Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome
Author(s): Nancy A. Kernan, Stephan Grupp, Angela R. Smith, Sally Arai, Brandon Triplett, Joseph H. Antin, Leslie Lehmann, Tsiporah Shore, Vincent T. Ho, Nancy Bunin, Massimo Iacobelli, Wei Liang, Robin Hume, William Tappe, Robert Soiffer, and Paul Richardson. Br J Haematol. 2018;181(6):816-827.
Published: May 2018
Copyright: © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.
Disclaimer
This journal reprint article is being provided as a professional courtesy by Jazz Pharmaceuticals, Inc. This scientific publication contains information that may or may not be contained within the accompanying package insert. Providing this reprint should not be construed as a recommendation for use of any Jazz Pharmaceuticals product for non-approved uses. Prior to prescribing, please refer to the accompanying Prescribing Information, which includes the approved indication and a discussion of the benefits and risks associated with our product.
The opinions expressed in this reprint do not necessarily reflect those of Jazz Pharmaceuticals. Readers are encouraged to contact the primary authors with questions regarding the content of the reprint. Jazz Pharmaceuticals does not assume responsibility for any injury and/or damage to persons or property out of or related to any use of the information contained in this reprint.
Please see Important Safety Information and accompanying full Prescribing Information for Defitelio (defibrotide sodium).
Financial Disclosure Statement
Jazz Pharmaceuticals provided funding for the defibrotide treatment-IND study.
Nancy A. Kernan received grants from Gentium during the conduct of the study, and her research was supported by National Cancer Institute of the National Institutes of Health under award number P30 CA008748; the content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health. Stephan A. Grupp has served as a consultant to Jazz Pharmaceuticals. Angela R. Smith, Sally Arai, Brandon M. Triplett, Leslie Lehmann, Tsiporah Shore, and Nancy Bunin have no relevant conflicts of interest to disclose. Joseph H. Antin has served on advisory committees with Jazz Pharmaceuticals. Vincent T. Ho has served as a consultant to Jazz Pharmaceuticals. Massimo Iacobelli was an employee of Gentium SpA during the conduct of the study. Wei Liang, Robin Hume, and William Tappe are employees of Jazz Pharmaceuticals and hold stock and/or stock options in Jazz Pharmaceuticals plc. Robert J. Soiffer has served on advisory committees with Jazz Pharmaceuticals. Paul G. Richardson has served on advisory committees and as a consultant and received research funding from Jazz Pharmaceuticals.
Detailed information on funding received by physicians is available at http://www.cms.gov/openpayments.
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.