- Low Molecular Weight Heparins
Chemical Name: Heparin, sodium salt
CAS Number: 9041-08-1
Medically reviewed by Drugs.com. Last updated on March 9, 2020.
- Spinal/Epidural Hematoma Risk
Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of low molecular weight heparins (LMWHs) or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture.1 35 77
Optimal timing between administration of dalteparin and neuraxial procedures not known.1
Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for thromboprophylaxis with anticoagulants.1 35 (See Spinal/Epidural Hematomas under Cautions.)
Uses for Dalteparin
Unstable Angina and Non-ST-Segment-Elevation MI (NSTEMI)
Used to reduce the risk of acute cardiac ischemic events (death, MI) in patients with unstable angina or NSTEMI (i.e., non-ST-segment-elevation acute coronary syndromes [NSTE ACS]).1 51 52 53 54 66 103 104 991 Used concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blockers, a P2Y12 inhibitor [e.g., clopidogrel, prasugrel, ticagrelor], platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors).1 51 52 53 54 66 103 104 991
If an LMWH is selected for initial parenteral anticoagulation in patients with NSTE ACS, the American Heart Association (AHA) and American College of Cardiology Foundation (ACCF) recommend the use of enoxaparin; other parenteral anticoagulants with established efficacy include heparin, bivalirudin (only in patients being managed with an early invasive strategy), and fondaparinux.1100
Thromboprophylaxis in Hip-Replacement, Knee-Replacement, or Hip-Fracture Surgery
ACCP recommends routine thromboprophylaxis with a pharmacologic (e.g., LMWH) and/or mechanical method in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.1003
Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose heparin, warfarin, aspirin) are recommended by ACCP for pharmacologic prophylaxis during major orthopedic surgery.1003 When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, safety, logistics, and compliance.1003
Thromboprophylaxis in General/Abdominal Surgery
ACCP recommends pharmacologic (e.g., LMWHs) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general and abdominal-pelvic surgery, including GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding.1002 In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.1002
If pharmacologic prophylaxis is used in patients undergoing general and abdominal-pelvic surgery, ACCP states that an LMWH or low-dose heparin is preferred.1002
Because risk of venous thromboembolism is particularly high in patients undergoing abdominal or pelvic surgery for cancer, extended (4 weeks) prophylaxis with an LMWH is recommended in such patients.1002
ACCP states that the recommendations for use of antithrombotic agents in general and abdominal-pelvic surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.1002
Medical Conditions Predisposing to Thromboembolism
In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.1001
ACCP recommends anticoagulant prophylaxis (e.g., LMWH) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding.1001 Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or until hospital discharge, whichever comes first.1001
Use of LMWHs also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.1001
Risk of venous thromboembolism particularly high in patients with cancer.1001 Use of LMWH prophylaxis suggested by ACCP in cancer outpatients with solid tumors who have additional risk factors for thromboembolism provided risk of bleeding is low.1001
Thromboprophylaxis in Cardiac Surgery
Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that an LMWH may be considered for thromboprophylaxis in cardiac surgery† patients with a complicated postoperative course.1002
Thromboprophylaxis in Thoracic Surgery
Thromboprophylaxis in Neurosurgery
LMWHs have been used for prevention of venous thromboembolism in patients undergoing craniotomy†; however, benefits of such prophylaxis may be outweighed by possible increased risk of intracranial hemorrhage.1002 ACCP states that LMWH prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.1002
Thromboprophylaxis with LMWHs also may be considered in high-risk patients undergoing spinal surgery† (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.1002
Thromboprophylaxis in Trauma
LMWHs may be used for thromboprophylaxis in patients with major trauma†.1002 For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests use of both a pharmacologic and mechanical method of prophylaxis unless contraindications exist.1002
Extended Treatment of Acute Venous Thromboembolism in Cancer Patients
Used for extended (6 months' duration) treatment of symptomatic DVT and/or PE in patients with cancer to reduce recurrence (secondary prevention) of venous thromboembolism.1 Manufacturer states that safety and efficacy of treatment durations >6 months not established.1
Acute Venous Thromboembolism
Manufacturer states that dalteparin not indicated for the acute treatment of venous thromboembolism;†1 however, has been recommended by ACCP as an appropriate option for initial treatment of acute proximal DVT and/or PE.1005
LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment.1005 IV heparin also may be preferred over LMWHs in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.1005
For long-term anticoagulant therapy, warfarin generally preferred in patients without cancer; however, ACCP suggests use of an LMWH in patients with cancer because of a possible reduced response to warfarin.1005
Continue anticoagulant therapy for ≥3 months and possibly longer depending on individual clinical situation.1005
Treatment of Symptomatic Venous Thromboembolism in Pediatric Patients
Most episodes of venous thromboembolism in children are secondary to an identifiable risk factor such as the presence of a central venous access device (e.g., central venous catheter or umbilical venous catheter).1013
ACCP recommends an LMWH or heparin for both initial and ongoing treatment of venous thromboembolism in children.1013 Potential advantages of an LMWH over heparin include reduced need for monitoring, lack of drug or dietary interactions, reduced risk of heparin-induced thrombocytopenia (HIT), and possible reduced risk of osteoporosis.1013
In children with central venous catheter-related thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation is suggested prior to removal.1013 If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.1013
Treatment of Superficial Vein Thrombosis
LMWHs also have been used for spontaneous superficial vein thrombosis (superficial thrombophlebitis)†; ACCP suggests use of prophylactic dosages for 45 days in patients with superficial vein thrombosis of ≥5 cm in length.1005
Treatment of Renal Vein Thrombosis
Although use of anticoagulant therapy for renal vein thrombosis† (the most common cause of spontaneous venous thromboembolism in neonates) is controversial, LMWHs are suggested by ACCP as a possible treatment option.1013
Thromboprophylaxis in Acute Ischemic Stroke
Heparin anticoagulants (i.e., LMWHs or heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke†; those with additional risk factors for venous thromboembolism are more likely to benefit from such prophylaxis.1009 1017
ACCP suggests thromboprophylaxis with an LMWH, sub-Q heparin, or intermittent pneumatic compression in patients with acute ischemic stroke† and restricted mobility; LMWH is preferred over heparin.1009
Prophylactic-dose heparin (heparin or an LMWH) usually initiated within 48 hours of onset of stroke and is continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.1009
LMWHs also recommended by ACCP as an option for initial management of acute arterial ischemic stroke in children† until dissection and embolic causes have been excluded.1013 If arterial ischemic stroke is associated with dissection or a cardioembolic origin, continued anticoagulant therapy suggested.1013
Thromboembolism During Pregnancy
Used during pregnancy for prevention and treatment of venous thromboembolism† and for prevention and treatment of systemic embolism associated with mechanical heart valves†.138 996 1012 (See Prevention and Treatment of Thromboembolism During Pregnancy under Dosage and Administration.)
LMWHs (rather than heparin or warfarin) are recommended by ACCP for prevention and treatment of thromboembolism during pregnancy.1012
In pregnant women with an acute venous thromboembolic event†, ACCP recommends an LMWH for initial treatment and secondary prevention throughout the remainder of the pregnancy.1012 To prevent recurrence, postpartum anticoagulation (for ≥6 weeks and for a total duration of ≥3 months) is suggested.1012
In general, thromboprophylaxis (e.g., with an LMWH) is suggested during the antepartum period only in pregnant women who have a history of thromboembolism† and are considered to be at moderate to high risk of recurrent events (e.g., those with a single episode of unprovoked venous thromboembolism, pregnancy- or estrogen-related venous thromboembolism, history of multiple unprovoked events).1012
Postpartum thromboprophylaxis† for 6 weeks suggested in all pregnant women with a prior venous thromboembolic event; an LMWH (in prophylactic or intermediate dosages) or warfarin (INR 2–3) may be used for such prophylaxis.1012
ACCP suggests antepartum and postpartum prophylaxis with an LMWH in some pregnant women with high-risk hereditary thrombophilias† (e.g., homozygous genetic mutations for factor V Leiden or prothrombin G20210A) who have not experienced a prior venous thromboembolic event, but have a family history of thromboembolism.1012
Discontinue LMWH therapy ≥24 hours prior to induction of labor or cesarean section (or expected time of neuraxial anesthesia) to avoid an unwanted anticoagulant effect on fetus.1012
Cardioversion of Atrial Fibrillation/Flutter
As an alternative to prolonged anticoagulation (e.g., usually with warfarin) prior to cardioversion in patients with atrial fibrillation lasting >48 hours or of unknown duration, an LMWH (in therapeutic dosages) may be used at the time of transesophageal echocardiography (TEE), followed by cardioversion within 24 hours if no thrombus is detected.999 1007
In patients with atrial fibrillation of short duration (e.g., ≤48 hours), an LMWH (in therapeutic dosages) may be used at presentation, followed by immediate cardioversion.1007
In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of a parenteral anticoagulant (in therapeutic dosages) prior to cardioversion if possible; however, such anticoagulant therapy must not delay any emergency intervention.999 1007
Thromboprophylaxis in Patients with Prosthetic Heart Valves
ACCP suggests bridging anticoagulation (an LMWH in either prophylactic or therapeutic dosages or IV heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve in patients without bleeding risk, until an adequate response to warfarin is obtained.1008
Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., those undergoing major surgery).1004
Treatment of Cerebral Venous Sinus Thrombosis
Reasonable to use full-dose LMWH rather than heparin for treatment of acute cerebral venous sinus thrombosis during pregnancy.1017 Prophylaxis with an LMWH during pregnancy and the postpartum period is reasonable in women with history of cerebral venous sinus thrombosis.1017
Recommended by ACCP as an option for initial and follow-up anticoagulation in children with cerebral venous sinus thrombosis† without substantial intracranial hemorrhage.1013 Also has been suggested for use in children with substantial intracranial hemorrhage.1013
Perioperative Antithrombotic Prophylaxis
ACCP suggests use of an LMWH or IV heparin during temporary interruption of warfarin therapy (bridging anticoagulation†) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves undergoing surgery or other invasive procedures; use and type of bridging anticoagulation depend on patients' risk of developing thromboembolism without warfarin therapy.1004
In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.1004
Dalteparin Dosage and Administration
Monitoring of anti-factor Xa concentrations may be helpful in high-risk groups, such as pregnant patients, patients with renal impairment, patients at extremes of weight, or if abnormal coagulation parameters or bleeding occurs during treatment.1 152
After initiation of dalteparin in pediatric patients, manufacturer recommends measuring anti-factor Xa concentration prior to the 4th dose; obtain blood samples for measurement of anti-factor Xa concentration 4 hours after administration of dalteparin.1 Monitor anti-factor Xa concentration periodically in pediatric patients to maintain an anti-factor Xa concentration between 0.5–1 unit/mL; obtain sample 4 hours after administration of dalteparin.1 Alternatively, ACCP suggests if an LMWH is used for anticoagulation in children, dosage should be adjusted to a target anti-factor Xa concentration of 0.5–1 unit/mL based on a sample taken 4–6 hours following sub-Q administration or 0.5–0.8 units/mL based on a sample taken 2–6 hours following sub-Q administration.1013
Whenever possible, use preparations of dalteparin that do not contain benzyl alcohol (prefilled syringes) in pediatric patients.1 (See Benzyl Alcohol in Neonates and Infants and see Pediatric Use, under Cautions.)
Administer by deep sub-Q injection; do not give IM.1
Patient should be sitting or supine during administration.1
When injecting, insert entire length of needle at 45–90° angle.1 Administer injections into the U-shaped area around the navel, upper outer aspect of the thigh, or upper outer quadrangle of the buttock.1 Alternate injection sites daily.1 When injecting into area around the navel or the thigh, insert needle into a skin fold created by thumb and forefinger.1 Hold skin until needle is withdrawn.1
Injection is commercially available in prefilled syringes equipped with a 27-gauge ½-inch needle.1
Treatment of Symptomatic Venous Thromboembolism in Pediatric Patients
Initial dosage based on age and body weight.1 (See Table 1.)
4 Weeks to <2 years
150 units/kg twice daily
2 Years to <8 years
125 units/kg twice daily
8 Years to <17 years
100 units/kg twice daily
After dalteparin has been initiated, measure anti-factor Xa concentration prior to the 4th dose.1 Obtain blood samples for measurement of anti-factor Xa concentration 4 hours after administration of dalteparin.1 Adjust dosage by increments of 25 units/kg to achieve a target anti-factor Xa concentration between 0.5–1 unit/mL.1 Maintenance dosage is the dosage that achieves the target anti-factor Xa concentration in blood collected 4 hours after administration of dalteparin.1 Monitor anti-factor Xa concentrations periodically in pediatric patients to maintain an anti-factor Xa concentration between 0.5–1 unit/mL.1
Reduce daily dosage of dalteparin sodium by 50% in pediatric patients (4 weeks to <17 years of age) with platelet counts of 50,000–100,000/mm3 until platelet count recovers to ≥100,000/mm3.1 If platelet counts decrease to ≤50,000/mm3, discontinue dalteparin until recovery of platelet count to >50,000/mm3.1
Unstable Angina and NSTEMI
120 units/kg every 12 hours (up to a maximum of 10,000 units every 12 hours) until patient is clinically stabilized, generally for 5–8 days.1 Concurrent aspirin therapy recommended in all patients unless contraindicated.1
Prevention of DVT and/or PE
Initiate therapy either preoperatively or postoperatively; several regimens are recommended by manufacturer.1
Preoperative start, evening before surgery: 5000 units 10–14 hours before surgery, followed by 5000 units 4–8 hours after surgery, or later if hemostasis has not been achieved.1
Preoperative start, day of surgery: 2500 units within 2 hours prior to surgery, followed by 2500 units 4–8 hours after surgery, or later if hemostasis has not been achieved.1
Postoperative start: 2500 units 4–8 hours after surgery, or later if hemostasis has not been achieved.1
Continue with 5000 units once daily throughout postoperative period (manufacturer states generally for 5–10 days, but up to 14 days has been well tolerated).1 ACCP recommends a minimum of 10–14 days of thromboprophylaxis, with extended prophylaxis suggested for up to 35 days on an outpatient basis.1003
Usual dosage: 2500 units initially,1 5 6 7 8 9 27 30 given 1–2 hours before surgery.1 6 8 9 19 21 Continue with 2500 units once daily throughout postoperative period, generally for 5–10 days.1 6 7 8 9 10 19 20 21
Patients undergoing abdominal surgery associated with a high risk of thromboembolism (e.g., surgery for malignancy): 5000 units, initiated on the evening prior to surgery, followed by daily administration of 5000 units throughout postoperative period.1 Alternatively, in patients with malignancy, may administer 2500 units 1–2 hours prior to surgery and repeat dose 12 hours later; follow with 5000 units daily throughout postoperative period, generally for 5–10 days.1 30 33
Extended prophylaxis (for up to 4 weeks) recommended by ACCP in patients undergoing abdominal or pelvic surgery for cancer.1002
Medical Conditions Predisposing to ThromboembolismSub-Q
Acute illness with severely restricted mobility: 5000 units once daily, generally for 12–14 days.1
Extended Treatment of Venous Thromboembolism in Cancer Patients
First 30 days of treatment: 200 units/kg (not to exceed total daily dosage of 18,000 units) once daily.1
Months 2–6 of treatment: Approximately 150 units/kg (not to exceed total daily dosage of 18,000 units) once daily.1
Safety and efficacy of treatment periods >6 months not established.1
Patients with thrombocytopenia: Reduce daily dosage by 2500 units in patients with platelet counts of 50,000–100,000/mm3 until platelet count recovers to ≥100,000/mm3.1 Discontinue therapy if platelet count ≤50,000/mm3 until platelet count recovers to >50,000/mm3.1
Prevention and Treatment of Thromboembolism During Pregnancy†
Treatment of acute venous thromboembolism: ACCP recommends 200 units/kg daily in 1 or 2 divided doses throughout the remainder of pregnancy; continue anticoagulation for ≥6 weeks postpartum (minimum total duration of 3 months).1012
Postpartum prophylaxis in patients with a prior venous thromboembolic event: Prophylactic (5000 units once daily) or intermediate (5000 units every 12 hours) dosage suggested.1012
Pregnant women receiving long-term coumarin anticoagulation (e.g., warfarin): An LMWH may be used throughout pregnancy in a weight-adjusted dosage (e.g., dalteparin sodium 100 units/kg twice daily or dalteparin sodium 200 units/kg daily) or 75% of a weight-adjusted dosage; resume long-term anticoagulation postpartum.1012
Primary prevention of venous thromboembolism in pregnant women with high-risk thrombophilias: Prophylactic (5000 units once daily) or intermediate (5000 units every 12 hours) dosage suggested.1012
Pregnant women with APLA syndrome: Antepartum administration of an LMWH in prophylactic dosages recommended by ACCP; combine with low-dose aspirin (75–100 mg daily).1012
Pregnant women with mechanical heart valves: ACCP recommends an LMWH throughout pregnancy or, alternatively, an LMWH until 13th week of pregnancy, substituting warfarin until close to delivery, then resuming LMWH therapy.1012 Dosage adjustment suggested to maintain manufacturer-recommended peak anti-factor Xa concentration 4 hours after dosing.1012 Resume usual long-term anticoagulation postpartum.1012 (See Patients with Mechanical Prosthetic Heart Valves under Cautions.)
To avoid an unwanted anticoagulant effect on the fetus during delivery, discontinue LMWH ≥24 hours prior to induction of labor or cesarean section.1012
Cardioversion of Atrial Fibrillation/Flutter†
For prevention of stroke and systemic embolism in patients undergoing cardioversion for atrial fibrillation or atrial flutter, use of full venous thromboembolism treatment dosages recommended.1007
Perioperative Antithrombotic Prophylaxis†
For bridging anticoagulation during temporary interruption of warfarin therapy in patients undergoing surgery or other invasive procedures, ACCP generally recommends therapeutic dosages of an LMWH (e.g., dalteparin sodium 100 units/kg twice daily or 200 units/kg once daily).1004
Unstable Angina or NSTEMI
Maximum 10,000 units every 12 hours.1
Patients with Cancer
Maximum total daily dose of 18,000 units.1
No specific dosage recommendations at this time; use with caution.1
Use with caution in patients with severe renal insufficiency; monitor anti-factor Xa concentrations to determine appropriate dosage in such patients.1 ACCP suggests that dosage be reduced in patients with severe renal impairment (Clcr <30 mL/minute).1000
In adults with severe renal impairment (Clcr <30 mL/minute) who have cancer and are receiving extended treatment for acute symptomatic venous thromboembolism, adjust dosage of dalteparin sodium to achieve a target anti-factor Xa concentration of 0.5–1.5 units/mL.1 Perform sampling for anti-factor Xa concentrations 4–6 hours after dosing in such patients and only after patient has received 3 or 4 doses.1
Careful attention to dosing intervals and concomitant medications (particularly antiplatelet drugs) is advised, particularly in geriatric patients with low body weight (<45 kg).1
Cautions for Dalteparin
Active major bleeding.1
History of HIT with or without thrombosis.1
Known hypersensitivity to dalteparin, heparin, or pork products.1
Use for unstable angina or NSTEMI or for prolonged prophylaxis of venous thromboembolism in patients undergoing neuraxial (epidural/spinal) anesthesia.1
Epidural or spinal hematoma reported with concurrent use of anticoagulants (e.g., LMWHs, heparinoids) and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.1 35 77 161 163 Such hematomas have resulted in neurologic injury, including long-term or permanent paralysis.1 161 (See Boxed Warning.)
Prior to performing a spinal or epidural procedure, determine whether a patient is receiving anticoagulants.161
Carefully consider the timing of spinal catheter placement and removal in relation to anticoagulant use, considering both dosage and pharmacokinetic properties (e.g., elimination half-life) of the anticoagulant.1 161
Assume that patients receiving dalteparin thromboprophylaxis prior to surgery have altered coagulation; administer first postoperative prophylactic dose (2500 units) 6–8 hours after surgery and second dose (2500 or 5000 units) no sooner than 24 hours after first dose.1
Insertion or removal of catheter is best performed when the anticoagulant effect of dalteparin is minimal (e.g., at least 12 hours post dose in patients receiving 2500 units once daily, at least 15 hours post dose in patients receiving 5000 units once daily, or at least 24 hours after higher dosages [200 units/kg once daily or 120 units/kg twice daily]); optimal timing to achieve sufficiently low anticoagulant effect not known.1 Consider doubling these recommended time delays in patients with renal impairment.1
Frequently monitor for signs of neurologic impairment (e.g., midline back pain, numbness or weakness in lower limbs, bowel or bladder dysfunction).1 If spinal hematoma suspected, diagnose and treat immediately; consider spinal cord decompression even though it may not prevent or reverse neurologic sequelae.1
Other Warnings Related to Hemorrhage
Use with extreme caution in patients with an increased risk of hemorrhage.1 Such patients include those with bacterial endocarditis; congenital or acquired bleeding disorders; active ulceration and angiodysplastic GI disease; hemorrhagic stroke; or recent brain, spinal, or ophthalmologic surgery.1 Increased risk for hemorrhage in patients with thrombocytopenia, platelet defects, those treated concomitantly with platelet-aggregation inhibitors; patients with uncontrolled arterial hypertension; and those with a history of recent GI ulceration, diabetic retinopathy, renal dysfunction, or hemorrhage.1
Periodic CBCs, including platelet counts, and stool occult blood tests recommended.1 If abnormal coagulation parameters or bleeding should occur, may use anti-factor Xa concentrations to monitor anticoagulant effects of dalteparin.1
Patients with Mechanical Prosthetic Heart Valves
Valve thrombosis resulting in death (including maternal and fetal deaths) and/or requiring surgical intervention reported during thromboprophylaxis with another LMWH (enoxaparin) in some patients (including pregnant women) with mechanical prosthetic heart valves.101 107 108 109 110 111 112 113 114 115 996 Women with mechanical prosthetic heart valves are at higher risk for thromboembolism during pregnancy,112 132 133 134 138 139 and the manufacturer states that dalteparin has not been studied systematically in patients with prosthetic heart valves.102 (See Prevention and Treatment of Thromboembolism during Pregnancy under Dosage and Administration.)
Benzyl Alcohol in Neonates and Infants
The multiple-dose vial of dalteparin sodium (Fragmin) contains 14 mg of benzyl alcohol per mL as a preservative; the prefilled syringes are preservative free.1 Benzyl alcohol has been associated with serious and fatal adverse effects in neonates and low-birth weight infants.1 (See Pediatric Use under Cautions.)
Benzyl alcohol used as a preservative in multiple-dose vials of dalteparin may cross the placenta.1 67 Use caution when administering dalteparin in multiple-dose vials containing benzyl alcohol to pregnant women; use preservative-free formulations when possible.1 67
Small amounts distributed into milk in humans.1 5 36 Consider developmental and health benefits of breast-feeding along with the mother's clinical need for dalteparin and any potential adverse effects on the breast-fed child from dalteparin or from the underlying maternal condition.1 ACCP recommends that LMWHs be continued in nursing women who are already receiving such therapy.1012
Safety and efficacy established in pediatric patients ≥1 month of age.1 (See Treatment of Symptomatic Venous Thromboembolism in Pediatric Patients under Uses.)
Long-term effects of treatment with dalteparin in pediatric patients (e.g., effects on growth, bone metabolism) unknown.1
Multiple-dose vials contain benzyl alcohol as a preservative.1 Administration of injections preserved with benzyl alcohol to neonates and low-birth weight infants has, in large amounts, been associated with toxicity and fatal “gasping syndrome”.1 67 68 69 70 71 72 Minimum amount of benzyl alcohol at which serious adverse effects may occur not known.1
Possible increased risk of bleeding in geriatric patients; however, no substantial differences in safety relative to younger adults reported.1 Pay careful attention to dosing intervals and concomitant agents (particularly antiplatelet agents), particularly in geriatric patients with low body weight (<45 kg) and those predisposed to decreased renal function.1
Use with caution in patients with severe renal impairment; greater drug accumulation can be expected in such patients.1
Common Adverse Effects
Interactions for Dalteparin
Increased risk of bleeding1
Use concomitantly with care1
Increased risk of bleeding1
Use concomitantly with care1
Increased risk of bleeding1
Use concomitantly with care1
Adults: Mean peak plasma concentrations of anti-factor Xa activity generally attained about 4 hours after a single sub-Q injection.1
3 to <8 weeks of age: 181 mL/kg.1
≥8 weeks to <2 years of age: 175 mL/kg.1
≥2 to <8 years of age: 160 mL/kg.1
≥8 to <12 years of age: 165 mL/kg.1
≥12 to <20 years of age: 171 mL/kg.1
Adults: 40–60 mL/kg (based on anti-factor Xa activity).1
3 to <8 weeks of age: 2.25 hours.1
≥8 weeks to <2 years of age: 3.02 hours.1
≥2 to <8 years of age: 4.27 hours.1
≥8 to <12 years of age: 5.11 hours.1
≥12 to <20 years of age: 6.28 hours.1
Adults: 3–5 hours following sub-Q administration.1
Terminal half-life prolonged (to approximately 5.7 hours) in patients with chronic renal insufficiency requiring hemodialysis compared with healthy individuals.1
Solution for Injection
For information on systemic interactions resulting from concomitant use, see Interactions.
Should not be mixed with other injections or infusions unless specific compatibility data support such admixtures.1
Advice to Patients
Importance of advising patients who have had neuraxial anesthesia or spinal puncture to monitor for manifestations of spinal or epidural hematoma (e.g., tingling or numbness in lower limbs, muscle weakness), particularly if they are receiving concomitant NSAIAs, platelet-aggregation inhibitors, or other anticoagulants; importance of immediately contacting a clinician if any of these manifestations occur.1
If therapy is to continue following hospital discharge, importance of instructing patient and/or caregiver regarding dalteparin administration procedures.1
Importance of informing patients that they may bruise and/or bleed more easily and that a longer than normal time may be required to stop bleeding when taking enoxaparin.1 Importance of reporting any unexplained bleeding, bruising, or signs of thrombocytopenia (rash of dark red spots under skin) to clinician.1
Advise patient to inform dentists and physicians about dalteparin therapy before scheduling surgery or taking new drugs.1
Importance of informing patients of the risks associated with benzyl alcohol-containing preparations in neonates, infants, and pregnant women.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., aspirin, other NSAIAs).1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Injection, for subcutaneous use only
2500 units/0.2 mL
Fragmin (available as single-dose prefilled syringes)
5000 units/0.2 mL
Fragmin (available as single-dose prefilled syringes)
7500 units/0.3 mL
Fragmin (available as single-dose prefilled syringes)
12,500 units/0.5 mL
Fragmin (available as single-dose prefilled syringes)
15,000 units/0.6 mL
Fragmin (available as single-dose prefilled syringes)
18,000 units/0.72 mL
Fragmin (available as single-dose prefilled syringes)
10,000 units/ mL
Fragmin (available as single-dose graduated syringes)
95,000 units/3.8 mL (25,000 units/mL)
Fragmin (available as multiple-dose vial)
AHFS DI Essentials™. © Copyright 2021, Selected Revisions March 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. Pfizer. Fragmin (dalteparin sodium injection) prescribing information. New York, NY; 2019 May.
2. Pharmacia & Upjohn, Inc. Product information form for American hospital formulary service: Fragmin (dalteparin sodium injection). Columbus, OH; undated.
3. Hirsh J, Levine MN. Low molecular weight heparin. Blood. 1992; 79:1-17. http://www.ncbi.nlm.nih.gov/pubmed/1309422?dopt=AbstractPlus
4. Noble S, Peters DH, Goa KL. Enoxaparin: a reappraisal of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disease. Drugs. 1995; 49:388-410. http://www.ncbi.nlm.nih.gov/pubmed/7774513?dopt=AbstractPlus
5. Simoneau G, Bergmann JF, Kher A et al. Pharmacokinetics of a low molecular weight heparin [Fragmin] in young and elderly subjects. Thromb Res. 1992; 66:603-7. http://www.ncbi.nlm.nih.gov/pubmed/1326135?dopt=AbstractPlus
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