defibrotide

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 hematopoietic stem-cell transplantation.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Minimal distribution to tissues.

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 concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

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

Use Cautiously in:

OB: Safety not established in pregnancy.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension

GI: diarrhea, nausea, vomiting

Hemat: bleeding

Metab: hyperuricemia

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 ≥21 days; may continue for up to 60 days if signs/symptoms of veno-occlusive disease persist after 21 days.

Availability ⬆ ⬇

Solution for injection: 80 mg/mL

Assessment ⬆ ⬇

Monitor for signs/symptoms of bleeding (blood in stool or urine, epistaxis) during therapy. If persistent, severe or potentially life-threatening bleeding occurs, 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, permanently discontinue defibrotide.
Monitor for signs/symptoms of hypersensitivity reactions (rash, urticaria, pruritus, flushing, dizziness, vomiting, abdominal pain) and angioedema (swelling of throat, lips, tongue, face, dyspnea, wheezing, hoarseness). If reaction occurs, permanently discontinue defibrotide 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 ≥ 2 hrs prior to invasive procedures. Resume infusion as soon as procedure-related bleeding risk resolved.

IV Administration:

Intermittent 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 particulates. Solution is stable for 4 hr at room temperature or 24 hr if refrigerated.Concentration: 4–20 mg/mL.
Rate: Infuse through a 0.2 micron in-line filter over 2 hr. Flush IV line with 0.9% NaCl or D5W immediately before and after infusion.
Y-Site Compatibility: Y-Site Incompatibility:
- acetaminophen
- acyclovir
- albumin (human)
- amphotericin B liposomal
- caspofungin
- ceftazidime
- ceftriaxone
- ciprofloxacin
- clonidine
- cyclosporine
- deferoxamine
- fluconazole
- foscarnet
- fosfomycin
- ganciclovir
- heparin
- hydrocortisone
- imipenem/cilastatin
- mesna
- metronidazole
- nalbuphine
- naloxone
- ondansetron
- pantoprazole
- sulfamethoxazole/trimethoprim
- tranexamic acid
- amikacin
- mycophenolate mofetil
- nicardipine
- tobramycin
- vancomycin

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of defibrotide Do not stop receiving drug without consulting health care provider. If an appointment is missed, reschedule as soon as possible. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
Instruct patient to notify health care professional immediately if signs/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 patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Prior to administering defibrotide to pregnant women, advise of the risk of miscarriage.

Evaluation/Desired Outcomes ⬆ ⬇

Improved survival after hematopoietic stem-cell transplantation.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

68225- Patheon Italia S.p.A.
- 68225-107-
  - 68225-107-00- 24 VIAL, GLASS in 1 CASE (68225-107-00) / 2.5 mL in 1 VIAL, GLASS

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 ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇