Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/174
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Elitek (Kit)
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| dailymed-instance:dosage |
The recommended dose and
schedule of ELITEK is 0.15 or 0.20 mg/kg as a single daily dose for
5 days. Because the safety and effectiveness of other schedules have
not been established, dosing beyond 5 days or administration of more
than one course of ELITEK is not recommended. Chemotherapy should
be initiated 4 to 24 hours after the first dose of ELITEK. DO NOT ADMINISTER AS A BOLUS INFUSION.
ELITEK should be administered as an intravenous infusion over 30 minutes. TWO DIFFERENT STRENGTHS ARE AVAILABLE (1.5 mg vial
and 7.5 mg vial)<br/>Reconstitution Procedure: Determine the number
of vials of ELITEK needed to achieve the proper dosage, based on the
individual patient's weight and the dose per kilogram. ELITEK
must be reconstituted in the diluent provided. To each 1.5 mg vial of ELITEK, add 1 mL of the provided reconstitution
solution (diluent) and mix by swirling very gently. Do not shake or vortex. To each 7.5 mg vial of
ELITEK, add 5 mL of the provided reconstitution solution (diluent)
and mix by swirling very gently. Do not
shake or vortex. Reconstituted ELITEK
should be inspected visually for particulate matter and discoloration
prior to administration, and discarded if particulate matter is visible
or if product is discolored.<br/>Further Dilution and Administration: Using aseptic technique
and syringes of appropriate volume, remove the predetermined dose
of ELITEK from the reconstituted vials and inject into an infusion
bag containing the appropriate volume of 0.9% sterile sodium chloride,
to achieve a final total volume of 50 mL. This final solution for
injection is to be infused over 30 minutes. No filters should be used for the infusion. The reconstituted ELITEK
contains no preservatives and must be administered within 24 hours
of reconstitution. The reconstituted or diluted solution can be stored
up to 24 hours at 2���8��C. Discard any unused product. ELITEK should be infused
through a different line than that used for the infusion of other
concomitant medications. If use of a separate line is not possible,
the line should be flushed with at least 15 mL of saline solution
prior to and after infusion with ELITEK.
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| dailymed-instance:descripti... |
ELITEK (rasburicase) is
a recombinant urate-oxidase enzyme produced by a genetically modified Saccharomyces cerevisiae strain. The
cDNA coding for rasburicase was cloned from a strain of Aspergillus flavus. Rasburicase is a tetrameric protein with identical subunits of a
molecular mass of about 34kDa. The molecular formula of the monomer
is CHNOS. The monomer, made up of a single 301 amino acid polypeptide
chain, has no intra- or inter-disulfide bridges and is N-terminal
acetylated. The drug product is a sterile, white to off-white, lyophilized
powder intended for intravenous administration following reconstitution.
ELITEK is supplied in 3-mL and 10-mL colorless, glass vials. Each
3-mL vial contains 1.5 mg rasburicase, 10.6 mg mannitol, 15.9 mg L-alanine,
and between 12.6 and 14.3 mg of dibasic sodium phosphate. Each 10-mL
vial contains7.5 mg rasburicase, 53 mg mannitol, 79.5 mg L-alanine,
and between 63 and 71.5 mg dibasic sodium phosphate. The diluent solution for reconstitution is supplied in a 2-mL or
5-mL clear, glass ampule. The 2-mL ampule contains 1 mL Water for
Injection, USP, and 1 mg Poloxamer 188. The 5-mL ampule contains 5
mL Water for Injection, USP, and 5 mg Poloxamer 188. The product reconstituted
with diluent is a clear, colorless solution.
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| dailymed-instance:clinicalP... |
In humans, uric acid is
the final step in the catabolic pathway of purines. Rasburicase catalyzes
enzymatic oxidation of uric acid into an inactive and soluble metabolite
(allantoin). Rasburicase is only active at the end of the purine catabolic
pathway. Pharmacokinetics
of rasburicase were evaluated in two studies that enrolled patients
with lymphoid leukemia (B and T cell), non-Hodgkin's lymphoma
(including Burkitt's lymphoma) or acute myelogenous leukemia.
ELITEK exposure, as measured by AUCand C, tended to increase linearly with doses over a limited
dose range (0.15 to 0.20 mg/kg). The overall elimination half-life
was 18 hours. No accumulation of rasburicase was observed between
days 1 and 5 of dosing. ELITEK mean volume of distribution was 110
to 127 mL/kg in pediatric patients. There are insufficient data to
characterize pharmacokinetics in adult patients.
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| dailymed-instance:supply |
NDC 0024-5150-10: One carton
containing 3 single-use vials each containing 1.5 mg of rasburicase
and 3 ampules each containing 1 mL Water for Injection, USP, and 1
mg Poloxamer 188. NDC
0024-5151-75: One carton containing 1 single-use vial containing 7.5
mg of rasburicase and 1 ampule containing 5 mL Water for Injection,
USP, and 5 mg Poloxamer 188.<br/>Storage and Handling: The lyophilized
drug product and the diluent for reconstitution should be stored at
2���8��C (36���46��F). Do not freeze. Protect from
light.
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| dailymed-instance:boxedWarn... |
BOXED WARNINGS:<br/>Anaphylaxis: ELITEK may cause
severe hypersensitivity reactions including anaphylaxis. ELITEK should
be immediately and permanently discontinued in any patient developing
clinical evidence of a serious hypersensitivity reaction .<br/>Hemolysis: ELITEK administered
to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency
can cause severe hemolysis. ELITEK administration should be immediately
and permanently discontinued in any patient developing hemolysis.
It is recommended that patients at higher risk for G6PD deficiency
(e.g., patients of African or Mediterranean ancestry) be screened
prior to starting ELITEK therapy .<br/>Methemoglobinemia: ELITEK use has been
associated with methemoglobinemia. ELITEK administration should be
immediately and permanently discontinued in any patient identified
as having developed methemoglobinemia .<br/>Interference with Uric Acid Measurements: ELITEK will cause
enzymatic degradation of the uric acid within blood samples left at
room temperature, resulting in spuriously low uric acid levels. To
ensure accurate measurements, blood must be collected into pre-chilled
tubes containing heparin anticoagulant and immediately immersed and
maintained in an ice water bath; plasma samples must be assayed within
4 hours of sample collection .
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| dailymed-instance:precautio... |
General: Patients on ELITEK
should receive intravenous hydration according to standard medical
practice for the management of plasma uric acid in patients at risk
for tumor lysis syndrome.<br/>Drug Interactions: No studies of interactions
with other drugs have been conducted in humans. Rasburicase does not metabolize allopurinol, cytarabine, methylprednisolone,
methotrexate, 6-mercaptopurine, thioguanine, etoposide, daunorubicin,
cyclophosphamide or vincristine in vitro. No metabolic-based drug interactions are therefore anticipated
with these agents in patients. In preclinical in vivo studies,
rasburicase did not affect the activity of isoenzymes CYP1A, CYP2A,
CYP2B, CYP2C, CYP2E, and CYP3A, suggesting no induction nor inhibition
potential. Clinically relevant P450-mediated drug-drug interactions
are therefore not anticipated in patients treated with the recommended
ELITEK dose and dosing schedule.<br/>Laboratory Test Interactions: At room temperature,
ELITEK causes enzymatic degradation of the uric acid in blood/plasma/serum
samples potentially resulting in spuriously low plasma uric acid assay
readings. The following special sample handling procedure must be
followed to avoid ex vivo uric
acid degradation. Uric acid must be analyzed in plasma. Blood must be collected into
pre-chilled tubes containing heparin anticoagulant. Samples must be immediately immersed in an ice water bath. Plasma samples must be prepared by centrifugation in a pre-cooled
centrifuge (4��C). Finally, the plasma must be maintained in an
ice water bath and analyzed for uric acid within four hours of collection
(see BOXED WARNINGS, Interference with
Uric Acid Measurements).<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies
in animals to evaluate carcinogenic potential have not been performed. ELITEK was non-genotoxic
in the Ames, unscheduled DNA synthesis, chromosome analysis, mouse
lymphoma, and micronucleus tests. ELITEK did not affect reproductive performance or fertility in male
or female rats at doses 8-fold higher than the human dose when corrected
for differences in body surface area.<br/>Pregnancy Category C: Rasburicase is teratogenic
in rabbits and rats. Pregnant rabbits were dosed with rasburicase
at levels of 2, 10 or 20 mg/kg (equivalent to 10, 50 and 100 times
the human equivalent dose). Mortality occurred at 2 and 20 mg/kg,
abortions at 10 mg/kg and clinical signs of toxicity appeared at all
dose levels. At doses equal to or greater than 10 mg/kg, decreases
were observed in uterine weight and viable fetuses while increases
were observed in the number of fetal resorptions and post-implantation
loss. Additionally, fetal body weights were decreased while increases
occurred in heart and great vessel malformation at all doses levels.
In offspring of pregnant rats given 50 mg/kg (equivalent to 250 times
the human dose), multiple heart and great vessel malformations were
observed. There are no adequate and well-controlled studies in pregnant
women. Because animal studies are not always predictive of human response,
ELITEK should be used during pregnancy only if the potential benefit
to the mother justifies the potential risk to the fetus.<br/>Nursing Mothers: It is not known
whether this drug is excreted in human milk. Because many drugs are
excreted in human milk and because of the potential for serious adverse
reactions in nursing infants, a decision should be made whether to
discontinue nursing or to discontinue ELITEK, taking into account
the importance of the drug to the mother.<br/>Pediatric Use: The efficacy and
safety of ELITEK was studied in 246 pediatric patients ranging in
age from 1 month to 17 years. There were an insufficient number of
patients in the 0���6 months age group (n=7) to determine whether
they respond differently from older children. These patients were
pooled into the<2 years of age group (n=24). Children<2 years
of age had a higher mean uric acid AUCthan
those age 2���17 years (150��s.e. 16 mg���hr/dL vs.
108��s.e. 4 mg���hr/dL, respectively). In addition, the
data suggest that children<2 years of age had a lower rate of
success at achieving maintenance uric acid concentration by 48 hours
[83% (95% CI of 62 to 95) vs. 93% (95% CI of 89 to 95), respectively].
Children<2 years old also experienced more toxicity. The following
adverse events were observed more frequently in children less than
2 years of age compared to those age 2���17 years respectively:
vomiting (75% vs. 55%), diarrhea (63% vs. 20%), fever (50% vs. 38%),
and rash (38% vs. 10%).<br/>Geriatric Use: Five of the 19 adults
among the 265 patients enrolled in clinical studies of ELITEK, were
age 65 or greater. Therefore, there are insufficient data to determine
whether geriatric subjects, or adults in general, respond differently
from pediatric subjects.
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| dailymed-instance:overdosag... |
Several cases of overdosage
with ELITEK have been reported without any specific adverse events
associated with the overdose. The maximum dose of ELITEK that has
been administered as a single dose is 1.3 mg/kg; the maximum daily
dose that has been administered is 1.3 mg/kg/day. According to the
mechanism of action of ELITEK, an overdose will lead to low or undetectable
plasma uric acid concentration, which has no known clinical consequences.
Patients suspected of receiving an overdose should be monitored,
and general supportive measures should be initiated as no specific
antidote for ELITEK has been identified.
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rasburicase
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Elitek (Kit)
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| dailymed-instance:adverseRe... |
Because clinical trials
are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared
to rates in the clinical trials of another drug and may not reflect
the rates observed in practice. The adverse reaction information from
clinical trials does, however, provide a basis for identifying the
adverse events that appear to be related to drug use and for approximating
rates. The data described
below reflect exposure to ELITEK in 703 patients [63% male, 37% female;
median age 10 years (range 10 days to 88 years); 73% Caucasian, 9%
African, 4% Asian, 14% other/unknown]. ELITEK was studied for adverse
reactions, regardless of severity, in 347 patients (265 pediatric
and 82 adults) enrolled in one active-controlled trial (Study 1),
two uncontrolled trials (Studies 2 and 3), and one uncontrolled safety
trial (n=82). Additionally, an expanded access experience enrolled
356 patients, for whom reliably collected data were limited to serious
adverse reactions. Among the 703 patients for whom serious adverse reactions were assessed,
the most serious adverse reactions caused by ELITEK were allergic
reactions including anaphylaxis (<1%), rash (1%), hemolysis (<1%),
and methemoglobinemia (<1%) . The commonly observed serious adverse reactions were fever (5%),
neutropenia with fever (4%), respiratory distress (3%), sepsis (3%),
neutropenia (2%), and mucositis (2%). The following additional serious
adverse reactions were observed in���1% of patients regardless
of causality: acute renal failure, arrhythmia, cardiac failure, cardiac
arrest, cellulitis, cerebrovascular disorder, chest pain, convulsions,
cyanosis, diarrhea, dehydration, hot flushes, ileus, infection, intestinal
obstruction, hemorrhage, myocardial infarction, paresthesia, pancytopenia,
pneumonia, pulmonary edema, pulmonary hypertension, retinal hemorrhage,
rigors, thrombosis, and thrombophlebitis. Among the 347 patients for whom all adverse reactions regardless
of severity were assessed, the most frequently observed adverse reactions
(incidence���10%) were vomiting (50%), fever (46%), nausea (27%),
headache (26%), abdominal pain (20%), constipation (20%), diarrhea
(20%), mucositis (15%), and rash (13%). In Study 1, an active control
study, the following adverse events occurred more frequently in ELITEK-treated
subjects than allopurinol-treated subjects: vomiting, fever, nausea,
diarrhea, and headache. Although the incidence of rash was similar
in the two arms, severe rash (NCI CTC, Grade 3 or 4) was
reported only in one ELITEK-treated patient.<br/>Immunogenicity: ELITEK is immunogenic
in healthy volunteers, and can elicit antibodies that inhibit the
activity of rasburicase in vitro . In a study
of 28 healthy volunteers, the incidence of antibody responses to either
a single dose or to 5 daily doses was assessed. Binding antibodies
to rasburicase were detected by ELISA in 17/28 (61%) volunteers and
neutralizing antibodies were detected in 18/28 (64%) volunteers. Time
to detection of antibodies ranged from 1 to 6 weeks after ELITEK exposure.
In two subjects with extended follow-up, antibodies persisted for
333 and 494 days. The incidence of antibody responses in patients with hematologic
malignancy has not been adequately assessed. In clinical trials of
patients with hematologic malignancies, 24 of the 218 patients tested
(11%) developed antibodies by day 28 following ELITEK administration.
However, this is not a reliable estimate of the true incidence of
antibody responses in patients with hematologic malignancies, because
the data from the healthy volunteer study indicate that antibody may
not be detectable until some time point beyond day 28. The incidence of antibody
responses detected is highly dependent on the sensitivity and specificity
of the assay, which have not been fully evaluated. Additionally, the
observed incidence of antibody positivity in an assay may be influenced
by several factors, including serum sampling, timing and methodology,
concomitant medications, and underlying disease. For these reasons,
comparison of the incidence of antibodies to ELITEK with the incidence
of antibodies to other products may be misleading.
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| dailymed-instance:indicatio... |
ELITEK is indicated for
the initial management of plasma uric acid levels in pediatric patients
with leukemia, lymphoma, and solid tumor malignancies who are receiving
anti-cancer therapy expected to result in tumor lysis and subsequent
elevation of plasma uric acid.
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| dailymed-instance:name |
Elitek
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