The importance of endothelial protection: the emerging role of defibrotide in reversing endothelial injury and its sequelae. Bone Marrow Transplantation
Author(s): Paul G. Richardson, Marta Palomo, Nancy A. Kernan, Gerhard C. Hildebrandt, Nelson Chao & Enric Carreras
Published: September 2021
Copyright: © The Author(s) 2021
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Disclaimer
This journal article reprint 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 nonapproved 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.
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Financial Disclosure Statement
Paul G. Richardson has served on advisory committees and has received research funding from Jazz Pharmaceuticals. Marta Palomo has received honoraria in speaker’s fee for a symposium from Jazz Pharmaceuticals. Nancy A. Kernan received grants from Gentium during the conduct of the study, and her research was supported by the 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. Gerhard C. Hildebrandt has stocks/ownership interests in Sangamo Bioscience, Axim Biotechnologies, Juno Therapeutics, Kite Pharma, Novartis, Insys Therapeutics, AbbVie, GW Pharmaceuticals, Cardinal Health, Immunomedics, Endocyte, Clovis Oncology, Cellectis, Aetna, CVS Health, Celgene, Bluebird Bio, Bristol Myers Squibb/Medarex, CRISPR Therapeutics, IDEXX Laboratories, Johnson & Johnson, Pfizer, Procter & Gamble, Vertex, Bayer, and Scotts-Miracle; has served in advisory/consulting roles for Pfizer, Kite Pharma, Incyte, and Jazz Pharmaceuticals; has received research funding from Takeda, Jazz Pharmaceuticals, Astellas, Incyte, and Pharmacyclics; and has received travel, accommodations, and/or expense reimbursement from Kite Pharma, Incyte, Pfizer, Falk Foundation, Jazz Pharmaceuticals, and Astellas Pharma. Nelson Chao has nothing to disclose. Enric Carreras has received research funds and honoraria in speaker’s fees for symposia from Jazz Pharmaceuticals/Gentium Inc.
Detailed information on funding amounts received by the authors of this publication 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.