage
Haemorrhagic anaemia
Headache
Hepatocellular damage
Hyperkalaemia
Hypersensitivity reactions
Immunologically mediated thrombocytopenia
Increases in hepatic enzymes
Inflammation (injection site)
Intracranial bleeding
Intraspinal haematoma
Irritation (localised)
Necrosis (injection site)
Nodules (injection site)
Oedema
Osteoporosis
Pain on injection
Pruritus
Purpura
Reduced platelet count
Retroperitoneal bleeding
Shock
Skin necrosis
Thrombocytopenia
Thrombocytosis
Urticaria
Valve thrombosis in patients with prosthetic heart valves
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: July 2019
Reference Sources
Summary of Product Characteristics: Arovi 10,000 IU (100mg/1ml) pre-filled syringe with safety device. ROVI Biotech Limited. Revised November 2018.
Summary of Product Characteristics: Arovi 12,000 IU (120mg/0.8ml) pre-filled syringe with safety device. ROVI Biotech Limited. Revised November 2018.
Summary of Product Characteristics: Arovi 15,000 IU (150mg/1ml) pre-filled syringe with safety device. ROVI Biotech Limited. Revised November 2018.
Summary of Product Characteristics: Arovi 2,000 IU (20mg/0.2ml) pre-filled syringe with safety device. ROVI Biotech Limited. Revised November 2018.
Summary of Product Characteristics: Arovi 4,000 IU (40mg/0.4ml) pre-filled syringe with safety device. ROVI Biotech Limited. Revised November 2018.
Summary of Product Characteristics: Arovi 6,000 IU (60mg/0.6ml) pre-filled syringe with safety device. ROVI Biotech Limited. Revised November 2018.
Summary of Product Characteristics: Arovi 8,000 IU (80mg/0.8ml) pre-filled syringe with safety device. ROVI Biotech Limited. Revised November 2018.
Summary of Product Characteristics: Clexane Forte Syringes. Sanofi. Revised February 2022.
Summary of Product Characteristics: Clexane Multidose Vial. Sanofi. Revised February 2022.
Summary of Product Characteristics: Clexane pre-filled syringes PREVENTIS needle guard safety system. Sanofi. Revised February 2022.
Summary of Product Characteristics: Clexane Pre-filled Syringes with ERIS needle guard safety system. Sanofi. Revised February 2022.
Summary of Product Characteristics: Inhixa 2,000 IU (20 mg) in 0.2 mL solution for injection in pre-filled syringe. Techdow Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Inhixa 4,000 IU (40 mg) in 0.4 mL solution for injection. Techdow Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Inhixa 6,000 IU (60 mg) in 0.6 mL solution for injection. Techdow Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Inhixa 8,000 IU (80 mg) in 0.8 mL solution for injection in pre-filled syringe. Techdow Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Inhixa 10,000 IU (100 mg) in 1.0 mL solution for injection in pre-filled syringe. Techdow Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Inhixa 12,000 IU (120 mg) in 0.8 mL solution for injection. Techdow Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Inhixa 15,000 IU (150 mg) in 1 mL solution for injection. Techdow Pharma Ltd. Revised March 2022.
Summary of Product Characteristics: Ledraxen 2,000 IU (20 mg) in 0.2 mL solution for injection in pre-filled syringe. Venipharm. Revised January 2021.
Summary of Product Characteristics: Ledraxen 4,000 IU (40 mg) in 0.4 mL solution for injection in pre-filled syringe. Venipharm. Revised January 2021.
Summary of Product Characteristics: Ledraxen 6,000 IU (60 mg) in 0.6 mL solution for injection in pre-filled syringe. Venipharm. Revised January 2021.
Summary of Product Characteristics: Ledraxen 8,000 IU (80 mg) in 0.8 mL solution for injection in pre-filled syringe. Venipharm. Revised January 2021.
Summary of Product Characteristics: Ledraxen 10,000 IU (100 mg) in 1.0 mL solution for injection in pre-filled syringe. Venipharm. Revised January 2021.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 08 April 2021
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