Home › Drugs › Dalteparin Sodium

Dalteparin Sodium

FDA Drug Information • Also known as: Fragmin

Brand Names
Fragmin
Route
SUBCUTANEOUS
Dosage Form
INJECTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: SPINAL/EPIDURAL HEMATOMAS Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

  • Use of indwelling epidural catheters
  • Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants.
  • A history of traumatic or repeated epidural or spinal punctures
  • A history of spinal deformity or spinal surgery
  • Optimal timing between the administration of FRAGMIN and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis [see Warnings and Precautions (5.1) and Drug Interactions (7) ] . WARNING: SPINAL/EPIDURAL HEMATOMAS See full prescribing information for complete boxed warning. Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH) or heparinoids and are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:
  • Use of indwelling epidural catheters
  • Concomitant use of other drugs that affect hemostasis, such as non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants.
  • A history of traumatic or repeated epidural or spinal punctures
  • A history of spinal deformity or spinal surgery
  • Optimal timing between the administration of FRAGMIN and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis ( 5.1 , 7 ).

    • Description

    11 DESCRIPTION FRAGMIN Injection (dalteparin sodium injection) is a sterile, low molecular weight heparin. It is available in single-dose, prefilled syringes preassembled with a needle guard device, and multiple-dose vials. With reference to the W.H.O. First International Low Molecular Weight Heparin Reference Standard, each syringe contains either 2,500 units, 5,000 units, 7,500 units, 10,000 units, 12,500 units, 15,000 units or 18,000 anti-Xa international units (units), equivalent to 16 mg, 32 mg, 48 mg, 64 mg, 80 mg, 96 mg or 115.2 mg dalteparin sodium, respectively. Each multiple-dose vial contains 25,000 anti-Xa units per 1 mL (equivalent to 160 mg dalteparin sodium), for a total of 95,000 anti-Xa units per vial. Each single-dose vial contains 2,500 anti-Xa units per 1 mL (equivalent to 16 mg dalteparin sodium) for a total of 10,000 anti-Xa units per vial. Each prefilled syringe also contains Water for Injection and sodium chloride, when required, to maintain physiologic ionic strength. The prefilled syringes are preservative-free. Each multiple-dose vial also contains Water for Injection and 14 mg of benzyl alcohol per mL as a preservative. The pH of both formulations is 5.0 to 7.5. When necessary, the pH of FRAGMIN is adjusted with hydrochloric acid and/or sodium hydroxide [see Dosage and Administration (2.7) and How Supplied/Storage and Handling (16) ] . Dalteparin sodium is produced through controlled nitrous acid depolymerization of sodium heparin from porcine intestinal mucosa followed by a chromatographic purification process. It is composed of strongly acidic sulfated polysaccharide chains (oligosaccharide, containing 2,5-anhydro-D-mannitol residues as end groups) with an average molecular weight of 5,000 and about 90% of the material within the range 2,000–9,000. The molecular weight distribution is: <3000 daltons 3.0–15% 3,000 to 8,000 daltons 65.0–78.0% >8,000 daltons 14.0–26.0% Structural Formula Chemical Structure

    What Is Dalteparin Sodium Used For?

    1 INDICATIONS AND USAGE FRAGMIN is a low molecular weight heparin (LMWH) indicated for

  • Prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction ( 1.1 )
  • Prophylaxis of deep vein thrombosis (DVT) in abdominal surgery, hip replacement surgery or medical patients with severely restricted mobility during acute illness ( 1.2 )
  • Extended treatment of symptomatic venous thromboembolism (VTE) to reduce the recurrence in adult patients with cancer. In these patients, the FRAGMIN therapy begins with the initial VTE treatment and continues for six months ( 1.3 )
  • Treatment of symptomatic venous thromboembolism (VTE) to reduce the recurrence in pediatric patients from birth (gestational age at least 35 weeks) ( 1.4 )
  • Limitations of Use FRAGMIN is not indicated for the acute treatment of VTE ( 1.5 ) 1.1 Prophylaxis of Ischemic Complications in Unstable Angina and Non-Q-Wave Myocardial Infarction FRAGMIN Injection is indicated for the prophylaxis of ischemic complications in unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin therapy [see Clinical Studies (14.1) ] . 1.2 Prophylaxis of Deep Vein Thrombosis FRAGMIN is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE):
  • In patients undergoing hip replacement surgery [see Clinical Studies (14.2) ] ;
  • In patients undergoing abdominal surgery who are at risk for thromboembolic complications [see Clinical Studies (14.3) ] ;
  • In medical patients who are at risk for thromboembolic complications due to severely restricted mobility during acute illness [see Clinical Studies (14.4) ] . 1.3 Extended Treatment of Symptomatic Venous Thromboembolism (VTE) in Adult Patients with Cancer FRAGMIN is indicated for the extended treatment of symptomatic venous thromboembolism (VTE) (proximal DVT and/or PE), to reduce the recurrence of VTE in adult patients with cancer. In these patients, the FRAGMIN therapy begins with the initial VTE treatment and continues for six months [see Clinical Studies (14.5) ] . 1.4 Treatment of Symptomatic Venous Thromboembolism (VTE) in Pediatric Patients FRAGMIN is indicated for the treatment of symptomatic venous thromboembolism (VTE) to reduce the recurrence of VTE in pediatric patients from birth (gestational age at least 35 weeks) . 1.5 Limitations of Use FRAGMIN is not indicated for the acute treatment of VTE.

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION Indication Dosing Regimen Unstable angina and non-Q-wave MI 120 units/kg subcutaneous every 12 hours (with aspirin) ( 2.1 ) DVT prophylaxis in abdominal surgery 2,500 units subcutaneous once daily or 5,000 units subcutaneous once daily or 2,500 units subcutaneous followed by 2,500 units subcutaneous 12 hours later and then 5,000 units subcutaneous once daily ( 2.2 ) DVT prophylaxis in hip replacement surgery Postoperative start – 2,500 units subcutaneous 4 hours to 8 hours after surgery, then 5,000 units subcutaneous once daily, or Preoperative start – day of surgery 2,500 units subcutaneous 2 hours before surgery followed by 2,500 units subcutaneous 4 hours to 8 hours after surgery, then 5,000 units subcutaneous once daily ( 2.2 ) Preoperative start – Evening Before Surgery 5,000 units subcutaneous followed by 5,000 units subcutaneous 4 hours to 8 hours after surgery ( 2.2 ) DVT prophylaxis in medical patients 5,000 units subcutaneous once daily ( 2.2 ) Extended treatment of VTE in adult patients with cancer Month 1: 200 units/kg subcutaneous once daily ( 2.3 ) Months 2 to 6: 150 units/kg subcutaneous once daily ( 2.3 ) Treatment of VTE in pediatric patients (see Table 5 ) ( 2.4 ) Age Group Starting Dose Birth (gestational age at least 35 weeks) to less than 2 Years 150 units/kg twice daily 2 Years to less than 8 Years 125 units/kg twice daily 8 Years to less than 17 Years 100 units/kg twice daily Do not use as intramuscular injection. FRAGMIN should not be mixed with other injections or infusions ( 2.7 ) 2.1 Recommended Dosage for Prophylaxis of Ischemic Complications in Unstable Angina and Non-Q-Wave Myocardial Infarction In patients with unstable angina or non-Q-wave myocardial infarction, the recommended dose of FRAGMIN Injection is 120 units/kg of body weight, but not more than 10,000 units, subcutaneously every 12 hours with concurrent oral aspirin (75 mg to 165 mg once daily) therapy. Treatment should be continued until the patient is clinically stabilized. The usual duration of administration is 5 days to 8 days. Concurrent aspirin therapy is recommended except when contraindicated. Table 1 lists the volume of FRAGMIN in mL (based on the 3.8 mL multiple-dose vial 25,000 units/mL) and quantity of FRAGMIN in units, to be administered for a range of patient weights. Table 1 Quantity and Volume of FRAGMIN to be Administered by Patient Weight Patient weight (kg) <50 kg 50 kg to 59 kg 60 kg to 69 kg 70 kg to 79 kg 80 kg to 89 kg ≥90 kg Quantity of FRAGMIN (units) 5,500 units 6,500 units 7,500 units 9,000 units 10,000 units 10,000 units Volume of FRAGMIN (mL) 95,000 units / 3.8 mL 0.22 mL 0.26 mL 0.3 mL 0.36 mL 0.4 mL 0.4 mL 2.2 Prophylaxis of Deep Vein Thrombosis Prophylaxis of VTE Following Hip Replacement Surgery : Table 2 presents the dosing options for patients undergoing hip replacement surgery. The usual duration of administration is 5 days to 10 days after surgery; up to 14 days of treatment with FRAGMIN...

    Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in more detail in other sections of the prescribing information .

  • Risk of Hemorrhage including Spinal/Epidural Hematomas [see Warnings and Precautions (5.1) ]
  • Thrombocytopenia [see Warnings and Precautions (5.2) ]
  • Benzyl Alcohol Preservative Risk to Premature Infants [see Warnings and Precautions (5.3) ] Most common adverse reactions (>1%) are: bleeding (including hemorrhage), thrombocytopenia (Type I), hematoma at the injection site, pain at the injection site, transient elevation of transaminases ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not accurately reflect the rates observed in practice. Hemorrhage The most commonly reported adverse reactions are hematoma at the injection site and hemorrhagic complications. The risk for bleeding varies with the indication and may increase with higher doses. Unstable Angina and Non-Q-Wave Myocardial Infarction Table 7 summarizes major bleeding reactions that occurred with FRAGMIN, heparin, and placebo in clinical trials of unstable angina and non-Q-wave myocardial infarction. Table 7 Major Bleeding Reactions in Unstable Angina and Non-Q-Wave Myocardial Infarction Indication Dosing Regimen Unstable Angina and Non-Q-Wave MI FRAGMIN 120 units/kg/12 hours subcutaneous Treatment was administered for 5 days to 8 days. n (%) Heparin Heparin intravenous infusion for at least 48 hours, APTT 1.5 to 2 times control, then 12,500 units subcutaneously every 12 hours for 5 days to 8 days. intravenous and subcutaneous n (%) Placebo every 12 hours subcutaneous n (%) Major Bleeding Reactions Aspirin (75 mg to 165 mg per day) and beta blocker therapies were administered concurrently. , Bleeding reactions were considered major if: 1) accompanied by a decrease in hemoglobin of ≥2 g/dL in connection with clinical symptoms; 2) a transfusion was required; 3) bleeding led to interruption of treatment or death; or 4) intracranial bleeding. 15/1497 (1.0) 7/731 (1.0) 4/760 (0.5) Hip Replacement Surgery Table 8 summarizes: 1) all major bleeding reactions and, 2) other bleeding reactions possibly or probably related to treatment with FRAGMIN (preoperative dosing regimen), warfarin sodium, or heparin in two hip replacement surgery clinical trials. Table 8 Bleeding Reactions Following Hip Replacement Surgery Indication FRAGMIN vs Warfarin Sodium FRAGMIN vs Heparin Dosing Regimen Dosing Regimen Hip Replacement Surgery FRAGMIN Includes three treated patients who did not undergo a surgical procedure. 5,000 units once daily subcutaneous Warfarin Sodium Warfarin sodium dosage was adjusted to maintain a prothrombin time index of 1.4 to 1.5, corresponding to an International Normalized Ratio (INR) of approximately 2.5. oral FRAGMIN Includes two treated patients who did not undergo a surgical procedure. 5,000 units once daily subcutaneous Heparin 5,000 units three times a day subcutaneous n (%) n (%) n (%) n (%) Major Bleeding Reactions A bleeding event was considered major if: 1) hemorrhage caused a significant clinical event, 2) it was associated with a hemoglobin decrease of ≥2 g/dL or transfusion of 2 or more units of blood products, 3) it resulted in reoperation due to bleeding, or 4) it involved retroperitoneal or intracranial hemorrhage. 7/274 (2.6) 1/279 (0.4) 0 3/69 (4.3) Other Bleeding Reactions Occurred at a rate of at least 2% in the group treated with FRAGMIN 5,000 units once daily. Hematuria 8/274 (2.9) 5/279 (1.8) 0 0 Wound Hematoma 6/274 (2.2) 0 0 0 Injection Site Hematoma 3/274 (1.1) NA 2/69 (2.9) 7/69 (10.1) Six of the patients treated with FRAGMIN experienced seven major...

    • Drug Interactions

    7 DRUG INTERACTIONS The use of FRAGMIN in patients receiving oral anticoagulants, platelet inhibitors, and thrombolytic agents may increase the risk of bleeding [see Warnings and Precautions (5) ] . The use of FRAGMIN in patients receiving oral anticoagulants, platelet inhibitors, and thrombolytic agents may increase the risk of bleeding ( 7 )

    Contraindications

    4 CONTRAINDICATIONS FRAGMIN is contraindicated in:

  • Patients with active major bleeding.
  • Patients with a history of heparin induced thrombocytopenia or heparin induced thrombocytopenia with thrombosis.
  • Patients with prior hypersensitivity to dalteparin sodium (e.g., pruritis, rash, anaphylactic reactions) [see Adverse Reactions (6.1) ] .
  • Patients undergoing Epidural/Neuraxial anesthesia, do not administer FRAGMIN [see Boxed Warning and Warnings and Precautions (5.1) ] ; o As a treatment for unstable angina and non-Q-wave MI. o For prolonged VTE prophylaxis.
  • Patients with prior hypersensitivity to heparin or pork products.
  • Active major bleeding ( 4 )
  • History of heparin induced thrombocytopenia or heparin induced thrombocytopenia with thrombosis ( 4 )
  • Hypersensitivity to dalteparin sodium ( 4 , 6.1 )
  • In patients undergoing Epidural/Neuraxial anesthesia, do not administer FRAGMIN ( 5.1 ) o As a treatment for unstable angina and non-Q-wave MI o For prolonged VTE prophylaxis ( 4 )
  • Hypersensitivity to heparin or pork products ( 4 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Available data from published literature and postmarketing reports have not reported a clear association with FRAGMIN and adverse developmental outcomes. There are risks to the mother associated with untreated VTE in pregnancy, and a potential for adverse effects on the preterm infant when FRAGMIN is used in pregnancy (see Clinical Considerations ) . In animal reproduction studies, there was no evidence of embryo-fetal toxicity or teratogenicity when dalteparin sodium was administered to pregnant rats and rabbits during organogenesis at doses 2 to 4 times (rats) and 4 times (rabbits) the human dose of 100 units/kg dalteparin based on the body surface area (see Data ) . Because animal reproduction studies are not always predictive of human response, FRAGMIN should be used during pregnancy only if clearly needed. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data describe that women with a previous history of VTE in pregnancy are at higher risk for recurrence during subsequent pregnancies compared to those with no risk factor for VTE (4.5% versus 2.7% respectively, relative risk 1.7, 95% CI: 1.0–2.8). Fetal/Neonatal Adverse Reactions Cases of "gasping syndrome" have occurred in premature infants when large amounts of benzyl alcohol have been administered (99 mg/kg/day to 404 mg/kg/day). The 3.8 mL multiple-dose vials of FRAGMIN contain 14 mg/mL of benzyl alcohol [see Warnings and Precautions (5.3) ] . Data Animal Data In reproductive and developmental toxicity studies, pregnant rats and rabbits received dalteparin sodium during...

    Overdosage

    10 OVERDOSAGE An excessive dosage of FRAGMIN Injection may lead to hemorrhagic complications. These may generally be stopped by slow intravenous injection of protamine sulfate (1% solution), at a dose of 1 mg protamine for every 100 anti-Xa units of FRAGMIN given. If the APTT measured 2 hours to 4 hours after the first infusion remains prolonged, a second infusion of 0.5 mg protamine sulfate per 100 anti-Xa units of FRAGMIN may be administered. Even with these additional doses of protamine, the APTT may remain more prolonged than would usually be found following administration of unfractionated heparin. In all cases, the anti-Xa activity is never completely neutralized (maximum about 60% to 75%). Take particular care to avoid overdosage with protamine sulfate. Administration of protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Because fatal reactions, often resembling anaphylaxis, have been reported with protamine sulfate, give protamine sulfate only when resuscitation techniques and treatment for anaphylactic shock are readily available. For additional information, consult the labeling of Protamine Sulfate Injection, USP, products.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING FRAGMIN (dalteparin sodium) injection, USP, is a sterile, aqueous, clear, colorless or straw-colored solution available as follows: Presentation Strength Package Size NDC Number Single-dose prefilled syringe Single-dose prefilled syringe, affixed with a 27-gauge × 1/2 inch needle and preassembled with UltraSafe Passive™ Needle Guard devices. Discard unused portion. 2,500 units / 0.2 mL 10 Syringes 0069-0195-02 5,000 units / 0.2 mL 10 Syringes 0069-0196-02 7,500 units / 0.3 mL 10 Syringes 0069-0206-02 Single-dose graduated syringe Single-dose graduated syringe, affixed with a 27-gauge × 1/2 inch needle and preassembled with UltraSafe Passive™ Needle Guard devices. UltraSafe Passive™ Needle Guard is a trademark of Safety Syringes, Inc. Discard unused portion. 10,000 units / mL 10 Syringes 0069-0217-02 Single-dose prefilled syringe 12,500 units / 0.5 mL 10 Syringes 0069-0220-02 15,000 units / 0.6 mL 10 Syringes 0069-0223-02 18,000 units / 0.72 mL 10 Syringes 0069-0228-02 Multiple-dose vial 95,000 units / 3.8 mL (25,000 units / mL) 3.8 mL vial 0069-0232-01 Single-dose vial 10,000 units / 4 mL (2,500 units / mL) 10 vials 0069-0253-10 Store at 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Latex Allergy: The needle shield of the prefilled syringe may contain natural rubber latex [see Dosage and Administration (2.7) ] .

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.