Pediatric Tumor Lysis Syndrome Medication

Management of tumor lysis syndrome (TLS), other than hydration and alkalinization, necessitates the use of drugs to correct metabolic disturbances. Use of medications must be instituted before the start of chemotherapy; the goal is to achieve optimal metabolic stability.

An alternative to allopurinol for decreasing uric acid load is rasburicase (urate oxidase), which controls hyperuricemia by converting uric acid to water-soluble allantoin.^{[5, 6, 7, 8]} This drug is widely used in Europe and was approved by the Food and Drug Administration (FDA) in the United States.

Class Summary

Allopurinol is used to inhibit xanthine oxidase, thereby reducing uric acid. The intravenous form (Aloprim) may be used for patients unable to tolerate oral administration.

Caution is necessary because of the high uric acid concentration in the urine. In 1986, Andreoli and associates explained some cases of renal failure on the basis of effects of allopurinol in altering purine excretion.^[9] In the presence of allopurinol, the excretion of uric acid, xanthine, and hypoxanthine increases several hundred folds, enough to exceed their solubility limit in the renal tubules even at a urinary pH level of 7. Also, at a urinary pH level higher than 7.5, crystallization of hypoxanthine may occur, which necessitates withdrawal of bicarbonate from intravenous fluids.

Allopurinol (Aloprim, Zyloprim)

Inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine and xanthine, thus decreasing production and excretion of uric acid and increasing the levels of more soluble xanthine and hypoxanthine. Reduces the synthesis of uric acid without disrupting the biosynthesis of vital purines.

Class Summary

These agents metabolize uric acid to a soluble form, thus preventing acute renal failure (ARF).

Rasburicase (Elitek)

Recombinant form of the enzyme urate oxidase that oxidizes uric acid to allantoin. Used in management and prophylaxis of severe hyperuricemia associated with treatment of malignancy. Hyperuricemia causes a precipitant in kidneys, which leads to acute renal failure. Unlike uric acid, allantoin is soluble and easily excreted by kidneys.

Class Summary

Calcium is used to treat arrhythmias due to hyperkalemia or hypocalcemia. Frank or impending renal failure requires additional therapeutic measures. Hyperkalemia is the most common life-threatening emergency. Chemotherapy may have to be discontinued temporarily. The entire potassium intake should be immediately discontinued. The use of calcium does not lower serum potassium levels. It is primarily used to protect the myocardium from the deleterious effects of hyperkalemia (ie, arrhythmias) by antagonizing the membrane actions of potassium.

Calcium chloride

Administer IV calcium gluconate or calcium chloride to stabilize myocardial conduction in a patient with cardiac arrhythmias. Also moderates nerve and muscle performance by regulating action potential excitation threshold. IV calcium indicated in all cases of severe hyperkalemia (ie, >6 mEq/L), especially when accompanied by ECG changes. Calcium chloride contains about 3 times more elemental calcium than an equal volume of calcium gluconate. Therefore, when hyperkalemia is accompanied by hemodynamic compromise, calcium chloride is preferred over calcium gluconate.

Administration of calcium should be accompanied by the use of other therapies that actually help lower the serum levels of potassium. Other calcium salts (eg, glubionate, gluceptate) have even less elemental calcium than calcium gluconate and are not generally recommended for the therapy of hyperkalemia.

Calcium chloride 1 g = 270 mg (13.5 mEq) of elemental calcium.

Calcium gluconate 1 g = 90 mg (4.5 mEq) of elemental calcium.

Class Summary

Sodium bicarbonate, insulin, and glucose cause a transcellular shift of potassium into muscle cells, thereby lowering (temporarily) serum levels of potassium.

Sodium bicarbonate

Intracellularly shifts potassium. May be considered in the treatment of hyperkalemia, even in the absence of metabolic acidosis.

Insulin and dextrose, IV (Novolin, Humulin, Lente Iletin)

Induces intracellular flux of potassium. Presence of insulin results in the intracellular movement of glucose, followed by entry of potassium into muscle cells. Effect is almost immediate, but temporary, and should therefore be followed by therapy that actually enhances potassium clearance (eg, sodium polystyrene sulfonate).

Class Summary

Sodium polystyrene sulfonate is an exchange resin that can be used to treat mild-to-moderate hyperkalemia. Each mEq of potassium is exchanged for 1 mEq of sodium.

Sodium polystyrene sulfonate (Kayexalate)

Exchanges sodium for potassium and binds it in the gut, primarily in the large intestine and decreases total-body potassium. Onset of action after PO administration is 2-12 h and is longer when administered rectally. Used in the second stage of therapy to reduce total-body potassium.

Class Summary

These agents are used to treat hyperphosphatemia.

Aluminum hydroxide (AlternaGEL, Alu-Cap, Amphojel, Dialume)

Has been shown to be an effective phosphate binder. However, aluminum salts are not first-line because of their potential for toxicity.

Sevelamer hydrochloride (Renagel)

Polymeric phosphate binder for PO administration. Does not contain aluminum and, thus, aluminum intoxication is not a concern.