ARSENIC TRIOXIDE-AFT

What it is

ARSENIC TRIOXIDE-AFT is available as a concentrated solution for injection in two strengths: 10 mg/10 mL in ampoules and 12 mg/12 mL in vials. The solution is clear and colourless. ARSENIC TRIOXIDE-AFT must be diluted before use.

Approved indications

— Induction of remission and consolidation in patients with acute promyelocytic leukaemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterised by the presence of the t(15:17) translocation or PML/RAR-alpha gene expression. — Induction of remission and consolidation in patients with previously untreated acute promyelocytic leukaemia (APL) in combination with all-trans retinoic acid (ATRA) and/or chemotherapy and whose APL is characterised by the presence of the t(15:17) translocation or PML/RAR-alpha gene expression.

Dosing overview

ARSENIC TRIOXIDE-AFT is administered at 0.15 mg/kg/day diluted with 100–250 mL of 5% glucose injection or 0.9% sodium chloride injection and given intravenously over two hours. For relapsed or refractory disease, induction comprises daily infusions of 0.15 mg/kg/day continued until bone marrow remission is obtained; if bone marrow remission is not obtained by day 60, dosing must be discontinued. Consolidation treatment may begin 3–4 weeks after completion of induction, using the same dose but with 25 daily doses administered over a period of up to 5 weeks. For previously untreated APL, dosing regimens differ by risk category. In low-to-intermediate risk patients, induction consists of 0.15 mg/kg/day from day 1 until haematological complete remission or for a maximum of 60 days; if no haematological complete remission is achieved by day 60, treatment is discontinued.

Key safety warnings

Some patients with APL treated with ARSENIC TRIOXIDE-AFT experience APL differentiation syndrome, characterised by fever, dyspnoea, weight gain, pulmonary infiltrates and pleural or pericardial effusions with or without leukocytosis, which can be fatal. High dose steroids have been used at the first suspicion of APL differentiation syndrome and appear to mitigate signs and symptoms. ARSENIC TRIOXIDE-AFT can cause QT interval prolongation and complete atrioventricular block, and QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal. Prior to initiating therapy with ARSENIC TRIOXIDE-AFT, a 12-lead ECG should be performed and serum electrolytes (potassium, calcium and magnesium) and creatinine should be assessed; pre-existing electrolyte abnormalities should be corrected and, if possible, drugs that are known to prolong the QT interval should be discontinued. During therapy with ARSENIC TRIOXIDE-AFT, potassium concentrations should be kept above 4 mmol/L and magnesium concentrations should be kept above 0.8 mmol/L. Peripheral neuropathy has been associated with the use of ARSENIC TRIOXIDE-AFT, and patients should be monitored periodically for symptoms or signs of neuropathy. In relapsed or refractory APL patients, treatment with ARSENIC TRIOXIDE-AFT was associated with the development of hyperleukocytosis (≥ 10 × 10⁹/L) in some patients.

Contraindications

ARSENIC TRIOXIDE-AFT is contraindicated in patients who are hypersensitive to arsenic or any of the excipients. ARSENIC TRIOXIDE-AFT is contraindicated in pregnancy or when there is a possibility of pregnancy.

Regulatory history

ARSENIC TRIOXIDE-AFT was first listed on the ARTG in September 2021 in the 10 mg/10 mL ampoule formulation, and in February 2023 in the 12 mg/12 mL vial formulation. In November 2015, the PBAC recommended extension of the PBS listing to include first-line treatment of APL in combination with ATRA and/or chemotherapy, based on cost-effectiveness.