Defibrotide Sodium- Defitelio -@- (2016)- Hepatobilliary drug
Drug Name:Defibrotide Sodium- Defitelio -@- (2016)- Hepatobilliary drug
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
DEFITELIO may enhance the activity of antithrombotic/fibrinolytic drugs.
Indication:
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
6. Defitelio Defibrotide 3/30/2016 To treat adults and children who
Sodium develop hepatic veno-occlusive
with additional kidney or lung
abnormalities after they receive
a stem cell transplant from
blood or bone marrow called
hematopoietic stem cell
transplantation
Press Release Drug trials Snapshot
Approved by FDA on 3/30/2016 (Ref- FDA approved List- 2016)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to
use DEFITELIO safely and effectively.
See full prescribing information for DEFITELIO.
DEFITELIO (defibrotide sodium) injection, for intravenous use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
DEFITELIO 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).
Adverse Reaction:
ADVERSE REACTIONS
The most common adverse reactions (incidence =10% and independent of
causality) with DEFITELIO treatment were hypotension, diarrhea, vomiting,
nausea and epistaxis.
Contra-Indications:
CONTRAINDICATIONS
Concomitant administration with systemic anticoagulant or fibrinolytic therapy.
Known hypersensitivity to DEFITELIO or to any of its excipients.
WARNINGS AND PRECAUTIONS
Hemorrhage: Monitor patients for bleeding. Withhold or discontinue
DEFITELIO if significant bleeding occurs.
Hypersensitivity Reactions: If severe or life threatening allergic reaction
occurs, discontinue DEFITELIO, treat according to standard of care, and
monitor until signs and symptoms resolve.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
DEFITELIO 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).
DOSAGE AND ADMINISTRATION
Administer DEFITELIO 6.25 mg/kg every 6 hours given as a 2-hour
intravenous infusion.
Treat for a minimum of 21 days. If after 21 days signs and symptoms of
VOD have not resolved, continue treatment until resolution.
DOSAGE FORMS AND STRENGTHS
Injection: 200 mg/2.5 mL (80 mg/mL) in a single-patient-use vial.
OVERDOSAGE
There are no known cases of overdose with DEFITELIO. There is no known
antidote for DEFITELIO, and DEFITELIO is not dialyzable.
If an overdose occurs, institute general supportive measures.
Patient Information:
PATIENT COUNSELING INFORMATION
Hemorrhage:
Advise patients and caregivers that DEFITELIO may increase the risk of bleeding
(hemorrhage). Instruct patients to immediately report any signs or symptoms
suggestive of hemorrhage (unusual bleeding, easy bruising, blood in urine or
stool, headache, confusion, slurred speech, or altered vision).
Hypersensitivity Reactions:
Ask patients if they have been treated with defibrotide sodium previously.
Instruct patients on the risk of allergic reactions, including anaphylaxis.
Describe the symptoms of allergic reactions, including anaphylaxis,
and instruct the patient to seek medical attention immediately if they
experience such symptoms .
This products label may have been updated. For full prescribing information,
please visit labels.fda.gov.
Distributed by:
Jazz Pharmaceuticals, Inc.
Palo Alto, CA 94304
DEFITELIO® is a registered trademark of
Jazz Pharmaceuticals plc or its subsidiaries.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
The mechanism of action of defibrotide sodium has not been fully elucidated.
In vitro, defibrotide sodium enhances the enzymatic activity of plasmin
to hydrolyze fibrin clots.
Studies evaluating the pharmacological effects of defibrotide sodium on
endothelial cells (ECs) were conducted primarily in the human
microvascular endothelial cell line.
In vitro, defibrotide sodium increased tissue plasminogen activator (t-PA)
and thrombomodulin expression, and decreased von Willebrand factor (vWF)
and plasminogen activator inhibitor-1 (PAI-1) expression, thereby reducing
EC activation and increasing EC-mediated fibrinolysis.
Defibrotide sodium protected ECs from damage caused by chemotherapy,
tumor necrosis factor-a (TNF-a), serum starvation, and perfusion.
2. Pharmacokinetics
Absorption
After intravenous administration, peak plasma concentrations of defibrotide
sodium occur approximately at the end of each infusion.
Distribution
Defibrotide sodium is highly bound to human plasma proteins (average 93%)
and has a volume of distribution of 8.1 to 9.1 L.
Elimination
Metabolism followed by urinary excretion is likely the main route of elimination.
The estimated total clearance was 3.4 to 6.1 L/h. The elimination half-life
of defibrotide sodium is less than 2 hours. Similar plasma concentration profiles
were observed in VOD patients after initial and multiple-dose administration
of 6.25 mg/kg every 6 hours for 5 days. Therefore, no accumulation is expected
following multiple-dose administration.
Metabolism
Though the precise pathway of defibrotide sodium degradation in plasma in
vivo is largely unknown, it has been suggested that nucleases, nucleotidases,
nucleosidases, deaminases, and phosphorylases metabolize polynucleotides
progressively to oligonucleotides, nucleotides, nucleosides, and then to the
free 2-deoxyribose sugar, purine and pyrimidine bases.
Excretion
After administration of 6.25 mg/kg to 15 mg/kg doses of DEFITELIO
as 2-hour infusions, approximately 5-15% of the total dose was excreted in
urine as defibrotide sodium, with the majority excreted during the first 4 hours
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no available data on DEFITELIO use in pregnant women.
When administered to pregnant rabbits during the period of organogenesis
at doses that were comparable to the recommended human dose based
on body surface area, defibrotide sodium decreased the number of
implantations and viable fetuses.
Advise pregnant women of the potential risk of miscarriage.
The estimated background risk of major birth defects and miscarriage for
the indicated population is unknown. In the U.S. general population,
the estimated background risks of major birth defects and miscarriage
in clinically recognized pregnancies are 2-4% and 15-20%, respectively.
2. Lactation
Risk Summary
There is no information regarding the presence of DEFITELIO in human milk,
the effects on the breastfed infant, or the effects on milk production.
Because of the potential for serious adverse reactions, including bleeding in a
breastfed infant, advise patients that breastfeeding is not recommended during
treatment with DEFITELIO.
3. Pediatric Use
The safety and effectiveness of DEFITELIO have been established in
pediatric patients. Use of DEFITELIO is supported by evidence from
an adequate and well-controlled study and a dose finding study of
DEFITELIO in adult and pediatric patients with VOD with evidence of
renal or pulmonary dysfunction following HSCT.
4. Geriatric Use
Clinical studies of DEFITELIO did not include sufficient numbers of subjects
aged 65 and over to determine whether they respond differently from younger
subjects. Other reported clinical experience has not identified differences
in responses between the elderly and younger patients.
5. OVERDOSAGE
There are no known cases of overdose with DEFITELIO. There is no known
antidote for DEFITELIO, and DEFITELIO is not dialyzable.
If an overdose occurs, institute general supportive measures.
