Tumor Lysis Syndrome Medication

The management of tumor lysis syndrome, other than hydration and alkalinization, necessitates the administration of drugs to correct metabolic disturbances. Use of these medications must be instituted before the start of chemotherapy; the goal is to achieve optimal metabolic stability.

Allopurinol, a xanthine oxidase inhibitor, reduces the conversion of nucleic acid byproducts to uric acid, in this way preventing urate nephropathy and subsequent oliguric renal failure.^[26]

An alternative to allopurinol for decreasing uric acid load is rasburicase (urate oxidase), which controls hyperuricemia by converting uric acid to water-soluble allantoin.^{[27, 28, 29, 30]}

Class Summary

These agents control hyperuricemia and are used to attempt to prevent urate nephropathy and subsequent oliguric renal failure.

Allopurinol inhibits xanthine oxidase, thereby reducing uric acid. The IV 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. Andreoli and associates explained some cases of renal failure on the basis of effects of allopurinol in altering purine excretion.^[33] In the presence of allopurinol, the excretion of uric acid, xanthine, and hypoxanthine increases several hundred fold, 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 IV fluids.

Allopurinol (Zyloprim, Aloprim)

Allopurinol 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. The drug reduces the synthesis of uric acid without disrupting the biosynthesis of vital purines. Patient response is measured by serum uric acid levels assessed at 48 hours after the initiation of therapy. Dosage adjustments are made as needed.

Rasburicase (Elitek)

Rasburicase is a recombinant form of the enzyme urate oxidase, which oxidizes uric acid to allantoin. It is indicated for the treatment and prophylaxis of severe hyperuricemia associated with the treatment of malignancy. Hyperuricemia causes a precipitant in the kidneys, which leads to acute renal failure. Unlike uric acid, allantoin is soluble and easily excreted by the kidneys. Elimination half-life for rasburicase is 18 hours.

Class Summary

These agents are used to prevent and treat hyperkalemia and restore electrolyte balance.

Dextrose (D-glucose) plus insulin

Insulin promotes the redistribution of potassium from extracellular to intracellular space. It stimulates the cellular uptake of potassium within 20-30 minutes. Glucose should be administered along with insulin to prevent hypoglycemia. Monitor blood sugar levels frequently.

Class Summary

These agents should be reserved for well-hydrated patients with insufficient diuresis.

Furosemide (Lasix)

Furosemide increases the excretion of water by interfering with the chloride-binding cotransport system. This, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule. Furosemide has not proven to be beneficial as front-line therapy in tumor lysis syndrome. It may contribute to uric acid or calcium phosphate precipitation in renal tubules in volume-contracted patients.

Class Summary

These agents may prevent the crystallization of uric acid.

Acetazolamide (Diamox)

Acetazolamide is a carbonic anhydrase inhibitor. It may be added to decrease proximal tubule bicarbonate reabsorption, thereby increasing urinary pH.

Sodium bicarbonate (Neut)

Sodium bicarbonate is used intravenously to alkalinize urine. It promotes alkaline diuresis, with the potential benefits of solubilizing, and thus minimizing, intratubular precipitation of uric acid. The goal is to increase urinary pH to 7 to maximize uric acid solubility in renal tubules and vessels.

Routine urine alkalinization is controversial, and if employed, it must include close monitoring of urinary pH, serum bicarbonate, and uric acid levels. Consider withdrawing sodium bicarbonate from IV solutions once serum bicarbonate levels reach 30 mEq/L, urinary pH is greater than 7.5, or serum uric acid levels have normalized.

Intracellularly, sodium bicarbonate shifts potassium. It may be considered in the treatment of hyperkalemia, even in the absence of metabolic acidosis.

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 gluconate

Calcium gluconate is used for cardioprotection when potassium levels are greater than 6.5 mmol/L or for patients with electrocardiographic alterations. This agent moderates nerve and muscle performance and facilitates normal cardiac function.

Calcium chloride

Administer IV calcium gluconate or calcium chloride to stabilize myocardial conduction in a patient with cardiac arrhythmias. Calcium also moderates nerve and muscle performance by regulating the action potential excitation threshold. IV calcium is indicated in all cases of severe hyperkalemia (ie, >6 mEq/L), especially when accompanied by electrocardiographic 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.

The administration of calcium should be accompanied by the use of other therapies that actually help to 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 treatment of hyperkalemia.

Class Summary

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

Sodium polystyrene sulfonate (Kayexalate, Kalexate, Kionex)

Sodium polystyrene sulfonate is used in the second stage of therapy to reduce total-body potassium. This agent exchanges sodium for potassium and binds it in the gut, primarily in the large intestine. Its onset of action after oral administration is 2-12 hours and is longer when administered rectally.

Aluminum hydroxide (AlternaGEL)

Aluminum hydroxide has been shown to be an effective phosphate binder. Because of their potential for toxicity, however, aluminum salts are not used as first-line therapy.

Sevelamer hydrochloride (Renagel, Renvela)

This is a polymeric phosphate binder for oral administration. It does not contain aluminum; thus, aluminum intoxication is not a concern.