Heparin sodium parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of heparin sodium.
Drugs List
Therapeutic Indications
Uses
Acute peripheral arterial occlusion: treatment
Catheter patency - maintenance of
Deep vein thrombosis - treatment
Haemodialysis - prevention of clotting
Prevention of clotting in extracorporeal circulation
Prophylaxis of mural thrombosis post myocardial infarction
Pulmonary embolism - treatment
Treatment of unstable angina pectoris
Venous thromboembolism in medical patients: prophylaxis
Venous thromboembolism in pregnancy: prophylaxis
Venous thromboembolism in surgical patients: prophylaxis
Unlicensed Uses
Neonatal umbilical arterial catheter: maintenance of
Dosage
Adults
Treatment of thromboembolic disorders, treatment of unstable angina and acute peripheral arterial occlusion
Dosage adjustment: Dose should be adjusted to maintain a thrombin clotting time, whole blood clotting time or activated partial thromboplastin time (APTT) 1.5 to 2.5 times that of midpoint of normal range on blood withdrawn 4 to 6 hours after the first injection or commencement of infusion. Monitoring of clotting times and any necessary dose adjustment should be undertaken at daily intervals (ideally at the same time each day) until the patient is stabilised.
Intravenous injection
Initial loading dose: 5000units (or 75units/kg), although 10,000units (or 150units/kg) may be required in severe pulmonary embolism.
Maintenance dose: 1000units/hour to 2000units/hour (or 18units/kg/hour) by continuous intravenous infusion or 500units/kg daily as a continuous intravenous infusion or 5000units to 10,000units every 4 hours by continuous intravenous infusion. The use of intermittent intravenous administration is no longer recommended.
Subcutaneous administration
Initial dose: 250units/kg. Further doses should be given every 12 hours, adjusted according to coagulation tests (15,000units every 12 hours has been recommended). Some manufacturers suggest a dose of 10,000units to 20,000units given every 12 hours subcutaneously for the treatment of deep vein thrombosis and pulmonary embolism indications only. An equivalent intravenous total daily dose can be administered by subcutaneous injection in two divided doses.
Prophylaxis of thromboembolic events
Standard prophylactic regimens do not normally require routine laboratory monitoring. If monitoring is considered necessary, anti-Xa assays should be used as the APTT is not significantly prolonged.
Prophylaxis in medical patients
5000units every 8 to 12 hours by subcutaneous injection.
Major elective general surgery
5000units given by subcutaneous injection 2 hours pre-operatively and then every 8 to 12 hours post-operatively for seven to fourteen days or until the patient is ambulant, whichever is longer.
Major orthopaedic surgery
Due to an increased risk in major orthopaedic surgery an adjusted dosage regime with monitoring or a Low Molecular Weight Heparin (LMWH) may be used which may be more effective. In patients at high risk of thromboembolism warfarin may be used. (Refer to individual monographs).
Prophylaxis of mural thrombosis following myocardial infarction
Different manufacturers recommend different doses, refer to product information when prescribing for this indication. 5000units subcutaneously twice daily for ten days or until patient is mobile or 12,500units subcutaneously 12 hourly for at least ten days.
Prophylaxis of venous thromboembolism in pregnancy
5000units to 10,000units every 12 hours, subcutaneously, adjusted according to APTT or anti-Xa assay.
In extracorporeal circulation and haemodialysis
Cardiopulmonary bypass
Initial dose: 300units/kg intravenously, adjusted thereafter to maintain an activated clotting time of 400 to 500 seconds.
Haemodialysis and haemofiltration
Initial dose: 1000units to 5000units.
Maintenance dose: 1000units/hour to 2000units/hour by continuous intravenous infusion (another source suggests 250units to 1000units could be given), adjusted to maintain a clotting time greater than 40 minutes.
Maintenance of catheter patency
By intravenous infusion, dose should be adapted to catheter characteristics and the clinical condition of the patient.
Elderly
Treatment of thromboembolic disorders
(See Dosage; Adult).
Lower dosages may be required, however standard dosages should be given initially. Adjust subsequent dosages and/or dosage intervals according to changes in thrombin clotting time, whole blood clotting time and/or APTT. Elderly women appear to be especially susceptible to haemorrhage after heparin administration.
Prophylaxis of thromboembolic events in susceptible patients
(See Dosage; Adult).
Dose adjustment from adult dosage is generally unnecessary, if dose reduction is considered monitor anti-Xa or APTT although APTT may not be significantly prolonged.
Children
Standard treatment dosages should be given initially. Adjust subsequent dosages and/or dosage intervals according to thrombin clotting time, whole blood clotting time and/or APTT (See Dosage; Adult).
A suggested regime may be:
Treatment of deep vein thrombosis and pulmonary embolism
Loading dose: 50units/kg intravenously. Maintenance: 15 to 25units/kg/hour by intravenous infusion, or 250units/kg every 12 hours subcutaneously, or 100units/kg every 4 hours by intravenous injection.
Treatment of unstable angina pectoris and acute peripheral arterial occlusion
Loading dose: 50units/kg intravenously. Maintenance: 15 to 25units/kg/hour by intravenous infusion, or 100units/kg every 4 hours by intravenous injection.
The following alternative dosing schedules may be suitable:
Treatment of thrombotic episodes (unlicensed)
Children aged 1 to 18 years
Initial dose: 75units/kg by intravenous injection.
Maintenance dose: By continuous intravenous infusion 20units/kg/hour, adjusted according to APTT.
Children aged 1 month to 1 year
Initial dose: 75units/kg by intravenous injection
Maintenance dose: By continuous intravenous infusion, 25units/kg/hour, adjusted according to APTT.
OR
Children aged 1 month to 18 years
250units/kg subcutaneously twice daily, adjusted according to APTT.
Prophylaxis of thromboembolic disorders (unlicensed)
Children aged 1 month to 18 years
100units/kg (maximum of 5000units) subcutaneously twice daily, adjusted according to the APTT.
Neonates
Some brands contain benzyl alcohol and these must not been given to premature babies or neonates.
Maintenance of neonatal umbilical arterial catheter (unlicensed)
0.5units/hour.
Treatment of thrombotic episodes (unlicensed)
Initial dose: 75units/kg (50units/kg if below 35 weeks corrected gestational age) by intravenous injection.
Maintenance dose: 25units/kg/hour by continuous intravenous, adjusted according to APTT.
Patients with Renal Impairment
Lower doses are usually indicated in patients with renal impairment or advanced renal disease. Patients with severe renal impairment are at an increased risk of bleeding. Coagulation times should be checked frequently and dosage adjusted accordingly.
Patients with Hepatic Impairment
Lower doses are usually indicated in hepatic impairment. Coagulation times should be checked frequently and dosage adjusted accordingly.
Additional Dosage Information
Heparin resistance
Patients with an altered heparin responsiveness or heparin resistance may require disproportionately higher doses.
Treatment of thromboembolic events
An oral anticoagulant, usually warfarin, is started at the same time as heparin. Heparin is continued for at least five days and until the INR has been in the appropriate therapeutic range for two consecutive days (See monograph for warfarin and local protocols).
Administration
For administration by intravenous injection, continuous intravenous infusion or subcutaneous injection (depending on indication). Intermittent intravenous injection is licensed for some brands but is no longer recommended as the effects of heparin are short-lived. Some manufacturers indicate that intravenous injection volumes should not exceed 15ml.
Therapeutic Drug Monitoring
A baseline blood count including platelet count, coagulation screen, urea, electrolytes and liver function tests before starting treatment is recommended. Use of clotting time, APTT or anti-Xa may be required depending on the patient characteristics and dosage.
Contraindications
Haemorrhagic diathesis
Heparin treatment with concurrent locoregional anaesthesia
High alcohol intake
Hypersensitivity to benzyl alcohol
Intraspinal haemorrhage
Recent trauma
Bacterial endocarditis
Bleeding haemorrhoids
Central nervous system surgery
Cerebrovascular accident
Coagulopathy
Haemophilia
Hiatus hernia
History of heparin-induced thrombocytopenia
Increased capillary permeability
Intracranial haemorrhage
Neoplasia
Ocular surgery
Oesophageal varices
Peptic ulcer
Proliferative retinopathy
Purpura
Recent cerebral haemorrhage
Severe hepatic impairment
Severe hypertension
Threatened abortion
Thrombocytopenia
Tuberculosis
Precautions and Warnings
Children under 3 years
Elderly
Restricted sodium intake
Risk of haemorrhage
Spinal/epidural anaesthesia
Tobacco smoking
Chronic renal failure
Diabetes mellitus
Hepatic impairment
Hyperkalaemia
Hypertension
Metabolic acidosis
Pregnancy
Renal impairment
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Some formulations contain more than 1mmol (23mg) sodium per dose
Not all available brands are licensed for all indications
Not all available brands are licensed for all routes of administration
Not all available products are licensed for all age groups
Not all available strengths are licensed for all indications
Some formulations contain hydroxybenzoate
Some presentations may contain benzyl alcohol
It is advisable to give a trial dose to patients with a history of allergy
Monitor platelets before starting and during treatment
Perform full blood count before treatment
Daily monitoring is essential during full-dose heparin treatment
Heparin resistance may occur at standard doses
Monitor activated partial thromboplastin time and adjust dose accordingly
Monitor coagulation effects in patients undergoing major surgery
Monitor for unexplained fall in blood pressure or haematocrit
Monitor patients undergoing spinal or epidural anaesthesia closely
Monitor plasma potassium in patients at risk of hyperkalaemia
Patients at risk of osteoporosis should have bone density assessed
Adrenal suppression may occur leading to hyperkalaemia
Discontinue if thrombocytopenia occurs
Spinal anaesthesia: tell patient-report symptoms of neurological impairment
May affect results of some laboratory tests
Discontinue if skin necrosis at injection site occurs
Dose adjustment required if patient starts/stops smoking during therapy
Advise patient not to take aspirin unless advised by clinician
Advise patient not to take NSAIDs unless advised by clinician
Advise patient of risk of bleeding
Some manufacturers suggest that preparations containing benzyl alcohol should be avoided during pregnancy as benzyl alcohol may cross the placenta.
Caution should be exercised in patients known to be hypersensitive to low molecular weight heparins. In patients with a history of allergy, although heparin hypersensitivity is rare, it is advisable to give a trial dose of 1,000 units.
Consider offering synthetic alternatives to patients who are concerned about the animal origin of heparins.
All patients should be warned of a risk of bleeding. If haemorrhage occurs it is usually sufficient to withdraw heparin, but if rapid reversal of the effects of heparin is required, protamine sulfate is a specific antidote.
Inflammatory reactions may occur at subcutaneous injection site, after 3 to 21 days treatment, causing firm erythematous nodules or infiltrated and sometimes eczema-like plaques. Treatment should be discontinued if cutaneous necrosis, sometimes preceded by purpura or painful erythematous blotches, occur.
Risk of thrombocytopenia
Measure platelet counts before treatment and in patients receiving heparin for longer than 4 to 5 days. Heparin may cause two types of thrombocytopenia (HIT). Type I HIT (typically occurring within 1 to 4 days of initiation), is frequent, mild (usually above 50x10 to the power 9/L), transient and does not require treatment cessation. Type II HIT is less frequent, typically occurring between days 5 to 11 although as late as 40 days, but often associated with severe thrombocytopenia (usually below 50x10 to the power 9/L). Type II HIT is immune mediated and is associated with the production of a platelet aggregating antibody and thromboembolic complications which may precede the onset of thrombocytopenia. Discontinue immediately if Type II thrombocytopenia occurs.
Discontinued heparin treatment if thromboembolic complications occur. An alternative anticoagulant should be given (e.g. argatroban or danaparoid). HIT (with/without thrombosis) can occur for several weeks after discontinuation of heparin. Patients presenting with HIT symptoms (30% reduction in platelet count, thrombosis or skin allergy) should be evaluated for HIT.
Risk of hyperkalaemia
Adrenal secretion of aldosterone is suppressed by heparin and leads to hyperkalaemia. Monitor plasma potassium in patients at risk before starting treatment and regularly during treatment particularly if treatment last longer than 7 days. Patients with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, a raised plasma potassium level or who are taking potassium sparing drugs are at increased risk of hyperkalaemia. Risk of hyperkalaemia appears to increase with duration of therapy and is usually reversible.
Heparin resistance
There is considerable variation in individual anticoagulation responses to heparin. Heparin resistance, defined as an inadequate response to heparin at a standard dose for achieving a therapeutic goal occurs in approximately 5% to 30% of patients. Heparin resistance is often observed in acutely ill patients, patients with malignancy, during pregnancy or in the post-partum period. Factors predisposing to the development of heparin resistance include:
Antithrombin III activity less that 60% of normal (antithrombin III-dependent heparin resistance). Reduced Antithrombin III activity may be hereditary or acquired (secondary to preoperative heparin therapy in the main, chronic liver disease, nephrotic syndrome, cardiopulmonary bypass, low grade disseminated intravascular coagulation or drug induced (e.g. by aprotinin, oestrogen or possible glyceryl trinitrate).
Normal or supra normal antithrombin III levels (antithrombin III-independent heparin resistance), thromboembolic disorders, increased heparin clearance, elevated levels of heparin binding proteins, factor VIII, von Willebrand factor, fibrinogen, platelet factor 4 or histidine-rich glycoprotein, active infections, preoperative intra-aortic balloon counterpulsation, thrombocytopenia, thrombocytosis, advanced age, plasma albumin concentration less than or equal to 35g/dl, relative hypovolaemia.
Pregnancy and Lactation
Pregnancy
Use heparin sodium with caution in pregnancy.
The manufacturers advise caution if heparin sodium is used during pregnancy. Available reports indicate no increased risk in teratogenic or developmental effects, however there is an increased risk of haemorrhage and reported reduced bone density during pregnancy.
In addition to the above risks, heparin sodium is contraindicated in women with abortus imminens. There are further instructions when using heparin around labour. APTT monitoring is required if spontaneous labour occurs. Women on heparin treatment should be advised to stop treatment once they are established in labour or think they are in labour. Subcutaneous unfractionated heparin should be discontinued 12 hours before induction of labour or region anaesthesia. Intravenous unfractionated heparin should be stopped 6 hours before induction of labour or regional anaesthesia. If epidural anaesthesia is planned, heparin therapy should be discontinued.
Lactation
Heparin sodium is considered safe for use in breastfeeding.
The manufacturer states heparin sodium may be used safely when breastfeeding. Heparin sodium is not excreted in human milk. Some brands contain benzyl alcohol, which can cause 'Gasping Syndrome' in infants. These brands should not be used when breastfeeding.
Side Effects
Adrenal suppression
Alopecia
Anaphylactoid reaction
Anaphylaxis
Angioedema
Antibody formation
Asthma
Bronchospasm
Chills
Conjunctivitis
Contusion
Cyanosis
Eczema-like plaques
Elevated serum lipase
Epistaxis
Erythema
Fever
Fluid and electrolyte disturbances
Haematoma
Haematuria
Haemorrhage
Hyperkalaemia
Hyperlipaemia
Hypersensitivity reactions
Hypoaldosteronism
Increase in serum transaminases
Increased partial thromboplastin time
Increased risk of fractures
Increases in hepatic enzymes
Inflammatory erythematous nodules
Irritation (localised)
Local reaction at injection site
Necrosis (injection site)
Osteoporosis
Priapism
Pruritus
Pulmonary oedema
Rash
Rhinitis
Sense of oppression
Skin necrosis
Tachypnoea
Thrombocytopenia
Thrombosis
Urticaria
Withdrawal symptoms
Effects on Laboratory Tests
Interference with diagnostic tests may be associated with pseudo-hypocalcaemia (in haemodialysis patients), artefactual increases in total thyroxine and triiodothyronine, simulated metabolic acidosis and inhibition of the chromogenic lysate assay for endotoxin. Heparin may interfere with the determination of aminoglycosides by immunoassay.
Withdrawal Symptoms and Signs
Heparin is associated with release of lipoprotein lipase and rebound hyperlipidaemia may follow heparin withdrawal.
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: October 2019
Reference Sources
Summary of Product Characteristics: Heparin (Mucous) injection B.P. Leo Laboratories Ltd. Revised September 2016.
Summary of Product Characteristics: Heparin sodium 1,000 i.u./ml solution for injection or concentrate for solution for infusion (without preservative). Wockhardt UK Ltd. Revised September 2018.
Summary of Product Characteristics: Heparin sodium 1,000 i.u./ml solution for injection or concentrate for solution for infusion (with preservative). Wockhardt UK Ltd. Revised September 2018.
Summary of Product Characteristics: Heparin sodium 5,000 i.u./ml solution for injection or concentrate for solution for infusion (without preservative). Wockhardt UK Ltd. Revised September 2018.
Summary of Product Characteristics: Heparin sodium 5,000 i.u./ml Solution for injection or concentrate for solution for infusion (with preservative). Wockhardt UK Ltd. Revised September 2018.
Summary of Product Characteristics: Heparin sodium 25,000 i.u./ml Solution for injection or concentrate for solution for infusion (without preservative). Wockhardt UK Ltd. Revised September 2018.
Summary of Product Characteristics: Heparin sodium 25,000 i.u./ml Solution for injection or concentrate for solution for infusion (with preservative). Wockhardt UK Ltd. Revised September 2018.
Summary of Product Characteristics: Heparin sodium BP 1,000units/L in 0.9% Sodium Chloride IV infusion. Baxter Healthcare Ltd. Revised November 2014.
Summary of Product Characteristics: Heparin sodium BP 2,000units/L in 0.9% Sodium Chloride IV infusion. Baxter Healthcare Ltd. Revised November 2014.
Summary of Product Characteristics: Heparin sodium BP 2,500units/L in 0.9% Sodium Chloride IV infusion. Baxter Healthcare Ltd. Revised November 2014.
Summary of Product Characteristics: Heparin sodium BP 5,000units/L in 0.9% Sodium Chloride IV infusion. Baxter Healthcare Ltd. Revised November 2014.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 October 2022
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