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BlankFixed-Dose Rasburicase 6 mg for Hyperuricemia and Tumor Lysis Syndrome in

High-Risk Cancer Patients(October)

Ashleigh N Vines 1, Carl B Shanholtz MD2, L PharmD BCOP3*

1 PharmD student, School of Pharmacy, University of land, Baltimore, MD

2 Associate Professor of Medicine, University of land School of Medicine,

Division of Pulmonary and Critical Care Medicine, University of land Medical

Center, Baltimore

3 Oncology Clinical Specialist, Department of Pharmacy Services, University of

land Medical Center

* To whom correspondence should be addressed. E-mail: jthompson2@... .

Abstract

BACKGROUND: Rasburicase is indicated for the initial management of plasma uric

acid levels in adults receiving anticancer therapy who are at risk for acute

tumor lysis syndrome (TLS) and subsequent hyperuricemia. The labeled dose is 0.2

mg/kg/day administered intravenously over 30 minutes for up to 5 days. Our

institutional adult guidelines recommend rasburicase 6 mg for uric acid levels

>8 mg/dL in most adults with TLS, or 4-8 mg/dL in high-risk patients. Repeat

dosing is indicated for uric acid levels >4 mg/dL determined >=12 hours

following the initial dose.

OBJECTIVE: To determine the efficacy of a single dose of rasburicase 6 mg per

institutional adult TLS guidelines to decrease uric acid levels to <4 mg/dL by

day 3, as well as to determine the effect on serum creatinine and phosphorus

concentrations. The secondary objectives were to evaluate the appropriateness of

our institutional guidelines and identify TLS risk factors.

METHODS: The study was approved by the University of land Medical Center

Institutional Review Board. A retrospective review of all adults between July

2008 and February 2009 who received at least one 6-mg dose of rasburicase, with

redosing, if indicated, before day 3, was conducted. Subsequent TLS monitoring

over 7 days after initial dosing was recorded. Patients were excluded if dosing

did not adhere to institutional guidelines.

RESULTS: We observed a decline in median uric acid levels from 9.2 mg/dL

(interquartile range 8.1-10.4) on day 1 to between 1.8 (1.0-3.8) on day 3 and

3.8 mg/dL (2.1-4.4) on day 7 (p < 0.0001) with 2 patients requiring repeat

dosing before day 3 (n = 34). The majority of the population was hyperuricemic

(>8 mg/dL; 76%) or at high risk for TLS (85%).

CONCLUSIONS: A 6-mg dose of rasburicase effectively decreased uric acid to <4

mg/dL by day 3, rarely requiring repeat dosing, in a high-risk population.