Allison Weddington, PharmD PGY1 Pharmacy Resident St. Louis Children’s Hospital November 14, 2011 How Much is Too Much? How Much is Too Much? The Use of Rasburicase The Use of Rasburicase in the Treatment of in the Treatment of Tumor Lysis Syndrome Tumor Lysis Syndrome
58
Embed
Allison Weddington, PharmD PGY1 Pharmacy Resident St. Louis Childrens Hospital November 14, 2011 How Much is Too Much? The Use of Rasburicase in the Treatment.
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Allison Weddington, PharmDPGY1 Pharmacy Resident
St. Louis Children’s HospitalNovember 14, 2011
How Much is Too Much?How Much is Too Much?The Use of Rasburicase in The Use of Rasburicase in
the Treatment of Tumor the Treatment of Tumor Lysis SyndromeLysis Syndrome
Describe the clinical background of tumor lysis syndrome, including risk factors and disease presentation.
Compare and contrast rasburicase versus allopurinol in the treatment of tumor lysis syndrome.
Assess the cost effectiveness of rasburicase compared to allopurinol.
Critique the current dosage regimen for rasburicase and formulate possible alternative dosing regimens.
Goals & ObjectivesGoals & Objectives
Group of metabolic disturbances as a result of intracellular constituents being released into the blood due to lysis of malignant cells
7 year old– weight 23kg and height 111.7cm; BSA: 0.84m2
Allopurinol dose: 300mg/m2/day Patient’s dose: 252mg daily x 7 days Allopurinol cost: $4.90
Rasburicase dose: 0.2mg/kg daily x 5 days Patient’s dose: 4.5mg daily x 5 days Rasburicase cost: $10,560.75 Rasburicase cost/day: $2,112.15
Cost for Pediatric PatientCost for Pediatric Patient
16 year old– weight 100kg and height 170cm; BSA 2.17m2
Allopurinol dose: 300mg/m2/day Patient’s dose: 650mg daily x 7 days Allopurinol cost: $11.62
Rasburicase dose: 0.2mg/kg daily x 5 days Patient’s dose: 20mg daily x 5 days Rasburicase cost: $49,284.10 Rasburicase cost/day: $9,856.82
Cost for Pediatric PatientCost for Pediatric Patient
Eaddy M, Seal B, Tangirala M, Davies E, O’Day K
Am J Health-Sys Pharm. 67(24):2110-4
December 2010
Economic Comparison of Economic Comparison of Rasburicase and Allopurinol for Rasburicase and Allopurinol for
Treatment of Tumor Lysis Treatment of Tumor Lysis Syndrome in Pediatric PatientsSyndrome in Pediatric Patients
Compare the economic outcomes, including hospitalization costs, length of stay, and duration of critical care, of pediatric patients receiving rasburicase or allopurinol for tumor lysis syndrome
ObjectiveObjective
Retrospective study
Premier Perspective Database to collect data
Rasburicase and allopurinol treated patients were propensity score matched
DesignDesign
Costs per hospitalization
Length of stay
Duration of critical care
Primary EndpointsPrimary Endpoints
Inclusion criteria Pediatric patients Diagnosis of lymphoma or leukemia Received allopurinol or rasburicase within 2
days of hospital admission
Exclusion criteria Age > 18 years Received hemodialysis on hospital admission
MethodsMethods
Primary outcome differences Assessed using the γ-distributed generalized
linear models with a log-link function
Baseline demographics Categorical variables
Chi-Square Continuous variables
T-test
Significance level set at 0.05
StatisticsStatistics
126 patients were included in analysis 63 rasburicase treated patients matched with
63 allopurinol treated patients
Patient demographics Groups were not similar in regards to provider
type, admission source, and critical care admission on day 1
Average age: 7.4 years old 27% females and 73% males
ResultsResults
ResultsResults
Eaddy M, et al. Am J Health-Sys Pharm. 2010 Dec 15;67(24):2110-4.
“Examination of claims from a large hospital database showed that treatment with rasburicase, compared with allopurinol, was associated with a significant reduction in critical care days but not with a significant difference in mean LOS or total cost.”
Authors’ ConclusionsAuthors’ Conclusions
Lack of randomization Possible confounding factors No account for patient acuity Greater percent of patients in the
rasburicase treated group considered critical care admissions
Clinical outcomes not assessed between groups
Small sample size
LimitationsLimitations
One of the first studies to look at cost effectiveness of allopurinol and rasburicase in the pediatric population
Primary endpoints were appropriate
StrengthsStrengths
Statistically significant results Mean duration of critical care days
Standard of practice should not be altered based on this study
Applicable ConclusionsApplicable Conclusions
Weight Based Dosing vs. Weight Based Dosing vs. Single-Fixed Dosing in Single-Fixed Dosing in
AdultsAdults
6 mg rasburicase x 1 dose
Baseline median uric acid: 11.7mg/dL Decreased to 2 mg/dL 82.9% decrease within 24 hours
1 patient redosed
8 patients presented with secondary renal dysfunction 7 returned to baseline
Single-Dose Rasburicase 6mg in the Single-Dose Rasburicase 6mg in the Management of Tumor Lysis Syndrome Management of Tumor Lysis Syndrome
in Adultsin Adults
McDonnell AM, et al. Pharmacother. 2006;26(6):806-12.
0.15 mg/kg vs. 7.5 mg dose Average dose in control group = 12 mg
Uric acid measured at 12 and 24 hours
5 patients redosed in control group
1 patient redosed in 7.5 mg group
No changes in serum creatinine
Evaluation of a Single Fixed Dose of Evaluation of a Single Fixed Dose of Rasburicase 7.5mg for the Treatment of Rasburicase 7.5mg for the Treatment of
Hyperuricemia in Adults with CancerHyperuricemia in Adults with Cancer
Reeves DJ, et al.. Pharmacother. 2008;28(6):685-90.
Dose based on ideal or adjusted body weight Average dose = 11 mg
Baseline mean uric acid: 11.4 mg/dL Decreased to 1.4 mg/dL 89.7% decrease in 24 hours
No patients required second dose
Mean serum creatinine at baseline: 2.3 mg/dL Decreased in 13 patients 1 increased > 0.5 mg/dL 2 increased > 0.1 mg/dL but < 0.5 mg/dL
Single-Dose Rasburicase for Tumor Lysis Single-Dose Rasburicase for Tumor Lysis Syndrome in Adults: Weight-Based ApproachSyndrome in Adults: Weight-Based Approach
Campara M, et al. J Clin Pharm Ther. 2009;34:207-13.
0.05 mg/kg rasburicase x 1 dose Median dose = 4.5 mg
Treatment group Baseline median uric acid: 9.35 mg/dL
Decreased to 3.3 mg/dL – 64.7% decrease
Prophylaxis group Baseline median uric acid: 6.5 mg/dL
Decreased to 1.45 mg/dL – 77% decrease
8 patients redosed
No changes in serum creatinine
Evaluation of a Low, Weight-Based Dose of Evaluation of a Low, Weight-Based Dose of Rasburicase in Adult Patients for the Treatment Rasburicase in Adult Patients for the Treatment
or Prophylaxis of Tumor Lysis Syndromeor Prophylaxis of Tumor Lysis Syndrome
Knoebel R, et al. J Oncol Pharm Pract. 2010;17(3):147-54.
6mg rasburicase x 1 dose
Baseline median uric acid: 9.2mg/dL Decreased to 1.8mg/dL on day 3 & 3.8mg/dL on day 7 80.4% decrease in 24 hours
2 patients redosed 1 received 2 additional doses 1 received 3 additional doses
Baseline median serum creatinine: 1.9mg/dL Decreased to 1.1mg/dL on day 7
Fixed-Dose Rasburicase 6mg for Fixed-Dose Rasburicase 6mg for Hyperuricemia and Tumor Lysis Syndrome in Hyperuricemia and Tumor Lysis Syndrome in
High Risk Cancer PatientsHigh Risk Cancer Patients
Vines AN, et al. Ann Pharmacother. 2010;44:1529-37.
3mg rasburicase x 1 dose
Baseline median uric acid: 9.3 mg/dL Decreased to 5.3 mg/dL – 45%decrease
Baseline serum creatinine : 1.7 mg/dL 28% of patients had renal failure (2.5 mg/dL) at baseline Decreased to 1.6 mg/dL at 24 hours
Effectiveness of a Single 3mg Rasburicase Dose Effectiveness of a Single 3mg Rasburicase Dose for the Management of Hyperuricemia in Patients for the Management of Hyperuricemia in Patients
with Hematological Malignancieswith Hematological Malignancies
Trifilio SM, et al. Bone Marrow Transplant. 2011;46:800-5.
Flat dosing shown to be effective in adults
Same dose and possibly even lower dose should be effective in pediatric patients
Literature is lacking in pediatric population
Weight Based Dosing vs. Single-Weight Based Dosing vs. Single-Fixed Dosing in PediatricsFixed Dosing in Pediatrics
3 case summaries in pediatric patients All diagnosed with acute lymphoblastic leukemia 2 cases given standard dose of rasburicase
Case White blood count: 198,000/mm3
Uric acid: 11.4mg/dL Serum creatinine: 0.6mg/dL Allopurinol and hydration initiated Rasburicase 4.5 mg (0.08mg/kg) was given No additional rasburicase doses were needed
Treatment of Impending Tumor Treatment of Impending Tumor Lysis with Single Dose RasburicaseLysis with Single Dose Rasburicase
Lee A, et al. Ann Pharmacother. 2003;37:1614-7.
TLS: Oncologic emergency characterized by metabolic disturbances
Identify patient risk and initiate appropriate therapy
Treatment consists of fluids and allopurinol or rasburicase
Studies have shown that a maximum doses of 6mg and 7.5mg is effective in adults
SummarySummary
Based on the published literature, single-fixed dosing shows to be effective in the adult population
A single-fixed dose of rasburicase 6mg should be administered in adult patients
Dosing in the pediatric population should remain weight-based but with a max dose of 6mg
RecommendationsRecommendations
Allison Weddington, PharmDPGY1 Pharmacy Resident
St. Louis Children’s HospitalNovember 14, 2011
How Much is Too Much?How Much is Too Much?The Use of Rasburicase in The Use of Rasburicase in
the Treatment of Tumor the Treatment of Tumor Lysis SyndromeLysis Syndrome