FRAGMIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FRAGMIN (FRAGMIN).
Fragmin (dalteparin) is a low molecular weight heparin that binds to antithrombin III, potentiating its inhibition of factor Xa and, to a lesser extent, thrombin, thereby preventing thrombus formation.
| Metabolism | Dalteparin is primarily metabolized in the liver via desulfation and depolymerization, with some renal excretion. |
| Excretion | Primarily renal excretion (up to 70% as unchanged drug via glomerular filtration); minor biliary/fecal elimination (<15%) |
| Half-life | 2-4 hours (anti-Xa activity) after subcutaneous administration; prolonged in renal impairment (creatinine clearance <30 mL/min: up to 6-12 hours) |
| Protein binding | Highly bound to antithrombin III (specific binding); non-specific protein binding negligible |
| Volume of Distribution | 3-7 L/kg; indicates extensive distribution into extravascular fluid and peripheral tissues |
| Bioavailability | Subcutaneous: approximately 87% (based on anti-Xa activity) |
| Onset of Action | Subcutaneous: anti-Xa activity detectable within 20-30 minutes; peak effect at 3-5 hours |
| Duration of Action | Duration of anti-Xa effect approximately 8-12 hours after single therapeutic dose; once-daily dosing maintains effect for 24 hours |
| Molecular Weight | 5000 Da (average molecular weight of dalteparin, a low molecular weight heparin, range 5000-6000 Da) |
Deep vein thrombosis prophylaxis: 2500 IU subcutaneously once daily, starting 1-2 hours before surgery and continuing postoperatively for 5-10 days or until ambulatory. Treatment of acute DVT: 200 IU/kg subcutaneously once daily, or 100 IU/kg twice daily. Unstable angina/NSTEMI: 120 IU/kg subcutaneously every 12 hours (max 10,000 IU per dose) with aspirin.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl <30 mL/min: Contraindicated for treatment of VTE. For prophylaxis: reduce dose by 50% (e.g., 2500 IU once daily) and monitor anti-Xa levels. CrCl 30-50 mL/min: No dose adjustment for prophylaxis; for treatment, consider anti-Xa monitoring and reduce dose by 25%. CrCl >50 mL/min: No adjustment. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Caution; monitor anti-Xa levels; consider 50% dose reduction. Child-Pugh Class C: Contraindicated due to increased bleeding risk and lack of data. |
| Pediatric use | Neonates and infants: 0.5 mg/kg (50 IU/kg) subcutaneously twice daily. Children >1 year: 1 mg/kg (100 IU/kg) subcutaneously once daily, or 0.5 mg/kg twice daily. Adjust based on anti-Xa monitoring (target 0.5-1.0 IU/mL for twice daily, 1.0-2.0 IU/mL for once daily). Maximum dose: 10,000 IU/day. |
| Geriatric use |
| 1st trimester | Fragmin (dalteparin) does not cross the placenta and is not associated with fetal harm in animal studies or human data. Use is considered safe in the first trimester for anticoagulation when indicated. |
| 2nd trimester | Continued use is safe in the second trimester as placental transfer remains negligible. No evidence of teratogenicity or fetal adverse effects. |
| 3rd trimester | Use is safe in the third trimester, but monitor for bleeding risk during delivery. Protamine sulfate reversal is available if needed. |
Clinical note
Comprehensive clinical and safety monograph for FRAGMIN (FRAGMIN).
| Placental transfer | Does not cross the placenta due to its high molecular weight and negative charge, as documented in pharmacokinetic studies. |
| Breastfeeding | Dalteparin is not excreted into breast milk due to its high molecular weight and low lipid solubility, making it safe for use during breastfeeding. No adverse effects reported in nursing infants. |
■ FDA Black Box Warning
Spinal/epidural hematomas have been reported with concurrent use of low molecular weight heparins and neuraxial anesthesia or spinal puncture. These hematomas may result in long-term or permanent paralysis.
| Common Effects | Bruise Increased liver enzymes Injection site hematoma Hemorrhagic complications Injection site bruising Nosebleeds |
| Serious Effects |
Active major bleedingHistory of heparin-induced thrombocytopenia (HIT) within the past 100 days or presence of HIT antibodiesSevere uncontrolled hypertensionKnown hypersensitivity to dalteparin or other low molecular weight heparinsBacterial endocarditis (acute or subacute)Major trauma or surgery involving the central nervous system, eyes, or earsHemophilia or other bleeding disorders (e.g., von Willebrand disease)
| Precautions | Monitor for signs of bleeding; risk of heparin-induced thrombocytopenia; use with caution in patients with renal impairment; avoid in patients with history of heparin-induced thrombocytopenia; increased risk of bleeding in patients with thrombocytopenia or platelet defects. |
Loading safety data…
| Patients ≥65 years: No routine dose adjustment; however, increased risk of bleeding due to age-related renal impairment. Monitor renal function; consider anti-Xa monitoring. For treatment of VTE, reduce initial dose to 100 IU/kg once daily if CrCl <60 mL/min. Avoid use if CrCl <30 mL/min. |
| Lactation Rating | L1 (Compatible) |
| Teratogenic Risk | FDA Category B. No evidence of teratogenicity in animal studies. In humans, first trimester exposure does not increase major malformations. Second and third trimester use is associated with risk of bleeding, placental abruption, and fetal hemorrhage; anticoagulant therapy may cause fetal or neonatal bleeding. Heparin does not cross placenta due to high molecular weight, reducing direct fetal exposure. |
| Fetal Monitoring | Monitor maternal platelet counts (risk of heparin-induced thrombocytopenia), anti-Xa levels for dose adjustment, and signs of bleeding. Fetal surveillance with ultrasound for growth and placental health; assess for fetal distress. Monitor for signs of placental abruption or preterm labor. |
| Fertility Effects | No known adverse effects on fertility. Heparin does not affect ovulation, implantation, or sperm function. No specific fertility studies in humans; animal studies show no reproductive impairment. |
| Food/Dietary | No specific food interactions reported. However, avoid excessive consumption of foods high in vitamin K (e.g., spinach, kale, broccoli) if also taking warfarin, as this may reduce anticoagulant effect. No dietary restrictions required with dalteparin alone. |
| Clinical Pearls | FRAGMIN (dalteparin) is a low molecular weight heparin (LMWH) used for prophylaxis and treatment of thromboembolic disorders. It does not require routine monitoring of aPTT; however, anti-factor Xa levels may be measured in special populations (e.g., renal impairment, obesity, pregnancy). For DVT prophylaxis, administer subcutaneously once daily; for treatment of DVT/PE, give twice daily. Contraindicated in patients with active major bleeding, history of heparin-induced thrombocytopenia (HIT), or hypersensitivity to heparin. Use cautiously in renal impairment (CrCl <30 mL/min) as clearance is reduced; consider dose adjustment. Protamine sulfate partially reverses anticoagulant effect but is not complete. Avoid concurrent use with medications that increase bleeding risk (e.g., NSAIDs, antiplatelets, other anticoagulants). |
| Patient Advice | FRAGMIN is an injectable blood thinner that helps prevent and treat blood clots. · Inject the medication exactly as prescribed, usually into the fatty layer of the skin (subcutaneous). · Do not rub the injection site after administering. · Rotate injection sites (e.g., abdomen, thigh) to prevent bruising. · Watch for signs of bleeding: unusual bruising, nosebleeds, blood in urine or stool, coughing up blood, or bleeding from gums. · Seek immediate medical attention if you experience severe headache, confusion, difficulty speaking, or weakness (signs of bleeding in the brain). · Avoid taking aspirin, ibuprofen, naproxen, or other blood thinners unless directed by your doctor. · Tell your doctor if you have kidney problems, a history of heparin-induced thrombocytopenia, or are pregnant/breastfeeding. · Do not stop taking FRAGMIN abruptly without consulting your doctor. · Store at room temperature away from light and moisture. Do not freeze. |