Arsenic trioxide

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. 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.

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.

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. 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. Relapsed or refractory APL: Induction: Administer 0.15 mg/kg/day intravenously daily until bone marrow remission. Consolidation: Administer 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks.

TRISENOX is contraindicated in patients with hypersensitivity to arsenic. Hypersensitivity to arsenic.

Boxed 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. Hepatotoxicity: Elevated aspartate aminotransferase (AST), alkaline phosphatase and serum bilirubin have occurred in patients with newly-diagnosed low-risk APL treated with TRISENOX in combination with tretinoin. Monitor hepatic function tests at least twice weekly during induction and at least once weekly during consolidation. Withhold TRISENOX for certain elevations in AST, alkaline phosphatase and bilirubin and resume at reduced dose upon resolution. Carcinogenesis: Arsenic trioxide is a human carcinogen. Monitor patients for the development of second primary malignancies.

The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome Cardiac Conduction Abnormalities Encephalopathy Hepatotoxicity Carcinogenesis The most common adverse reactions (> 30%) are nausea, cough, fatigue, pyrexia, headache, abdominal pain, vomiting, tachycardia, diarrhea, dyspnea, hypokalemia, leukocytosis, hyperglycemia, hypomagnesemia, insomnia, dermatitis, edema, QTc prolongation, rigors, sore throat, arthralgia, paresthesia, and pruritus.

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. 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. Avoid concomitant use of drugs that can lead to electrolyte abnormalities. Monitor electrolytes more frequently in patients who must receive concomitant use of these drugs and TRISENOX. Drugs That Can Lead to Hepatotoxicity Concomitant use of these drugs and TRISENOX, particularly when given in combination with tretinoin, may increase the risk of serious hepatotoxicity.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze.