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Dalteparin Sodium

Pronunciation

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

Warning(s)

Special Alerts:

[Posted 11/06/2013] ISSUE: The U.S. Food and Drug Administration (FDA) is recommending that health care professionals carefully consider the timing of spinal catheter placement and removal in patients taking anticoagulant drugs, such as enoxaparin, and delay dosing of anticoagulant medications for some time interval after catheter removal to decrease the risk of spinal column bleeding and subsequent paralysis after spinal injections, including epidural procedures and lumbar punctures. These new timing recommendations, which can decrease the risk of epidural or spinal hematoma, will be added to the labels of anticoagulant drugs known as low molecular weight heparins, including Lovenox and generic enoxaparin products and similar products.

BACKGROUND: Epidural or spinal hematomas are a known risk of enoxaparin in the setting of spinal procedures and are already described in the Boxed Warning and the Warnings and Precautions sections of the labels for Lovenox and generic enoxaparin products. However, these serious adverse events continue to occur (see Data Summary). To address this safety concern, FDA worked with the manufacturer of Lovenox, Sanofi-Aventis, to further evaluate this risk and to update the Warnings and Precautions section of the Lovenox label with these additional timing recommendations. The labels for generic enoxaparin products will also be revised accordingly, as will those of other low molecular weight heparin-type products.

It is important to note that all anticoagulants carry the risk of causing spinal bleeding when used in conjunction with epidural/spinal anesthesia or spinal puncture. We are continuing to evaluate the safety of other anticoagulants to determine if additional label changes are needed.

RECOMMENDATION: Health care professionals and institutions involved in performing spinal/epidural anesthesia or spinal punctures should determine, as part of a preprocedure checklist, whether a patient is receiving anticoagulants and identify the appropriate timing of enoxaparin dosing in relation to catheter placement or removal. To reduce the potential risk of bleeding, consider both the dose and the elimination half-life of the anticoagulant:

  • For enoxaparin, placement or removal of a spinal catheter should be delayed for at least 12 hours after administration of prophylactic doses such as those used for prevention of deep vein thrombosis. Longer delays (24 hours) are appropriate to consider for patients receiving higher therapeutic doses of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily).

  • A postprocedure dose of enoxaparin should usually be given no sooner than 4 hours after catheter removal.

  • In all cases, a benefit-risk assessment should consider both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors.

For more information visit the FDA website at: and .

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, heparin (referring throughout this monograph to unfractionated heparin), bivalirudin, or fondaparinux for anticoagulant therapy.991

In patients undergoing a conservative management strategy, recommended anticoagulants include an LMWH, 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 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

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

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

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

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

Treatment of 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 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 heparin, or intermittent pneumatic compression in patients with acute ischemic stroke and restricted mobility; LMWH is preferred over heparin.1009

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

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

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

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

Treatment of 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 heparin or placebo.145 147 148 149 150 151

LMWHs may be preferred over heparin in patients who have preserved renal function (Scr ≤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 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 LMWHs or 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 Xa 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 (Clcr <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 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

  • Has less effect than heparin on thrombin 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 02/2014. 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

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions November 5, 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.

References

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