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Table 3 Pharmacologic therapies for the treatment of tumor lysis syndrome (TLS)[3]

From: Recognizing and managing the expanded risk of tumor lysis syndrome in hematologic and solid malignancies

 

Medication

Mechanism of Action

Dosage/Administration

Comments

Hyperuricemia

Allopurinol

Potent inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine to uric acid.

PO: 200–300 mg/m2 qd; administration of >300 mg should be given in divided doses (max, 800 mg/d); should initiate therapy 24 to 48 hours prior to chemotherapy.

Adverse events include maculopapular rash, dyspepsia, nausea/ vomiting, fever, and eosinophilia; rare reports of interstitial nephritis; decreases in serum uric acid occur in 1 to 2 days with a nadir ~7 days; dosage adjustment in renal dysfunction is necessary to avoid accumulation of the active metabolite oxypurinol (alloxanthine); removed by dialysis, so administer post-hemodialysis or administer 50% supplemental dose; significant drug interactions with azathioprine and 6-mercaptopurine; the dose of concomitant azathioprine or 6-mercaptopurine should be reduced to one third to one fourth of their usual dose.

   

Adult (IV): 200–400 mg/m2/d as a single infusion or divided doses (max, 600 mg/d); infuse over 15–60 minutes; final concentration no greater than 6 mg/mL.

 
   

Pediatric (IV): Starting dose 200 mg/m2/d.

 
 

Rasburicase

Recombinant protein that catalyzes enzymatic oxidation of uric acid into an inactive metabolite, allantoin, that is 5 to 10 times more soluble than uric acid.

Adult: 0.2 mg/kg infusion over 30 minutes once daily for up to 5 days*; no dosing adjustment required in renal or hepatic dysfunction.

Adverse events include nausea/vomiting, fever, headache, abdominal pain, constipation, diarrhea, and rash. Rare (<1%) but serious reactions have occurred such as severe hypersensitivity reactions, including anaphylaxis, hemolysis, and methemoglobinemia. Caution is advised in patients who have atopic allergies/asthma.

   

Pediatric: 0.15-0.2 mg/kg IV infusion over 30 minutes daily × 5 days*; no dosing adjustment required in renal or hepatic dysfunction.

 
   

*Studies using single dose in the treatment of hyperuricemia has been reported [55].

 
    

Contraindicated in individuals deficient in glucose-6-phosphatase dehydrogenase (G6PD). Rasburicase will cause enzymatic degradation of uric acid within blood samples left at room temperature, resulting in spuriously low uric acid levels—blood must be collected into prechilled tubes containing heparin anticoagulant and immediately immersed and maintained in an ice water bath; plasma samples must be assayed within 4 hours of sample collection.

Hyperkalemia

Sodium polystyrene sulfonate

Removes potassium (K+) by exchanging sodium ions (Na+) for K+ in the intestine.

Adult: 15 g PO (60 mL) 1 to 4 times per day

1 g resin binds approximately 1 mEq of K+; onset is variable ~2 to 24 hours; administer orally or nasogastrically with a laxative such as sorbitol to avoid fecal impaction and facilitate elimination; chilling the solution will increase palatability; enema route is usually less effective.

   

Pediatric: 1 g/kg/dose PO q6h or q2-6h rectally.

 
 

Calcium gluconate

Raises threshold potential and reestablishes cardiac excitability.

Adult: 1–3 g over 3 to 5 minutes IV push.

Antagonizes the action of hyperkalemia on the heart; should be monitored closely by ECG when given; onset ~1 to 2 minutes; duration is ~10 to 30 minutes.

   

Pediatric: 60–200 mg/kg over 3 to 5 minutes slow IV push.

 
 

Loop diuretics

Inhibits reabsorption of Na+ and chloride, thus causing increased excretion of fluid, K+, and phosphate.

Adult: bumetanide: 0.5-1 mg IV or PO 1 to 2 times per day (1 mg = 40 mg furosemide); ethacrynic acid (PO) or ethacrynate sodium (IV [Edecrin, Merck]): 0.5-1 mg/kg/dose IV or PO q8-12h prn; furosemide: 20–80 mg/dose IV or PO q6-12h prn; torsemide: 10–20 mg IV or PO every day prn (20–30 mg = 40 mg furosemide).

Onset: IV ~5 minutes; PO ~30 to 60 minutes; duration ~6 to 12 hours, depending on agent; monitor for blood pressure, electrolytes, and renal function.

   

Pediatric: bumetanide (>6 months): 0.015-0.1 mg/kg/dose once or twice daily (safety and efficacy have not been established in children <18); ethacrynic acid: 25 mg PO daily (maximum dose, 2–3 mg/kg/d); furosemide 1– 2 mg/kg/dose IV or PO q6-8h prn (maximum daily dose, 40 mg).

 
 

Dextrose and regular insulin

Shifts K+ intracellularly.

Adult: D5W at 0.5-1 mL/kg and regular insulin 1 unit for every 4–5 g of dextrose given.

Onset is usually within 30 to 60 minutes; effects are temporary, usually lasting 2 to 6 hours.

   

Pediatric: The dosage of regular insulin is 1 unit for every 4–5 g of dextrose; usually dextrose 25% or 50% (0.5-1 g/kg) is used with insulin; dextrose 0.5-1 g/kg can also be infused over 15 to 30 minutes followed by insulin 0.1 unit/kg.

 
 

Sodium bicarbonate

Increases serum pH and causes a temporary shift of K+ into cells.

Adult: 50 mEq as IV bolus, or 50–150 mEq added to 1 liter D5W and administered as an infusion.

Indicated for patients with acidosis; onset ~30 to 60 minutes and may last 2 to 6 hours, but effects are temporary (Sodium acetate may be substituted for Sodium bicarbonate when in shortage).

   

Pediatric: When sodium bicarbonate is determined to be necessary, an initial dose of 1 mEq/kg may be given initially either IV or per intraosseous route, followed by not more than half of that dose every 10 minutes as needed.

 

Hyperphosphatemia

Calcium acetate (PhosLo, Nabi)

Binds to phosphate taken in through diet to form insoluble calcium phosphate, which is then excreted from the body without being absorbed.

Adult: 2 tablets or gelcaps (667 mg) with each meal; dosage may be increased gradually to bring serum phosphate value <6 mg/dL as long as hypercalcemia does not develop.

Adverse events include nausea, mild hypercalcemia (manifested as constipation, anorexia, nausea and vomiting), severe hypercalcemia (associated with confusion, delirium, stupor, coma), and pruritus. Not recommended unless patient is symptomatic because of potential for Ca/PO4 precipitates to form, especially if alkalinizing the urine.

 

Sevelamer (Renagel, Genzyme)

Cross-linked poly(allylamine hydrochloride) is a cationic polymer that binds intestinal phosphate. The compound contains multiple amines that are protonated in the intestinal tract and interact with phosphate via ion-exchange and hydrogen bonding.

Adult (PO): Recommended starting dose is 800–1,600 mg 3 times daily.

Adverse events include nausea/vomiting, constipation, diarrhea, flatulence, and dyspnea. Sevelamer is a calcium- and aluminum-free phosphate binder so it may be advantageous when calcium-phosphate complexes are of concern.

   

Pediatric (PO): Clinical data are lacking.

 

Hypocalcemia

Calcium supplementation

Exogenous calcium (Ca++) replacement.

Adult: 500–2,000 mg elemental calcium PO in divided doses; 2–3 g Ca++ gluconate IV over 1 to 2 hours.

Reserved for patients who are symptomatic; elemental Ca++ content: carbonate (40%) > chloride (27%) > acetate (25%) > gluconate (9%); IV Ca++ gluconate is less irritating than other Ca++ salts.

   

Pediatric: 200–2,000 mg elemental calcium PO in divided doses; Ca++ gluconate 100 mg/kg dose IV over 1 to 2 hours.

 
  1. ECG, electrocardiogram; IV, intravenous; PO, by mouth, mEq; milliequivalent.