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.
The adult dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editor: Edith A Nutescu, PharmD, MS, FCCP.
Anticoagulant for hemodialysis and hemofiltration (off-label use): IV: (Fragmin Canadian product labeling):
Chronic renal failure with no other bleeding risks:
Hemodialysis/filtration ≤4 hours:
IV bolus: 5,000 units; 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. Alternatively, may administer an IV bolus of 30 to 40 units/kg, followed by an infusion of 10 to 15 units/kg/hour. Note: Both regimens typically produce plasma concentrations of 0.5 to 1 units anti-Factor Xa/mL.
Hemodialysis/filtration >4 hours: IV bolus: 30 to 40 units/kg, followed by an infusion of 10 to 15 units/kg/hour (typically produces plasma concentrations of 0.5 to 1 units anti-Factor Xa/mL).
Acute renal failure and high bleeding risk: IV bolus: 5 to 10 units/kg, followed by an infusion of 4 to 5 units/kg/hour (typically produces plasma concentrations of 0.2 to 0.4 units anti-Factor Xa/mL).
Mechanical heart valve (bridging anticoagulation) (off-label use): Note: Bridging during intervals of subtherapeutic anticoagulation should be considered for patients with mechanical mitral or tricuspid 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 (ACC/AHA [Otto 2021]).
SubQ: 100 units/kg/dose every 12 hours; adjust dose based on anti-Factor Xa monitoring (ACCP [Douketis 2012]). For additional information regarding anti-Factor Xa monitoring, refer to the Reference Range field.
Non-ST elevation acute coronary syndromes: For medical management when an invasive approach is not planned: SubQ: 120 units/kg (maximum dose: 10,000 units) every 12 hours with concurrent aspirin therapy; continue until patient is clinically stable (usual duration of therapy is 5 to 8 days).
Superficial vein thrombosis, acute symptomatic (off-label use):
Note: 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 (ACCP [Kearon 2012]; Rathbun 2012).
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 (ACCP [Kahn 2012]; ASCO [Key 2020]). Extended prophylaxis beyond acute hospital stay is not routinely recommended (ACCP [Kahn 2012]; Sharma 2012). 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) (Cuker 2021).
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 (ASCO [Key 2020]).
or
SubQ: 2,500 units started 2 to 4 hours before surgery and 5,000 units once daily thereafter (ASCO [Key 2020]).
or
SubQ: 5,000 units once daily started ~6 to 12 hours after surgery (Bauer 2021; Pai 2019a).
Note: 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 (ASCO [Key 2020]).
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) and then 5,000 units once daily thereafter is recommended by some experts for all nonorthopedic surgeries. 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 days (ACCP [Gould 2012]; Pai 2019a).
Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. In low and moderate risk patients: SubQ: 2,500 units 1 to 2 hours prior to surgery, then 2,500 units once daily thereafter.
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.
Prophylactic dose: SubQ: 5,000 units once every 24 hours (ACOG 2018).
Intermediate dose: SubQ: 5,000 units every 12 hours (ACOG 2018); however, some experts use an alternative intermediate regimen of 5,000 units once daily, increasing as pregnancy progresses to 100 units/kg once daily (Bauer 2019b; Malhotra 2018).
Adjusted dose (therapeutic): SubQ: 100 units/kg every 12 hours; or 200 units/kg once daily reserved for patients at the highest risk (eg, history of recurrent thrombosis or severe thrombophilia) (ACCP [Bates 2012]; ACOG 2018).
Note: Anticoagulation management prior to delivery is individualized. Options include replacing with unfractionated heparin (UFH) at ~36 to 37 weeks' gestation or extending to 38 to 39 weeks' gestation in patients at very low risk of delivery while on dalteparin (Bauer 2019b). In such patients, discontinue dalteparin ≥12 hours before delivery (for prophylactic doses) or ≥24 hours before delivery (for higher doses), particularly if neuraxial anesthesia is planned; may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred (ACOG 2018). Anticoagulation should continue for up to 6 weeks postpartum, but potentially longer (ACCP [Bates 2012]; ACOG 2018; Bauer 2019b).
Total hip arthroplasty or total knee arthroplasty (total knee arthroplasty is an off-label use):
SubQ: 5,000 units once daily, with initial dose administered ≥12 hours preoperatively or ≥12 hours postoperatively once hemostasis is achieved (ACCP [Falck-Ytter 2012]; Pai 2019b); other regimens include 2,500 units pre- or postoperatively with a maintenance dosage of 5,000 units once daily. 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 (ACCP [Falck-Ytter 2012]; Dahl 1997; Lassen 1998; Pai 2019b; Sobieraj 2012); some experts suggest a duration at the higher end of range (eg, 30 days) for total hip arthroplasty and at the lower end of range (eg, 10 to 14 days) for total knee arthroplasty (Pai 2019b).
Venous thromboembolism treatment: Note: For timing of initiating oral anticoagulant, see Transitioning between anticoagulants.
Deep vein thrombosis and/or pulmonary embolism (off-label use): Inpatient treatment: SubQ: 200 units/kg once daily or 100 units/kg every 12 hours (AHA [Jaff 2011]; Feissinger 1996; Wells 2005). Note: In select low-risk patients, may consider outpatient treatment for the remainder of the course after first dose administered in hospital or urgent care center (ACCP [Kearon 2016]; Kovacs 2000; Erkens 2010).
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) (ACCP [Kearon 2016]).
Unprovoked venous thromboembolism: ≥3 months depending on risk of VTE recurrence and bleeding (ACCP [Kearon 2012]; ACCP [Kearon 2016]; ISTH [Baglin 2012]).
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: SubQ:
Initial (month 1): 200 units/kg once daily for 30 days, followed by maintenance therapy during months 2 to 6.
Maintenance (months 2 to 6): 150 units/kg once daily. Alternatively, warfarin may be used for maintenance therapy; however, meta-analyses and randomized control trials have validated the superiority of low molecular weight heparin (LMWH) over warfarin. If warfarin is to be used for maintenance therapy, overlap dalteparin with warfarin for a minimum of 5 to 7 days and continue until INR in therapeutic range for at least 48 hours (ASCO [Key 2020]; Bauer 2019c).
Maintenance beyond 6 months (off label): ACCP and ASCO guidelines for VTE prophylaxis/treatment recommend considering continuing anticoagulation beyond 6 months in selected patients due to the persistent high risk of recurrence in those with active cancer; consider risk vs benefit of bleeding and recurrence (ACCP [Kearon 2012]; ACCP [Kearon 2016]; ASCO [Key 2020]).
Dosage adjustment for thrombocytopenia: If platelet count is between 50,000 to 100,000/mm3, reduce daily dose by 2,500 units for patients weighing 46 to 82 kg and by 3,000 units for patients weighing ≥83 kg 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. Some experts suggest anti-Factor Xa monitoring for dose adjustment (ACCP [Bates 2012]). For additional information regarding anti-Factor Xa monitoring, refer to the Reference Range field.
Note: Anticoagulation management prior to delivery is individualized. Options include replacing with UFH at ~36 to 37 weeks' gestation or extending to 38 to 39 weeks' gestation in patients at very low risk of delivery while on dalteparin (Bauer 2019b). In such patients, discontinue dalteparin ≥24 hours before delivery, particularly if neuraxial anesthesia is planned; may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding occurred (ACOG 2018). 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 (ACOG 2018; Malhotra 2018).
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 UFH infusion to therapeutic-dose dalteparin: Discontinue UFH and begin dalteparin within 1 hour. Note: If aPTT is not in therapeutic range at the time UFH is discontinued, consult local protocol (Nutescu 2007).
Transitioning from dalteparin to another anticoagulant:
Transitioning from therapeutic-dose dalteparin to therapeutic IV UFH infusion: Start IV UFH (rate based on indication) 1 to 2 hours before the next dose of dalteparin would have been due. Note: Omit IV UFH loading dose (Nutescu 2007).
Transitioning from prophylactic dalteparin to therapeutic IV UFH: UFH should be started without delay. A UFH bolus/loading dose may be used if indicated (Nutescu 2007).
Transitioning from therapeutic-dose dalteparin to warfarin: Start warfarin and continue dalteparin until INR is within therapeutic range (Hull 2022a; Wittkowsky 2018). Note: For the treatment of VTE, overlap dalteparin with warfarin until INR is ≥2 for at least 2 measurements taken ~24 hours apart (duration of overlap is usually 4 to 5 days) (ACCP [Ageno 2012]; Hull 2022b).
Transitioning from therapeutic-dose dalteparin to a direct oral anticoagulant (DOAC): Note: In treatment of VTE, some DOACs (dabigatran, edoxaban) require 5 days of parenteral anticoagulation prior to transitioning.
General transition recommendation: Start DOAC within 2 hours prior to the next scheduled dose of dalteparin.
Venous thromboembolism initial treatment transition (alternative recommendation): For acute VTE, some experts start DOAC within 6 to 12 hours after the last dose of a twice-daily LMWH regimen or within 12 to 24 hours after a once-daily LMWH regimen (Hull 2022b).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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 (expert opinion).
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) (Rammohan 2003).
Venous thromboembolism prophylaxis:
CrCl ≥30 mL/minute: No dosage adjustment necessary (manufacturer's labeling).
CrCl <30 mL/minute: No dosage adjustment necessary (Atiq 2015; Douketis 2008; Pai 2018; Schmid 2009a). 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 (Nutescu 2009; Schmid 2009a; expert opinion).
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 (Schmid 2009b). Some expert guidelines recommend switching to an alternative anticoagulant that provides specific renal dose adjustment or that is less dependent on renal clearance (Witt 2018); if necessary, start with full dose and make dose adjustments according to anti-factor Xa levels (Shprecher 2005; manufacturer's labeling). No specific dose reduction suggested because of wide inter-individual variation and small numbers of patients studied (Park 2016; Schmid 2009b; Shprecher 2005).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (expert opinion):
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 (Douketis 2008).
Therapeutic dose: Avoid use; significantly accumulates in patients on dialysis (Rodger 2012).
Anticoagulant for hemodialysis and hemofiltration (IV use): Refer to adult dosing.
Peritoneal dialysis: Unlikely to be significantly dialyzable (expert opinion):
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 (expert opinion). In one pharmacokinetic study, patients on peritoneal dialysis tolerated prophylactic doses with limited accumulation at day 4 (Schmid 2010).
Therapeutic dose: Avoid use (expert opinion).
CRRT or PIRRT (eg, sustained, low-efficiency diafiltration):
Prophylactic dose: No dosage adjustment necessary (Douketis 2008); however, limit to short-term use (eg, ≤7 days); may need to consider conversion to an alternative agent if extended prophylaxis is necessary (expert opinion).
Therapeutic dose: Avoid use (expert opinion).
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution in patients with severe hepatic impairment; accumulation may occur with repeated dosing, increasing the risk for bleeding.
(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 (O’Brien 2014); reported experience may not be appropriate for all patients (small infants, etc). For infants, avoid dosage forms that contain benzyl alcohol.
Prophylaxis, VTE: 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) (ACCP [Monagle 2012]; Nohe 1999).
Treatment, symptomatic VTE:
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 (O’Brien 2014); 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 (ACCP [Monagle 2012]; O’Brien 2014; Warad 2015); however, levels after the first and second doses (4 to 6 hours postdose) have also been used (O’Brien 2014); in one trial, dose adjustments were made in 10% to 20% increments (O'Brien 2014); 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) (O’Brien 2014; manufacturer labeling).
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 (ASH [Monagle 2018]).
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.
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 (Warad 2015).
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.
Refer to adult dosing.
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 (Nutescu 2009).
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 (Al-Yaseen 2005; Smith 2003; Wilson 2001).
Class 1, 2, or 3 obesity (BMI ≥ 30 kg/m2): SUBQ: Use actual body weight for dosing calculation (maximum weight: 190 kg) (Al-Yaseen 2005; Smith 2003; Wilson 2001). Anti-Factor Xa monitoring is recommended in select patients (high risk of bleeding and/or ≥150 kg) (ACCP [Garcia 2012]; expert opinion). 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 (expert opinion).
Class 1 or 2 obesity (BMI 30 to 39 kg/m2): SUBQ: 5,000 units once daily (Kucher 2005).
Class 3 obesity (BMI ≥ 40 kg/m2): SUBQ: 7,500 units once daily (Simoneau 2010; Streiff 2015). Note: Higher doses may be necessary in patients who weigh >180 kg, based on limited data (Simoneau 2010). Anti-Factor Xa monitoring is recommended in patients >180 kg (expert opinion).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Subcutaneous:
Fragmin: 95,000 units/3.8 mL (3.8 mL) [contains benzyl alcohol]
Solution, Subcutaneous [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)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Fragmin: 3500 units/0.28 mL (0.28 mL); 16,500 units/0.66 mL (0.66 mL)
Solution, Subcutaneous:
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); 10,000 units/0.4 mL (0.4 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)
Fragmin: 25,000 units/mL (3.8 mL) [contains benzyl alcohol]
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.
To convert from IV unfractionated heparin (UFH) infusion to SubQ dalteparin (Nutescu 2007): Calculate specific dose for dalteparin based on indication, discontinue UFH and begin dalteparin within 1 hour.
To convert from SubQ dalteparin to IV UFH infusion (Nutescu 2007): Discontinue dalteparin; calculate specific dose for IV UFH infusion based on indication; omit heparin bolus/loading dose.
Converting from SubQ dalteparin dosed every 12 hours: Start IV UFH infusion 10 to 11 hours after last dose of dalteparin.
Converting from SubQ dalteparin dosed every 24 hours: Start IV UFH infusion 22 to 23 hours after last dose of dalteparin.
IV (off-label route): May administer as a bolus IV injection or as a continuous infusion; recommended concentration for infusion: 20 units/mL (Fragmin Canadian product labeling).
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.
Anticoagulant for hemodialysis and hemofiltration (Fragmin [Canadian product only]): Prevention of clotting in the extracorporeal system during hemodialysis and hemofiltration in connection with acute renal failure or chronic renal insufficiency
Non-ST elevation acute coronary syndromes: Prevention of ischemic complications in patients with unstable angina or non-Q-wave myocardial infarction on concurrent aspirin therapy.
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.
Deep vein thrombosis and/or pulmonary embolism treatment; Mechanical heart valve (bridging anticoagulation); 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
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
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).
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
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
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, renal 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 severe hepatic impairment; accumulation may occur with repeated dosing increasing the risk for bleeding.
• Renal impairment: Use with caution in patients with renal impairment, especially severe renal impairment (CrCl <30 mL/minute); accumulation may occur with repeated dosing increasing the risk for bleeding.
Special populations:
• Elderly: Use with caution in the elderly due to increased bleeding risks.
• Obesity: There is no consensus for adjusting/correcting the weight-based dosage of low molecular weight heparin (LMWH) for patients who are morbidly obese (BMI ≥40 kg/m2). Monitoring of anti-Factor Xa levels 4 to 6 hours after the dose may be warranted. The American College of Chest Physicians Practice Guidelines suggest consulting with a pharmacist regarding dosing in bariatric surgery patients and other obese patients who may require higher doses of LMWH (Gould 2012).
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: [US Boxed Warning]: Epidural or spinal hematomas, including subsequent long term or permanent paralysis, may occur in patients anticoagulated with LMWH or heparinoids who are receiving neuraxial anesthesia (epidural or spinal anesthesia) or undergoing spinal puncture. Consider risk versus benefit prior to spinal procedures; risk is increased by the use of concomitant agents which may alter hemostasis, the use of indwelling epidural catheters, a history of spinal deformity or spinal surgery, or a history of traumatic or repeated epidural or spinal punctures. Optimal timing between neuraxial procedures and dalteparin administration is not known. 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. Upon removal of catheter, consider delaying next dose of dalteparin for at least 4 hours. 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.
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.
None known.
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
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. Risk C: Monitor therapy
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
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
Eplerenone: Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
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
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 (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
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. Management: Monitor serum potassium concentrations closely. The spironolactone Canadian product monograph lists its combination with heparin or low molecular weight heparins as contraindicated. 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
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
Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Risk C: Monitor therapy
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. Risk X: Avoid combination
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
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
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]).
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]). Consult current recommendations for appropriate use in 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]).
LMWH is recommended for pregnant patients hospitalized with severe COVID-19, taking into consideration risk factors for bleeding, including threatened delivery. Prophylactic doses are recommended during hospitalization if there are no contraindications to use. Patients prescribed antithrombotic therapy prior to a COVID-19 diagnosis should continue their therapy (NIH 2021).
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.
Anti-Factor Xa activity was noted in breast milk of women 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]).
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 renal 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 women 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]).
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 2018). 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 women: 0.2 to 0.6 units/mL (ACCP [Bates 2012]).
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).
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.
Renal function impairment: 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.
Solution (Fragmin Subcutaneous)
2500 units/0.2 mL (per 0.2 mL): $33.55
5000 units/0.2 mL (per 0.2 mL): $54.44
7500 unit/0.3 mL (per 0.3 mL): $81.67
10000 units/mL (per mL): $108.88
12500 units/0.5 mL (per 0.5 mL): $136.10
15000 unit/0.6 mL (per 0.6 mL): $163.32
18000 units (per 0.72 mL): $195.98
95000 unit/3.8ml (per mL): $246.28
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