TREATMENT MODIFICATIONS FOR SPECIFIC EVENTS OR PROCEDURES

TREATMENT MODIFICATIONS FOR TOXICITY OR INVASIVE PROCEDURES1
Event Recommended action
Hypersensitivity reaction
  • Severe or life-threatening (anaphylaxis)
  1. Discontinue Defitelio permanently; do not resume treatment.
Bleeding
  • Persistent, severe, or potentially life-threatening
  1. Withhold Defitelio.
  2. Treat the cause of bleeding and give supportive care as clinically indicated.
  3. Consider resuming treatment (at the same dose and infusion volume) when bleeding has stopped and the patient is hemodynamically stable.
  • Recurrent significant bleeding
  1. Discontinue Defitelio permanently; do not resume treatment.
Invasive procedures
  1. There is no known reversal agent for the profibrinolytic effects of Defitelio. Discontinue Defitelio infusion at least 2 hours prior to an invasive procedure.
  2. Resume Defitelio treatment after the procedure, as soon as any procedure-related risk of bleeding is resolved.

Indication

Defitelio® (defibrotide sodium) is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).

Important Safety Information

Contraindications

Defitelio is contraindicated in the following conditions:
  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Warnings and Precautions

Hemorrhage

Defitelio may increase the risk of bleeding in patients with VOD after HSCT. Do not initiate Defitelio in patients with active bleeding. Monitor patients on Defitelio for signs of bleeding. If bleeding occurs, withhold or discontinue Defitelio.

Concomitant systemic anticoagulant or fibrinolytic therapy may increase the risk of bleeding and should be discontinued prior to Defitelio treatment. Consider delaying Defitelio administration until the effects of the anticoagulant have abated.

Hypersensitivity Reactions

Hypersensitivity reactions including rash, urticaria, and angioedema have occurred in less than 2% of patients treated with Defitelio. One case of an anaphylactic reaction was reported in a patient who had previously received Defitelio. Monitor patients for hypersensitivity reactions, especially if there is a history of previous exposure. If a severe hypersensitivity reaction occurs, discontinue Defitelio, treat according to the standard of care, and monitor until symptoms resolve.

Most Common Adverse Reactions

The most common adverse reactions (incidence ≥10% and independent of causality) with Defitelio treatment were hypotension, diarrhea, vomiting, nausea, and epistaxis.

Please see full Prescribing Information.

Reference:
  1. Defitelio [package insert]. Palo Alto, CA: Jazz Pharmaceuticals.