Linked Life Data

Elitek (Kit)

Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/174

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dailymed-drugs:174rdfs:labelElitek (Kit)lld:dailymed
dailymed-drugs:174dailymed-instance:dosageThe 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.lld:dailymed
dailymed-drugs:174dailymed-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.lld:dailymed
dailymed-drugs:174dailymed-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.lld:dailymed
dailymed-drugs:174dailymed-instance:activeIng...dailymed-ingredient:rasburi...lld:dailymed
dailymed-drugs:174dailymed-instance:supplyNDC 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.lld:dailymed
dailymed-drugs:174dailymed-instance:genericDr...http://www4.wiwiss.fu-berli...lld:dailymed
dailymed-drugs:174dailymed-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 .lld:dailymed
dailymed-drugs:174dailymed-instance:activeMoi...dailymed-ingredient:rasburi...lld:dailymed
dailymed-drugs:174dailymed-instance:inactiveI...dailymed-ingredient:mannito...lld:dailymed
dailymed-drugs:174dailymed-instance:inactiveI...dailymed-ingredient:dibasic...lld:dailymed
dailymed-drugs:174dailymed-instance:inactiveI...dailymed-ingredient:L-alani...lld:dailymed
dailymed-drugs:174dailymed-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.lld:dailymed
dailymed-drugs:174dailymed-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.lld:dailymed
dailymed-drugs:174dailymed-instance:genericMe...rasburicaselld:dailymed
dailymed-drugs:174dailymed-instance:fullNameElitek (Kit)lld:dailymed
dailymed-drugs:174dailymed-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.lld:dailymed
dailymed-drugs:174dailymed-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.lld:dailymed
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