KA is a 45-year-old female who presented to the oncology clinic for a follow up after finishing her first round of chemotherapy: Docetaxel 75mg/m² IV + Carboplatin AUC 6 IV + Trastuzumab 8mg/kg IV loading dose followed by 6 mg/kg IV. She complains of flank pain and feeling lethargic but denies feeling any chest tightness/pain or dyspnea.

PMH: Depression, Hypertension

Home Medications: Zestril 40mg PO QD, Metoprolol Succinate 25mg PO QD

Pertinent Labs:

•      Na: 137 mg/dL, K: 6.3 meq/L, Phosphorous: 5 mg/dL, Ca:  9 mg/dL, WBC: 9.4K, Uric Acid: 10 mg/dl, SCr: 1.5 mg/dl (baseline 0.8 mg/dl)
•      Vitals: BP: 120/76, HR 78, RR 13, Temp 98.7°F
•      Weight – 70kg    Height 67 inches
•      HR (-) HER 2 (+)  

KA is diagnosed with Tumor Lysis Syndrome (TLS). Along with aggressive hydration and frequent monitoring, antihyperuricemic therapy is being evaluated, specifically Elitek and Zyloprim. The intern is only vaguely familiar with these two agents and asks the clinical pharmacist for more information. Select all the following statements that are true regarding these agents.

A. Elitek is a recombinant urate oxidase that converts uric acid to allantoin

B. Zyloprim is a xanthine oxidase inhibitor that eliminates existing uric acid

C. Elitek blood samples should be refrigerated immediately upon obtaining them

D. G6PD deficient patients are at increased risk of experiencing hemolysis and methemoglobinemia when receiving Elitek

E. Both Elitek and Zyloprim increase the solubility of uric acid

Answers with rationale

Brand/generics of agents discussed: Lisinopril (Zestril), Metoprolol Tartrate (Lopressor), Rasburicase (Elitek), Allopurinol (Zyloprim)

Tumor lysis syndrome, known as TLS, is a medical emergency that requires quick action to correct the hyperuricemia. Lysis of cells by chemotherapy leads to breakdown of nucleic acids leading to hyperuricemia. Furthermore, release of electrolyes such as potassium and phosphorus can lead to hyperkalemia, hyperphosphatemia, and thus secondary hypocalcemia. To prevent TLS in high risk patients, allopurinol or rasburicase are administered based on risk profile with allopurinol generally given to those at low-moderate risk with rasburicase administered to moderate-high risk patients. 

Answers A and D are correct. 

Answer A is correct. Rasburicase is an enzyme that works quickly and effectively in converting uric acid into allantoin. Allantoin has a higher solubility and can be excreted through the kidneys.

Answer B is incorrect. Allopurinol is a xanthine oxidase inhibitor that prevents the conversion of hypoxanthine into uric acid. It reduces the amount of endogenous uric acid made by your body rather than decrease the amount of current uric acid present in your body.

Answer C is incorrect. If you pull a blood sample of rasburicase and place it in room temperature, the enzyme will continue to work in the blood sample causing falsely low levels of uric acid. While refrigeration might help, ice is recommended as this will freeze the enzyme in the blood sample and provide the most accurate reading.

Answer D is correct. Patients that are deficient in G6PD have an increased risk of hemolysis and methemoglobinemia. Patients of Mediterranean and African decent are at an increased risk of G6PD deficiency and ideally should be tested before receiving rasburicase therapy. Allopurinol is associated with a rare hypersensitivity reaction most seen in patients with the HLA-B 58:01 allele documented most often in Asian patients. 

Answer E is incorrect. Rasburicase increases the solubility of uric acid by converting it into allantoin while allopurinol inhibits the conversion of hypoxanthine into uric acid.

NAPLEX Competencies Covered: Area 2 (Identify Drug Characteristics): 2.1 Pharmacology, mechanism of action, or therapeutic class; 2.2 Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied. Area 5 (Compound, Dispense, or Administer Drugs, or Manage Delivery Systems): 5.6 Packaging, storage, handling, or disposal

A fantastic reference can be found in the latest edition of Dipiro's Pharmacotherapy (12e) written by my good friend and colleague at UGA, Dr. Amber Clemmons.

1. Clemmons AB, Glode AE. Supportive Care in Cancer. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Michael Posey LL. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12e. McGraw Hill; 2023. Accessed February 09, 2023. https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=268554485

Have a great week!

Dr. B