Treatment of hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary impairment following hematopoietic stem-cell transplantation (HSCT).
Enhances plasmin enzymatic activity to hydrolyze fibrin clots. Also increases tissue plasminogen activator and thrombomodulin expression, and decreases von Willebrand factor and plasminogen activator inhibitor-1 expression, which reduces endothelial cell activation and increases endothelial cell-mediated fibrinolysis.
Improved survival after HSCT.
Absorption: IV administration results in complete bioavailability.
Distribution: 8.1–9.1 L.
Protein Binding: 93%.
Metabolism and Excretion: Metabolized by nucleases, nucleotidases, nucleosidases, deaminases, and phosphorylases; does not undergo hepatic metabolism. 5–15% excreted unchanged in urine.
Half-life: <2 hr.
TIME/ACTION PROFILE (plasma levels)
- Concurrent use with systemic anticoagulants or fibrinolytics;
- Active bleeding;
- Lactation: Avoid breast feeding.
Use Cautiously in:
OB: Safety not established in pregnancy.
Adverse Reactions/Side Effects
GI: diarrhea, nausea, vomiting
Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), graft versus host disease, infection
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
IV (Adults and Children) 6.25 mg/kg every 6 hr for at least 21 days; may continue for up to 60 days if signs/symptoms of VOD persist after 21 days.
Solution for IV infusion (must be diluted): 80 mg/mL
- Monitor for signs and symptoms of bleeding (blood in stool or urine, nose bleeding) during therapy. If persistent, severe or potentially life-threatening, hold defibrotide, treat cause of bleeding and give supportive care. Consider resuming therapy at same dose and infusion volume when bleeding stopped and patient is hemodynamically stable. If recurrent significant bleeding occurs, discontinue defibrotide permanently.
- Monitor for signs and symptoms of hypersensitivity reactions (rash, urticaria, angioedema) during therapy, especially if patient received defibrotide previously. If severe reaction occurs, discontinue defibrotide permanently and provide supportive care.
- Deficient fluid volume (Adverse Reaction)
- Confirm patient is not experiencing clinically significant bleeding and is hemodynamically stable on no more than one vasopressor before starting infusion.
- Discontinue infusion at least 2 hrs prior to invasive procedures. Resume infusion as soon as procedure-related bleeding risk resolved.
- Intermittent Infusion: Flush IV line with 0.9% NaCl or D5W immediately before and after infusion. Diluent: Dilute in D5W or 0.9% NaCl. Diluted solution is colorless to light yellow; do not infuse solutions that are discolored or contain particulate matter. Solution is stable for 4 hrs at room temperature or 24 hrs if refrigerated.Concentration: 4 mg/mL or 20 mg/mL.
- Rate: Infuse through a 0.2 micron in-line filter over 2 hrs.
- Y-Site Incompatibility: Do not infuse other medication in same line as defibrotide.
- Explain purpose of defibrotide to patient.
- Instruct patient to notify health care professional immediately if signs and symptoms of bleeding (unusual bleeding, easy bruising, blood in urine or stool, headache, confusion, slurred speech, altered vision) or hypersensitivity reactions (rash, pruritus, laryngeal edema, wheezing, swelling of lips or face) occur.
- Advise female patients to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding during therapy.
Improved survival after HSCT.
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