Defibrotide: Difference between revisions
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==Mechanism of action== |
==Mechanism of action== |
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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.<ref name=UKlabel/><ref name=USlabel/> |
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.<ref name=UKlabel/><ref name=USlabel/> |
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==Chemistry== |
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Defibrotide is a mixture of single-stranded [[oligonucleotide]]s. The chemical name is polydeoxyribonucleotide, sodium salt.<ref name=USlabel/> |
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==Society and culture== |
==Society and culture== |
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Revision as of 02:45, 20 July 2017
 | This article needs more reliable medical references for verification or relies too heavily on primary sources. (July 2017) |  |
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| Routes of administration | oral, i.m., i.v. |
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| Bioavailability | 58 - 70% orally (i.v. and i.m. = 100%) |
| Elimination half-life | t1/2-alpha = minutes; t1/2-beta = a few hours |
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Defibrotide (Defitelio) is a deoxyribonucleic acid derivative (single-stranded) derived from cow lung or porcine mucosa that is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant.[1] It is an anticoagulant with a multiple modes of action.
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, 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]
Mechanism of action
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]
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]
The drug was marketed under the brand names Dasovas (FM), Noravid, and Prociclide in a variety of countries. In the USA it is marketed as Defitelio.
References
- ^ a b c d e f g h "Defitelio 80 mg/mL concentrate for solution for infusion - Summary of Product Characteristics". UK Electronic Medicines Compendium. 26 May 2016. Retrieved 20 July 2017.
- ^ a b c d e "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. 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 Drug for Severe Hepatic VOD After HSCT. April 2016