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Dalteparin: Drug information

Dalteparin: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Dalteparin: Patient drug information" and "Dalteparin: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Spinal/Epidural hematoma:

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWHs) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include use of indwelling epidural catheters; concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants; a history of traumatic or repeated epidural or spinal punctures; or a history of spinal deformity or spinal injury. Optimal timing between the administration of dalteparin and neuraxial procedures is not known.

Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

Brand Names: US
  • Fragmin
Brand Names: Canada
  • Fragmin
Pharmacologic Category
  • Anticoagulant;
  • Anticoagulant, Low Molecular Weight Heparin
Dosing: Adult

The adult dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editor: Edith A Nutescu, PharmD, MS, FCCP.

Hemodialysis, intermittent, anticoagulation of circuit

Hemodialysis, intermittent, anticoagulation of circuit (off-label use):

Note: Consider for use in patients with end-stage kidney disease receiving regular intermittent hemodialysis sessions ≤4 hours in length with no increased bleeding risks. Standard dosing has not been established. Recommendations provided below are examples. Refer to institutional protocols. May need to individualize dose based on patient-specific needs (eg, bleeding or thrombotic complications with previous hemodialysis sessions).

Injection into arterial line of hemodialysis circuit or IV bolus: 2,500 to 5,000 units as a single dose at the beginning of hemodialysis; may adjust dose during subsequent dialysis sessions in increments of 500 to 1,000 anti-factor Xa units based on the outcome of the previous dialysis session (Ref).

Non-ST elevation acute coronary syndrome

Non-ST elevation acute coronary syndrome:

Note: For medical management when an invasive approach is not planned.

SUBQ: 120 units/kg every 12 hours in combination with an appropriate antiplatelet regimen; maximum dose: 10,000 units every 12 hours. Continue until patient is clinically stable; usual duration of therapy is 5 to 8 days.

Periprocedural bridging anticoagulation

Periprocedural bridging anticoagulation:

Periprocedural bridging anticoagulation for patients at high risk of thromboembolism, with atrial fibrillation, venous thromboembolism, or other high-risk conditions (off-label use):

Note: Bridging anticoagulation is only considered in patients who are at high risk of thromboembolism (eg, atrial fibrillation with a high stroke risk score or recent stroke or transient ischemic attack, venous thromboembolism within 3 months, history of thromboembolism during interruption in therapy) and who use warfarin for maintenance anticoagulation. Risk of bleeding is increased when bridging; balance risk versus benefit when making treatment decisions (Ref).

SUBQ: 100 units/kg every 12 hours; a reduced dose of 5,000 units every 12 hours may be considered when bleeding is a concern; start dalteparin ~3 days prior to the procedure when INR is subtherapeutic; the last dose of dalteparin is administered ~24 hours before the planned procedure. Dalteparin may be resumed ≥24 hours after procedures with low bleeding risk and ≥48 to 72 hours after procedures with high bleeding risk. Continue dalteparin until warfarin has been resumed and INR is therapeutic (Ref).

Mechanical heart valve, bridging anticoagulation (off-label use):

Note: Bridging during intervals of subtherapeutic anticoagulation should be considered for patients with mechanical mitral, tricuspid, or pulmonary valve replacement; however, for patients with mechanical aortic valve replacement, bridging is not required unless an additional thromboembolic risk factor is present or patient has an older generation mechanical aortic valve (Ref).

SUBQ: 100 units/kg/dose every 12 hours; dose may be adjusted perioperatively based on anti-factor Xa monitoring (eg, for surgeries/procedures with high bleeding risk) (Ref). For additional information regarding anti-factor Xa monitoring, refer to "Reference Range." If patient is to undergo an invasive procedure, the last dose should be given ~24 hours prior to the procedure; reinitiate therapy ≥24 hours after the procedure when bleeding risk is acceptable (Ref).

Superficial vein thrombosis, acute symptomatic

Superficial vein thrombosis, acute symptomatic (alternative agent) (off-label use):

Note: Consider as an alternative to fondaparinux or rivaroxaban for use in patients at increased risk for thromboembolism or with recurrent superficial vein thrombosis.

SUBQ: 5,000 units every 12 hours for 45 days (Ref).

Venous thromboembolism prophylaxis

Venous thromboembolism prophylaxis:

Medical patients with acute illness at moderate and high risk for venous thromboembolism: SUBQ: 5,000 units once daily; continue for length of hospital stay or until patient is fully ambulatory and risk of venous thromboembolism (VTE) has diminished (Ref). Extended prophylaxis beyond acute hospital stay is not routinely recommended (Ref). However, in high-risk coronavirus disease 2019 (COVID-19) patients who are discharged from the hospital, some experts would consider extended prophylaxis with a direct oral anticoagulant (eg, rivaroxaban) (Ref).

Nonorthopedic surgery (off-label use):

Patients with active cancer:

SUBQ: 5,000 units started 10 to 12 hours before surgery and 5,000 units once daily thereafter (Ref).

or

SUBQ: 2,500 units started 2 to 4 hours before surgery and 5,000 units once daily thereafter (Ref).

or

SUBQ: 5,000 units once daily started ~12 to 24 hours after surgery (Ref).

Duration: The optimal duration of prophylaxis has not been established. It is usually given for a minimum of 7 to 10 days. Extending for up to 4 weeks may be reasonable in those undergoing major abdominal or pelvic surgery (Ref).

Patients without active cancer:

Note: For patients with moderate and high risk of VTE and low risk of bleeding:

SUBQ: 5,000 units ~12 hours before surgery (or the evening prior to surgery), followed by 5,000 units once daily. Alternatively, may postpone pharmacologic prophylaxis until after surgery (eg, high bleeding risk) when it is safe to initiate. Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 to 14 days (Ref).

Pregnancy (off-label use): Note: For patients at moderate and high VTE risk during antepartum and postpartum periods. Dose intensity is individualized based on risks of thrombosis and bleeding complications.

Low dose: SUBQ: 5,000 units once daily for patients <100 kg (Ref) or 7,500 units once daily for patients ≥100 kg (Ref).

Intermediate dose: SUBQ: 5,000 units every 12 hours (Ref); however, some experts use an alternative intermediate regimen of 5,000 units once daily, then increasing the dose as pregnancy progresses to 100 units/kg once daily (Ref).

Adjusted dose (therapeutic): Note: Reserved for patients at the highest VTE risk (eg, history of recurrent thrombosis or severe thrombophilia) (Ref).

SUBQ: 100 units/kg every 12 hours or 200 units/kg once daily (Ref).

Management around labor and delivery:

Prior to delivery: Anticoagulation management is individualized. Options include replacing with unfractionated heparin at ~36 weeks' gestation or continuing until ~39 weeks' gestation in patients at very low risk of delivery. Discontinue dalteparin ≥12 hours before delivery (for low dose) or ≥24 hours before delivery (for intermediate or adjusted therapeutic doses), particularly if neuraxial anesthesia is planned (Ref).

Postpartum: In patients at high risk of VTE who require an adjusted therapeutic dose, may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred. In patients not at high risk of VTE, restart low or intermediate dose 6 to 12 hours after vaginal delivery and 12 to 24 hours after cesarean delivery (Ref). Anticoagulation should continue for up to 6 weeks postpartum, but potentially longer (Ref).

Total hip arthroplasty:

SUBQ: 5,000 units once daily, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved (Ref);

or

SUBQ: 2,500 units 2 hours before surgery, followed by 2,500 units again 4 to 8 hours after surgery if hemostasis is achieved, then a maintenance dose of 5,000 units once daily (Ref).

or

SUBQ: 2,500 units 4 to 8 hours after surgery if hemostasis is achieved then a maintenance dose of 5,000 units once daily (Ref).

Duration: Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days (Ref); some experts suggest a duration of 35 days in most patients (Ref).

Total knee arthroplasty (off-label use) :

SUBQ: 5,000 units once daily, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved. Optimal duration of prophylaxis is unknown, but it is usually given for a minimum of 10 to 14 days and can be extended for up to 35 days in patients who are not fully ambulatory (Ref).

Venous thromboembolism treatment

Venous thromboembolism treatment:

Note: For timing of initiating oral anticoagulant, see Transitioning between anticoagulants.

Deep vein thrombosis and/or pulmonary embolism (off-label use): SUBQ: 200 units/kg once daily or 100 units/kg every 12 hours (Ref).

Duration of therapeutic anticoagulation (first episode, general recommendations): Optimal duration of therapy is unknown and depends on many factors, such as whether provoking events were present, patient risk factors for recurrence and bleeding, and individual preference.

Provoked venous thromboembolism: 3 months (provided the provoking risk factor is no longer present) (Ref).

Unprovoked venous thromboembolism or provoked venous thromboembolism with a persistent risk factor: ≥3 months depending on risk of VTE recurrence and bleeding (Ref).

Note: All patients receiving indefinite therapeutic anticoagulation with no specified stop date should be reassessed at periodic intervals.

Venous thromboembolism treatment in patients with active cancer:

Initial (month 1): SUBQ: 200 units/kg once daily for 30 days.

Maintenance (months 2 to 6): SUBQ: 150 units/kg once daily. Alternatively, transition to a direct oral anticoagulant (DOAC) or warfarin to complete therapy (Ref). Consider continuing anticoagulation beyond 6 months due to persistent high risk of recurrence in patients with active cancer; consider risk vs benefit of bleeding and VTE recurrence (Ref).

Dosage adjustment for thrombocytopenia: If platelet count is between 50,000 to 100,000/mm3, reduce daily dose by 2,500 units until platelet count recovers to ≥100,000/mm3. If platelet count <50,000/mm3, discontinue dalteparin until platelet count recovers to >50,000/mm3.

Venous thromboembolism treatment in pregnancy (off-label use): SUBQ: 200 units/kg/dose once daily or 100 units/kg/dose every 12 hours; consider anti-factor Xa monitoring for dose adjustment (Ref). For additional information regarding anti-factor Xa monitoring, refer to the Reference Range field.

Management around labor and delivery:

Prior to delivery: Anticoagulation management is individualized. Options include replacing with unfractionated heparin at ~36 weeks' gestation or continuing until ~39 weeks' gestation in patients at very low risk of delivery. Discontinue dalteparin ≥24 hours before delivery, particularly if neuraxial anesthesia is planned (Ref).

Postpartum: May restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred. Optimal duration of anticoagulation is unknown. In general, total duration of anticoagulation (antepartum plus postpartum) should be at least 3 to 6 months with at least 6 weeks postpartum (Ref).

Transitioning between anticoagulants: Note: This provides general guidance on transitioning between anticoagulants; also refer to local protocol for additional detail:

Transitioning from another anticoagulant to dalteparin:

Transitioning from therapeutic IV unfractionated heparin infusion to therapeutic-dose dalteparin: Discontinue unfractionated heparin and begin dalteparin within 1 hour. Note: If aPTT is not in therapeutic range at the time unfractionated heparin is discontinued, consult local protocol (Ref).

Transitioning from dalteparin to another anticoagulant:

Transitioning from therapeutic-dose dalteparin to therapeutic IV unfractionated heparin infusion: Start IV unfractionated heparin (rate based on indication) 1 to 2 hours before the next dose of dalteparin would have been due. Note: Omit IV unfractionated heparin loading dose (Ref).

Transitioning from prophylactic dalteparin to therapeutic IV unfractionated heparin: Unfractionated heparin should be started without delay. A unfractionated heparin bolus/loading dose may be used if indicated (Ref).

Transitioning from therapeutic-dose dalteparin to warfarin: Start warfarin and continue dalteparin until INR is within therapeutic range (Ref). Note: For treatment of VTE, overlap dalteparin with warfarin until INR is ≥2 for at least 2 measurements taken ~24 hours apart (duration of overlap is at least 5 days) (Ref).

Transitioning from therapeutic-dose dalteparin to a DOAC: Start DOAC within 2 hours prior to the next scheduled dose of dalteparin.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

SUBQ:

Altered kidney function:

Non-ST elevation acute coronary syndromes:

CrCl ≥30 mL/minute: No dosage adjustment necessary (Ref).

CrCl <30 mL/minute: Use not recommended; patients with serum creatinine >2 mg/dL were excluded from acute coronary syndrome trials. Consider use of an alternative agent (eg, unfractionated heparin) (Ref).

Venous thromboembolism prophylaxis:

CrCl ≥30 mL/minute: No dosage adjustment necessary (Ref).

CrCl <30 mL/minute: No dosage adjustment necessary (Ref). Limited safety data for long-term use; for therapy durations longer than ~10 days, consider monitoring anti-factor Xa levels or use of an alternative agent (Ref).

Venous thromboembolism treatment:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Use not recommended, as therapeutic doses of dalteparin have been shown to accumulate in patients with CrCl <30 mL/minute (Ref). Some expert guidelines recommend switching to an alternative anticoagulant that provides specific renal dose adjustment or that is less dependent on renal clearance (Ref); if necessary, start with full dose and make dose adjustments according to anti-factor Xa levels (Ref). No specific dose reduction suggested because of wide inter-individual variation and small numbers of patients studied (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (Ref):

Prophylactic dose: No dosage adjustment necessary; however, limit to short-term use (eg, ≤7 days); may need to consider conversion to an alternative agent if extended prophylaxis is necessary (Ref).

Therapeutic dose: Avoid use; significantly accumulates in patients on dialysis (Ref).

Anticoagulant for hemodialysis and hemofiltration (IV use): Refer to adult dosing.

Peritoneal dialysis: Unlikely to be significantly dialyzable (Ref):

Prophylactic dose: No dosage adjustment necessary; however, limit to short-term use (eg, ≤7 days); may need to consider conversion to an alternative agent if extended prophylaxis is necessary (Ref). In one pharmacokinetic study, patients on peritoneal dialysis tolerated prophylactic doses with limited accumulation at day 4 (Ref).

Therapeutic dose: Avoid use (Ref).

CRRT or PIRRT (eg, sustained, low-efficiency diafiltration):

Prophylactic dose: No dosage adjustment necessary (Ref); however, limit to short-term use (eg, ≤7 days); may need to consider conversion to an alternative agent if extended prophylaxis is necessary (Ref).

Therapeutic dose: Avoid use (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Use with caution in patients with hepatic impairment as these patients may have potentially higher risk of bleeding.

Dosing: Obesity: Adult

The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Acute coronary syndromes: Note: There are limited data for dalteparin dosing in patients with obesity.

Class 1, 2, or 3 obesity (BMI ≥ 30 kg/m2):

Non-ST elevation acute coronary syndromes: SUBQ: 120 units/kg (maximum dose: 10,000 units) every 12 hours using actual body weight for dosing calculation; also refer to adult dosing (Ref).

Venous thromboembolism treatment: Note: There are limited data for dalteparin dosing in patients with obesity. The maximum weight reported in studies evaluating venous thromboembolism was 190 kg (Ref).

Class 1, 2, or 3 obesity (BMI ≥ 30 kg/m2): SUBQ: Use actual body weight for dosing calculation (maximum weight: 190 kg) (Ref). Anti-Factor Xa monitoring is recommended in select patients (high risk of bleeding and/or ≥150 kg) (Ref). Refer to indication-specific dosing.

Venous thromboembolism prophylaxis: Note: Potentially reduced absorption following SUBQ dosing in patients with obesity can result in variable exposure. Due to the uncertainty of weight-based dosing metrics, dose adjustment using anti-Factor Xa monitoring is recommended, where available (Ref).

Class 1 or 2 obesity (BMI 30 to 39 kg/m2): SUBQ: 5,000 units once daily (Ref).

Class 3 obesity (BMI ≥ 40 kg/m2): SUBQ: 7,500 units once daily (Ref). Note: Higher doses may be necessary in patients who weigh >180 kg, based on limited data (Ref). Anti-Factor Xa monitoring is recommended in patients >180 kg (Ref).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Dalteparin: Pediatric drug information")

Note: Each 2,500 units of anti-Xa activity is equal to 16 mg of dalteparin (World Health Organization First International Low Molecular Weight Heparin Reference Standard). In a pediatric thrombosis treatment trial, doses for patients ≥4.4 kg were rounded to the nearest 100 unit and in obese patients, doses were based on lean body weight (Ref); reported experience may not be appropriate for all patients (small infants, etc). For infants, avoid dosage forms that contain benzyl alcohol.

Symptomatic venous thromboembolism, treatment

Symptomatic venous thromboembolism, treatment:

Initial:

Infants to Children <2 years: SubQ: 150 units/kg/dose every 12 hours.

Children 2 years to <8 years: SubQ: 125 units/kg/dose every 12 hours.

Children ≥8 years and Adolescents: SubQ: 100 units/kg/dose every 12 hours (Ref); a maximum dose has not been defined; based on experience in adult patients, maximum dose: 18,000 units/dose could be considered.

Dosing adjustment: Titrate dose in increments of 25 unit/kg to achieve a 4 to 6 hour post-dose target anti-Xa level: 0.5 to 1 units/mL; evaluate anti-Xa levels after the third dose (Ref); however, levels after the first and second doses (4 to 6 hours postdose) have also been used (Ref); in one trial, dose adjustments were made in 10% to 20% increments (Ref); reported median time to achieve target anti-Xa levels was 2.6 days (range: 1 to 7 days).

Data suggest that therapeutic dosing requirements per kg (units/kg/dose) are higher in infants than older pediatric patients; in one trial, the reported median effective dose in patients <2 years of age was 208 units/kg/dose; another trial reported an infant median effective dose of 180 units/kg/dose (range: 146 to 181 units/kg/dose) (Ref).

Duration of therapy: The exact duration of therapy for optimal anticoagulation has not been determined; sufficient pediatric data is lacking; experts suggest for provoked deep vein thrombosis (DVT) or pulmonary embolism (PE) a duration of therapy ≤3 months although, if the causative risk factor persists, a longer duration of therapy may be necessary; for unprovoked DVT/PE, a duration of anticoagulation for 6 to 12 months (Ref).

Venous thromboembolism prophylaxis

Venous thromboembolism prophylaxis: Limited data available:

Infants, Children, and Adolescents <16 years:

<50 kg: SubQ: Initial: 100 units/kg/dose every 24 hours; titrated to achieve anti-Xa levels: 0.2 to 0.4 units/mL (drawn 4 to 6 hours after the third dose); maximum dose: 5,000 units/dose.

≥50 kg: SubQ: 5,000 units every 24 hours; dose was not titrated to achieve a goal anti-Xa level.

Adolescents ≥16 years: SubQ: 5,000 units every 24 hours; dose was not titrated to achieve a goal anti-Xa level.

Note: Dosing was reported in a retrospective study of 116 pediatric patients (Warad 2015); a small trial of 10 pediatric patients reported after titration a mean dose of 92 ± 52 units/kg/dose every 24 hours achieved anti-Xa levels of 0.2 to 0.4 units/mL (drawn 4 hours after a dose) (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity:

Thrombocytopenia: Infants, Children, and Adolescents:

Platelet count: 50,000 to 100,000/mm3: Reduce daily dose by 50% until platelet count recovers to ≥100,000/mm3.

Platelet count ≤50,000/mm3: Hold dalteparin therapy until platelet count recovers to above 50,000/mm3.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling. Monitor anti-Xa levels, dosing adjustment may be required; in reported experience of dalteparin in pediatric patients with renal dysfunction (reported as CrCl <30 mL/minute [Cockcroft-Gault equation]), reduced doses (43 units/kg/day and 50 units/kg/day; starting dose not reported) were used in 2 patients with observed therapeutic efficacy and without bleeding complications; another patient required a 41% dose reduction after developing renal dysfunction during treatment (Ref).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; adult data suggest accumulation may occur with repeated dosing, increasing the risk for bleeding; use with caution in patients with severe hepatic impairment.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Hematologic & oncologic: Thrombocytopenia (infants, children, and adolescents: 21% to 37%; adults: 11% to 14%; grades 3/4: ≤7%), hemorrhage (3% to 14%), bruise (infants, children, and adolescents: 12%)

Local: Bruising at injection site (infants, children, and adolescents: 30%)

1% to 10%:

Hematologic & oncologic: Major hemorrhage (1% to 4%), wound hematoma (≤3%)

Hepatic: Increased serum alanine aminotransferase (4% to 10%), increased serum aspartate aminotransferase (5% to 9%)

Local: Pain at injection site (5% to 12%), hematoma at injection site (≤6%)

Respiratory: Epistaxis (infants, children, and adolescents: 10%)

Miscellaneous: Re-operation due to bleeding (≤1%)

<1%: Gastrointestinal hemorrhage, hemoptysis, skin necrosis

Frequency not defined:

Cardiovascular: Spinal hematoma

Central nervous system: Epidural intracranial hemorrhage

Postmarketing: Alopecia, hypersensitivity reaction, nonimmune anaphylaxis, osteoporosis, postoperative wound bleeding

Contraindications

Hypersensitivity to dalteparin (eg, pruritus, rash, anaphylactic reactions), heparin, pork products, or any component of the formulation; history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis; active major bleeding; patients with unstable angina, non-Q-wave MI, or prolonged venous thromboembolism prophylaxis undergoing epidural/neuraxial anesthesia.

Note: Use of dalteparin in patients with current HIT or HIT with thrombosis is not recommended and considered contraindicated due to high cross-reactivity to heparin-platelet factor-4 antibody (ACCP [Guyatt 2012]; Warkentin 1999).

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to LMWHs; history of confirmed or suspected HIT and/or patients in whom an in vitro platelet-aggregation test in the presence of dalteparin is positive; septic endocarditis (endocarditis lenta, acute or subacute endocarditis); major blood clotting disorders; acute gastroduodenal ulcer; cerebral hemorrhage; severe uncontrolled hypertension; diabetic or hemorrhagic retinopathy; other conditions or diseases that increase risk of hemorrhage; injuries to and operations on the CNS, eyes, and ears

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: Bleeding may occur at any site during therapy. Monitor patient closely for signs or symptoms of bleeding. Use with extreme caution in patients at increased risk of bleeding; risk factors include bacterial endocarditis; congenital or acquired bleeding disorders; active ulcerative or angiodysplastic GI diseases; severe uncontrolled hypertension; hemorrhagic stroke; or use shortly after brain, spinal, or ophthalmology surgery; in patients treated concomitantly with other drugs known to cause bleeding (eg, platelet inhibitors, selective serotonin reuptake inhibitors); recent GI bleeding or ulceration; thrombocytopenia or platelet defects; hypertensive or diabetic retinopathy; or in patients undergoing invasive procedures. Discontinue if bleeding occurs; use is contraindicated with active major bleeding. Protamine may be considered as a partial reversal agent in overdose situations (consult Protamine monograph for dosing recommendations).

• Hyperkalemia: Monitor for hyperkalemia; can cause hyperkalemia possibly by suppressing aldosterone production. Most commonly occurs in patients with risk factors for the development of hyperkalemia (eg, kidney dysfunction, concomitant use of potassium-sparing diuretics or potassium supplements, hematoma in body tissues).

• Thrombocytopenia: Cases of thrombocytopenia including thrombocytopenia with thrombosis have occurred. Monitor platelet count closely. Use is contraindicated in patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis. Interrupt or discontinue therapy in patients with platelet counts <100,000/mm3and/or thrombosis related to initiation of dalteparin, especially when associated with a positive in vitro test for antiplatelet antibodies. Use caution in patients with congenital or drug-induced thrombocytopenia or platelet defects.

Disease-related concerns:

• GI ulceration: Use with caution in patients with a history of GI ulcer.

• Hepatic impairment: Use with caution in patients with hepatic impairment as these patients may have potentially higher risk of bleeding.

• Kidney impairment: Use with caution in patients with kidney impairment, especially severe kidney impairment (CrCl <30 mL/minute); accumulation may occur with repeated dosing increasing the risk for bleeding.

Special populations:

• Elective surgery/procedure: In patients receiving bridging anticoagulation with therapeutic-dose dalteparin, the last dose should be administered ~24 hours prior to the surgery/procedure. For patients on a twice-daily regimen, administer 1 dose in the morning the day before surgery. For patients on a once-daily regimen, administer 50% of the dose in the morning the day before surgery. Reinitiate therapy ≥24 hours after the surgery/procedure when bleeding risk is acceptable (ACCP [Douketis 2022]).

• Older adult: Use with caution in the elderly due to increased bleeding risks.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and should not be used in pregnant women. In neonates, large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”); the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

• Latex: The packaging (needle shield of prefilled syringe) may contain natural rubber latex.

Other warnings/precautions:

• Conversion to other products: Not to be used interchangeably (unit for unit) with heparin or any other LMWHs.

• Neuraxial anesthesia: Delay placement or removal of catheter for at least 12 hours after administration of 2,500 units once daily, at least 15 hours after the administration of 5,000 units once daily, and at least 24 hours after the administration of higher doses (200 units/kg once daily, 120 units/kg twice daily) and consider doubling these times in patients with creatinine clearance <30 mL/minute; risk of neuraxial hematoma may still exist since anti-Factor Xa levels are still detectable at these time points. Indwelling catheters should be removed prior to initiation of dalteparin. Upon removal of catheter, withhold dalteparin for at least 4 hours. Prophylactic or therapeutic doses of dalteparin should be given no earlier than 12 or 24 hours after needle/catheter placement, respectively, and only in the presence of adequate hemostasis. Frequently monitor patients for signs and symptoms of neurological impairment (eg, midline back pain, sensory and motor deficits, bowel and/or bladder dysfunction) following anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture. If neurological compromise is noted, urgent treatment is necessary. If spinal hematoma is suspected, diagnose and treat immediately; spinal cord decompression may be considered although it may not prevent or reverse neurological sequelae. Use is contraindicated in patients with unstable angina and non-Q-wave myocardial infarction, or for prolonged venous thromboembolism prophylaxis in patients who will be undergoing epidural/neuraxial anesthesia (ASRA [Horlocker 2018]; manufacturer’s labeling).

Warnings: Additional Pediatric Considerations

Thrombocytopenia has been observed at a higher incidence in pediatric patients with or without cancer than adults and was the most common reason for discontinuation of therapy in 2 pediatric clinical trials; after 3 months of therapy, platelet counts <100,000/mm3 were reported in 37% of pediatric subjects (adults with cancer after 6 months of therapy: 13.6%) and of these, platelet counts were <50,000/mm3 in 21% of pediatric subjects (adults with cancer after 6 months of therapy: 6.5%). Monitor platelet counts closely with therapy; dosage adjustments or interruption/discontinuation of therapy may be necessary.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Fragmin: 10,000 units/4 mL (4 mL)

Solution, Subcutaneous, as sodium:

Fragmin: 95,000 units/3.8 mL (3.8 mL) [contains benzyl alcohol]

Solution Prefilled Syringe, Subcutaneous, as sodium [preservative free]:

Fragmin: 10,000 units/mL (1 mL); 2500 units/0.2 mL (0.2 mL); 5000 units/0.2 mL (0.2 mL); 7500 units/0.3 mL (0.3 mL); 12,500 units/0.5 mL (0.5 mL); 15,000 units/0.6 mL (0.6 mL); 18,000 units/0.72 mL (0.72 mL)

Generic Equivalent Available: US

No

Pricing: US

Solution (Fragmin Subcutaneous)

10000 units/4 mL (per mL): $8.39

95000 unit/3.8ml (per mL): $327.81

Solution Prefilled Syringe (Fragmin Subcutaneous)

2500 units/0.2 mL (per 0.2 mL): $44.66

5000 units/0.2 mL (per 0.2 mL): $72.46

7500 unit/0.3 mL (per 0.3 mL): $108.70

10000 units/mL (per mL): $144.92

12500 units/0.5 mL (per 0.5 mL): $181.16

15000 unit/0.6 mL (per 0.6 mL): $217.38

18000 units (per 0.72 mL): $260.86

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Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Subcutaneous:

Fragmin: 10,000 units/mL ([DSC])

Fragmin: 25,000 units/mL (3.8 mL) [contains benzyl alcohol]

Solution Prefilled Syringe, Subcutaneous:

Fragmin: 3500 units/0.28 mL (0.28 mL); 10,000 units/0.4 mL (0.4 mL); 16,500 units/0.66 mL (0.66 mL)

Solution Prefilled Syringe, Subcutaneous, as sodium:

Fragmin: 2500 units/0.2 mL (0.2 mL); 5000 units/0.2 mL (0.2 mL); 7500 units/0.3 mL (0.3 mL); 12,500 units/0.5 mL (0.5 mL); 15,000 units/0.6 mL (0.6 mL); 18,000 units/0.72 mL (0.72 mL)

Administration: Adult

SubQ: For deep SubQ injection; do not administer IM. May inject in a U-shape to the area surrounding the navel, the upper outer side of the thigh, or the upper outer quadrangle of the buttock. Use thumb and forefinger to lift up a fold of skin when injecting in the navel area or thigh. Insert entire needle length at a 45- to 90-degree angle. Do not expel air bubble from prefilled syringe prior to injection. Air bubble (and extra solution, if applicable) may be expelled from graduated syringes. In order to minimize bruising, do not rub injection site. Rotate injection sites daily.

IV (off-label route): May administer as a bolus IV injection or as a continuous infusion; recommended concentration for infusion: 20 units/mL (Ref).

Administration: Pediatric

SubQ: For deep SubQ injection only; do not administer IM. Utilize benzyl-alcohol free formulations for administration to infants. May be injected in a U-shape to the area surrounding the navel, the upper outer side of the thigh, or the upper outer quadrangle of the buttock. Apply pressure to injection site; do not massage. Use thumb and forefinger to lift a fold of skin when injecting dalteparin to the navel area or thigh. Insert needle at a 45- to 90-degree angle. The entire length of needle should be inserted. Do not expel air bubble from fixed-dose syringe prior to injection. Air bubble (and extra solution, if applicable) may be expelled from graduated syringes. In order to minimize bruising, do not rub injection site. Rotate injection sites daily.

Use: Labeled Indications

Non-ST elevation acute coronary syndromes: Prevention of ischemic complications in patients with unstable angina or non-Q-wave myocardial infarction in combination with an appropriate antiplatelet regimen.

Venous thromboembolism prophylaxis: Prevention of DVT which may lead to PE, in patients requiring abdominal surgery who are at risk for thromboembolism complications (eg, >40 years, obesity, malignancy, history of DVT or PE, surgical procedures requiring general anesthesia lasting >30 minutes); patients undergoing total hip arthroplasty; or in patients who are at risk for thromboembolism complications due to severe immobility during an acute illness.

Venous thromboembolism treatment in patients with active cancer: Extended treatment (6 months) of acute symptomatic VTE (ie, DVT and/or PE) to reduce the recurrence of VTE in cancer patients.

Venous thromboembolism treatment in pediatric patients: Treatment of symptomatic VTE (ie, DVT and/or PE) to reduce the recurrence of VTE in infants ≥1 month of age, children, and adolescents.

Use: Off-Label: Adult

Deep vein thrombosis and/or pulmonary embolism treatment; Hemodialysis, intermittent, anticoagulation of circuit; Mechanical heart valve, bridging anticoagulation; Periprocedural bridging anticoagulation for patients at high risk of thromboembolism, with atrial fibrillation, venous thromboembolism, or other high-risk conditions; Superficial vein thrombosis, acute symptomatic; Venous thromboembolism prophylaxis, nonorthopedic surgery; Venous thromboembolism prophylaxis, pregnancy; Venous thromboembolism prophylaxis, total knee arthroplasty; Venous thromboembolism treatment in pregnancy

Medication Safety Issues
High alert medication:

High alert medication:The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (anticoagulants, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

National Patient Safety Goals:

The Joint Commission (TJC) requires healthcare organizations that provide anticoagulant therapy to have approved protocols and evidence-based practice guidelines in place to reduce the risk of anticoagulant-associated patient harm. Patients receiving anticoagulants should receive individualized care through a defined process that includes medication selection, dosing (including adjustments for age, renal function, or liver function), drug-drug interactions, drug-food interactions, other applicable risk factors, monitoring, patient and family education, proper administration, reversal of anticoagulation, management of bleeding events, and perioperative management. This does not apply to routine short-term use of anticoagulants for prevention of venous thromboembolism during procedures or hospitalizations (NPSG.03.05.01).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Aliskiren: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Aliskiren. Risk C: Monitor therapy

Alteplase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Anacaulase: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Anagrelide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Angiotensin II Receptor Blockers: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Antithrombin: May enhance the anticoagulant effect of Heparins (Low Molecular Weight). Risk C: Monitor therapy

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Defibrotide: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Risk D: Consider therapy modification

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Risk X: Avoid combination

Factor X (Human): Anticoagulants (Inhibitors of Factor Xa) may diminish the therapeutic effect of Factor X (Human). Risk C: Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Icosapent Ethyl: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Kanamycin: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Lecanemab: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Risk C: Monitor therapy

Lipid Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Risk X: Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Palifermin: Heparins (Low Molecular Weight) may increase the serum concentration of Palifermin. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Pentoxifylline: May enhance the anticoagulant effect of Heparins (Low Molecular Weight). Risk C: Monitor therapy

Pirtobrutinib: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Potassium Salts: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium Salts. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy

Protein C Concentrate (Human): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Reteplase: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Risk X: Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Streptokinase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Tenecteplase: May enhance the anticoagulant effect of Anticoagulants. Risk X: Avoid combination

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Management: Consider avoiding this combination due to an increased risk of hemorrhage. If anticoagulants are coadministered with urokinase, monitor patients closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Volanesorsen: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Risk X: Avoid combination

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Risk C: Monitor therapy

Reproductive Considerations

Patients undergoing assisted reproduction therapy (ART) may be at increased risk for thrombosis. Venous thromboembolism prophylaxis is not routinely recommended for patients undergoing ART; however, prophylactic doses of low-molecular-weight heparin (LMWH) are recommended for patients who develop severe ovarian hyperstimulation syndrome (ACCP [Bates 2012]; ASH [Bates 2018]; SOGC [Shmorgun 2017]). In addition, prophylactic doses of LMWH are recommended in patients undergoing ART who have a positive antiphospholipid antibody test but are not diagnosed with antiphospholipid syndrome (APS), as well as patients diagnosed with obstetric APS. Therapeutic doses of LMWH are recommended in patients undergoing ART diagnosed with thrombotic APS (ACR [Sammaritano 2020]).

Pregnancy Considerations

Low-molecular-weight heparin (LMWH) does not cross the placenta (ACOG 2018).

An increased risk of fetal bleeding or teratogenic effects have not been reported (ACCP [Bates 2012]).

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of LMWH may be altered; dosing adjustment may be required. Prophylactic doses of LMWH may also need modified in pregnant patients at extremes of body weight (ACOG 2018).

The risk of venous thromboembolism (VTE) is increased in pregnant patients, especially during the third trimester and first week postpartum. LMWH is recommended over unfractionated heparin for the treatment of acute VTE in pregnant patients. LMWH is also recommended over unfractionated heparin for VTE prophylaxis in pregnant patients with certain risk factors (eg, homozygous factor V Leiden, antiphospholipid antibody syndrome with ≥3 previous pregnancy losses) (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]; ESC [Regitz-Zagrosek 2018]). LMWH may also be considered for VTE prophylaxis in pregnant patients with COVID-19 (NIH 2023). Consult current recommendations for appropriate use during pregnancy.

LMWH may be used prior to cesarean delivery in patients with additional risk factors for developing VTE. Risk factors may include a personal history of deep vein thrombosis or pulmonary embolism, inherited thrombophilia, or patients with class III obesity (SMFM [Pacheco 2020]).

LMWH may also be used in pregnant patients with mechanical heart valves. When choosing therapy, fetal outcomes (ie, pregnancy loss, malformations), maternal outcomes (ie, VTE, hemorrhage), burden of therapy, and maternal preference should be considered. Patients with mechanical heart valves have an increased risk of adverse fetal and maternal outcomes (including valve thrombosis) and these risks are greater without appropriate anticoagulation. Increased monitoring of anti-factor Xa levels is required; frequent dose titration may be needed to maintain adequate therapeutic anti-factor Xa concentrations during pregnancy (consult current recommendations for details) (ACC/AHA [Otto 2021]; ESC [Regitz-Zagrosek 2018]).

Multiple-dose vials contain benzyl alcohol (avoid in pregnant patients due to association with gasping syndrome in premature infants); use of preservative-free formulation is recommended.

Breastfeeding Considerations

Anti-factor Xa activity was noted in breast milk of patients receiving prophylactic doses of dalteparin.

Oral absorption of low molecular weight heparin (LMWH) via breast milk is expected to be low. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. LMWH is considered compatible with breastfeeding (ACCP [Bates 2012]; ACOG 2018; ASH [Bates 2018]).

Monitoring Parameters

Platelet count, hemoglobin, hematocrit, fecal occult blood, signs and symptoms of bleeding, anti-factor Xa levels (as appropriate), and serum creatinine at baseline and during therapy; monitoring of PT and/or aPTT is not necessary. Routine monitoring of anti-factor Xa activity is not required but has been utilized in patients with obesity and/or kidney insufficiency. Anti-factor Xa activity is an appropriate measure for therapeutic effect but is a poor predictor of hemorrhagic risk.

For patients >190 kg, if anti-factor Xa monitoring is available, adjusting dose based on anti-factor Xa levels is recommended; if anti-factor Xa monitoring is unavailable, reduce dose if bleeding occurs (Garcia 2012; Nutescu 2009). Monitor obese patients closely for signs/symptoms of thromboembolism.

Monitoring anti-factor Xa activity is recommended in pregnant patients receiving therapeutic doses of dalteparin or when receiving dalteparin for the prevention of thromboembolism with mechanical heart valves (ACCP [Guyatt 2012]; ACC/AHA [Otto 2021]).

Reference Range

The following therapeutic ranges for anti-Factor Xa activity have been suggested but have not been validated in a controlled trial. Anti-Factor Xa activity should be measured 4 to 6 hours after a dose and after the patient has received 3 to 4 doses (ACCP [Garcia 2012]; ACOG 2018; ACC/AHA [Otto 2021]; manufacturer's labeling).

Mechanical heart valve (bridging anticoagulation):

Anti-Factor Xa activity target:

Non-pregnant patients: Monitoring anti-Factor Xa activity is not necessary. However, some experts recommend monitoring, if possible, and targeting a range of 0.5 to 1 units/mL (ESC/EACTS [Baumgartner 2017]).

Pregnant patients: 0.8 to 1.2 units/mL (ACC/AHA [Otto 2021]). Some experts recommend higher anti-Factor Xa targets (eg, 1 to 1.2 units/mL) for mechanical mitral valves and lower targets (0.8 to 1 units/mL) for mechanical aortic valves (Nelson-Piercy 2023). Note: Target trough anti-Factor Xa activity should be ≥0.6 units/mL (Goland 2014).

Venous thromboembolism treatment (pulmonary embolism and/or deep vein thrombosis):

Anti-Factor Xa activity target:

Once-daily dosing: >1.05 units/mL (ACCP [Garcia 2012]); manufacturer’s labeling recommends a target of 0.5 to 1.5 units /mL.

Twice-daily dosing: 0.6 to 1 units/mL. Note: Twice-daily dosing is recommended in pregnant patients (ACCP [Garcia 2012]; ACOG 2018).

Venous thromboembolism prophylaxis in pregnant patients:

Prophylactic regimen: 0.2 to 0.6 unit/mL (ACCP [Bates 2012]).

Adjusted dose (therapeutic) regimen: 0.6 to 1 unit/mL (ACOG 2018).

Mechanism of Action

Low molecular weight heparin analog with a molecular weight of 4,000 to 6,000 daltons; the commercial product contains 3% to 15% heparin with a molecular weight <3,000 daltons, 65% to 78% with a molecular weight of 3,000 to 8,000 daltons and 14% to 26% with a molecular weight >8,000 daltons. While dalteparin has been shown to inhibit both factor Xa and factor IIa (thrombin), the antithrombotic effect of dalteparin is characterized by a higher ratio of anti-Factor Xa to anti-Factor IIa activity (2.7:1) (Dager 2018).

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Anti-Factor Xa activity: Within 1 to 2 hours.

Duration: >12 hours.

Distribution: Vd:

Pediatric:

3 to <8 weeks: 181 ± 15.3 mL/kg.

≥8 weeks to <2 years: 175 ± 55.3 mL/kg.

≥2 years to <8 years: 160 ± 25.6 mL/kg.

≥8 years to <12 years: 165 ± 27.3 mL/kg.

≥12 years to <20 years: 171 ± 38.8 mL/kg.

Adult: 40 to 60 mL/kg.

Protein binding: Low affinity for plasma proteins (Howard 1997).

Bioavailability: SubQ: 87% ± 6%.

Half-life elimination (route dependent):

IV: Mean terminal half-life: 2.1 ± 0.3 hours (40 unit/kg/dose) to 2.3 ± 0.4 hours (60 unit/kg/dose); mean terminal half-life (anti-Factor Xa activity): 5.7 ± 2.0 hours (5,000 unit dose in chronic renal impairment requiring hemodialysis).

SubQ:

Pediatric: Age-dependent changes were observed.

3 to <8 weeks: 2.25 ± 0.173 hours.

≥8 weeks to <2 years: 3.02 ± 0.688 hours.

≥2 years to <8 years: 4.27 ± 1.05 hours.

≥8 years to <12 years: 5.11 ± 0.509 hours.

≥12 years to <20 years: 6.28 ± 0.937 hours.

Adult: Mean terminal half-life: 3 to 5 hours.

Time to peak, serum: SubQ: Anti-Factor Xa activity: ~4 hours.

Excretion: Primarily renal (Howard 1997).

Clearance: In pediatric subjects, age-dependent changes were observed.

3 to <8 weeks: 55.8 ± 3.91 mL/hour/kg.

≥8 weeks to <2 years: 40.4 ± 8.49 mL/hour/kg.

≥2 years to <8 years: 26.7 ± 4.75 mL/hour/kg.

≥8 years to <12 years: 22.4 ± 3.41 mL/hour/kg.

≥12 years to <20 years: 18.8 ± 3.02 mL/hour/kg.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Mean terminal half-life of anti-Factor Xa activity was prolonged to 5.7 hours ± 2 hours following IV administration to adult patients with chronic renal impairment requiring hemodialysis.

Pediatric: Clearance was observed to decrease with increasing age during infancy and early childhood. Although Vdss in pediatric patients is larger than adult patients, this difference was not observed to be affected by age.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Fragmin;
  • (AR) Argentina: Ligofragmin;
  • (AT) Austria: Fragmin;
  • (AU) Australia: Fragmin;
  • (BE) Belgium: Fragmin;
  • (BG) Bulgaria: Fragmin;
  • (BR) Brazil: Fragmin;
  • (CI) Côte d'Ivoire: Fragmine;
  • (CL) Chile: Fragmin;
  • (CN) China: Fragmin | Wan mai ning;
  • (CO) Colombia: Dalteparina | Fragmin;
  • (CZ) Czech Republic: Fragmin;
  • (DE) Germany: Fragmin;
  • (EC) Ecuador: Fragmin;
  • (EE) Estonia: Fragmin;
  • (EG) Egypt: Fragmin;
  • (ES) Spain: Fragmin;
  • (FI) Finland: Fragmin;
  • (FR) France: Fragmine;
  • (GB) United Kingdom: Fragmin;
  • (GR) Greece: Fragmin;
  • (HK) Hong Kong: Fragmin;
  • (HR) Croatia: Fragmin;
  • (HU) Hungary: Fragmin;
  • (IL) Israel: Fragmin;
  • (IN) India: Daltehep | Daltepin | Fragmin;
  • (IT) Italy: Fragmin;
  • (JO) Jordan: Fragmin;
  • (JP) Japan: Daltepan | Dalteparin na | Dalteparin na hk | Fluzepamin | Fragmin | Fresubaru | Hepachron | Hepagumin | Resolmin;
  • (KE) Kenya: Fragmin;
  • (KR) Korea, Republic of: Fragmin;
  • (KW) Kuwait: Fragmin;
  • (LT) Lithuania: Fragmin;
  • (LU) Luxembourg: Fragmin;
  • (LV) Latvia: Fragmin;
  • (MA) Morocco: Fragmin;
  • (MX) Mexico: Fragmin;
  • (NL) Netherlands: Fragmin;
  • (NO) Norway: Fragmin;
  • (NZ) New Zealand: Fragmin;
  • (PE) Peru: Fragmin;
  • (PH) Philippines: Eurodal | Fragmin;
  • (PK) Pakistan: Fragmin;
  • (PL) Poland: Fragmin;
  • (PR) Puerto Rico: Fragmin;
  • (PT) Portugal: Fragmin;
  • (QA) Qatar: Fragmin;
  • (RO) Romania: Fragmin;
  • (RU) Russian Federation: Daltep | Fragmin;
  • (SE) Sweden: Dalteparinnatrium | Fragmin;
  • (SG) Singapore: Fragmin;
  • (SI) Slovenia: Fragmin;
  • (SK) Slovakia: Fragmin;
  • (TN) Tunisia: Fragmin | Fragmine;
  • (TR) Turkey: Fragmin;
  • (TW) Taiwan: Fragmin;
  • (UA) Ukraine: Fragmin;
  • (UY) Uruguay: Fragmin;
  • (VE) Venezuela, Bolivarian Republic of: Fragmin;
  • (ZA) South Africa: Fragmin
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  2. Ahlfors CE. Benzyl alcohol, kernicterus, and unbound bilirubin. J Pediatr. 2001;139(2):317-319. [PubMed 11487763]
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  5. Atiq F, van den Bemt PM, Leebeek FW, van Gelder T, Versmissen J. A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins (LMWHs) in patients with renal insufficiency. Eur J Clin Pharmacol. 2015;71(8):921-929. doi:10.1007/s00228-015-1880-5 [PubMed 26071276]
  6. Baglin T, Bauer K, Douketis J, et al. Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost. 2012;10(4):698-702. doi: 10.1111/j.1538-7836.2012.04662.x. [PubMed 22332937]
  7. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2)(suppl):e691S-e736S. doi:10.1378/chest.11-2300. [PubMed 22315276]
  8. Bates SM, Rajasekhar A, Middeldorp S, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv. 2018;2(22):3317-3359. doi:10.1182/bloodadvances.2018024802 [PubMed 30482767]
  9. Bauer KA. Risk and prevention of venous thromboembolism in adults with cancer. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 28, 2023a.
  10. Bauer KA. Use of anticoagulants during pregnancy and postpartum. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 7, 2023b.
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