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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FRAGMIN (FRAGMIN).
| Breastfeeding | Excretion into breast milk is negligible; M/P ratio not reported. Heparin is not absorbed orally, thus no gastrointestinal absorption by infant. Considered compatible with breastfeeding; monitor infant for bruising or bleeding. |
| 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. |
■ 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 bleeding","History of heparin-induced thrombocytopenia","Hypersensitivity to heparin or pork products","Not recommended in patients with severe renal impairment (CrCl < 30 mL/min)"]
| 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. |
| 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. |