• Assess for APL differentiation syndrome (fever, dyspnea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or without leukocytosis). Syndrome can be fatal. If signs and symptoms of syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest sounds or radiologic abnormalities) occur, initiate high dose corticosteroids (dexamethasone 10 mg IV every 12 hr for at least 3 days until signs and symptoms resolve) irrespective of leukocyte count. Resume therapy at 50% dose. If symptoms do not recur, increase dose after 7 days. If symptoms recur, decrease dose to previous dose. Most patients do not require discontinuation of therapy.
• Monitor ECG prior to starting therapy and weekly or more frequently for clinically unstable patients during induction or consolidation phase. May cause QT interval prolongation and may lead to a torsade de pointes-type arrhythmia, potentially fatal, and complete atrioventricular block. Risk of arrhythmia is increased with increased QT prolongation, concurrent administration of QT prolonging drugs, history of torsade de pointes, pre-existing QT interval prolongation, HF, administration of potassium-wasting diuretics, or other conditions resulting in hypokalemia or hypomagnesemia. For QTc >450 msec for men or >460 msec for women, discontinue drugs causing prolonged QT interval. Replace electrolytes. Once QTc normalizes, resume dose at 50% for 7 days. If no QTc prolongation, increase dose to 0.11 mg/kg daily for 7 days. If no QTc prolongation, increase dose to 0.15 mg/kg .
• Monitor vital signs periodically throughout therapy. May cause hypotension or hypertension.
• Monitor for signs and symptoms of encephalopathy (confusion, decreased level of consciousness, seizures, cognitive deficits, ataxia, visual symptoms, ocular motor dysfunction) during therapy. In patients at risk for thiamine deficiency (chronic alcohol use, malabsorption, nutritional deficiency, concomitant use of furosemide), monitor thiamine levels to prevent Wernicke's encephalopathy. May require IV thiamine.

Lab Test Considerations:

• Verify negative pregnancy test prior to starting therapy.Monitor electrolyte, hematologic, and coagulation profiles at least twice weekly and more frequently for clinically unstable patients during induction phase and at least weekly during consolidation phase. May cause hypokalemia, hyperkalemia, hypomagnesemia, hyperglycemia, hypoglycemia, hypocalcemia, and acidosis. Keep potassium levels > 4 mEq/dL and magnesium concentrations > 1.8 mg/dL during therapy.
  • May cause ↑ ALT and AST and total bilirubin concentrations. If total bilirubin >3 times upper limit of normal (ULN), AST >5 times ULN, or ALT >5 times ULN, hold therapy. When total bilirubin <1.5 times ULN and AST/ALT <3 times ULN, resume therapy at 50% dose. If no increased total bilirubin or AST/ALT levels after 7 days, return to initial dose. If hepatotoxicity returns, permanently discontinue therapy.
  • May cause leukocytosis. If WBC >10,000/mm³, administer hydroxyurea. When WBC <10,000/mm³, discontinue hydroxyurea.
  • May cause thrombocytopenia, febrile neutropenia, and neutropenia. If absolute neutrophil count (ANC) <1000/mm³ or platelet count <50,000/mm³, reduce dose to 0.11 mg/kg. If myelosuppression lasts ≥50 days or occurs on 2 consecutive cycles, assess remission status with marrow aspirate. If molecular remission, decrease dose to 0.10 mg/kg.
  • May cause anemia and disseminated intravascular coagulation.

Toxicity and Overdose:

• Symptoms of acute arsenic toxicity include convulsions, muscle weakness, and confusion. If symptoms occur, discontinue therapy immediately and consider chelation therapy.