Defibrotide
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| Routes of administration | Intravenous |
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| Bioavailability | 58 - 70% by mouth (i.v. and i.m. = 100%) |
| Biological half-life | t1/2-alpha = minutes; t1/2-beta = a few hours |
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Defibrotide, sold under the brandname Defitelio, is a mixture of single-stranded oligonucleotides that is purified from the intestinal mucosa of pigs.[1] It is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant.[1] It works by protecting the cells lining bloods vessels and preventing blood clotting; the way it does this is not well understood.
There is a strong risk of bleeding in the brain, eyes, lungs, gastrointestinal tract, urinary tract, and nose. Some people have hypersensitivity reactions.[1]
It was approved in Europe in 2013 and in the US in 2014.
Medical uses
Defibrotide is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant.[1][2] As of 2016, however, randomized placebo controlled trials have not been done.[3]
It is administered by intravenous infusion in a doctor's office or clinic.[1]
Pregnant women should not take defibrotide and women should not become pregnant while taking it; it has not been tested in pregnant but at normal doses it caused hemolytic abortion in rats. [1]
Contraindications
Use of defibrotide for people who are already taking anticoagulants is dangerous and use of other drugs that affect platelet aggregation, like NSAIDs, should be done with care. Defibrotide should not be given to people who have a difficult time maintaining a steady blood pressure.[1]
Adverse effects
There is a strong risk of hemorrhage and some people have had hypersensitivity reactions to defibrotide.[1][2]
Common adverse effects, occurring in between 1 and 10% of people, included impaired blood clotting, cerebral hemorrhage, bleeding in the eyes, low blood pressure, bleeding lungs, bleeding stomach or intestines, vomiting, blood in the urine, and bleeding at catheterization sites.[1]
Other side effects have included diarrhea, nosebleeds, sepsis, graft vs host disease, pneumonia, and infections.[2]
Pharmacology
The mechanism of action is not well understood. In vitro studies have shown that it protects the endothelium lining blood vessels from damage by [[[fludarabine]], a chemotherapy drug, and from a few other insults like serum starvation. It also appears to increase t-PA function and decrease plasminogen activator inhibitor-1 activity.[1][2]
Chemistry
Defibrotide is a mixture of single-stranded oligonucleotides. The chemical name is polydeoxyribonucleotide, sodium salt.[2] It is purified from the intestinal mucosa of pigs.[1]
Society and culture
Defibrotide was approved in Europe for use in treating veno-occlusive disease of the liver of people having had a bone marrow transplant in 2013; Gentium had developed it.[4] At the end of that year, Jazz Pharmaceuticals acquired Gentium.[4] In April 2016 the US FDA approved it for this use.[5]
References
- 1 2 3 4 5 6 7 8 9 10 11 "Defitelio 80 mg/mL concentrate for solution for infusion - Summary of Product Characteristics". UK Electronic Medicines Compendium. 26 May 2016. Retrieved 20 July 2017.
- 1 2 3 4 5 "Defibrotide sodium label" (PDF). FDA. March 2016. Retrieved 20 July 2017. For label updates see FDA index page for NDA 208114
- ↑ Dalle, JH; Giralt, SA (March 2016). "Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment.". Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 22 (3): 400–9. PMID 26431626. doi:10.1016/j.bbmt.2015.09.024.
- 1 2 "Jazz Pharma Acquiring Gentium for $1B". GEN Genetic Engineering & Biotechnology News. December 20, 2013.
- ↑ FDA Approves First Drug for Severe Hepatic VOD After HSCT. April 2016