defibrotide

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).

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.

Availability ⬆ ⬇

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

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.

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 HSCT.

Classifications ⬆ ⬇

Therapeutic Classification: anticoagulants

Pharmacologic Classification: fibrinolysis inhibitors

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

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.

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Indications ⬇