Drugs List

Therapeutic Indications

Uses

For the treatment of thrombo-embolic disorders such as deep vein thrombosis, acute peripheral arterial occlusion, pulmonary embolism and unstable angina.
For prophylaxis of thrombo-embolic events such as deep vein thrombosis and pulmonary embolism.
For prophylaxis of mural thrombosis following myocardial infarction.
In extracorporeal circulation and haemodialysis
For prophylaxis of venous thrombosis in surgical patients.
For prevention of re-occlusion of coronary arteries following thrombosis in myocardial infarction.
For prophylaxis of venous thrombosis in pregnancy.

Unlicensed Uses

For maintenance of neonatal umbilical catheter.

Administration

For administration by intravenous injection, continuous intravenous infusion or subcutaneous injection (depending on indication). As the effects of heparin are short lived, administration by intravenous infusion or subcutaneous injection is preferable to intermittent intravenous injections.

Handling

The product should be used immediately. If not used immediately, the in-use storage times/conditions are the responsibility of the user.

Reconstitution

For use as an intravenous infusion: Heparin may be diluted in glucose intravenous infusion 5% OR sodium chloride intravenous infusion 0.9%.

Compatibilities

Glucose infusion 5%
Sodium chloride infusion 0.9%

Incompatibilities

Heparin has been reported to be incompatible in aqueous solution with some antibiotics, hydrocortisone, phenothiazines, opioid analgesics and some antihistamines.
Heparin is also reported to be incompatible with; alteplase, amiodarone, aprotinin, cisatracurium, cytarabine, dacarbazine, daunorubicin, diazepam, doxorubicin, hyaluronidase, labetalol, nicardipine, vinblastine. A mixture of dobutamine hydrochloride and heparin will precipitate.
Heparin is also incompatible with reteplase and if they are to be administered via the same line or Y-site these must be thoroughly flushed with sodium chloride infusion 0.9% or dextrose infusion 5% before and after the reteplase.

Contraindications

The relative risks and benefits of heparin should be carefully assessed in patients with a bleeding tendency or those with actual or potential bleeding sites. Menstruation is not a contraindication

Patients with uncorrected bleeding, risk of haemorrhage or potential bleeding lesions:
Active bleeding site likely:
Confirmed intracranial or intraspinal bleed
Local and/or regional anaesthesia in elective surgical procedures
Recent cerebrovascular accident
Recent trauma
Recent or imminent surgery of brain, spinal cord or eye
Recent organ biopsy
Peptic ulcer
Bleeding haemorrhoids

Potential bleeding site, increased risk or bleeding tendency:
Coagulopathy
Haemophilia
Haemorrhagic diathesis
Purpura
Proliferative retinopathy
Thrombocytopenia or history of heparin induced thrombocytopenia
Severe hepatic impairment including oesophageal varices
Patients who consume large quantities of alcohol
Hiatus hernia
Aneurysm
Severe hypertension (e.g. systolic greater than 200mmHg or diastolic greater than 120mmHg)
Bacterial endocarditis
Threatened abortion
Cerebral thrombosis
Active tuberculosis
Neoplasm
Increased capillary permeability
Recent cerebral haemorrhage.

Precautions and Warnings

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 1,000units.

Neonates - see Dosage neonates

Aspirin/NSAIDs should be used with care.
Nicotine (tobacco smoke) may partially counteract the anticoagulation effect of heparin. Increased dose may be required.
Consider offering synthetic alternatives to patients who are concerned about the animal origin of heparins

Due to individual patient response it is essential clotting be assessed in patients undergoing major surgery

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. Special care is warranted in the following patient groups who have an increased risk of bleeding:
Renal impairment (see Dosage; Renal Impairment)
Hepatic impairment (see Dosage; Hepatic Impairment)
Pregnancy (see Pregnancy and Dosage; Additional Dosage sections)
Elderly and particularly women over 60 years of age (see Dosage; Elderly)
Hypertension

Monitoring of bone density may be considered in patients at risk from osteoporosis.

Inflammatory reactions may occur at subcutaneous injection site, after 3-31 days treatment, causing firm erythematous nodules or infiltrated and sometimes eczema-like plaques. Treatment should be discontinued if cutaneous necrosis occur.

Adrenal insufficiency secondary to adrenal haemorrhage has been associated with heparin, heparin induced thrombocytopenia may be implicated.

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 1-4 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 5-11 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. lepirudin or danaparoid). HIT (with/without thrombosis) can occur for several weeks after discontinuation of heparin. Signs of HIT include 50% reduction in platelet count, thrombosis or skin allergy.

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.

Peridural/spinal anaesthesia or spinal puncture: During these procedures the prophylactic use of heparin may be rarely associated with epidural/spinal haematomas resulting in prolonged/permanent paralysis. The risk is increased by the use of a peridural catheter or spinal catheter for anaesthesia, additional anti-coagulant/anti-platelet medication and traumatic/repeated puncture. Patients undergoing spinal/epidural anaesthesia or spinal puncture should be under careful observation to identify such neurologic complications rapidly. Patients should be advised to inform a clinician or nurse if they experience symptoms indicative of neurological impairment such as back pain, sensory and motor deficits and bowel or bladder dysfunction.
In deciding the interval between the administration of the last dose of prophylactic heparin and the placement or removal of a peridural or spinal catheter the patient profile and product characteristics should be considered. At least 4 hours should elapse before a subsequent dose, re-administration should be delayed until the surgical procedure is complete.

Heparin resistance (See Additional Dosage section). 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

Heparin may interfere with some laboratory tests - see Effects on laboratory tests .

CSM Warnings

The CSM has recommended that platelet counts should be measured in patients under heparin treatment for longer than 5 days and that the treatment should be stopped immediately in those who develop thrombocytopenia.

Pregnancy and Lactation

Pregnancy

Use with caution. Heparin does not cross the placenta. However, it may indirectly affect the embryo/foetus, through its maternal effects. Uteroplacental haemorrhage may occur during pregnancy and during/after of delivery. Also, heparin resistance and allergic skin reactions may be observed. Reduced bone density and maternal osteopenia has been reported with prolonged heparin treatment during pregnancy. However, heparins are still the treatment of choice during pregnancy with LMWH preferable to unfractionated heparins, due to their reduced risk of the above mentions events. Schaefer (2007) comments that no definite recommendations can be given for the treatment of women with inherited thrombophilias. Platelet counts are recommended prior to treatment and regularly throughout treatment. See Dosage; Additional Dosage or refer to the Royal College of Obstetricians and Gynaecologists guidelines.

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.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Heparin are not detectable in breast milk. Due to its high molecular weight, heparin is unlikely to transfer into breast milk and any present in milk would be rapidly destroyed in the gastric content of the infant. No special precautions are required. The UK Drugs in Lactation Advisory Service states heparin may be administrated to breastfeeding mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk. Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Hypersensitivity reactions
Thrombocytopenia
Necrosis (injection site)
Haemorrhage
Increase in serum transaminases
Osteoporosis
Alopecia
Local reaction at injection site
Haematoma
Hypoaldosteronism
Hyperkalaemia
Priapism
Angioedema
Urticaria
Anaphylaxis
Rash
Pruritus
Conjunctivitis
Rhinitis
Asthma
Cyanosis
Tachypnoea
Sense of oppression
Fever
Chills
Skin necrosis
Eczema-like plaques
Elevated serum lipase
Irritation (localised)
Thrombosis
Adrenal suppression
Inflammatory erythematous nodules
Antibody formation
Increased risk of fractures
Rebound hyperlipidaemia on withdrawal

Presentation

Solution for injection or concentrate for infusion containing heparin calcium 5,000units in 0.2ml

Drugs List

Therapeutic Indications

Uses

For the treatment of thrombo-embolic disorders such as deep vein thrombosis, acute peripheral arterial occlusion, pulmonary embolism and unstable angina.
For prophylaxis of thrombo-embolic events such as deep vein thrombosis and pulmonary embolism.
For prophylaxis of mural thrombosis following myocardial infarction.
In extracorporeal circulation and haemodialysis
For prophylaxis of venous thrombosis in surgical patients.
For prevention of re-occlusion of coronary arteries following thrombosis in myocardial infarction.
For prophylaxis of venous thrombosis in pregnancy.

Unlicensed Uses

For maintenance of neonatal umbilical catheter.

Dosage

Adults

Elderly

Children

Neonates

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For administration by intravenous injection, continuous intravenous infusion or subcutaneous injection (depending on indication). As the effects of heparin are short lived, administration by intravenous infusion or subcutaneous injection is preferable to intermittent intravenous injections.

Handling

The product should be used immediately. If not used immediately, the in-use storage times/conditions are the responsibility of the user.

Reconstitution

For use as an intravenous infusion: Heparin may be diluted in glucose intravenous infusion 5% OR sodium chloride intravenous infusion 0.9%.

Compatibilities

Glucose infusion 5%
Sodium chloride infusion 0.9%

Incompatibilities

Heparin has been reported to be incompatible in aqueous solution with some antibiotics, hydrocortisone, phenothiazines, opioid analgesics and some antihistamines.
Heparin is also reported to be incompatible with; alteplase, amiodarone, aprotinin, cisatracurium, cytarabine, dacarbazine, daunorubicin, diazepam, doxorubicin, hyaluronidase, labetalol, nicardipine, vinblastine. A mixture of dobutamine hydrochloride and heparin will precipitate.
Heparin is also incompatible with reteplase and if they are to be administered via the same line or Y-site these must be thoroughly flushed with sodium chloride infusion 0.9% or dextrose infusion 5% before and after the reteplase.

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, activated partial thromboplastin time (APTT) or anti-Xa may be required depending on the patient characteristics and dosage. ( See Dosage sections and refer to local protocols )

Contraindications

The relative risks and benefits of heparin should be carefully assessed in patients with a bleeding tendency or those with actual or potential bleeding sites. Menstruation is not a contraindication

Patients with uncorrected bleeding, risk of haemorrhage or potential bleeding lesions:
Active bleeding site likely:
Confirmed intracranial or intraspinal bleed
Local and/or regional anaesthesia in elective surgical procedures
Recent cerebrovascular accident
Recent trauma
Recent or imminent surgery of brain, spinal cord or eye
Recent organ biopsy
Peptic ulcer
Bleeding haemorrhoids

Potential bleeding site, increased risk or bleeding tendency:
Coagulopathy
Haemophilia
Haemorrhagic diathesis
Purpura
Proliferative retinopathy
Thrombocytopenia or history of heparin induced thrombocytopenia
Severe hepatic impairment including oesophageal varices
Patients who consume large quantities of alcohol
Hiatus hernia
Aneurysm
Severe hypertension (e.g. systolic greater than 200mmHg or diastolic greater than 120mmHg)
Bacterial endocarditis
Threatened abortion
Cerebral thrombosis
Active tuberculosis
Neoplasm
Increased capillary permeability
Recent cerebral haemorrhage.

Precautions and Warnings

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 1,000units.

Neonates - see Dosage neonates

Aspirin/NSAIDs should be used with care.
Nicotine (tobacco smoke) may partially counteract the anticoagulation effect of heparin. Increased dose may be required.
Consider offering synthetic alternatives to patients who are concerned about the animal origin of heparins

Due to individual patient response it is essential clotting be assessed in patients undergoing major surgery

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. Special care is warranted in the following patient groups who have an increased risk of bleeding:
Renal impairment (see Dosage; Renal Impairment)
Hepatic impairment (see Dosage; Hepatic Impairment)
Pregnancy (see Pregnancy and Dosage; Additional Dosage sections)
Elderly and particularly women over 60 years of age (see Dosage; Elderly)
Hypertension

Monitoring of bone density may be considered in patients at risk from osteoporosis.

Inflammatory reactions may occur at subcutaneous injection site, after 3-31 days treatment, causing firm erythematous nodules or infiltrated and sometimes eczema-like plaques. Treatment should be discontinued if cutaneous necrosis occur.

Adrenal insufficiency secondary to adrenal haemorrhage has been associated with heparin, heparin induced thrombocytopenia may be implicated.

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 1-4 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 5-11 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. lepirudin or danaparoid). HIT (with/without thrombosis) can occur for several weeks after discontinuation of heparin. Signs of HIT include 50% reduction in platelet count, thrombosis or skin allergy.

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.

Peridural/spinal anaesthesia or spinal puncture: During these procedures the prophylactic use of heparin may be rarely associated with epidural/spinal haematomas resulting in prolonged/permanent paralysis. The risk is increased by the use of a peridural catheter or spinal catheter for anaesthesia, additional anti-coagulant/anti-platelet medication and traumatic/repeated puncture. Patients undergoing spinal/epidural anaesthesia or spinal puncture should be under careful observation to identify such neurologic complications rapidly. Patients should be advised to inform a clinician or nurse if they experience symptoms indicative of neurological impairment such as back pain, sensory and motor deficits and bowel or bladder dysfunction.
In deciding the interval between the administration of the last dose of prophylactic heparin and the placement or removal of a peridural or spinal catheter the patient profile and product characteristics should be considered. At least 4 hours should elapse before a subsequent dose, re-administration should be delayed until the surgical procedure is complete.

Heparin resistance (See Additional Dosage section). 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

Heparin may interfere with some laboratory tests - see Effects on laboratory tests .

CSM Warnings

The CSM has recommended that platelet counts should be measured in patients under heparin treatment for longer than 5 days and that the treatment should be stopped immediately in those who develop thrombocytopenia.

Pregnancy and Lactation

Pregnancy

Use with caution. Heparin does not cross the placenta. However, it may indirectly affect the embryo/foetus, through its maternal effects. Uteroplacental haemorrhage may occur during pregnancy and during/after of delivery. Also, heparin resistance and allergic skin reactions may be observed. Reduced bone density and maternal osteopenia has been reported with prolonged heparin treatment during pregnancy. However, heparins are still the treatment of choice during pregnancy with LMWH preferable to unfractionated heparins, due to their reduced risk of the above mentions events. Schaefer (2007) comments that no definite recommendations can be given for the treatment of women with inherited thrombophilias. Platelet counts are recommended prior to treatment and regularly throughout treatment. See Dosage; Additional Dosage or refer to the Royal College of Obstetricians and Gynaecologists guidelines.

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.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Heparin are not detectable in breast milk. Due to its high molecular weight, heparin is unlikely to transfer into breast milk and any present in milk would be rapidly destroyed in the gastric content of the infant. No special precautions are required. The UK Drugs in Lactation Advisory Service states heparin may be administrated to breastfeeding mothers.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk. Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

No effects on the ability to drive and use machines have been observed.

Counselling

Warn all patients of a risk of bleeding.
Advise patients not to self medicate with aspirin/NSAIDs unless under the direction of a clinician.
Advise that nicotine may partially counteract the effect of heparin.
Advise patients who receive epidural or spinal anaesthesia report any symptoms of neurological impairment (back pain, numbness or weakness in the lower limbs, bowel and/or bladder dysfunction) immediately.

Side Effects

Hypersensitivity reactions
Thrombocytopenia
Necrosis (injection site)
Haemorrhage
Increase in serum transaminases
Osteoporosis
Alopecia
Local reaction at injection site
Haematoma
Hypoaldosteronism
Hyperkalaemia
Priapism
Angioedema
Urticaria
Anaphylaxis
Rash
Pruritus
Conjunctivitis
Rhinitis
Asthma
Cyanosis
Tachypnoea
Sense of oppression
Fever
Chills
Skin necrosis
Eczema-like plaques
Elevated serum lipase
Irritation (localised)
Thrombosis
Adrenal suppression
Inflammatory erythematous nodules
Antibody formation
Increased risk of fractures
Rebound hyperlipidaemia on withdrawal

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 ).

Shelf Life and Storage

Do not store above 25 degrees C.
Store in the original packaging.

Further Information

Last Full Review Date: November 2011

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Heparin calcium 25,000i.u./ml Solution for injection or concentrate for solution for infusion. Wockhardt UK Ltd. Revised March 2011.

SIGN Guideline No 36: Antithrombotic therapy. Section 12. Available at: https://www.sign.ac.uk/guidelines/fulltext/36/index.html Last accessed: June 16, 2011.

Clinical Knowledge Summary - Deep vein thrombosis, Published May 2006. Available at https://cks.library.nhs.uk/deep_vein_thrombosis#-219198 Last accessed: June 16, 2011.

Guidelines on the use and monitoring of heparin, (2006) Baglin T, Barrowcliffe TW, Cohen A, Greaves M. Br J Haem; 133:19-34. Available at: https://www.bcshguidelines.com/documents/heparin_bjh_22052006.pdf Last accessed: June 16, 2011.

National Institute for Health and Clinical excellence (NICE) clinical guidance 92: Venous thromboembolism: Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. Issue date January 2010
Available at: https://www.nice.org.uk/CG92 Last accessed: June 16, 2011.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 25 August 2017

Thrombosis and embolism during pregnancy and the puerperium, the acute management of (Green-top 37b) (2007) Royal College of Obstetricians and Gynaecologists Green-top Guideline No.37b. Available at: https://www.rcog.org.uk/womens-health/clinical-guidance/thromboembolic-disease-pregnancy-and-puerperium-acute-management-gre Last accessed: June 16, 2011.

Thrombosis and embolism during pregnancy and the puerperium, reducing the risk (Green-top 37a) (2009) Royal College of Obstetricians and Gynaecologists Green-top Guideline No.37a. Available at: https://www.rcog.org.uk/womens-health/clinical-guidance/reducing-risk-of-thrombosis-greentop37aLast accessed: June 16, 2011.

UK Drugs in Lactation Advisory Service. Available at: https://www.ukmicentral.nhs.uk/drugpreg/qrg_p1.asp Last accessed: June 16, 2011.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed). Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT Heparin. Last revised: December 7, 2010. Last accessed: June 16, 2011.