Class: Heparins
Chemical Name: Heparin, sodium salt
CAS Number: 9041-08-1
Brands: Fragmin
Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of low molecular weight (LMW) heparins 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 traumatic or repeated epidural or spinal puncture.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 Neurologic Effects under Cautions.)
Introduction
Anticoagulant; a low molecular weight heparin.1 3 5 10 22 23 26
Uses for Dalteparin Sodium
Unstable Angina and Non-ST-Segment Elevation/Non-Q-Wave MI
Reduction in the risk of acute cardiac ischemic events (death and/or MI) in patients with unstable angina or non-ST-segment elevation/non-Q-wave MI (i.e., non-ST-segment elevation acute coronary syndromes).1 49 51 52 53 54 66 103 104 105 106 Used concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors) in such patients.1 49 51 52 53 54 66 103 104 105 106 121
ACC, AHA, and other clinicians prefer an LMW heparin over unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes unless renal failure is present or CABG is planned within 24 hours.105 121
Based on limited data, the ACC, AHA, and other experts consider the use of an LMW heparin to be a reasonable alternative to unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes undergoing PCI.94
Hip-Replacement Surgery
Prophylaxis of postoperative DVT and pulmonary embolism in patients undergoing hip-replacement surgery.1 27 60 63 64 73 90 118
Consider extended prophylaxis† in patients undergoing hip-replacement surgery who have ongoing risk factors for venous thromboembolism (e.g., obesity, delayed mobilization, cancer, history of venous thromboembolism).118
Hip-Fracture Surgery
An LMW heparin recommended by American College of Chest Physicians (ACCP) for prophylaxis of postoperative DVT and pulmonary embolism in patients undergoing hip-fracture surgery†.118
Consider extended prophylaxis† in patients undergoing hip-fracture surgery† who have ongoing risk factors for venous thromboembolism (e.g., obesity, delayed mobilization, cancer, history of venous thromboembolism).118
Knee-Replacement Surgery
Routine thromboprophylaxis with an LMW heparin recommended by ACCP in patients undergoing knee-replacement surgery†.118
Knee Arthroscopy
An LMW heparin suggested by ACCP based on limited data for prophylaxis of venous thromboembolism in high-risk patients undergoing knee arthroscopy† (e.g., those with preexisting thromboembolic risk factors or following a prolonged or complicated procedure).118
General Surgery
Prophylaxis of postoperative venous thromboembolism in patients undergoing general (e.g., abdominal, gynecologic, urologic) surgery who are at risk for thromboembolic complications.1 3 6 7 8 9 10 19 20 21 22 90 118
Early ambulation without specific thromboprophylaxis recommended by ACCP in patients undergoing general surgery who are at low risk for venous thromboembolism (those undergoing minor operations who are <40 years of age and who have no clinical risk factors).27 90 118
Recommended as alternative to fixed low-dose unfractionated heparin in moderate-risk general surgery patients (those undergoing nonmajor surgery who are 40–60 years of age or who have additional risk factors for thromboembolism, patients <40 years of age undergoing major surgery with no additional risk factors, and patients with risk factors who are undergoing minor surgery).90 118
Recommended as alternative to fixed low-dose unfractionated heparin in patients undergoing general surgery who are at higher risk for thromboembolism (those undergoing major surgery who are >40 years of age or who have additional risk factors and patients undergoing nonmajor surgery who are >60 years of age or who have additional risk factors).27 90 118
Recommended as alternative to low-dose unfractionated heparin and in combination with intermittent pneumatic compression or graduated compression stockings27 90 118 in high-risk general surgery patients (those >40 years of age with multiple risk factors such as a history of previous venous thromboembolism, cancer, or a hypercoagulable state).27 90 Continue LMW heparin after hospital discharge in selected high-risk general surgery patients, including those undergoing major cancer surgery.90 118
Thromboprophylaxis with low-dose unfractionated heparin, LMW heparin, intermittent pneumatic compression, graduated compression stockings, or a combination of these interventions suggested in patients undergoing laparoscopic gynecologic procedures who have additional risk factors for venous thromboembolic events (e.g., malignancy, older age, previous thromboembolism, prior pelvic radiation therapy, use of an abdominal surgical approach).118
Thromboprophylaxis with LMW heparin recommended as alternative to low-dose unfractionated heparin1 60 104 or intermittent pneumatic compression in patients undergoing major gynecologic surgery for benign disease who do not have additional risk factors for thromboembolism.118 Begin just prior to surgery and continue until hospital discharge or patient is ambulatory.118
Routine prophylaxis with LMW heparin or unfractionated heparin recommended in patients undergoing extensive gynecologic procedures for malignancy and in those with additional risk factors for venous thromboembolic events.118 Alternative regimens include intermittent pneumatic compression continued until hospital discharge, or the combination of low-dose unfractionated heparin or LMW heparin and intermittent pneumatic compression or graduated compression stockings.118 Continue extended prophylaxis† for 2–4 weeks following hospital discharge in those at particularly high risk for thromboembolism (e.g., previous cancer surgery, >60 years of age, history of thromboembolism).118
Thromboprophylaxis with an LMW heparin or low-dose unfractionated heparin recommended in patients undergoing major vascular surgery who have additional risk factors for thromboembolism (e.g., advanced age, limb ischemia, long duration of surgery, intraoperative local trauma).118
Medical Conditions Associated with Thromboembolism
Prophylaxis of thromboembolism in medical patients with CHF or severe lung disease or who have severely restricted mobility in conjunction with one or more additional risk factors (e.g., cancer, previous venous thromboembolism, sepsis, acute neurologic disease, inflammatory bowel disease).1 90 118 125
Neurosurgery
An LMW heparin recommended by ACCP as alternative therapy (e.g., instead of intermittent pneumatic compression with or without graduated compression stockings) for prophylaxis of thromboembolism in selected patients undergoing intracranial neurologic surgery†.118
Combination of an LMW heparin or low-dose unfractionated heparin with graduated compression stockings and/or intermittent pneumatic compression recommended in patients with multiple risk factors for venous thromboembolism.118
Elective Spinal Surgery
An LMW heparin recommended by ACCP for prevention of venous thromboembolism in patients undergoing elective spinal surgery† who have additional risk factors (e.g., advanced age, known malignancy, neurologic deficit, previous venous thromboembolic event, anterior surgical approach), as alternative to postoperative low-dose unfractionated heparin or perioperative intermittent pneumatic compression.118
Combine anticoagulant therapy with graduated compression stockings and/or intermittent pneumatic compression in patients with multiple risk factors for venous thromboembolism.118
Acute Spinal Cord Injury
An LMW heparin recommended by ACCP as first-line prophylaxis of thromboembolism in patients with acute spinal cord injury†.118
For prevention of thromboembolism in the rehabilitation phase of acute spinal cord injury†, continue therapy with an LMW heparin or, alternatively, convert to full-dose oral anticoagulation.73 118
Trauma
An LMW heparin recommended by ACCP as first-line prophylaxis of thromboembolism in patients with major trauma†.90
Initiate prophylaxis as soon as considered safe to do so and continue until hospital discharge, including during inpatient rehabilitation.73 118
Extended prophylaxis† after hospital discharge suggested in patients with major mobility impairment.118
Burns
An LMW heparin recommended by ACCP as alternative to low-dose unfractionated heparin in burn patients who have at least one additional risk factor for venous thromboembolism (e.g., advanced age, morbid obesity, extensive or lower extremity burns, concomitant lower extremity trauma, use of a femoral catheter, or prolonged immobility).118 Initiate prophylaxis as soon as the risk of bleeding is no longer high, provided no contraindications exist.118
Long-Distance Travel
Single prophylactic dose of an LMW heparin may be considered for thromboprophylaxis prior to travel† as alternative to below-knee graduated compression stockings in those with risk factors for venous thrombosis (e.g., previous DVT, coagulation disorder, limited mobility, current or recent cancer, large varicose veins, severe obesity).118 Data insufficient to support routine use in any group of travelers.118
Acute Ischemic Stroke
An LMW heparin recommended by ACCP as first-line prophylaxis of thromboembolism in patients with acute ischemic stroke† and impaired mobility who have no contraindications.120
Thromboembolism Occurring During Pregnancy
An LMW heparin recommended in selected patients for initial treatment and secondary prevention of thromboembolism during pregnancy†.88 90 91 96 97 98 99 117 153 154
Used alone or in combination with aspirin for prevention of pregnancy loss in women with antiphospholipid antibodies (APLAs) and previous pregnancy losses.117
Embolism Associated with Atrial Fibrillation/Flutter
An LMW heparin may be initiated at diagnosis to reduce the incidence of embolism in patients with atrial fibrillation/flutter of <48 hours' duration who are undergoing cardioversion†, provided no contraindications exist.119
Base the need for anticoagulation in such patients on the patient's individual risk of thromboembolism.98 In patients requiring immediate cardioversion because of hemodynamic instability, cardioversion should not be delayed for prior initiation of anticoagulation.98
An LMW heparin may be substituted for oral anticoagulant (e.g., warfarin) therapy in patients with atrial fibrillation† who require a series of diagnostic or surgical procedures that necessitate interruption of oral anticoagulation for >1 week or in selected high-risk patients who require interruption of oral anticoagulant therapy for shorter periods.98 Efficacy of these alternative therapies in this situation uncertain.98
Thromboembolism Associated with Prosthetic Heart Valves
An LMW heparin used with follow-up oral anticoagulation (e.g., warfarin) in selected patients for prevention of thromboembolism associated with prosthetic heart valves†.88 90 91 96 97 98 99 124
In patients with prosthetic heart valves in whom therapy with warfarin must be discontinued (e.g., those undergoing major surgery), substitution of an LMW heparin or unfractionated heparin is recommended by ACCP, AHA, and ACC.124 153
ACCP and other clinicians suggest that use of aggressive, adjusted-dose therapy with sub-Q LMW heparin or high-dose sub-Q unfractionated heparin therapy is reasonable in pregnant women with prosthetic mechanical heart valves†.88 117 153
DVT and Pulmonary Embolism
An LMW heparin recommended for treatment of suspected DVT† or acute nonmassive pulmonary embolism† while awaiting confirmation of diagnosis, provided no contraindications exist.116 117
Preferred over unfractionated heparin for treatment of confirmed DVT† or acute nonmassive pulmonary embolism†.116
Recommended by ACCP as alternative to oral anticoagulation (e.g., with warfarin) for long-term treatment of confirmed DVT† or acute nonmassive pulmonary embolism† in patients in whom oral anticoagulation is contraindicated or inconvenient.116
ACCP recommends that unfractionated heparin be substituted for LMW heparin in patients with severe renal failure.116
Superficial Thrombophlebitis
An LMW heparin suggested by ACCP as an alternative to unfractionated heparin for treatment of superficial thrombophlebitis†.116
Systemic Venous Thrombosis in Pediatric Patients
An LMW heparin suggested by ACCP for the treatment and prevention of systemic venous thrombosis in neonates and children†; data insufficient to make strong recommendations in neonates.123
Renal Vein Thrombosis
An LMW heparin suggested by ACCP for the treatment of renal vein thrombosis in neonates†; data limited and use of anticoagulant or thrombolytic therapy is controversial in such patients.123
Cerebral Venous Sinus Thrombosis
An LMW heparin recommended by ACCP with follow-up oral anticoagulation (e.g., warfarin) in adults with acute cerebral venous sinus thrombosis†, even in the presence of hemorrhagic venous infarcts.120 154
Neonates without large ischemic infarction or intracranial hemorrhage: Initial therapy with an LMW heparin or unfractionated heparin suggested, then administer LMW heparin for 3 months.123
Neonates with large infarcts or intracranial hemorrhage: Radiographic monitoring suggested; initiate anticoagulation if extension of thrombus detected.123
Children without major intracranial hemorrhage: LMW heparin or unfractionated heparin followed by LMW heparin or oral anticoagulation (e.g., with warfarin).123
Spontaneous Aortic Thrombosis
Neonates experiencing spontaneous aortic thrombosis with evidence of renal ischemia: Urgent, aggressive use of thrombolytic or surgical therapy supported by anticoagulation with an LMW heparin or unfractionated heparin suggested by ACCP.123
Acute Ischemic Complications Following ST-Segment Elevation MI
AHA, ACC, and ACCP suggest that adjunctive therapy with an LMW heparin may be considered in place of unfractionated heparin as adjunctive therapy for patients ≤75 years of age who have preserved renal function (Scr ≤2.5 mg/dL in men or ≤2 mg/dL in women).145 146
Most experience to date with enoxaparin as adjunct to tenecteplase in patients with ST-segment elevation MI†; additional study and experience recommended before routine use of LMW heparin instead of unfractionated heparin in such patients.145 146 148
ACC and AHA recommend use of an LMW heparin or unfractionated heparin for prevention of systemic embolism following ST-segment elevation MI† in high-risk patients (e.g., patients with large or anterior MI, atrial fibrillation, previous embolus, documented left ventricular thrombus, cardiogenic shock).145
Preferred by ACC and AHA over unfractionated heparin for prophylaxis of DVT and pulmonary embolism in patients with CHF after ST-segment elevation MI who are hospitalized for prolonged periods, nonambulatory, or are considered at high risk for DVT and are not receiving other anticoagulant therapy.145
Also recommended by ACC and AHA for prophylaxis in patients surviving ST-segment elevation MI with or without acute ischemic stroke who have cardiac sources of embolism (atrial fibrillation, mural thrombus, akinetic segment) after reperfusion therapy; administer until adequate anticoagulation with warfarin achieved.145
ACC and AHA suggest LMW heparin as reasonable alternative to unfractionated heparin in patients with ST-segment elevation MI who are not receiving thrombolytic therapy, provided no contraindications to anticoagulation exist.145
Based on limited evidence principally with enoxaparin, ACC, AHA, and other clinicians suggest use of an LMW heparin as an alternative to unfractionated heparin in patients with acute ST-segment elevation MI undergoing PCI.94
Dalteparin Sodium Dosage and Administration
General
Dosage adjustment and routine monitoring of coagulation parameters generally not necessary if recommended regimens are followed.1 152
Monitoring LMW heparin therapy may be helpful in high-risk patient groups, such as pregnant women, patients with renal impairment, or patients at extremes of weight; use anti-factor Xa concentrations to monitor the anticoagulant effects of dalteparin.152
In pregnant women with mechanical prosthetic heart valves, frequently monitor peak and trough anti-factor Xa concentrations; adjust dosage as necessary.111 153 ACCP and other clinicians recommend twice-daily dosing of LMW heparin in pregnant women, at least initially, because of the altered pharmacokinetics of these drugs (e.g., shorter half-life) in such women.117 153
Administration
Sub-Q Administration
Administer by deep sub-Q injection; do not give IM.1 Administer in sitting or supine position.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 regular (unfractionated heparin) or other LMW heparins 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
Adults
Unstable Angina and Non-ST-Segment Elevation/Non-Q-Wave 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 Venous Thrombosis and Pulmonary Embolism
Hip-Replacement Surgery
Sub-Q
Initiate therapy either preoperatively or postoperatively; several regimens have been used.1 118 ACCP recommends initiation 12–24 hours postoperatively following achievement of hemostasis in patients at high risk for bleeding.118
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 Continue with 5000 units daily throughout the postoperative period (generally 5–10 days, but up to 14 days has been well tolerated).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 Continue with 5000 units daily throughout the postoperative period (generally 5–10 days, but up to 14 days has been well tolerated).1
Alternative preoperative regimen recommended by ACCP: usual high-risk dosage (e.g., 5000 units) beginning 12 hours prior to surgery and continuing for ≥10 days postoperatively.118
Postoperative start: 2500 units 4–8 hours after surgery or later if hemostasis has not been achieved.1 Continue with 5000 units daily throughout the postoperative period (generally 5–10 days, but up to 14 days has been well tolerated).1
Alternative postoperative regimen recommended by ACCP: half the usual high-risk dosage (e.g., 2500 units) 4–6 hours after surgery , followed by the usual high-risk dosage (e.g., 5000 units daily) the next day for ≥10 days.118
Another alternative regimen recommended by ACCP: Usual high-risk dosage (e.g., 5000 units) 12–24 hours after surgery and continuing for ≥10 days.118
Extended prophylaxis: ACCP recommends continuation for ≤28–35 days postoperatively in patients considered at high risk for thromboembolism.118
Hip-Fracture Surgery
Sub-Q
ACCP recommends the usual high-risk dosage (e.g., 5000 units daily) initiated either preoperatively or postoperatively.118 If surgery likely to be delayed, initiate preoperatively and reinstitute postoperatively after hemostasis achieved.118
Continue prophylaxis for ≥10 days (i.e., most patients will continue anticoagulation following hospital discharge).118
Extended prophylaxis: ACCP recommends continuation for ≤28–35 days postoperatively in patients considered at high risk for thromboembolism.118
Knee-Replacement Surgery
Sub-Q:
ACCP recommends the usual high-risk dosage (e.g., 5000 units daily) initiated either preoperatively or postoperatively.118
Continue prophylaxis for ≥10 days (i.e., most patients will continue anticoagulation following hospital discharge).118
General Surgery
Sub-Q
Patients at moderate to high risk for thromboembolic complications: 2500 units initially,1 5 6 7 8 9 27 30 90 given 1–2 hours before surgery.1 6 8 9 19 21 90 Continue with 2500 units once daily throughout postoperative period, generally for 5–10 days, until the risk of DVT has diminished.1 6 7 8 9 10 19 20 21 90 118
Patients who are at high risk for thromboembolic complications: 5000 units on the evening prior to surgery (e.g., 8–12 hours prior to surgery).1 90 Such patients include those with malignant disease or a history of DVT or pulmonary embolism.1 90 Continue with 5000 units daily throughout the postoperative period, generally for 5–10 days.1 27 30 33
Patients with malignancy: 2500 units given 1–2 hours prior to surgery and repeated 12 hours later.1 Continue with 5000 units daily throughout the postoperative period, generally for 5–10 days.1 27 30 33
Extended prophylaxis: ACCP suggests continuation for 2–3 weeks after hospital discharge in patients at high risk for thromboembolism (e.g., major cancer surgery).
Medical Conditions Associated with Thromboembolism
Sub-Q
5000 units once daily, generally for 12–14 days.1 Alternatively, ACCP recommends a dosage of 2500 units daily in general medical patients with high-risk factors for thromboembolism (e.g., cancer, CHF, severe lung disease, patients confined to bedrest).90
Thromboembolism Occurring During Pregnancy
Sub-Q
Treatment of acute venous thromboembolism: 200 units/kg daily in 1 or 2 divided doses throughout pregnancy.117 Continue oral anticoagulation (e.g., with warfarin) for at least 6 weeks postpartum.117
Primary prevention in women with inherited causes of thrombophilia (e.g., antithrombin deficiency, heterozygous genetic mutation of both prothrombin G20210A and factor V Leiden, or homozygous genetic mutation for factor V Leiden or prothrombin G20210A): 5000 units once daily or every 12 hours throughout pregnancy suggested, followed by postpartum oral anticoagulation (e.g., with warfarin) for at least 4–6 weeks.117
Primary prevention in other patients with confirmed thrombophilia: 5000 units once daily throughout pregnancy suggested, followed by postpartum oral anticoagulation (e.g., with warfarin) for at least 4–6 weeks.117
Secondary prevention after a single episode of idiopathic venous thromboembolism in women not receiving long-term anticoagulation: 5000 units once daily throughout pregnancy suggested, followed by postpartum oral anticoagulation (e.g., with warfarin) for at least 4–6 weeks.117
Secondary prevention after a single episode of venous thromboembolism in women with risk factors (e.g., confirmed thrombophilia, strong family history of thrombosis) not receiving long-term anticoagulation: 5000 units once daily or every 12 hours throughout pregnancy suggested, followed by postpartum oral anticoagulation (e.g., with warfarin) for at least 4–6 weeks.117
Secondary prevention after >2 episodes of venous thromboembolism in women receiving long-term anticoagulation: 200 units/kg daily in 1 or 2 divided doses throughout pregnancy suggested, followed by postpartum resumption of long-term anticoagulation.117
Adjust dosage for extremes of body weight.117
Discontinue 24 hours prior to elective induction of labor.117
Embolism Associated with Atrial Fibrillation/Flutter
Sub-Q
Patients with atrial fibrillation duration <48 hours undergoing cardioversion who have no contraindications to anticoagulation: 200 units/kg daily in 1 or 2 divided doses.116 117 126 127
ACCP suggests same regimen for anticoagulation in patients undergoing cardioversion for atrial flutter.119
Treatment of DVT and Nonmassive Pulmonary Embolism
Sub-Q
200 units/kg daily in 1 or 2 divided doses for at least 5 days has been recommended; administer on outpatient basis in selected patients with acute uncomplicated DVT.116
ACCP recommends against routine monitoring of anticoagulation (e.g., anti-factor Xa activity) with heparin treatment of acute venous thromboembolism.116
Initiate concurrently with oral anticoagulation (e.g., with warfarin) and overlap therapy until response to warfarin is adequate.116 Continue oral anticoagulation for at least 3 months.117 126 127
Patients with cancer or in whom oral anticoagulation contraindicated or inconvenient:39 59 116 200 units/kg once daily for 1 month, followed by 150 units/kg once daily for at least 3–6 months.116 Continue anticoagulation indefinitely or until cancer is resolved.116
Prescribing Limits
Adults
Unstable Angina or Non-ST-Segment Elevation/Non-Q-Wave MI
Sub-Q
Maximum 10,000 units every 12 hours.1
Cautions for Dalteparin Sodium
Contraindications
Known hypersensitivity to dalteparin, heparin, or pork products.1
Active major bleeding or thrombocytopenia associated with positive in vitro tests for anti-platelet antibody in the presence of the drug.1
Patients with unstable angina or non-ST-segment elevation/non-Q-wave MI undergoing regional anesthesia.1
Warnings/Precautions
Warnings
Neurologic Effects
Epidural or spinal hematomas and neurologic injury, including long-term or permanent paralysis, associated with concurrent use of low molecular weight (LMW) heparins and neuraxial (spinal/epidural) anesthesia or spinal puncture procedures.1 35 77 Frequent monitoring for signs of neurologic impairment recommended.35 (See Boxed Warning.)
Hematologic Effects
As with other anticoagulants, bleeding may occur at any site during therapy.1 Use with extreme caution in patients with an increased risk of hemorrhage.1 Such patients include those with severe uncontrolled hypertension, bacterial endocarditis, congenital or acquired bleeding disorders, active ulceration and angiodysplastic GI disease, hemorrhagic stroke, or recent brain, spinal, or ophthalmologic surgery.1 Use with caution in patients with bleeding diathesis or recent GI bleeding.1
An unexpected decrease in hematocrit or BP may indicate hemorrhage and should prompt evaluation to determine a bleeding site.1 If severe hemorrhage or dalteparin overdosage occurs, administer protamine sulfate immediately.1
If a thromboembolic event occurs despite dalteparin prophylaxis, the drug should be discontinued and appropriate therapy initiated.1
Thrombocytopenia with thrombosis reported rarely.1 Heparin-induced thrombocytopenia can occur.1
Use with extreme caution in patients with a history of heparin-induced thrombocytopenia.1 Use with caution in patients with thrombocytopenia or platelet defects.1
Monitor thrombocytopenia of any degree closely.1
Sensitivity Reactions
Allergic reactions1 19 33 34 (including pruritus,1 6 11 rash,1 fever,1 injection site reactions,1 6 11 12 and bullous eruptions)1 and skin necrosis1 34 have occurred rarely.1 Anaphylactoid reactions1 also reported.1
General Precautions
Hepatic Effects
Increases in serum aminotransferase concentrations reported.1 21 34
Because serum aminotransferase determinations are important in the differential diagnosis of MI, liver disease, and pulmonary emboli, interpret elevation of these enzymes during therapy with caution.1
Specific Populations
Pregnancy
Category B.1 Because benzyl alcohol may cross the placenta, dalteparin in multiple-dose vials containing benzyl alcohol should not be used in pregnant women.67
Lactation
Small amounts distributed into breast milk.5 36 Use with caution in nursing women.1
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 has been associated with toxicity in neonates.1 67 68 69 70 71 72 However, the presence of small amounts of benzyl alcohol in a commercially available injection should not proscribe its use in neonates.
Geriatric Use
Because geriatric patients may have decreased renal function and because patients with severe renal impairment may be at increased risk of dalteparin-induced toxicity.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
Hepatic Impairment
Use with caution in patients with severe hepatic impairment.1
Renal Impairment
Use with caution in patients with severe renal impairment or hypertensive or diabetic nephropathy.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
|
|---|
Oral anticoagulants
|
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
Distribution
Extent
40–60 mL/kg (based on anti-Factor Xa activity).1
Not known if distributed into milk.1
Elimination
Half-life
3–5 hours (sub-Q administration).1
Special Populations
Terminal half-life prolonged (to 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
ActionsActions
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 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.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 (preservative-free; available as 0.2-mL disposable syringe)
|
Eisai
|
|
|
5000 units/0.2 mL
|
Fragmin (preservative-free; available as 0.2-mL disposable syringe)
|
Eisai
|
|
|
7500 units/0.3 mL
|
Fragmin (preservative-free; available as 0.3 mL disposable syringe)
|
Eisai
|
|
|
10,000 units/ mL
|
Fragmin (preservative-free; available as 1 mL disposable syringe and with benzyl alcohol 14 mg/mL available in 9.5 mL multiple-dose vial)
|
Eisai
|
|
|
25,000 units/mL
|
Fragmin (with benzyl alcohol 14 mg/mL available 3.8 mL multiple-dose vial)
|
Eisai
|
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 re
