defibrotide

Therapeutic Classification: anticoagulants

Pharmacologic Classification: fibrinolysis inhibitors

Indications ⬆ ⬇

REMS

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).

Action ⬆ ⬇

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.

Therapeutic effects:

Improved survival after HSCT.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: 8.1–9.1 L.

Protein Binding: 93%.

Metabolism/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)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	2 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use with systemic anticoagulants or fibrinolytics;
Active bleeding;
Lactation: Avoid breast feeding.

Use Cautiously in:

OB: Safety not established in pregnancy.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension

Endo: hyperuricemia

GI: diarrhea, nausea, vomiting

Hemat: bleeding

Misc: graft versus host disease, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), infection

Interactions ⬆ ⬇

Drug-drug:

↑risk of bleeding with anticoagulants and fibrinolytics, including unfractionated heparin, low-molecular weight heparin, alteplase, or tenecteplase; concurrent use contraindicated.

Route/Dosage ⬆ ⬇

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.

Availability ⬆ ⬇

Solution for IV infusion (must be diluted): 80 mg/mL

Assessment ⬆ ⬇

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.

Implementation ⬆ ⬇

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.

IV Administration:

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.

Patient/Family Teaching ⬆ ⬇

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.

Evaluation/Desired Outcomes ⬆ ⬇

Improved survival after HSCT.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

68727- Jazz Pharmaceuticals, Inc.
- 68727-800- DEFITELIO
  - 68727-800-01- 2.5 mL in 1 VIAL (68727-800-01)

68727- Jazz Pharmaceuticals, Inc.
- 68727-800- DEFITELIO
  - 68727-800-02- 25 mL in 1 CARTON (68727-800-02)

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Pronunciation ⬇

Classifications ⬆ ⬇