4 CONTRAINDICATIONS The use of DEFITELIO is contraindicated in the following conditions: •Concomitant administration with systemic anticoagulant or fibrinolytic therapy [see Warnings and Precautions (5.1)] •Known hypersensitivity to DEFITELIO or to any of its excipients [see Warnings and Precautions (5.2)] •Concomitant administration with systemic anticoagulant or fibrinolytic therapy.
(4) •Known hypersensitivity to DEFITELIO or to any of its excipients.
(6.1) To report SUSPECTED
6.1 Clinical Trials Experience Because clinical trials are conducted under widely
Patients were excluded from these trials if at time of study entry
For the purposes of
The median age of
A total of 60 % of patients were male, 78 % were white, 89 % had undergone allogeneic HSCT, and
At study entry, 13 % were dialysis dependent and 18 % were ventilator dependent.
DEFITELIO was administered for a median of 21 days (range: 1 to 83 days).
The most common serious
Hemorrhage events of any type and any grade were reported for 104 (59 %) of the patients, and the events were grade 4-5 in 35 (20 %).
Table 2 presents
2 % DEFITELIO (n=176)
and hypoxia b
2 DOSAGE AND ADMINISTRATION •Administer DEFITELIO 6.25 mg/kg every 6 hours given as a 2-hour intravenous infusion.
(2.1) •Treat for a minimum of 21 days.
The dose should be based on patient 's baseline body weight, defined as the patient 's weight prior to the preparative regimen for HSCT. Administer DEFITELIO for a minimum of 21 days.
2.2 Administration Instructions •DEFITELIO must be diluted prior to infusion [see Dosage and Administration (2.4)].
•Prior to administration of DEFITELIO, confirm that the patient is not experiencing clinically significant
•Administer DEFITELIO by constant intravenous infusion over a 2-hour period.
•Administer the diluted DEFITELIO solution using an infusion set equipped with a 0.2 micron in-line filter.
•Do not co?administer DEFITELIO and other intravenous drugs concurrently within the same intravenous line.
2.3 Treatment Modification Treatment modification, including
Table 1: Treatment Modifications for Toxicity or
2. Resume DEFITELIO treatment after the procedure as soon as any procedure-related risk of
2.4 Preparation Instructions Dilute DEFITELIO in 5 % Dextrose Injection, USP or 0.9 % Sodium Chloride Injection, USP to a concentration of 4 mg /mL to 20 mg /mL. Administer the diluted solution over 2 hours.
Use the diluted
DEFITELIO solution within 4 hours if stored at room temperature or within 24 hours if stored under refrigeration.
Up to four doses of DEFITELIO solution may be prepared at one time, if refrigerated.
Preparation Instructions: •Determine the dose (mg) and number of vials of DEFITELIO based on the individual patient 's baseline weight (weight prior to the preparative regimen for HSCT).
•Parenteral drug products should be inspected visually for particulate matter and
Depending on the type and amount of diluent,
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are
When administered to pregnant rabbits during the period of organogenesis at doses that were comparable to the
Advise pregnant women of the potential risk of
The estimated background risk of major birth
In the U.S. general population, the estimated background risks of major birth
Data Animal Data Embryo-Fetal toxicity assessment was attempted in
Pregnant rabbits were administered defibrotide sodium at 0, 30, 60, or 120 mg/kg/day from GD 6 to 18 by 2-hour infusions 4 times per day.
In another study in pregnant rabbits, 3 separate subgroups of animals were treated with doses of 80 mg/kg/day defibrotide sodium administered by 2-hour infusions 4 times per day for 5 days each in a staggered manner during the organogenesis period.
The dose of 80 mg/kg/day is approximately equivalent to the
Subgroup 1 was dosed from GD 6 to 10, subgroup 2 was dosed from GD 10 to 14, and subgroup 3 was dosed from GD 14 to 18.
Treatment with defibrotide sodium resulted in a decreased number of implantations and
8.2 Lactation Risk Summary There is
Because of the
The clinical trials enrolled 66 pediatric patients in the following age groups: 22 infants (1 month up to less than 2 years), 30 children (2 years up to less than 12 years), and 14 adolescents (12 years to less than 17 years).
Juvenile Animal Toxicity Data A juvenile toxicity study in 21-day-old
The dose of 40 mg/kg/day is approximately 0.4 times the clinical dose on a mg/ m2 basis for a child.
The relevance of this finding for the onset of male puberty in humans is unknown.
8.5 Geriatric Use Clinical studies of DEFITELIO did not include
Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
|Date Last Revised||30-03-2016|
|Type||HUMAN PRESCRIPTION DRUG|
|Marketing authorisation holder||Jazz Pharmaceuticals, Inc.|