Defibrotide
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| Routes of administration | Intravenous |
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| Bioavailability | 58 - 70% by mouth (i.v. and i.m. = 100%) |
| Elimination half-life | < 2 hours[1] |
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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. It is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant, with different limitations in the US and Europe. It works by protecting the cells lining blood vessels in the liver and preventing blood clotting; the way it does this is not well understood.[1][2]
Use of the drug is generally limited by a strong risk of life-threatening bleeding in the brain, eyes, lungs, gastrointestinal tract, urinary tract, and nose. Some people have hypersensitivity reactions.[2]
It was approved in Europe in 2013 and in the US in 2016.
Medical uses
Defibrotide is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant, with different limitations in the US and Europe.[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.[2]
Pregnant women should not take defibrotide and women should not become pregnant while taking it; it has not been tested in pregnant women but at normal doses it caused hemolytic abortion in rats. [2]
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.[2]
Adverse effects
There is a high risk of bleeding 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, vomiting, low blood pressure, bleeding in the brain, eyes, lungs, stomach or intestines, in the urine, and at catheterization sites.[2]
Other side effects have included diarrhea, nosebleeds, sepsis, graft vs host disease, and pneumonia.[1]
Pharmacology
Defibrotide's mechanism of action is poorly 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.[1] It is purified from the intestinal mucosa of pigs.[2]
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 March 2016 the US FDA approved it for a similar use.[5]
References
- ^ a b c d e f g "Defibrotide sodium label" (PDF). FDA. March 2016. Retrieved 20 July 2017. For label updates see FDA index page for NDA 208114
- ^ a b c d e f g h i j "Defitelio 80 mg/mL concentrate for solution for infusion - Summary of Product Characteristics". UK Electronic Medicines Compendium. 26 May 2016. Retrieved 20 July 2017.
- ^ 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. 22 (3): 400–9. doi:10.1016/j.bbmt.2015.09.024. PMID 26431626.
- ^ a b "Jazz Pharma Acquiring Gentium for $1B". GEN Genetic Engineering & Biotechnology News. December 20, 2013.
- ^ "FDA approves first treatment for rare disease in patients who receive stem cell transplant from blood or bone marrow". FDA. March 30, 2016.