• 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, radiologic abnormalities) occur, temporarily hold arsenic trioxide and initiate high-dose corticosteroids (dexamethasone 10 mg IV every 12 hr for ≥3 days) until signs and symptoms resolve irrespective of leukocyte count. Resume therapy at 50% dose. If symptoms do not recur, ↑ dose after 7 days. If symptoms recur, ↓ 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 torsades de pointes or complete atrioventricular block, both of which can be fatal. For QTc interval >450 msec (men) or >460 msec (women), discontinue drugs causing prolonged QT interval. Replace electrolytes. Once QTc interval normalizes, resume therapy at 50% dose for 7 days. If no QTc prolongation,↑ dose to 0.11 mg/kg daily for 7 days; if no QTc interval prolongation, ↑ 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, ↓ 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, concurrent use of furosemide), monitor thiamine levels to prevent Wernicke encephalopathy. Administer IV thiamine to patients at risk or with thiamine deficiency. If Wernicke encephalopathy occurs, hold arsenic trioxide and administer 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 ↑ ALT, AST, and total bilirubin. 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 arsenic trioxide.
  • 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 ANC <1000/mm³ or platelet count <50,000/mm³,↓ dose to 0.11 mg/kg. If myelosuppression lasts ≥50 days or occurs during two consecutive cycles, assess remission status with marrow aspirate. If molecular remission, ↓ dose to 0.1 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.