Chemical Name: Heparin, sodium salt
CAS Number: 9041-08-1
[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 .
- 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
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.)
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
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
Thromboprophylaxis in Hip-Replacement, Knee-Replacement, or Hip-Fracture Surgery
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 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
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
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.)
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
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
Thromboprophylaxis in Patients with Prosthetic Heart Valves
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
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
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
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
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
Unstable Angina and Non-ST-Segment Elevation MI
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
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
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 ThromboembolismSub-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
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†
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 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.)
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†
Unstable Angina or Non-ST-Segment Elevation MI
Maximum 10,000 units every 12 hours.1
Patients with Cancer
Maximum total daily dose of 18,000 units.1
No specific dosage recommendations at this time.1
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
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
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
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
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.)
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
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
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
Use with caution in patients with severe renal impairment; greater drug accumulation can be expected in such patients.1
Common Adverse Effects
Interactions for Dalteparin Sodium
Increased risk of bleeding1
Use concomitantly with care1
Increased risk of bleeding1
Use concomitantly with care1
Increased risk of bleeding1
Use concomitantly with care1
Dalteparin Sodium Pharmacokinetics
Mean peak plasma levels of anti-factor Xa activity generally attained about 4 hours after a single sub-Q injection.1
40–60 mL/kg (based on anti-factor Xa activity).1
3–5 hours following sub-Q administration.1
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
Solution for Injection
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
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.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Injection, for subcutaneous use only
2500 units/0.2 mL
Fragmin (available as single-dose prefilled syringes)
5000 units/0.2 mL
Fragmin (available as single-dose prefilled syringes)
7500 units/0.3 mL
Fragmin (available as single-dose prefilled syringes)
10,000 units/0.4 mL
Fragmin (available as single-dose prefilled syringes)
12,500 units/0.5 mL
Fragmin (available as single-dose prefilled syringes)
15,000 units/0.6 mL
Fragmin (available as single-dose prefilled syringes)
18,000 units/0.72 mL
Fragmin (available as single-dose prefilled syringes)
10,000 units/ mL
Fragmin (available as single-dose graduated syringes)
95,000 units/9.5 mL (10,000 units/mL)
Fragmin (available as multiple-dose vial)
Fragmin (available as multiple-dose vial)
95,000 units/3.8 mL (25,000 units/mL)
Fragmin (available as multiple-dose vial)
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 12/2013. 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
AHFS DI Essentials. © Copyright, 2004-2013, Selected Revisions November 5, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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2. Pharmacia & Upjohn, Inc. Product information form for American hospital formulary service: Fragmin (dalteparin sodium injection). Columbus, OH; undated.
3. Hirsh J, Levine MN. Low molecular weight heparin. Blood. 1992; 79:1-17. [IDIS 290001] [PubMed 1309422]
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5. Simoneau G, Bergmann JF, Kher A et al. Pharmacokinetics of a low molecular weight heparin [Fragmin] in young and elderly subjects. Thromb Res. 1992; 66:603-7. [PubMed 1326135]
6. Ockelford PA, Patterson J, Johns AS. A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin). Thromb Haemost. 1989; 62:1046-9. [PubMed 2559484]
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10. Bergqvist D, Burmark US, Frisell J et al. Thromboprophylactic effect of low molecular weight heparin started in the evening before elective general abdominal surgery: a comparison with low-dose heparin. Semin Thromb Hemost. 1990; 16(Suppl):19-24. [PubMed 1962900]
11. Phillips JK, Majumdar G, Hunt BJ et al. Heparin-induced skin reaction due to two different preparations of low molecular weight heparin (LMWH). Br J Haematol. 1993; 84:349-50. [PubMed 8398843]
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13. Monreal M, Lafoz E, Salvador R et al. Adverse effects of three different forms of heparin therapy: thrombocytopenia, increased transaminases, and hyperkalaemia. Eur J Clin Pharmacol. 1989; 37:415-8. [IDIS 261495] [PubMed 2557219]
14. Bell WR, Royall RM. Heparin-associated thrombocytopenia: a comparison of three heparin preparations. N Engl J Med. 1980; 303:902-7. [IDIS 121420] [PubMed 6997743]
15. Sandoz Pharmaceuticals Corporation. Embolex (dihydroergotamine mesylate and heparin sodium; with lidocaine hydrochloride) injection prescribing information. East Hanover, NJ; 1987 Jun 26.
16. Abbott Laboratories. Intravenous solutions with heparin sodium injection prescribing information. North Chicago, IL; 1985 Jan.
17. Wyeth Laboratories. Heparin sodium injection prescribing information. Philadelphia, PA; 1989 Sep 22.
18. King DJ, Kelton JG. Heparin-associated thrombocytopenia. Ann Intern Med. 1984; 100:535-40. [IDIS 183834] [PubMed 6367579]
19. Bergqvist D, Burmark US, Frisell J et al. Low molecular weight heparin once daily compared with conventional low-dose heparin twice daily. A prospective double-blind multicentre trial on prevention of postoperative thrombosis. Br J Surg. 1986; 73:204-8. [PubMed 3512031]
20. Bergqvist D, Mätzsch T, Burmark US et al. Low molecular weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis. Br J Surg. 1988; 75:888-91. [PubMed 2846113]
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