Dalteparin parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of dalteparin.
Unit = International anti Factor Xa units of the first International Standard for Low Molecular Weight Heparin.
Drugs List
Therapeutic Indications
Uses
Deep vein thrombosis - treatment
Extended treatment of VTE in patients with solid tumours
Haemodialysis or haemofiltration duration less than 4 hours
Haemodialysis or haemofiltration duration more than 4 hours
Long-term thromboprophylaxis in hip replacement surgery
Pulmonary embolism - treatment
Thromboprophylaxis - peri and post operative
Thromboprophylaxis in bedridden patients with predisposing factors for VTE
Unstable angina & non-Q wave myocardial infarction in females: Prophylaxis
Unstable angina & non-Q wave myocardial infarction in males: Prophylaxis
Prevention of clotting in the extracorporeal circulation during haemodialysis or haemofiltration, in patients with chronic renal insufficiency or acute renal failure.
Treatment of venous thromboembolism (VTE) presenting clinically as deep vein thrombosis (DVT), pulmonary embolism (PE) or both.
Unstable angina and non-Q wave myocardial infarction (unstable coronary artery disease-UCAD), administered concurrently with aspirin.
Patients with solid tumours: Extended treatment of symptomatic venous thromboembolism (VTE) and prevention of its recurrence.
Peri and post operative surgical thromboprophylaxis.
The prophylaxis of proximal deep venous thrombosis in patients bedridden due to a medical condition, including, but not limited to; congestive cardiac failure (NYHA class III or IV), acute respiratory failure or acute infection, who also have a predisposing risk factor for venous thromboembolism such as age over 75 years, obesity, cancer or previous history of VTE.
Unlicensed Uses
Thrombotic events in children: Prophylaxis
Thrombotic events in children: Treatment
Treatment of VTE in pregnancy
Dosage
Adults
Prevention of clotting during haemodialysis and haemofiltration (using ampoules)
In chronic renal insufficiency
Long term haemodialysis or haemofiltration of greater than 4 hours duration:
An intravenous bolus injection of 30units/kg to 40units/kg followed by an infusion of 10units/kg/hour to 15units/kg/hour.
The plasma anti Factor Xa levels should be within the range 0.5units/ml to 1units/ml.
Short-term haemodialysis or haemofiltration of less than 4 hours duration:
Intravenous bolus injection of 30units/kg to 40units/kg followed by an infusion of 10units/kg/hour to 15units/kg/hour.
OR
Single intravenous bolus injection of 5000units.
The plasma anti Factor Xa levels should be within the range 0.5units/ml to 1units/ml.
Acute renal failure or chronic renal failure in patients with a high risk of bleeding
Intravenous bolus injection of 5units/kg to 10units/kg, followed by an infusion of 4units/kg/hour to 5units/kg/hour.
The plasma anti Factor Xa range should be 0.2units/ml to 0.4units/ml.
Treatment of deep vein thrombosis and pulmonary embolism (using pre-filled syringes, 10,000unit/ml ampoules or 100,000unit/4ml multi-dose vial)
Pre-filled syringes
A single dose is administered subcutaneously once daily:
Bodyweight 83kg and over: 18,000units
Bodyweight 69kg to 82kg: 15,000units
Bodyweight 57kg to 68kg: 12,500units
Bodyweight 46kg to 56kg: 10,000units
Bodyweight less than 46kg: 7500units
Maximum single daily dose 18,000units. Patients with an increased risk of bleeding should be dosed according to the dosage regimen listed below for the ampoule or 100,000unit/4ml multi-dose vial.
Dalteparin should be taken with an oral anticoagulant until adequate oral anticoagulation is established.
The following alternative dosing schedule may be suitable:
Using the 10,000units/ml ampoule or the 100,000units/4ml multi-dose vial
By subcutaneous route either as a single daily injection or twice daily injections until adequate oral anticoagulation is established.
Once daily administration
200units/kg once daily, maximum 18,000units.
Twice daily administration for patients with increased risk of bleeding
100units/kg twice daily. Monitoring of anticoagulant effect is generally not necessary, but can be performed with a functional anti Factor Xa assay (not prolongation of APTT). Take samples three to four hours after injection when plasma levels are at maximum. Recommended plasma levels are 0.5units/ml to 1units/ml.
Simultaneous oral vitamin K antagonists can be started immediately. Treatment with dalteparin should continue until prothrombin complex levels (factor II, VII, IX, & X) have decreased to a therapeutic level. At least five days of combined treatment is normally required.
Unstable angina and non Q wave myocardial infarction (using the graduated syringe 10,000units/ml ampoule or 7500units/0.3ml pre-filled syringe)
120units/kg by subcutaneous injection every 12 hours, for up to eight days. Maximum 10,000units every 12 hours. Concurrent low dose aspirin is recommended.
Patients needing therapy beyond eight days (while awaiting angiography/revascularisation)
A fixed dose of either 5000units (women less than 80kg and men less than 70kg) or 7500units (women greater than or equal to 80kg and men greater than or equal to 70kg) every 12 hours should be given. Treatment is recommended to be given until the day of the revascularisation procedure (PTCA or CABG) but not more than forty five days.
Surgical thromboprophylaxis in patients at moderate risk of thrombosis (using prophylactic pre-filled syringes)
2500units administered subcutaneously 1 to 2 hours before the surgical procedure and thereafter 2500units subcutaneously each morning until the patient is mobilised (generally five to seven days or longer).
Surgical thromboprophylaxis in patients at high risk of thrombosis (using prophylactic pre-filled syringes)
2500units administered subcutaneously 1 to 2 hours before the surgical procedure and 2500units subcutaneously 8 to 12 hours later. On the following days, 5000units subcutaneously each morning.
As an alternative, 5000units is administered subcutaneously the evening before the surgical procedure and 5000units subcutaneously the following evenings. Treatment is continued until the patient is mobilised (generally five to seven days or longer).
Prolonged thromboprophylaxis in hip replacement surgery (using prophylactic pre-filled syringes)
5000units given subcutaneously the evening before the operation and 5000units subcutaneously the following evenings. Treatment is continued for five postoperative weeks. If preoperative administration of dalteparin is not considered appropriate due to a high risk of haemorrhage during the procedure, dalteparin may be administered postoperatively.
Prophylaxis of venous thromboembolism in medical patients (using 5000units/0.2ml pre-filled syringe only)
5000units by subcutaneous injection once daily. Treatment is prescribed for up to fourteen days.
Patients with solid tumours: Extended treatment of symptomatic venous thromboembolism (VTE) and prevention of its recurrence (using 5000, 7500, 10,000, 12,500, 15,000, 18,000units pre-filled syringes)
Month 1
Administer dalteparin 200units/kg total bodyweight subcutaneously once daily for the first thirty days of treatment. The total daily dose should not exceed 18,000units daily.
Bodyweight 83kg and over: 18,000units.
Bodyweight 69kg to 82kg: 15,000units.
Bodyweight 57kg to 68kg: 12,500units.
Bodyweight 46kg to 56kg: 10,000units.
Bodyweight less than 46kg: 7500units.
In the case of chemotherapy induced thrombocytopenia, dalteparin dose should be used as follows:
In patients receiving dalteparin who experience platelet counts between 50,000/mm cubed and 100,000/mm cubed, the daily dose of dalteparin should be reduced by 2500units until the platelet count recovers to or above 100,000/mm cubed. In patients receiving dalteparin who experience platelet counts less than 50,000/mm cubed, dalteparin should be discontinued until the platelet count recovers above 50,000/mm cubed.
Months 2 to 6
Dalteparin should be administered at a dose of approximately 150units/kg, subcutaneously, once daily using fixed dose syringes. Suggested doses are:
Bodyweight 99kg and over: 18,000units.
Bodyweight 83kg to 98kg: 15,000units.
Bodyweight 69kg to 82kg: 12,500units.
Bodyweight 57kg to 68kg: 10,000units.
Bodyweight less than 56kg: 7500units.
Recommended duration of treatment is six months (first month of dalteparin treatment is included). Relevance of continuing treatment beyond this period will be evaluated according to individual risk/benefit ratio, taking into account particularly the progression of cancer. No data is available with dalteparin beyond six months. In the case of chemotherapy-induced thrombocytopenia, dalteparin dose should be discontinued or adapted as follows:
With platelet counts less than 50,000/mm cubed, dalteparin dosing should be interrupted until the platelet count recovers above 50,000/mm cubed.
For platelet counts between 50,000/mm cubed and 100,000/mm cubed, dalteparin should be reduced as illustrated below depending on the patient's weight. Once the platelet count has recovered to 100,000/mm cubed, dalteparin should be re-instituted at full dose.
Reduced dalteparin dose (unit):
Bodyweight 99kg and over: 15,000units.
Bodyweight 83kg to 98kg: 12,500units.
Bodyweight 69kg to 82kg: 10,000units.
Bodyweight 57kg to 68kg: 7500units.
Bodyweight less than 56kg: 5000units.
For patients with an increased risk of bleeding it is recommended that dalteparin is administrated according to the twice daily regimen for dalteparin 10,000units/ml ampoules or the 100,000units/4ml multi-dose vial.
Treatment of thromboembolic disease in pregnancy (calculated using bodyweight in early pregnancy) (unlicensed)
By subcutaneous injection:
Bodyweight 90kg and above: 10,000units twice daily.
Bodyweight 70kg to 89kg: 8000units twice daily.
Bodyweight 50kg to 69kg: 6000units twice daily.
Bodyweight under 50kg: 5000units twice daily.
Children
Treatment of thromboembolism (unlicensed)
By subcutaneous injection.
Children aged 12 to 18 years: 200units/kg (maximum 18,000units) once daily, if increased risk of bleeding reduce to 100units/kg twice daily.
Children aged 1 month to 12 years: 100units/kg twice daily.
Venous thromboembolism in pregnancy (unlicensed)
Children aged 12 to 18 years
(See Dosage; Adult).
Prophylaxis of thromboembolism (unlicensed)
By subcutaneous injection.
Children aged 12 to 18 years: 2500units to 5000units once daily.
Children aged 1 month to 12 years: 100units/kg once daily.
Neonates
Treatment of thromboembolism (unlicensed)
By subcutaneous injection.
100units/kg twice daily.
Prophylaxis of thromboembolism (unlicensed)
By subcutaneous injection
100units/kg once daily.
Patients with Renal Impairment
Prevention of clotting during haemodialysis/haemofiltration
(See Dosage; Adults).
In significant renal failure adjust dalteparin dose based on anti-Factor Xa activity. If the anti-Factor Xa level is below/above the desired range, the dose of dalteparin should be increased/reduced respectively, and the anti-Factor Xa measurement should be repeated after three to four new doses. Repeat this dose adjustment until the desired anti-Factor Xa level is achieved.
Administration
Subcutaneous injection use: Treatment of deep vein thrombosis and pulmonary embolism, extended treatment of VTE in patients with solid tumours and thromboprophylaxis in; peri and post operative, hip replacement surgery, bedridden patients with predisposing factors for VTE.
Administer by subcutaneous injection, preferably into the abdominal subcutaneous tissue anterolaterally or posterolaterally, or into the lateral part of the thigh. Patients should be supine and the total length of the needle should be introduced vertically, not at an angle, into the thick part of a skin fold, produced by squeezing the skin between thumb and forefinger; the skin fold should be held throughout the injection.
Intravenous bolus injection: prevention of clotting in haemodialysis and prevention of clotting in haemofiltration.
Contraindications
Haemorrhage
Hypersensitivity to benzyl alcohol
Locoregional anaesthesia when receiving LMWH treatment
Bacterial endocarditis
Central nervous system surgery
Central nervous system trauma
Cerebrovascular haemorrhage
Coagulopathy
Ear surgery
Ear Trauma
Haemophilia
Haemorrhagic pericardial effusion
Haemorrhagic pleural effusion
History of heparin-induced thrombocytopenia
Ocular surgery
Ocular trauma
Peptic ulcer
Prosthetic heart valve with pregnancy
Severe hypertension
Thrombocytopenia
Precautions and Warnings
Children under 18 years
Hypersensitivity to latex
Predisposition to haemorrhage
Recent surgery
Recent trauma
Severe obesity
Spinal/epidural anaesthesia
Underweight patients
Breastfeeding
Chronic renal failure
Diabetes mellitus
Diabetic retinopathy
Hyperkalaemia
Hypertensive retinopathy
Metabolic acidosis
Pregnancy
Recent intracranial haemorrhage
Severe hepatic impairment
Severe renal impairment
Uncontrolled hypertension
Not recommended for anticoagulation with prosthetic heart valves
Avoid switching to an alternative low molecular weight heparin
Not all available brands are licensed for all routes of administration
Not all presentations are licensed for all indications
Needle cover contains a derivative of latex
Some presentations may contain benzyl alcohol
Avoid concurrent intramuscular injections - risk of haematoma
Different low molecular weight heparins may not be equivalent
Monitor platelets before starting and during treatment
Monitor anti-Factor Xa levels during haemodialysis
Monitor anti-Factor Xa levels in patients at risk of bleeding
Monitor elderly receiving therapeutic doses
Monitor patients undergoing spinal or epidural anaesthesia closely
Monitor plasma potassium in patients at risk of hyperkalaemia
Adrenal suppression may occur leading to hyperkalaemia
Discontinue if platelet count is significantly reduced
Increased risk of hyperkalaemia with K+ suppl. and K+ sparing diuretic
Spinal anaesthesia: tell patient-report symptoms of neurological impairment
Advise patient not to take NSAIDs unless advised by clinician
Caution is necessary in rapidly developing/severe thrombocytopenia associated with positive/unknown results of in vitro tests for anti-platelet antibody in the presence of low molecular weight heparins and/or heparin.
Heparin can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, raised plasma potassium and concurrent potassium sparing drugs. The risk of hyperkalaemia appears to increase with the duration of therapy but is usually reversible. Plasma potassium should be measured in patients at risk before starting heparin therapy and monitored regularly thereafter particularly if treatment is prolonged beyond about 7 days.
When neuraxial anaesthesia or spinal puncture is used, patients are at risk of developing an epidural or spinal haematoma which can result in long term or permanent paralysis. Insertion or removal of the epidural or spinal catheter should be postponed 10 to 12 hours after dalteparin doses administered for thrombosis prophylaxis, while in those receiving higher therapeutic dalteparin doses, the interval should be a minimum of 24 hours. If signs or symptoms of epidural or spinal haematoma are suspected, urgent diagnosis and treatment may include spinal cord decompression.
Limited data regarding the safety and efficacy of antithrombotic therapy in patients with primary or metastatic neoplasms of the brain who develop concurrent thromboembolic events. There is a risk of fatal intracranial bleeding in these patients. Therefore, if the treatment with dalteparin is considered, it should be monitored closely with regular re-assessment of the status of neoplasm involvement of the brain and other individual risks.
Pregnancy and Lactation
Pregnancy
Use dalteparin with caution in pregnancy.
Dalteparin does not cross the placenta. Data indicates no malformative or foetal/neonatal toxicity, however this possibility cannot be ruled out and therefore dalteparin should only be used if clearly necessary.
Animal studies have not shown teratogenic or fetotoxic properties of dalteparin.
Epidural anaesthesia during childbirth is contraindicated in women treated with high dose dalteparin. Caution is recommended when treating patients with a risk of haemorrhage.
Some formulations contain benzyl alcohol as a preservative, which can cross the placenta and should not be used during pregnancy. Dalteparin is not recommended in pregnancy women with prosthetic heart valves due to the absence of clear dosing, efficacy and safety information.
Lactation
Use dalteparin with caution in breastfeeding.
Limited data are available regarding the excretion of dalteparin in human milk. Small amounts of dalteparin are secreted into breast milk which may pose a risk to the suckling child.
Manufacturers recommend making a decision on whether to continue or discontinue breastfeeding or dalteparin therapy taking into account the benefits of breastfeeding to the child and therapy to the woman.
LactMed suggests no special precautions are required due to the small amounts ingested by the infant.
Side Effects
Alopecia
Anaphylactic reaction
Epidural haematoma
Haematoma (injection site)
Haemorrhage
Hyperkalaemia
Hypersensitivity reactions
Immunologically mediated thrombocytopenia
Increases in serum transaminases (transient)
Intracranial bleeding
Mild thrombocytopenia
Osteoporosis
Pain / soreness (injection site)
Pruritus
Rash
Retroperitoneal bleeding
Skin necrosis
Spinal Haematoma
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: February 2019
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Fragmin 10,000 IU/0.4ml solution for injection. Pfizer Ltd. Revised October 2020.
Summary of Product Characteristics: Fragmin 10,000 IU/1ml. Pfizer Ltd. Revised April 2020.
Summary of Product Characteristics: Fragmin 10,000 IU/4ml. Pfizer Ltd. Revised April 2020.
Summary of Product Characteristics: Fragmin 100,000 IU/4ml multidose vial. Pfizer Ltd. Revised April 2020.
Summary of Product Characteristics: Fragmin 12,500 IU/0.5ml solution for injection. Pfizer Ltd. Revised October 2020.
Summary of Product Characteristics: Fragmin 15,000 IU/0.6ml solution for injection. Pfizer Ltd. Revised October 2020.
Summary of Product Characteristics: Fragmin 18,000 IU/0.72ml solution for injection. Pfizer Ltd. Revised October 2020.
Summary of Product Characteristics: Fragmin 2500 IU. Pfizer Ltd. Revised October 2020.
Summary of Product Characteristics: Fragmin 5000 IU. Pfizer Ltd. Revised October 2020.
Summary of Product Characteristics: Fragmin 7,500 IU/0.3ml solution for injection. Pfizer Ltd. Revised October 2020.
Summary of Product Characteristics: Fragmin graduated syringe 10,000 IU/ml solution for injection. Pfizer Ltd. Revised October 2020.
NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 15 February 2019
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: 13 April 2015
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: 31 October 2018
Last accessed: 15 February 2019
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