Overview
11 DESCRIPTION TRISENOX is a sterile injectable solution of arsenic trioxide. The molecular formula of arsenic trioxide in the solid state is As 2 O 3 , with a molecular weight of 197.8 and the following structural formula: TRISENOX is available in 10 mL, single-dose vials containing 12 mg of arsenic trioxide.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of TRISENOX is not completely understood. 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 promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-alpha. 12.2 Pharmacodynamics Cardiac Electrophysiology In a single-arm trial of TRISENOX (0.15 mg/kg daily), 16 of 40 patients (40%) had a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after TRISENOX infusion, and then returned towards baseline by the end of 8 weeks after TRISENOX infusion. 12.
Indications
- 1 INDICATIONS AND USAGE TRISENOX is an arsenical indicated: In combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. ( 1.1 ) For induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression. ( 1.2 ) 1.
Common Doses
- 0.15 mg
- 22.5 mg
- 10 mg
- 0.5 mg
Dosage
2 DOSAGE AND ADMINISTRATION Newly-diagnosed low-risk APL: Induction: Administer 0.15 mg/kg/day intravenously daily in combination with tretinoin until bone marrow remission. Do not exceed 60 days. ( 2.1 ) Consolidation: Administer 0.15 mg/kg/day intravenously daily for 5 days per week during weeks 1-4 of each 8-week cycle for a total of 4 cycles in combination with tretinoin. ( 2.1 ) Relapsed or refractory APL: Induction: Administer 0.15 mg/kg/day intravenously daily until bone marrow remission. Do not exceed 60 days. ( 2.2 ) Consolidation: Administer 0.
Black Box Warning
WARNING: DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES AND ENCEPHALOPATHY INCLUDING WERNICKE'S Differentiation Syndrome: Patients with acute promyelocytic leukemia (APL) treated with TRISENOX have experienced differentiation syndrome, which may be life-threatening or fatal. Signs and symptoms may include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy, and multi-organ dysfunction, in the presence or absence of leukocytosis.
Contraindications
- 4 CONTRAINDICATIONS TRISENOX is contraindicated in patients with hypersensitivity to arsenic. Hypersensitivity to arsenic. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions ( 5.1 )] Cardiac Conduction Abnormalities [see Warnings and Precautions ( 5.2 )] Encephalopathy [see Warnings and Precautions ( 5.3 )] Hepatotoxicity [see Warnings and Precautions ( 5.4 )] Carcinogenesis [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (> 30%) are nausea, cough, fatigue, pyrexia, headache, abdominal pain, vomiting, tachycardia, diarrhea, dyspnea, hypokalemia, leukocytosis,...
Interactions
- 7 DRUG INTERACTIONS Drugs That Can Prolong the QT/QTc Interval Concomitant use of these drugs and TRISENOX may increase the risk of serious QT/QTc interval prolongation [see Warnings and Precautions ( 5.1 )] . Discontinue or replace with an alternative drug that does not prolong the QT/QTc interval while the patient is using TRISENOX. Monitor ECGs more frequently in patients when it is not feasible to avoid concomitant use. Drugs That Can Lead to Electrolyte Abnormalities Electrolyte abnormalities increase the risk of serious QT/QTc interval prolongation [see Warnings and Precautions ( 5.