TN is a 68-year-old female with a PMH of Burkitt’s lymphoma.  She is to start her first cycle of HyperCVAD chemotherapy tomorrow. Her pertinent labs are the following from today:

Labs:

Uric acid: 8.5 mg/dL

Potassium: 5.7 mEq/L

Phosphorus: 6 mg/dL

Corrected Ca: 6.3 mg/dL

SCr: 4.2 mg/dL

The medical resident is considering administration of rasburicase today for TN and asks for your assistance. Which of the following would you tell the medical resident about rasburicase? Select all that apply. 

A. It is a xanthine oxidase inhibitor that blocks the conversion of purines to uric acid

B. Post-dose blood samples need to be kept in an ice water bath

C. It is weight-based and given as 6 mg/kg intravenously X 1 dose

D. Its dose needs to be renally adjusted when eGFR < 30mL/min

E. It is contraindicated in patients who are G6PD deficient

Answer with rationale

Tumor Lysis Syndrome (TLS) is the most common oncologic emergency. It can occur as a result of cytotoxic chemotherapy rapidly lysing tumor cells. When tumor cells are lysed, their cell wall disintegrates allowing for the intracellular contents, potassium, phosphate, purines, and pyrimidines to be released into the bloodstream. The phosphate that is released binds to calcium causing hypocalcemia, and the formation of calcium and phosphate precipitates can lead to acute kidney injury. Low serum calcium can cause muscle cramps and neurologic symptoms, including seizures. Furthermore, xanthine oxidase converts the purines that are released into the blood into uric acid, resulting in hyperuricemia. The high uric acid may crystallize in the kidneys, leading to further renal injury. 

Some leukemias and lymphomas, such as Burkitt’s lymphoma, put the patient at a higher risk of developing TLS. TLS is more likely to occur when there are more tumor cells to lyse, therefore, in order to diagnose a patient with laboratory or clinical TLS, two or more laboratory changes must be observed within 3 days before or 7 days after chemotherapy administration. The Cairo Bishop Criteria is what we use to define TLS. The laboratory changes to look out for include uric acid ≥ 8 mg/dL, potassium ≥ 6 mEq/L, phosphorous ≥ 4.5 mg/dL, or any of the three > 25% from baseline, and calcium ≤ 7 mg/dL or < 25% from baseline. Clinical TLS is when the patient has confirmed laboratory TLS in addition to one of the following: SCr ≥ 1.5 times upper limit of normal, cardiac arrhythmia, sudden death, or seizure. 

In order to prevent TLS, ensure the patient is adequately hydrated in order to enhance urinary excretion of uric acid and phosphorus. Give fluids starting > 24 hours prior to chemotherapy. Additionally, you can give allopurinol prophylactically 1-2 days prior to chemo and continue for 3-7 days, depending on the patient’s risk factors. Rasburicase is also an option for preventing TLS often given within 24 hours of starting chemotherapy. Let's go through each answer to determine if correct or incorrect. 

Answer A is incorrect. Allopurinol is a xanthine oxidase inhibitor that prevents the formation of uric acid, while rasburicase is a recombinant urate-oxidase enzyme that converts uric acid to allantoin, its inactive and more water-soluble metabolite. 

Answer B is correct. Blood samples that are taken after rasburicase administration need to be kept on ice, otherwise the rasburicase will continue to break down uric acid in the blood sample making interpretation of levels not possible. 

Answer C is incorrect. The FDA-approved labeled dose is 0.2mg/kg IV daily for up to 5 days. In clinical practice, rasburicase is often given IV as a one-time fixed dose of 3mg or 6mg as this has demonstrated similar outcomes with less cost. 

Answer D is incorrect. Rasburicase does not require any renal dose adjustments as it is eliminated via enzymatic degradation. However, allopurinol does need to be renally adjusted in patients with kidney dysfunction. 

Answer E is correct. Rasburicase is contraindicated in patients who are G6PD deficient because it can cause hemolysis and methemoglobinemia. The highest risk groups include those with African, Southeast Asian, or Mediterranean ancestry. 

Brand/Generic: rasburicase (Elitek), allopurinol (Aloprim, Zyloprim)

NAPLEX Content Domains Covered:

1.A.1 Pharmacology

1.A.2 Pharmacokinetics, pharmacodynamics, or pharmacogenomics

2.A.2 Indications, usage, and dosing regimens

3.C.2 Appropriateness of therapy (eg contraindications)

3.C.3 Interactions (eg drug-laboratory)