| High Alert |
|
arsenic trioxide Classification |
| ONSET | PEAK | DURATION | |
| IV | unknown | unknown | unknown |
Assess patient for APL differentiation syndrome (fever, dyspnea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or without leukocytosis). Syndrome can be fatal. At first signs suggestive of syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest sounds or radiologic abnormalities) initiate high dose corticosteroids (dexamethasone 10 mg IV bid) irrespective of leukocyte count, and continue for at least 3 days or longer until symptoms have abated. Most patients do not require discontinuation of therapy. Monitor ECG prior to initiation of 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, which may be 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, CHF, administration of potassium-wasting diuretics, or other conditions resulting in hypokalemia or hypomagnesemia. Drugs known to cause prolonged QT interval should be discontinued if possible. For QTc >500 msec, corrective measures should be completed and QTc reassessed with serial ECGs prior to initiation of therapy. If QTc increases to >500 msec, reassess and take immediate corrective action and consider risk/benefit ratio of therapy. If syncope, rapid or irregular heartbeat develops, patient should be hospitalized for monitoring, serum electrolytes assessed, and therapy should be discontinued until the QTc interval is <460 msec, electrolyte abnormalities are corrected, and syncope and irregular heartbeat cease.Monitor vital signs periodically throughout therapy. May cause hypotension or hypertension.Lab Test Considerations:
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. Potassium levels should be kept above 4 mEq/dL and magnesium concentrations should be kept above 1.8 mg/dL during therapy
May cause increased ALT and AST concentrations.May cause leukocytosis, anemia, thrombocytopenia, febrile neutropenia, neutropenia, and disseminated intravascular coagulation.Toxicity and Overdose:
Symptoms of acute arsenic toxicity include convulsions, muscle weakness, and confusion. If these symptoms occur, discontinue therapy immediately and consider chelation therapy. Protocol for arsenic intoxication includes dimercaprol 3 mg/kg IM every 4 hr until immediate life-threatening toxicity has subsided. Then penicillamine 250 mg PO up to 4 times/day (<1 g/day) may be given.
High Alert: Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings. Arsenic trioxide should be administered under the supervision of a physician experienced in the management of patients with acute leukemia.Intermittent InfusionDilute arsenic trioxide with 100-250 ml of D5W or 0.9% NaCl immediately after withdrawal from ampule. Unused portions should be discarded, do not save for later use. Diluted solution is stable at room temperature for 24 hr and for 48 hr when refrigerated: . Rate: Administer over 1-2 hr; may be extended up to 4 hr if acute vasomotor reactions are observed. Does not require a central venous catheter.Explain purpose of arsenic trioxide to patient.Caution women of childbearing years to use effective contraception during therapy.Improved hematologic parameters in patients with APL.