ATO IV Infusion

ATO 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 Arsenic Trioxide 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. Do not exceed 60 days.
• Consolidation: Administer 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks.

Drugs That Can Prolong the QT/QTc Interval: Concomitant use of these drugs and ATO 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 ATO. 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 ATO.

Drugs That Can Lead to Hepatotoxicity: Concomitant use of these drugs and ATO, particularly when given in combination with tretinoin, may increase the risk of serious hepatotoxicity. Discontinue or replace with an alternative drug that does not cause hepatotoxicity while the patient is using ATO. Monitor liver function tests more frequently in patients when it is not feasible to avoid concomitant use.

Arsenic Trioxide is contraindicated in patients with hypersensitivity to arsenic.

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.

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: ATO is a human carcinogen. Monitor patients for the development of second primary malignancies.

Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception.

Pediatric Use: The safety and efficacy of ATO in combination with tretinoin in pediatric patients has not been established.

Geriatric Use: No overall differences in safety or effectiveness were observed between these patients and younger patients.

Renal Impairment: Exposure of ATO may be higher in patients with severe renal impairment.

Hepatic Impairment: Since limited data are available across all hepatic impairment groups, caution is advised in the use of ATO in patients with hepatic impairment.

Store at 20°C to 25°C. Do not freeze. ATO is a hazardous drug. Follow applicable special handling and disposal procedures.