Drugs List

Therapeutic Indications

Uses

Anticoagulation in heparin-induced thrombocytopenia (HIT) type II
Prevention of deep vein thrombosis in patients undergoing surgery

Administration

Prevention of deep vein thrombosis.
For subcutaneous injection administration.

Treatment of thrombo-embolic disorders in patients who have developed or have a history of heparin-induced thrombocytopenia (HIT).
For intravenous injection followed by intravenous infusion administration.

Contraindications

Haemorrhage
Haemorrhagic diathesis
Acute bacterial endocarditis
Diabetic retinopathy
Haemophilia
Haemorrhagic stroke
Idiopathic thrombocytopenic purpura
Peptic ulcer - unless this is the reason for surgery
Positive aggregation test for heparin induced Ab causing thrombocytopenia
Severe hepatic disorder
Severe hypertension
Severe renal impairment

Precautions and Warnings

Children under 18 years
Predisposition to haemorrhage
Spinal/epidural anaesthesia
Asthma
Breastfeeding
Gastrointestinal ulcer
Impaired haemostasis
Ischaemic cerebrovascular accident
Moderate hepatic impairment
Moderate renal impairment
Pregnancy

Avoid locoregional anaesthesia when anticoagulant used at treatment doses
Refer to product information for use in peridural/spinal anaesthesia
Some contraindications are relative - refer to product information
Contains sulfite. Discontinue if hypersensitivity reactions occur
Monitor platelets before starting and during treatment
Monitor anti-Xa activity in patients over 90kg
Monitor anti-Xa activity in renal impairment
Monitor patients undergoing spinal or epidural anaesthesia closely
Test for platelet cross reactivity in patients sensitive to heparin
Discontinue if thrombocytopenia occurs
Spinal anaesthesia: tell patient-report symptoms of neurological impairment
Prothrombin time and INR unreliable within 5 hours of injection

Danaparoid has a low incidence of platelet cross-reactivity with plasma from patients sensitised by heparin and it is therefore advisable to rule this out using an in-vitro aggregation test prior to treatment. The platelet count should be checked daily during the first week of treatment, on alternate days during the second and third weeks, and weekly to monthly thereafter. If a pre-treatment cross reactivity test with danaparoid is positive but the decision to use danaparoid is taken, then daily platelet counts are advised until danaparoid treatment is stopped. Therapy should be discontinued if antibody-induced thrombocytopenia occurs and alternative treatment considered.

No incidences of osteoporosis have been reported with the use of recommended doses, however, inappropriate doses of glycosaminoglycuronan may result in osteoporosis.

Since severe bleeding may occur post-operatively in HIT patients undergoing a cardiopulmonary bypass procedure, danaparoid is not recommended during the procedure unless no other antithrombotic treatment is available.

Note that the anti-Xa units of danaparoid have a different relationship to clinical efficacy from those of heparin and low molecular weight heparins.

Locoregional anaesthesia is contraindicated where danaparoid is being used for treatment rather than prophylaxis.

When considering the interval between the last administration of a prophylactic dose of danaparoid and the placement or removal of a peridural or spinal catheter the product characteristics and patient profile should be taken in to account. Subsequent doses should not occur before at least 4 hours have elapsed and re-administration should be delayed until completion of the surgical procedure.

When danaparoid is used in the context of peridural or spinal anaesthesia, extreme vigilance and frequent monitoring for signs and symptoms of neurological impairment must be carried out. Back pain, sensory and motor deficits (numbness and weakness) and bladder or bowel dysfunction should be considered and patients advised to inform staff immediately that any of these occur. Urgent diagnosis and treatment including spinal cord decompression should be initiated.

Plasma anti-Xa activity monitoring using an amidolytic assay is recommended in patients weighing over 90 kg.

Avoid in severe renal and hepatic impairment unless the patient has heparin induced thrombocytopenia and no alternative anti-thrombotic treatment is available.

Pregnancy and Lactation

Pregnancy

Use danaparoid with caution in pregnancy.

At the time of writing there is limited data on the use of danaparoid during pregnancy. The manufacturer states that if alternative antithrombotic treatment is unacceptable, danaparoid can be used.

Danaparoid has been used with success in a small number of pregnancies, however the available information is considered to be insufficient to assess its safety in pregnancy.

Danaparoid has a molecular weight of about 6500 daltons, and therefore it is likely that it will not cross the placenta. Schaefer (2007) concludes that in cases of heparin - induced thrombocytopenia danaparoid may be prescribed during pregnancy.

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

Use danaparoid with caution in breastfeeding.

At the time of writing there is limited data on the use of danaparoid during breastfeeding.

There is no data available regarding danaparoid secretion into human breast milk. It would not be expected to be excreted into breast milk due to its molecular weight, therefore amounts in breast milk are probably too small to be harmful and would be inactivated in the gastrointestinal tract. Schaefer (2007) concludes that theoretically, no problems should be expected for the breastfed infant and weaning does not seem to be justified.

The manufacturer states that if an alternative antithrombotic treatment is unacceptable, danaparoid can be used during breastfeeding.

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

Bleeding (surgical site)
Bruising at injection site
Epidural haematoma
Erythematous rash
Haematoma
Haemorrhage
Hypersensitivity reactions
Immunologically mediated thrombocytopenia
Injection site reactions
Irritation (injection site)
Local pain (injection site)
Maculopapular rash
Purpura
Rash
Rash at injection site
Spinal Haematoma
Swelling (injection site)
Urticaria

Presentation

Injection containing danaparoid sodium

Drugs List

Therapeutic Indications

Uses

Anticoagulation in heparin-induced thrombocytopenia (HIT) type II
Prevention of deep vein thrombosis in patients undergoing surgery

Dosage

Plasma anti Xa activity has a linear relationship to dose.
A functional antifactor Xa test should be used if anticoagulant activity monitoring or dose individualisation is required. Use danaparoid as the standard for construction of the reference curve and the test should be carried out using a chromogenic peptide substrate.

Adults

Children

Neonates

Additional Dosage Information

Administration

Prevention of deep vein thrombosis.
For subcutaneous injection administration.

Treatment of thrombo-embolic disorders in patients who have developed or have a history of heparin-induced thrombocytopenia (HIT).
For intravenous injection followed by intravenous infusion administration.

Contraindications

Haemorrhage
Haemorrhagic diathesis
Acute bacterial endocarditis
Diabetic retinopathy
Haemophilia
Haemorrhagic stroke
Idiopathic thrombocytopenic purpura
Peptic ulcer - unless this is the reason for surgery
Positive aggregation test for heparin induced Ab causing thrombocytopenia
Severe hepatic disorder
Severe hypertension
Severe renal impairment

Precautions and Warnings

Children under 18 years
Predisposition to haemorrhage
Spinal/epidural anaesthesia
Asthma
Breastfeeding
Gastrointestinal ulcer
Impaired haemostasis
Ischaemic cerebrovascular accident
Moderate hepatic impairment
Moderate renal impairment
Pregnancy

Avoid locoregional anaesthesia when anticoagulant used at treatment doses
Refer to product information for use in peridural/spinal anaesthesia
Some contraindications are relative - refer to product information
Contains sulfite. Discontinue if hypersensitivity reactions occur
Monitor platelets before starting and during treatment
Monitor anti-Xa activity in patients over 90kg
Monitor anti-Xa activity in renal impairment
Monitor patients undergoing spinal or epidural anaesthesia closely
Test for platelet cross reactivity in patients sensitive to heparin
Discontinue if thrombocytopenia occurs
Spinal anaesthesia: tell patient-report symptoms of neurological impairment
Prothrombin time and INR unreliable within 5 hours of injection

Danaparoid has a low incidence of platelet cross-reactivity with plasma from patients sensitised by heparin and it is therefore advisable to rule this out using an in-vitro aggregation test prior to treatment. The platelet count should be checked daily during the first week of treatment, on alternate days during the second and third weeks, and weekly to monthly thereafter. If a pre-treatment cross reactivity test with danaparoid is positive but the decision to use danaparoid is taken, then daily platelet counts are advised until danaparoid treatment is stopped. Therapy should be discontinued if antibody-induced thrombocytopenia occurs and alternative treatment considered.

No incidences of osteoporosis have been reported with the use of recommended doses, however, inappropriate doses of glycosaminoglycuronan may result in osteoporosis.

Since severe bleeding may occur post-operatively in HIT patients undergoing a cardiopulmonary bypass procedure, danaparoid is not recommended during the procedure unless no other antithrombotic treatment is available.

Note that the anti-Xa units of danaparoid have a different relationship to clinical efficacy from those of heparin and low molecular weight heparins.

Locoregional anaesthesia is contraindicated where danaparoid is being used for treatment rather than prophylaxis.

When considering the interval between the last administration of a prophylactic dose of danaparoid and the placement or removal of a peridural or spinal catheter the product characteristics and patient profile should be taken in to account. Subsequent doses should not occur before at least 4 hours have elapsed and re-administration should be delayed until completion of the surgical procedure.

When danaparoid is used in the context of peridural or spinal anaesthesia, extreme vigilance and frequent monitoring for signs and symptoms of neurological impairment must be carried out. Back pain, sensory and motor deficits (numbness and weakness) and bladder or bowel dysfunction should be considered and patients advised to inform staff immediately that any of these occur. Urgent diagnosis and treatment including spinal cord decompression should be initiated.

Plasma anti-Xa activity monitoring using an amidolytic assay is recommended in patients weighing over 90 kg.

Avoid in severe renal and hepatic impairment unless the patient has heparin induced thrombocytopenia and no alternative anti-thrombotic treatment is available.

Pregnancy and Lactation

Pregnancy

Use danaparoid with caution in pregnancy.

At the time of writing there is limited data on the use of danaparoid during pregnancy. The manufacturer states that if alternative antithrombotic treatment is unacceptable, danaparoid can be used.

Danaparoid has been used with success in a small number of pregnancies, however the available information is considered to be insufficient to assess its safety in pregnancy.

Danaparoid has a molecular weight of about 6500 daltons, and therefore it is likely that it will not cross the placenta. Schaefer (2007) concludes that in cases of heparin - induced thrombocytopenia danaparoid may be prescribed during pregnancy.

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

Use danaparoid with caution in breastfeeding.

At the time of writing there is limited data on the use of danaparoid during breastfeeding.

There is no data available regarding danaparoid secretion into human breast milk. It would not be expected to be excreted into breast milk due to its molecular weight, therefore amounts in breast milk are probably too small to be harmful and would be inactivated in the gastrointestinal tract. Schaefer (2007) concludes that theoretically, no problems should be expected for the breastfed infant and weaning does not seem to be justified.

The manufacturer states that if an alternative antithrombotic treatment is unacceptable, danaparoid can be used during breastfeeding.

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

Bleeding (surgical site)
Bruising at injection site
Epidural haematoma
Erythematous rash
Haematoma
Haemorrhage
Hypersensitivity reactions
Immunologically mediated thrombocytopenia
Injection site reactions
Irritation (injection site)
Local pain (injection site)
Maculopapular rash
Purpura
Rash
Rash at injection site
Spinal Haematoma
Swelling (injection site)
Urticaria

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: August 2016

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, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Danaparoid sodium 750 anti-Xa units, solution for injection. Aspen. Revised January 2016.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 27 June 2017.