24

August

Rasburicase (Elitek) for Treatment of Tumor Lysis Syndrome 

Written by: Marie C. Rush, PharmD, CPP, BCOP, Wake Forest Baptist Health
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The purpose of this PQI is to identify appropriate dosing and utilization of rasburicase based on uric acid levels

Background

Rasburicase is an FDA approved intravenous medication for the management of serum uric acid levels in the setting of anticancer therapy that is expected to result in tumor lysis.1,2

While rasburicase breaks down uric acid that has already formed in the body, allopurinol prevents the formation of additional uric acid. The two medications work concomitantly to actively decrease elevated uric acid levels while also preventing hyperuricemia in the future.3

In general, the risk of a patient developing TLS is higher with hematologic malignancies. Risk stratification can be found in the modified chart below, adapted from TLS stratification5 and prophylaxis10 references.5,10,12

Type of MalignancyHigh RiskIntermediate RiskLow Risk
Non-Hodgkin lymphoma (NHL)5Burkitt lymphomaDLBCLIndolent NHL
Acute lymphoblastic leukemia (ALL)10 

WBC  100,000

OR

WBC <100,000 and/or LDH  2X ULN

 

WBC <100,000 and LDH <2X ULNWBC <100,000
Acute myeloid leukemia (AML)10WBC  100,000, monoblasticWBC >25,000 but <100,000

OR

WBC <25,000 and LDH >/=2X ULN

 

WBC <25,000 and LDH <2X ULN
Chronic lymphocytic leukemia (CLL)10,12Venetoclax use

(lymph node > 10 cm or ALC > 25,000 and lymph node > 5 cm)

WBC 10,000 – 100,000

and treatment with targeted and/or biologic Therapy

(ex. Fludarabine or Venetoclax)

(lymph node 5-<10 cm or ALC > 25,000)

WBC < 10,000 and using only alkylating agents

 

Venetoclax use

(all lymph nodes < 5 cm and ALC < 25,000)

Other hematologic malignancies (chronic myeloid leukemia, multiple myeloma) and solid tumors (small cell lung cancer)5 

Rapid proliferation with expected rapid response to therapyRemainder of patients

While FDA approved dosing of rasburicase is weight-based (0.2 mg/kg daily for up to 5 days), several studies have been performed that evaluated the use of single, fixed doses of rasburicase.1,4,6,7,8,9 Trifilio and colleagues demonstrated that rasburicase 3 mg effectively lowered uric acid levels to ≤ 7 mg/dL in 72% of patients at 24 hours; uric acid levels continued to decrease without additional doses of rasburicase. Of note, patients with higher baseline uric acid levels (defined as ≥ 12 mg/dL) were found to be at risk of rasburicase failure. This patient population may require a higher initial dose of rasburicase at 6 mg, or a repeated dose of 3 mg if uric acid levels begin to rise again.6 McBride and colleagues found similar success with the 3 mg dose in their study. However, it is worth noting that patients who received 3 mg of rasburicase had lower baseline uric acid levels compared to the patients who received 6 mg of rasburicase.7

PQI Process:

  • Confirm the patient has an order/prescription for allopurinol
  • Confirm the patient is maintaining adequate oral hydration or initiated on IV hydration
  • Baseline and follow-up TLS labs (potassium, serum creatinine, uric acid, phosphorus, calcium, lactate dehydrogenase) should be obtained pre- and post-rasburicase administration
  • Rasburicase dosing may vary per institution guidelines/policies
    • Patients with malignancies that are classified as having a high risk for TLS may require upfront dosing of rasburicase
    • Consider rasburicase 3 mg for patients with baseline uric acid <12 mg/dL
      • Encourage use of allopurinol and aggressive hydration prior to initiation of rasburicase
  • Consider rasburicase 6 mg for patients with baseline uric acid ≥12 mg/dL OR consider an initial   dose of 3 mg and monitor the patient’s uric acid levels closely to determine if a repeat dose       of 3 mg is warranted
  • If warranted, repeated rasburicase dosing can be considered 24 hours after the initial dose
  • Ensure uric acid levels obtained after rasburicase administration are immediately put on ice. If left at room temperature, the enzymatic activity of rasburicase will continue to break down uric acid and can result in a falsely low uric acid level

Patient Centered Activities:

  • Patient Education
    • Although rare, hypersensitivity reactions have been reported with rasburicase
    • Methemoglobinemia can occur as a result of rasburicase administration
    • Hemolysis can occur after rasburicase administration in patients with G6PD deficiency
    • Counsel patients to maintain increased oral hydration

Supplemental Information

Table 1: Diagnosis of Tumor Lysis (Cairo-Bishop Classification)3,5

Laboratory Tumor LysisClinical TLS
Two or more of the following occurring in a patient with cancer within 3 days prior to or 7 days following initiation of cancer treatment:

  • Uric acid ≥ 8 mg/dL or 25% increase from baseline
  • Potassium ≥ 6 mmol/L (6 mg/L) or 25% increase from baseline
  • Phosphate ≥ 4.5 mg/dL or 25% increase from baseline
  • Calcium ≤ 7 mg/dL or 25% decrease from baseline
Laboratory tumor lysis plus one of the following:

  • Serum creatinine ≥ 1.5 x ULN
  • Cardiac arrhythmia/sudden death
  • Seizure

References:

  1. Elitek (rasburicase) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; July 2019.
  2. Cairo MS, Coiffier B, Reiter A, et al. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149:578-586.
  3. Cairo MS and Bishop M. Tumour lysis syndrome: new therapeutic strategies and classification. Br J Haematol 2004;127:3-11.
  4. Hutcherson DA, Gammon DC, Bhatt MS, et al. Reduced-Dose Rasburicase in the Treatment of Adults With Hyperuricemia Associated With Malignancy. Pharmacother. 2006;26(2):242-7.
  5. Coiffier B, Altman A, Pui C et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review.  J Clin Oncol.  2008;26:2767-78.
  6. Trifilio SM, Pi J, Zook J, et al. Effectiveness of a single 3-mg rasburicase dose for the management of hyperuricemia in patients with hematological malignancies. Bone Marrow Transplant 2011;46:800-805.
  7. McBride A, Lathon SC, Boehmer L, et al. Comparative evaluation of a single fixed dosing and weight-based dosing of rasburicase for tumor lysis syndrome. Pharmacother. 2013;33(3):295-303.
  8. McDonnell AM, Lenz KL, Frei-Lahr DA, et al. Single-Dose Rasburicase 6 mg in the Management of Tumor Lysis Syndrome in Adults. Pharmacother. 2006;26(6):806-12.
  9. Yu X, Liu L, Nie X et al. The optimal single-dose regimen of rasburicase for management of tumour lysis syndrome in chlidren and adults: a systematic review and meta-analysis. J Clin Pharm Ther. 2017;42:18-26.
  10. Cairo MS, Coiffier B, Reiter A, Younes A. BJH 2010; 149;578-586
  11. Howard N Eng J Med 2011;2011;364(19):1844-54
  12. Itchaki G, Brown JR. The potential of venetoclax (ABT-199) in chronic lymphocytic leukemia. Ther Adv Hematol. 2016 Oct; 7(5): 270-287
Important notice: National Community Oncology Dispensing Association, Inc. (NCODA), has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional. This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented. NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
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