defibrotide

REMS

Hepatic veno-occlusive disease, also known as sinusoidal obstruction syndrome, in patients with renal or pulmonary impairment following hematopoietic stem-cell transplantation.

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.

Availability ⬆ ⬇

Solution for injection: 80 mg/mL

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.

US Brand Names ⬆ ⬇

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 hematopoietic stem-cell transplantation.

Classifications ⬆ ⬇

Therapeutic Classification: anticoagulants

Pharmacologic Classification: fibrinolysis inhibitors

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

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.

Pronunciation ⬆ ⬇

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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Indications ⬇