Trade Names:Trisenox- Solution for injection 1 mg/mL in 10 mL ampules
Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein PML/RAR alpha.
Pentavalent arsenic is reduced to trivalent arsenic by arsenate reductase. Trivalent arsenic is methylated to monomethyl arsenic, which is then converted to dimethyl arsenic by methyltransferase. Methylation reactions are done in the liver.
Excreted in the urine as methylated metabolite.
Refractory or relapsed acute promyelocytic leukemia (APL). Safety and efficacy in children younger than 5 yr of age not established.
Standard considerations.
IV 0.15 mg/kg/day until bone marrow remission, do not exceed 60 doses.
Consolidation (adults/children)IV 0.15 mg/kg/day for 25 doses over a period of up to 5 wk. Begin 3 to 6 wk following induction.
Store at room temperature. Do not freeze.
May increase and decrease blood glucose levels, necessitating dosage adjustment of these drugs.
Medications that prolong the QT interval (eg, thioridazine, antiarrhythmics) or that cause electrolyte abnormalities (eg, amphotericin B, diuretics)Risk of arrhythmias may increase when arsenic trioxide is given concomitantly with these medications.
None well documented.
Tachycardia (55%); QTc interval greater than 500 msec (38%); palpitations; other ECG abnormalities; torsades de pointes; edema (40%); chest pain; hypotension; flushing; hypertension.
Fatigue; fever; headache (approximately 60%); insomnia; rigors; paresthesia; anxiety; dizziness; depression; tremor; weakness; convulsion; somnolence.
Dermatitis; pruritus; ecchymosis; dry skin; nonspecific erythema; increased sweating; pallor; facial edema; night sweats; petechiae; hyperpigmentation; nonspecific skin lesions; urticaria; local exfoliation; eyelid edema; injection site pain; erythema; edema (10% to 20%).
Moderate potential for nausea and vomiting; abdominal pain (58%); diarrhea; constipation; decreased appetite; elevated ALT and AST; abdominal discomfort.
Vaginal hemorrhage (21%); breakthrough bleeding (13%); fetal harm possible; bone marrow chromosome defects in pregnant mice and neural tube defects in pregnant hamsters.
Leukocytosis (50%); thrombocytopenia; anemia; neutropenia (nadir 14 to 21 days); hemorrhage; disseminated intravascular coagulation; lymphadenopathy.
Rash (up to 5%).
Hypokalemia, hypomagnesemia, hyperglycemia (up to 15% to 50%); hyperkalemia; weight gain; hypocalcemia; hypoglycemia.
Arthralgia; myalgia; bone pain; nonspecific back, neck, and limb pain.
Renal function impairment (up to 10%).
Cough; dyspnea; sore throat; epistaxis; hypoxia; pleural effusion; post nasal drip; wheezing; changes in breath sounds; hemoptysis; tachypnea.
Eye irritation, blurred vision, dry eyes, earache, tinnitus, painful red eyes (up to 10%).
Retinoic-acid acute promyelocytic leukemia (RA-APL) syndrome during induction in up to 31% characterized by fever, dyspnea, weight gain, radiographic pulmonary infiltrates, pleural or pericardial effusions. Mean time to diagnosis was 17 days after initiating treatment (range, 7 to 24 days).
Category D .
Arsenic is excreted in human milk. Decide whether to discontinue breast-feeding or the drug, taking into account the importance of the drug to the mother.
Safety and efficacy in children younger than 5 yr of age not studied.
Dosage reduction may be necessary in patients with renal function impairment; however, specific recommendations are not available. Use additional caution in these patients.
Arsenic trioxide is an irritant; mild injection site reactions have been reported (13%). Local irritation or phlebitis may occur. Refer to your institution specific protocol.
Common (50%) during arsenic trioxide therapy. Patients with higher baseline WBC (3,900 cells/mm 3 vs 1,200 cells/mm 3 ) may be at greater risk for developing hyperleukocytosis.
Convulsions, muscle weakness, confusion.
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