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Dalteparin

Class: Heparins
- Low Molecular Weight Heparins
- LMWHs
Chemical Name: Heparin, sodium salt
CAS Number: 9041-08-1
Brands: Fragmin

Medically reviewed by Drugs.com on Feb 28, 2022. Written by ASHP.

Warning

    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.

  • Risk increased by use of indwelling epidural catheters or by concomitant use of drugs affecting hemostasis (e.g., NSAIAs, platelet-aggregation inhibitors, other anticoagulants).

  • Risk also increased by history of traumatic or repeated epidural or spinal puncture, spinal deformity, or spinal surgery.

  • Optimal timing between administration of dalteparin and neuraxial procedures not known.

  • Monitor frequently for signs and symptoms of neurologic impairment and treat urgently if neurologic compromise noted.

  • Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for thromboprophylaxis with anticoagulants. (See Spinal/Epidural Hematomas under Cautions.)

Introduction

Anticoagulant; an LMWH.

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]). 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).

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.

Thromboprophylaxis in Hip-Replacement, Knee-Replacement, or Hip-Fracture Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing hip-replacement surgery.

LMWHs also have been used for prophylaxis of DVT and/or PE in patients undergoing total knee-replacement and 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.

Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose heparin, warfarin, aspirin) are recommended by ACCP for pharmacologic prophylaxis during major orthopedic surgery. When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, safety, logistics, and compliance.

Thromboprophylaxis in General/Abdominal Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing general/abdominal surgery who are at risk for thromboembolic complications.

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. 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.

If pharmacologic prophylaxis is used in patients undergoing general and abdominal-pelvic surgery, ACCP states that an LMWH or low-dose heparin is preferred.

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.

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.

Medical Conditions Predisposing to Thromboembolism

Prevention of DVT, which may lead to PE, in patients with severely restricted mobility during acute illness.

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.

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. Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or until hospital discharge, whichever comes first.

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.

Risk of venous thromboembolism particularly high in patients with cancer. 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.

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.

Thromboprophylaxis in Thoracic Surgery

Pharmacologic thromboprophylaxis (e.g., LMWH) recommended by ACCP in patients undergoing thoracic surgery who are at high risk of venous thromboembolism, provided risk of bleeding is low.

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. 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.

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.

Thromboprophylaxis in Trauma

LMWHs may be used for thromboprophylaxis in patients with major trauma. 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.

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. Manufacturer states that safety and efficacy of treatment durations >6 months not established.

Acute Venous Thromboembolism

Manufacturer states that dalteparin not indicated for the acute treatment of venous thromboembolism; however, has been recommended by ACCP as an appropriate option for initial treatment of acute proximal DVT and/or PE.

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment. 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.

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.

Continue anticoagulant therapy for ≥3 months and possibly longer depending on individual clinical situation.

Treatment of Symptomatic Venous Thromboembolism in Pediatric Patients

Used for the treatment of symptomatic venous thromboembolism to reduce the recurrence in pediatric patients ≥1 month of age.

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).

ACCP recommends an LMWH or heparin for both initial and ongoing treatment of venous thromboembolism in children. 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.

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. If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.

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.

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.

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.

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.

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.

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. If arterial ischemic stroke is associated with dissection or a cardioembolic origin, continued anticoagulant therapy suggested.

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy, ACCP recommends ongoing antithrombotic therapy (e.g., with an LMWH) for 3 months.

LMWHs may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source.

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. (See Prevention and Treatment of Thromboembolism During Pregnancy under Dosage and Administration.)

Also has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibody (APLA) syndrome.

LMWHs (rather than heparin or warfarin) are recommended by ACCP for prevention and treatment of thromboembolism during pregnancy.

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. To prevent recurrence, postpartum anticoagulation (for ≥6 weeks and for a total duration of ≥3 months) is suggested.

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).

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.

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.

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.

Cardioversion of Atrial Fibrillation/Flutter

LMWHs have been used for prevention of stroke and systemic embolism in patients with atrial fibrillation or atrial/flutter undergoing electrical or pharmacologic cardioversion.

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.

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.

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.

After successful cardioversion to sinus rhythm, all patients should receive therapeutic anticoagulation for ≥4 weeks.

Thromboprophylaxis in Patients with Prosthetic Heart Valves

Used during conversion to maintenance therapy with warfarin to reduce the incidence of thromboembolism in patients with prosthetic mechanical 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.

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).

Has been used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves. (See Thromboembolism During Pregnancy under Uses.)

Treatment of Cerebral Venous Sinus Thrombosis

May be used for the treatment of acute cerebral venous sinus (sinovenous) thrombosis in adults. Once patient stabilized, may convert to coumarin anticoagulant therapy.

Reasonable to use full-dose LMWH rather than heparin for treatment of acute cerebral venous sinus thrombosis during pregnancy. Prophylaxis with an LMWH during pregnancy and the postpartum period is reasonable in women with history of cerebral venous sinus thrombosis.

Recommended by ACCP as an option for initial and follow-up anticoagulation in children with cerebral venous sinus thrombosis without substantial intracranial hemorrhage. Also has been suggested for use in children with substantial intracranial hemorrhage.

LMWHs also suggested by ACCP as a treatment option for neonates with cerebral sinovenous thrombosis.

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.

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.

Dalteparin Dosage and Administration

General

  • Since routine coagulation parameters such as PT or aPTT are insensitive for monitoring dalteparin activity, routine monitoring of coagulation parameters generally is not required.

  • 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.

  • 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. 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. 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.

  • Whenever possible, use preparations of dalteparin that do not contain benzyl alcohol (prefilled syringes) in pediatric patients. (See Benzyl Alcohol in Neonates and Infants and see Pediatric Use, under Cautions.)

Administration

Sub-Q Administration

Administer by deep sub-Q injection; do not give IM.

Patient should be sitting or supine during administration.

When injecting, insert entire length of needle at 45–90° angle. Administer injections into the U-shaped area around the navel, upper outer aspect of the thigh, or upper outer quadrangle of the buttock. Alternate injection sites daily. When injecting into area around the navel or the thigh, insert needle into a skin fold created by thumb and forefinger. Hold skin until needle is withdrawn.

Injection is commercially available in prefilled syringes equipped with a 27-gauge ½-inch needle.

Dosage

Dosages for dalteparin sodium and other LMWHs or heparin cannot be used interchangeably on a unit-for-unit (or mg-for-mg) basis.

Available as dalteparin sodium; dosage expressed in anti-factor Xa international units (IU, units). Each mg of dalteparin sodium is equivalent to 156.25 units.

Pediatric Patients

Treatment of Symptomatic Venous Thromboembolism in Pediatric Patients
Sub-Q

Initial dosage based on age and body weight. (See Table 1.)

Table 1. Initial Dosages for Pediatric Patients with Symptomatic Venous Thromboembolism

Age Group

Initial Dosage

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. Obtain blood samples for measurement of anti-factor Xa concentration 4 hours after administration of dalteparin. Adjust dosage by increments of 25 units/kg to achieve a target anti-factor Xa concentration between 0.5–1 unit/mL. Maintenance dosage is the dosage that achieves the target anti-factor Xa concentration in blood collected 4 hours after administration of dalteparin. Monitor anti-factor Xa concentrations periodically in pediatric patients to maintain an anti-factor Xa concentration between 0.5–1 unit/mL.

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. If platelet counts decrease to ≤50,000/mm3, discontinue dalteparin until recovery of platelet count to >50,000/mm3.

Adults

Unstable Angina and NSTEMI
Sub-Q

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. Concurrent aspirin therapy recommended in all patients unless contraindicated.

Prevention of DVT and/or PE
Hip-Replacement Surgery
Sub-Q

Initiate therapy either preoperatively or postoperatively; several regimens are recommended by manufacturer.

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.

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.

Postoperative start: 2500 units 4–8 hours after surgery, or later if hemostasis has not been achieved.

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). ACCP recommends a minimum of 10–14 days of thromboprophylaxis, with extended prophylaxis suggested for up to 35 days on an outpatient basis.

General/Abdominal Surgery
Sub-Q

Usual dosage: 2500 units initially, given 1–2 hours before surgery. Continue with 2500 units once daily throughout postoperative period, generally for 5–10 days.

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. 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.

Extended prophylaxis (for up to 4 weeks) recommended by ACCP in patients undergoing abdominal or pelvic surgery for cancer.

Medical Conditions Predisposing to Thromboembolism
Sub-Q

Acute illness with severely restricted mobility: 5000 units once daily, generally for 12–14 days.

Extended Treatment of Venous Thromboembolism in Cancer Patients
Sub-Q

First 30 days of treatment: 200 units/kg (not to exceed total daily dosage of 18,000 units) once daily.

Months 2–6 of treatment: Approximately 150 units/kg (not to exceed total daily dosage of 18,000 units) once daily.

Safety and efficacy of treatment periods >6 months not established.

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. Discontinue therapy if platelet count ≤50,000/mm3 until platelet count recovers to >50,000/mm3.

Prevention and Treatment of Thromboembolism During Pregnancy†
Sub-Q

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).

Postpartum prophylaxis in patients with a prior venous thromboembolic event: Prophylactic (5000 units once daily) or intermediate (5000 units every 12 hours) dosage suggested.

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.

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.

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).

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. Dosage adjustment suggested to maintain manufacturer-recommended peak anti-factor Xa concentration 4 hours after dosing. Resume usual long-term anticoagulation postpartum. (See Patients with Mechanical Prosthetic Heart Valves under Cautions.)

ACCP and other clinicians suggest administering LMWHs twice daily in pregnant women, at least initially, because of altered pharmacokinetics of these drugs in such women.

To avoid an unwanted anticoagulant effect on the fetus during delivery, discontinue LMWH ≥24 hours prior to induction of labor or cesarean section.

Cardioversion of Atrial Fibrillation/Flutter†
Sub-Q

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.

Perioperative Antithrombotic Prophylaxis†
Sub-Q

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).

Prescribing Limits

Adults

Unstable Angina or NSTEMI
Sub-Q

Maximum 10,000 units every 12 hours.

Patients with Cancer
Sub-Q

Maximum total daily dose of 18,000 units.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time; use with caution.

Renal Impairment

Use with caution in patients with severe renal insufficiency; monitor anti-factor Xa concentrations to determine appropriate dosage in such patients. ACCP suggests that dosage be reduced in patients with severe renal impairment (Clcr <30 mL/minute).

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. 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.

Geriatric Patients

Careful attention to dosing intervals and concomitant medications (particularly antiplatelet drugs) is advised, particularly in geriatric patients with low body weight (<45 kg).

Cautions for Dalteparin

Contraindications

  • Active major bleeding.

  • History of HIT with or without thrombosis.

  • Known hypersensitivity to dalteparin, heparin, or pork products.

  • Use for unstable angina or NSTEMI or for prolonged prophylaxis of venous thromboembolism in patients undergoing neuraxial (epidural/spinal) anesthesia.

Warnings/Precautions

Spinal/Epidural Hematomas

Epidural or spinal hematoma reported with concurrent use of anticoagulants (e.g., LMWHs, heparinoids) and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures. Such hematomas have resulted in neurologic injury, including long-term or permanent paralysis. (See Boxed Warning.)

Prior to performing a spinal or epidural procedure, determine whether a patient is receiving anticoagulants.

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.

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.

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. Consider doubling these recommended time delays in patients with renal impairment.

Consider delaying subsequent doses of dalteparin for at least 4 hours after catheter removal based on patient's risk of bleeding versus thrombosis.

Frequently monitor for signs of neurologic impairment (e.g., midline back pain, numbness or weakness in lower limbs, bowel or bladder dysfunction). If spinal hematoma suspected, diagnose and treat immediately; consider spinal cord decompression even though it may not prevent or reverse neurologic sequelae.

Other Warnings Related to Hemorrhage

As with other anticoagulants, bleeding may occur at any site during therapy. The risk of bleeding with dalteparin therapy varies with the indication and may increase with higher dosages.

Use with extreme caution in patients with an increased risk of hemorrhage. 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. 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.

Periodic CBCs, including platelet counts, and stool occult blood tests recommended. If abnormal coagulation parameters or bleeding should occur, may use anti-factor Xa concentrations to monitor anticoagulant effects of dalteparin.

Thrombocytopenia

HIT can occur. Thrombocytopenia with thrombosis, amputation, and death reported. Closely monitor thrombocytopenia of any degree.

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. Women with mechanical prosthetic heart valves are at higher risk for thromboembolism during pregnancy, and the manufacturer states that dalteparin has not been studied systematically in patients with prosthetic heart valves. (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. Benzyl alcohol has been associated with serious and fatal adverse effects in neonates and low-birth weight infants. (See Pediatric Use under Cautions.)

Specific Populations

Pregnancy

Data from published literature and postmarketing reports have not reported a clear association between dalteparin and adverse developmental effects. Use during pregnancy only if clearly needed.

Benzyl alcohol used as a preservative in multiple-dose vials of dalteparin may cross the placenta. Use caution when administering dalteparin in multiple-dose vials containing benzyl alcohol to pregnant women; use preservative-free formulations when possible.

Lactation

Small amounts distributed into milk in humans. 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. ACCP recommends that LMWHs be continued in nursing women who are already receiving such therapy.

Pediatric Use

Safety and efficacy established in pediatric patients ≥1 month of age. (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.

Multiple-dose vials contain benzyl alcohol as a preservative. 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”. Minimum amount of benzyl alcohol at which serious adverse effects may occur not known.

Geriatric Use

Possible increased risk of bleeding in geriatric patients; however, no substantial differences in safety relative to younger adults reported. 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.

Renal Impairment

Use with caution in patients with severe renal impairment; greater drug accumulation can be expected in such patients.

Common Adverse Effects

Pediatric patients: Injection-site bruising, contusion, epistaxis.

Adults: Bleeding (including hemorrhage), thrombocytopenia (type 1), hematoma at the injection site, pain at the injection site, transient elevation of transaminases.

Interactions for Dalteparin

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral

Increased risk of bleeding

Use concomitantly with care

Platelet-aggregation inhibitors

Increased risk of bleeding

Use concomitantly with care

Thrombolytic agents

Increased risk of bleeding

Use concomitantly with care

Dalteparin Pharmacokinetics

Absorption

Bioavailability

Adults: Approximately 87% (absolute bioavailability). Greater bioavailability than heparin (based on anti-factor Xa activity).

Onset

Adults: Mean peak plasma concentrations of anti-factor Xa activity generally attained about 4 hours after a single sub-Q injection.

Distribution

Extent

3 to <8 weeks of age: 181 mL/kg.

≥8 weeks to <2 years of age: 175 mL/kg.

≥2 to <8 years of age: 160 mL/kg.

≥8 to <12 years of age: 165 mL/kg.

≥12 to <20 years of age: 171 mL/kg.

Adults: 40–60 mL/kg (based on anti-factor Xa activity).

Small amounts distributed into milk.

Elimination

Half-life

3 to <8 weeks of age: 2.25 hours.

≥8 weeks to <2 years of age: 3.02 hours.

≥2 to <8 years of age: 4.27 hours.

≥8 to <12 years of age: 5.11 hours.

≥12 to <20 years of age: 6.28 hours.

Adults: 3–5 hours following sub-Q administration.

Special Populations

Terminal half-life prolonged (to approximately 5.7 hours) in patients with chronic renal insufficiency requiring hemodialysis compared with healthy individuals.

Similar pharmacokinetics in geriatric and younger patients. In pediatric patients, mean elimination half-life increased with increasing age.

Stability

Storage

Parenteral

Solution for Injection

20–25°C.

Compatibility

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.

Actions

  • Has less effect than heparin on thrombin at a given level of anti-factor Xa activity.

  • At recommended dosages, does not substantially affect platelet aggregation, fibrinolysis, global clotting function tests (i.e., PT, thrombin time, aPTT), or lipoprotein lipase.

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.

  • If therapy is to continue following hospital discharge, importance of instructing patient and/or caregiver regarding dalteparin administration procedures.

  • 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. Importance of reporting any unexplained bleeding, bruising, or signs of thrombocytopenia (rash of dark red spots under skin) to clinician.

  • Advise patient to inform dentists and physicians about dalteparin therapy before scheduling surgery or taking new drugs.

  • Importance of informing patients of the risks associated with benzyl alcohol-containing preparations in neonates, infants, and pregnant women.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., aspirin, other NSAIAs).

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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.

Dalteparin Sodium (Porcine)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use only

2500 units/0.2 mL

Fragmin (available as single-dose prefilled syringes)

Pfizer

5000 units/0.2 mL

Fragmin (available as single-dose prefilled syringes)

Pfizer

7500 units/0.3 mL

Fragmin (available as single-dose prefilled syringes)

Pfizer

12,500 units/0.5 mL

Fragmin (available as single-dose prefilled syringes)

Pfizer

15,000 units/0.6 mL

Fragmin (available as single-dose prefilled syringes)

Pfizer

18,000 units/0.72 mL

Fragmin (available as single-dose prefilled syringes)

Pfizer

10,000 units/ mL

Fragmin (available as single-dose graduated syringes)

Pfizer

95,000 units/3.8 mL (25,000 units/mL)

Fragmin (available as multiple-dose vial)

Pfizer

AHFS DI Essentials™. © Copyright 2022, Selected Revisions March 9, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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