Dalteparin Sodium

Pronunciation

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

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Warning(s)

Spinal/Epidural Hematoma Risk
Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of low molecular weight heparins (LMWHs) or heparinoids and neuraxial (spinal/epidural) anesthesia or spinal puncture.¹ ³⁵ ⁷⁷
Risk increased by use of indwelling epidural catheters or by concomitant use of drugs affecting hemostasis (e.g., NSAIAs, platelet inhibitors, other anticoagulants).¹ ³⁵ ⁷⁷ ⁷⁸
Risk also increased by history of traumatic or repeated epidural or spinal puncture, spinal deformity, or spinal surgery.¹ ³⁵
Monitor frequently for signs and symptoms of neurologic impairment and treat urgently if neurologic compromise noted.¹ ³⁵ ⁷⁷ ⁷⁸
Consider potential benefits versus risks of spinal or epidural anesthesia or spinal puncture in patients receiving or being considered for thromboprophylaxis with anticoagulants.¹ ³⁵ (See Hematologic Effects under Cautions.)

Introduction

Anticoagulant; an LMWH.¹ ³ ⁵ ¹⁰ ²² ²³ ²⁶

Uses for Dalteparin Sodium

Unstable Angina and Non-ST-Segment Elevation MI (NSTEMI)

Used to reduce the risk of acute cardiac ischemic events (death, MI) in patients with unstable angina or NSTEMI.¹ ⁴⁹ ⁵¹ ⁵² ⁵³ ⁵⁴ ⁶⁶ ¹⁰³ ¹⁰⁴ ⁹⁹¹ Used concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors).¹ ⁴⁹ ⁵¹ ⁵² ⁵³ ⁵⁴ ⁶⁶ ¹⁰³ ¹⁰⁴ ⁹⁹¹

Initiate anticoagulant therapy as soon as possible after hospital admission.⁹⁹¹

In patients undergoing an invasive management strategy, the American College of Cardiology (ACC), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend use of an LMWH, unfractionated heparin, bivalirudin, or fondaparinux for anticoagulant therapy.⁹⁹¹

In patients undergoing a conservative management strategy, recommended anticoagulants include an LMWH, unfractionated heparin, or fondaparinux; fondaparinux is preferred in patients with an increased risk of bleeding.⁹⁹¹

ACC/AHA/ACCF state that limited data are available for the use of dalteparin compared with enoxaparin in patients with unstable angina or NSTEMI.⁹⁹¹

Thromboprophylaxis in General/Abdominal Surgery

Prevention of postoperative DVT and PE in patients undergoing general/abdominal surgery who are at risk for thromboembolic complications.¹ ³ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹⁹ ²⁰ ²¹ ²² ¹⁰⁰²

ACCP recommends pharmacologic (e.g., LMWHs) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding.¹⁰⁰² In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.¹⁰⁰²

If pharmacologic prophylaxis is used in patients undergoing general surgery, ACCP states that an LMWH or low-dose unfractionated heparin is preferred.¹⁰⁰²

Because risk of venous thromboembolism is particularly high in patients undergoing abdominal or pelvic surgery for cancer, extended (4 weeks) prophylaxis with an LMWH is recommended in such patients.¹⁰⁰²

ACCP states that the recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.¹⁰⁰²

Thromboprophylaxis in Cardiac Surgery

Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that an LMWH may be considered for thromboprophylaxis in cardiac surgery† patients with a complicated postoperative course.¹⁰⁰²

Thromboprophylaxis in Thoracic Surgery

Pharmacologic thromboprophylaxis (e.g., LMWH) recommended by ACCP in patients undergoing thoracic surgery† who are at high risk of venous thromboembolism, provided risk of bleeding is low.¹⁰⁰²

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

Prevention of postoperative DVT and PE in patients undergoing hip-replacement surgery.¹ ⁶⁰ ⁶³ ⁶⁴ ¹⁰⁰³

LMWHs also have been used for thromboprophylaxis in patients undergoing total knee-replacement† and hip-fracture surgery†.¹⁰⁰³

ACCP recommends routine thromboprophylaxis with a pharmacologic (e.g., LMWH) and/or mechanical method in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery.¹⁰⁰³

Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose unfractionated heparin, warfarin, aspirin) are recommended by ACCP for pharmacologic prophylaxis during major orthopedic surgery.¹⁰⁰³ When selecting an appropriate thromboprophylaxis regimen, consider factors such as relative efficacy, safety, logistics, and compliance.¹⁰⁰³

Medical Conditions Predisposing to Thromboembolism

Prevention of DVT and PE in patients with severely restricted mobility during acute illness.¹ ¹²⁵ ¹⁰⁰¹

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.¹⁰⁰¹

ACCP recommends anticoagulant prophylaxis (e.g., LMWH) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding.¹⁰⁰¹ Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or until hospital discharge, whichever comes first.¹⁰⁰¹

Use of LMWHs also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.¹⁰⁰¹

Risk of venous thromboembolism particularly high in patients with cancer.¹⁰⁰¹ Use of LMWH prophylaxis suggested by ACCP in cancer outpatients with solid tumors who have additional risk factors for thromboembolism provided risk of bleeding is low.¹⁰⁰¹

Treatment of Acute DVT and PE

Used for initial and extended (6 months) treatment of symptomatic DVT or PE in patients with cancer to reduce recurrence of venous thromboembolism.¹ Manufacturer states that safety and efficacy of treatment durations >6 months not established.¹

Recommended by ACCP as an appropriate choice of anticoagulant for initial treatment of acute proximal DVT or PE.¹⁰⁰⁵

LMWHs or fondaparinux generally preferred over unfractionated heparin for initial treatment of acute venous thromboembolism; however, unfractionated heparin may be preferred in patients with renal impairment.¹⁰⁰⁵ IV unfractionated heparin also may be preferred over LMWHs in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.¹⁰⁰⁵

For long-term anticoagulant therapy, warfarin generally preferred in patients without cancer; however, ACCP suggests use of an LMWH in patients with cancer because of a possible reduced response to warfarin.¹⁰⁰⁵

Continue anticoagulant therapy for ≥3 months and possibly longer depending on individual clinical situation.¹⁰⁰⁵

Treatment of Superficial Vein Thrombosis

LMWHs also have been used for spontaneous superficial vein thrombosis†; ACCP suggests use of prophylactic dosages for 45 days in patients with superficial vein thrombosis of ≥5 cm in length.¹⁰⁰⁵

Thromboprophylaxis in Neurosurgery

LMWHs have been used for prevention of venous thromboembolism in patients undergoing craniotomy†; however, benefits of such prophylaxis may be outweighed by possible increased risk of intracranial hemorrhage.¹⁰⁰² ACCP states that LMWH prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.¹⁰⁰²

LMWH prophylaxis also may be considered in high-risk patients undergoing spinal surgery† (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.¹⁰⁰²

Thromboprophylaxis in Trauma

LMWHs may be used for thromboprophylaxis in patients with major trauma†.¹⁰⁰² For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests use of both a pharmacologic and mechanical method of prophylaxis unless contraindications exist.¹⁰⁰²

Treatment of Renal Vein Thrombosis

Although use of anticoagulant therapy for renal vein thrombosis† (the most common cause of spontaneous venous thromboembolism in neonates) is controversial, LMWHs are suggested by ACCP as a possible treatment option.¹⁰¹³

Thromboprophylaxis in Acute Ischemic Stroke

Heparin anticoagulants (i.e., LMWHs or unfractionated heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke†; those with additional risk factors for venous thromboembolism are more likely to benefit from such prophylaxis.¹⁰⁰⁹

ACCP suggests thromboprophylaxis with an LMWH, sub-Q unfractionated heparin, or intermittent pneumatic compression in patients with acute ischemic stroke† and restricted mobility; LMWH is preferred over unfractionated heparin.¹⁰⁰⁹

Prophylactic-dose heparin (unfractionated heparin or an LMWH) usually initiated within 48 hours of onset of stroke and is continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.¹⁰⁰⁹

LMWHs also recommended by ACCP as an option for initial management of acute arterial ischemic stroke in children† until dissection and embolic causes have been excluded.¹⁰¹³ If arterial ischemic stroke is associated with dissection or a cardioembolic origin, continued anticoagulant therapy suggested.¹⁰¹³

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy, ACCP recommends ongoing antithrombotic therapy (e.g., with an LMWH) for 3 months.¹⁰¹³

LMWHs may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source.¹⁰¹³

Thromboembolism During Pregnancy

Used during pregnancy for prevention and treatment of venous thromboembolism and for prevention and treatment of systemic embolism associated with mechanical heart valves.¹³⁸ ⁹⁹⁶ ¹⁰¹² (See Prevention and Treatment of Thromboembolism During Pregnancy under Dosage and Administration.)

Also has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibody (APLA) syndrome†.¹⁰¹²

LMWHs (rather than unfractionated heparin or warfarin) are recommended by ACCP for prevention and treatment of thromboembolism during pregnancy.¹⁰¹²

In pregnant women with an acute venous thromboembolic event, ACCP recommends an LMWH for initial treatment and secondary prevention throughout the remainder of the pregnancy.¹⁰¹² To prevent recurrence, postpartum anticoagulation (for ≥6 weeks and for a total duration of ≥3 months) is suggested.¹⁰¹²

In general, thromboprophylaxis (e.g., with an LMWH) is suggested during the antepartum period only in pregnant women who have a history of thromboembolism and are considered to be at moderate to high risk of recurrent events (e.g., those with a single episode of unprovoked venous thromboembolism, pregnancy- or estrogen-related venous thromboembolism, history of multiple unprovoked events).¹⁰¹²

Postpartum thromboprophylaxis for 6 weeks suggested in all pregnant women with a prior venous thromboembolic event; an LMWH (in prophylactic or intermediate dosages) or warfarin (INR 2–3) may be used for such prophylaxis.¹⁰¹²

ACCP suggests antepartum and postpartum prophylaxis with an LMWH in some pregnant women with high-risk hereditary thrombophilias (e.g., homozygous genetic mutations for factor V Leiden or prothrombin G20210A) who have not experienced a prior venous thromboembolic event, but have a family history of thromboembolism.¹⁰¹²

Discontinue LMWH therapy ≥24 hours prior to induction of labor or cesarean section (or expected time of neuraxial anesthesia) to avoid an unwanted anticoagulant effect on fetus.¹⁰¹²

Cardioversion of Atrial Fibrillation/Flutter

LMWHs have been used for prevention of stroke and systemic embolism in patients with atrial fibrillation/flutter† undergoing electrical or pharmacologic cardioversion.⁹⁹⁹ ¹⁰⁰⁷

As an alternative to prolonged anticoagulation (e.g., usually with warfarin) prior to cardioversion in patients with atrial fibrillation lasting >48 hours or of unknown duration, an LMWH (in therapeutic dosages) may be used at the time of transesophageal echocardiography (TEE), followed by cardioversion within 24 hours if no thrombus is detected.⁹⁹⁹ ¹⁰⁰⁷

In patients with atrial fibrillation of short duration (e.g., ≤48 hours), an LMWH (in therapeutic dosages) may be used at presentation, followed by immediate cardioversion.¹⁰⁰⁷

In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of a parenteral anticoagulant (in therapeutic dosages) prior to cardioversion if possible; however, such anticoagulant therapy must not delay any emergency intervention.⁹⁹⁹ ¹⁰⁰⁷

After successful cardioversion to sinus rhythm, all patients should receive therapeutic anticoagulation for ≥4 weeks.⁹⁹⁹ ¹⁰⁰⁷

Thromboprophylaxis in Patients with Prosthetic Heart Valves

Used during conversion to maintenance therapy with warfarin to reduce the incidence of thromboembolism in patients with prosthetic mechanical heart valves†.¹⁰⁰⁸

ACCP suggests bridging anticoagulation (an LMWH in either prophylactic or therapeutic dosages or IV unfractionated heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve in patients without bleeding risk, until an adequate response to warfarin is obtained.¹⁰⁰⁸

Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., those undergoing major surgery).¹⁰⁰⁴

Used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves†.¹³⁸ ¹⁰¹² (See Thromboembolism During Pregnancy under Uses.)

Venous Thromboembolism in Pediatric Patients

An LMWH has been used for treatment of venous thromboembolism in pediatric patients†; venous thromboembolism usually occurs secondary to an identifiable risk factor (e.g., presence of central venous access device in such patients).¹⁰¹³

Recommendations regarding use of antithrombotic therapy in children generally based on extrapolation from adult guidelines.¹⁰¹³

ACCP recommends an LMWH or unfractionated heparin for both initial and ongoing treatment of venous thromboembolism in children.¹⁰¹³ Potential advantages of an LMWH over unfractionated heparin include reduced need for monitoring, lack of drug or dietary interactions, reduced risk of heparin-induced thrombocytopenia (HIT), and possible reduced risk of osteoporosis.¹⁰¹³

In children with central venous catheter-related thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation is suggested prior to removal.¹⁰¹³ If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.¹⁰¹³

Treatment of Cerebral Venous Sinus Thrombosis

May be used for the treatment of acute cerebral venous sinus (sinovenous) thrombosis† in adults.¹⁰⁰⁹ Once patient stabilized, may convert to coumarin anticoagulant therapy.¹³⁸ ¹⁰⁰⁹

Recommended by ACCP as an option for initial and follow-up anticoagulation in children with cerebral venous sinus thrombosis† without substantial intracranial hemorrhage.¹⁰¹³ Also has been suggested for use in children with substantial intracranial hemorrhage.¹⁰¹³

LMWHs also suggested by ACCP as a treatment option for neonates with cerebral sinovenous thrombosis.¹⁰¹³

Acute Ischemic Complications Following ST-Segment Elevation MI (STEMI)

LMWHs are used in combination with thrombolytic therapy and/or antiplatelet agents (e.g., aspirin, a P2Y12 receptor antagonist, GP IIb/IIIa-receptor inhibitor) during and after successful coronary artery reperfusion for the prevention of ischemic complications (e.g., death, reinfarction, stroke) in patients with acute STEMI†.¹⁴⁵

Adjunctive use of an LMWH in patients with STEMI associated with improvement in short-term clinical outcomes (e.g., death, reinfarction, recurrent ischemia) with generally similar rates of bleeding complications compared with adjunctive unfractionated heparin or placebo.¹⁴⁵ ¹⁴⁷ ¹⁴⁸ ¹⁴⁹ ¹⁵⁰ ¹⁵¹

LMWHs may be preferred over unfractionated heparin in patients who have preserved renal function (S_cr ≤2.5 mg/dL in men or ≤2 mg/dL in women).¹⁴⁵

Also used for prevention of systemic embolism following STEMI in high-risk patients (e.g., patients with large or anterior MI, atrial fibrillation, previous embolus, documented left ventricular thrombus, cardiogenic shock).¹⁴⁵

Perioperative Antithrombotic Prophylaxis

ACCP suggests use of an LMWH or IV unfractionated heparin (bridging anticoagulation†) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves who require temporary interruption of warfarin therapy during surgery or other invasive procedures; use and type of bridging anticoagulation depend on patients' risk of developing thromboembolism without warfarin therapy.¹⁰⁰⁴

In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.¹⁰⁰⁴

Dalteparin Sodium Dosage and Administration

General

Since routine coagulation parameters such as PT or aPTT are insensitive for monitoring dalteparin activity, routine monitoring of coagulation parameters generally is not required.¹ ¹⁵²
Monitoring of anti-factor Xa levels may be helpful in high-risk groups, such as pregnant patients, patients with renal impairment, patients at extremes of weight, or if abnormal coagulation parameters or bleeding occurs during treatment.¹ ¹⁵²
If an LMWH is used for anticoagulation in children, ACCP suggests that dosage be adjusted to a target anti-factor Xa level of 0.5–1 units/mL based on a sample taken 4–6 hours or 0.5–0.8 units/mL based on a sample taken 2–6 hours, following sub-Q administration.¹⁰¹³

Administration

Sub-Q Administration

Administer by deep sub-Q injection; do not give IM.¹

Patient should be sitting or supine during administration.¹

When injecting, insert entire length of needle at 45–90° angle.¹ Administer injections into the U-shaped area around the navel, upper outer aspect of the thigh, or upper outer quadrangle of the buttock.¹ Alternate injection sites daily.¹ When injecting into area around the navel or the thigh, insert needle into a skin fold created by thumb and forefinger.¹ Hold skin until needle is withdrawn.¹

Injection is commercially available in prefilled syringes equipped with a 27-gauge ½-inch needle.¹

Dosage

Dosages for dalteparin sodium and other LMW heparins or unfractionated heparin cannot be used interchangeably on a unit-for-unit (or mg-for-mg) basis.¹ ³ ⁵ ⁹

Available as dalteparin sodium; dosage expressed in anti-factor Xa international units (IU, units).¹ ² Each mg of dalteparin sodium is equivalent to 156.25 units.¹

Adults

Unstable Angina and Non-ST-Segment Elevation MI

Sub-Q

120 units/kg every 12 hours (up to a maximum of 10,000 units every 12 hours) until patient is clinically stabilized, generally for 5–8 days.¹ Concurrent aspirin therapy is recommended in all patients unless contraindicated.¹

Prevention of DVT and PE

General/Abdominal Surgery

Sub-Q

Usual dosage: 2500 units initially,¹ ⁵ ⁶ ⁷ ⁸ ⁹ ²⁷ ³⁰ given 1–2 hours before surgery.¹ ⁶ ⁸ ⁹ ¹⁹ ²¹ Continue with 2500 units once daily throughout postoperative period, generally for 5–10 days.¹ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹⁹ ²⁰ ²¹

Patients undergoing abdominal surgery associated with a high risk of thromboembolism (e.g., surgery for malignancy): 5000 units, initiated on the evening prior to surgery, followed by daily administration of 5000 units throughout postoperative period.¹ Alternatively, in patients with malignancy, may administer 2500 units 1–2 hours prior to surgery and repeat dose 12 hours later; follow with 5000 units daily throughout postoperative period, generally for 5–10 days.¹ ³⁰ ³³

Extended prophylaxis (for up to 4 weeks) recommended by ACCP in patients undergoing abdominal or pelvic surgery for cancer.¹⁰⁰²

Hip-Replacement Surgery

Sub-Q

Initiate therapy either preoperatively or postoperatively; several regimens are recommended by manufacturer.¹

Preoperative start, evening before surgery: 5000 units 10–14 hours before surgery, followed by 5000 units 4–8 hours after surgery, or later if hemostasis has not been achieved.¹

Preoperative start, day of surgery: 2500 units within 2 hours prior to surgery, followed by 2500 units 4–8 hours after surgery, or later if hemostasis has not been achieved.¹

Postoperative start: 2500 units 4–8 hours after surgery, or later if hemostasis has not been achieved.¹

Continue with 5000 units once daily throughout postoperative period (manufacturer states generally for 5–10 days, but up to 14 days has been well tolerated).¹ ACCP recommends a minimum of 10–14 days of thromboprophylaxis, with extended prophylaxis suggested for up to 35 days on an outpatient basis.¹⁰⁰³

Medical Conditions Predisposing to Thromboembolism

Sub-Q

Acute illness with severely restricted mobility: 5000 units once daily, generally for 12–14 days.¹

Treatment of DVT or PE in Cancer Patients

Sub-Q

First month of treatment: 200 units/kg (≤18,000 units) once daily.¹

Months 2–6 of treatment: Approximately 150 units/kg (≤18,000 units) once daily.¹

Safety and efficacy of treatment periods >6 months not established.¹

Patients with thrombocytopenia: Reduce daily dosage by 2500 units in patients with platelet counts of 50,000–100,000/mm³ until platelet count recovers to ≥100,000/mm³.¹ Discontinue therapy if platelet count <50,000/mm³ until platelet count recovers to >50,000/mm³.¹

Prevention and Treatment of Thromboembolism During Pregnancy†

Sub-Q

Treatment of acute venous thromboembolism: ACCP recommends 200 units/kg daily throughout the remainder of pregnancy; continue anticoagulation for ≥6 weeks postpartum (minimum total duration of 3 months).¹⁰¹²

Postpartum prophylaxis in patients with a prior venous thromboembolic event: Prophylactic (5000 units once daily) or intermediate (5000 units every 12 hours) dosage suggested.¹⁰¹²

Pregnant women receiving long-term coumarin anticoagulation (e.g., warfarin): An LMWH may be used throughout pregnancy in a weight-adjusted dosage (e.g., dalteparin sodium 100 units/kg twice daily or dalteparin sodium 200 units/kg daily) or 75% of a weight-adjusted dosage; resume long-term anticoagulation postpartum.¹⁰¹²

Primary prevention of venous thromboembolism in pregnant women with high-risk thrombophilias: Prophylactic (5000 units once daily) or intermediate (5000 units every 12 hours) dosage suggested.¹⁰¹²

Pregnant women with APLA syndrome†: Antepartum administration of an LMWH in prophylactic dosages recommended by ACCP; combine with low-dose aspirin (75–100 mg daily).¹⁰¹²

Pregnant women with mechanical heart valves: ACCP recommends an LMWH throughout pregnancy or, alternatively, an LMWH until 13th week of pregnancy, substituting warfarin until close to delivery, then resuming LMWH therapy.¹⁰¹² Dosage adjustment suggested to maintain manufacturer-recommended peak anti-factor X_a concentration 4 hours after dosing.¹⁰¹² Resume usual long-term anticoagulation postpartum.¹⁰¹² (See Patients with Prosthetic Heart Valves under Cautions.)

ACCP and other clinicians suggest administering LMWHs twice daily in pregnant women, at least initially, because of altered pharmacokinetics of these drugs in such women.⁹⁹⁶ ¹⁰¹²

To avoid an unwanted anticoagulant effect on the fetus during delivery, discontinue LMWH ≥24 hours prior to induction of labor or cesarean section.¹⁰¹²

Cardioversion of Atrial Fibrillation/Flutter†

Sub-Q

For prevention of stroke and systemic embolism in patients undergoing cardioversion for atrial fibrillation or atrial flutter†, use of full venous thromboembolism treatment dosages recommended.¹⁰⁰⁷

Prescribing Limits

Adults

Unstable Angina or Non-ST-Segment Elevation MI

Sub-Q

Maximum 10,000 units every 12 hours.¹

Patients with Cancer

Sub-Q

Maximum total daily dose of 18,000 units.¹

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹

Renal Impairment

Use with caution in patients with severe renal insufficiency; monitor anti-factor Xa levels to determine appropriate dosage in such patients.¹ ³ ACCP suggests that dosage be reduced in patients with severe renal impairment (Cl_cr <30 mL/minute).¹⁰⁰⁰

Geriatric Patients

Careful attention to dosing intervals and concomitant medications (particularly antiplatelet drugs) is advised, particularly in geriatric patients with low body weight (<45 kg).¹

Cautions for Dalteparin Sodium

Contraindications

Active major bleeding.¹
History of heparin-induced thrombocytopenia (HIT) with or without thrombosis.¹
Known hypersensitivity to dalteparin, heparin, or pork products.¹
Patients with unstable angina or NSTEMI undergoing neuraxial (epidural/spinal) anesthesia.¹

Warnings/Precautions

Hematologic Effects

Epidural or spinal hematoma and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of LMWH and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.¹ ³⁵ ⁷⁷ Frequent monitoring for signs of neurologic impairment recommended.³⁵ (See Boxed Warning.)

The risk of bleeding with dalteparin therapy varies with the indication and may increase with higher dosages.¹

Thrombocytopenia with thrombosis reported.¹ HIT can occur.¹ Monitor thrombocytopenia of any degree closely.¹

Periodic CBCs, including platelet counts, and stool occult blood tests recommended.¹ If abnormal coagulation parameters or bleeding should occur, may use anti-factor Xa levels to monitor anticoagulant effects of dalteparin.¹

Patients with Prosthetic Heart Valves

Valve thrombosis resulting in death (including maternal and fetal deaths) and/or requiring surgical intervention reported during thromboprophylaxis with another LMWH (enoxaparin) in some patients (including pregnant women) with prosthetic heart valves.¹⁰¹ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹ ¹¹⁰ ¹¹¹ ¹¹² ¹¹³ ¹¹⁴ ¹¹⁵ ⁹⁹⁶ Women with mechanical prosthetic heart valves are at higher risk for thromboembolism during pregnancy,¹¹² ¹³² ¹³³ ¹³⁴ ¹³⁸ ¹³⁹ and the manufacturer states that dalteparin has not been studied systematically in patients with prosthetic heart valves.¹⁰² (See Prevention and Treatment of Thromboembolism during Pregnancy under Dosage and Administration.)

Specific Populations

Pregnancy

Category B.¹ Benzyl alcohol used as a preservative in multiple-dose vials of dalteparin may cross the placenta.¹ ⁶⁷ Use caution when administering dalteparin in multiple-dose vials containing benzyl alcohol to pregnant women; use preservative-free formulations when possible.¹ ⁶⁷

Lactation

Small amounts distributed into milk in humans.¹ ⁵ ³⁶ Use caution in nursing women.¹ ACCP recommends that LMWHs be continued in nursing women who are already receiving such therapy.¹⁰¹²

Pediatric Use

Safety and efficacy not established.¹ ³⁰

Multiple-dose vials contain benzyl alcohol as a preservative.¹ Administration of injections preserved with benzyl alcohol to premature infants has, in large amounts, been associated with toxicity and fatal “gasping syndrome”.¹ ⁶⁷ ⁶⁸ ⁶⁹ ⁷⁰ ⁷¹ ⁷²

Geriatric Use

Possible increased risk of bleeding in geriatric patients; however, no substantial differences in safety relative to younger adults reported.¹ Pay careful attention to dosing intervals and concomitant agents (particularly antiplatelet agents), particularly in geriatric patients with low body weight (<45 kg) and those predisposed to decreased renal function.¹

Renal Impairment

Use with caution in patients with severe renal impairment; greater drug accumulation can be expected in such patients.¹

Common Adverse Effects

Hematoma at the injection site.¹ ⁸ ⁹ ¹⁰ ¹⁹ ²⁰ ²¹ ³³ ³⁴

Interactions for Dalteparin Sodium

Specific Drugs

Drug	Interaction	Comments
Anticoagulants, oral	Increased risk of bleeding¹	Use concomitantly with care¹
Platelet-aggregation inhibitors	Increased risk of bleeding¹	Use concomitantly with care¹
Thrombolytic agents	Increased risk of bleeding¹	Use concomitantly with care¹

Dalteparin Sodium Pharmacokinetics

Absorption

Bioavailability

Approximately 87% (absolute bioavailability).¹ Greater bioavailability than unfractionated heparin (based on anti-factor Xa activity).¹ ³ ⁵ ⁶ ⁷ ⁸ ²⁷ ²⁹

Onset

Mean peak plasma levels of anti-factor Xa activity generally attained about 4 hours after a single sub-Q injection.¹

Distribution

Extent

40–60 mL/kg (based on anti-factor Xa activity).¹

Small amounts distributed into milk.¹ ³⁶

Elimination

Half-life

3–5 hours following sub-Q administration.¹

Special Populations

Terminal half-life prolonged (to approximately 5.7 hours) in patients with chronic renal insufficiency requiring hemodialysis compared with healthy individuals.¹

Similar pharmacokinetics in geriatric and younger patients.⁵

Stability

Storage

Parenteral

Solution for Injection

20–25°C.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Should not be mixed with other injections or infusions unless specific compatibility data support such admixtures.¹

Actions

Less effect on thrombin than unfractionated heparin at a given level of anti-factor Xa activity.¹ ³ ²⁷
At recommended dosages, does not substantially affect platelet aggregation, fibrinolysis, global clotting function tests (i.e., PT, thrombin time, aPTT), or lipoprotein lipase.¹ ⁸ ²⁴ ²⁵ ³¹

Advice to Patients

Importance of reporting any unexplained bleeding, bruising, or signs of thrombocytopenia (rash of dark red spots under skin) to clinician.¹ Advise patient that they may bleed or bruise more easily and that bleeding may take longer than usual to stop.¹
Advise patient to inform dentists and physicians about dalteparin therapy before scheduling surgery or taking new drugs.¹
Instruct patient and/or caregiver regarding dalteparin administration procedures if therapy is to continue following hospital discharge.¹
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., aspirin, other NSAIAs).¹
Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Dalteparin Sodium (Porcine)
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use only	2500 units/0.2 mL	Fragmin (available as single-dose prefilled syringes)	Pfizer
		5000 units/0.2 mL	Fragmin (available as single-dose prefilled syringes)	Pfizer
		7500 units/0.3 mL	Fragmin (available as single-dose prefilled syringes)	Pfizer
		10,000 units/0.4 mL	Fragmin (available as single-dose prefilled syringes)	Pfizer
		12,500 units/0.5 mL	Fragmin (available as single-dose prefilled syringes)	Pfizer
		15,000 units/0.6 mL	Fragmin (available as single-dose prefilled syringes)	Pfizer
		18,000 units/0.72 mL	Fragmin (available as single-dose prefilled syringes)	Pfizer
		10,000 units/ mL	Fragmin (available as single-dose graduated syringes)	Pfizer
		95,000 units/9.5 mL (10,000 units/mL)	Fragmin (available as multiple-dose vial)	Pfizer
		25,000 units/mL	Fragmin (available as multiple-dose vial)	Pfizer
		95,000 units/3.8 mL (25,000 units/mL)	Fragmin (available as multiple-dose vial)	Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Fragmin 10000UNIT/ML Solution (EISAI): 1/$76.99 or 3/$225.96

Fragmin 2500UNIT/0.2ML Solution (EISAI): 0/$30.99 or 1/$75.59

Fragmin 25000UNIT/ML Solution (EISAI): 4/$623.96 or 11/$1,828.97

Fragmin 5000UNIT/0.2ML Solution (EISAI): 0/$42.19 or 1/$189.87

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions February 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

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