Indications

Arsenic Trioxide 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.

Composition

Pharmacology

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.

Dosage & 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. 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.

Contraindications

Arsenic Trioxide is contraindicated in patients with hypersensitivity to arsenic.

Side Effects

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.

Pregnancy & Lactation

Precautions & Warnings

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

Therapeutic Class

Storage Conditions

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