PHENASEN

What it is

Phenasen is a clear, colourless concentrated solution for infusion containing 10 mg arsenic trioxide as the active ingredient in a 10 mL glass vial. Phenasen 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

The standard dose is 0.15 mg/kg/day diluted with 100–250 mL of 5% glucose injection or 0.9% sodium chloride injection and administered intravenously over two hours. Cycles of treatment are given to achieve complete remission, defined as the complete disappearance of all leukaemic myeloblasts and promyelocytes and fewer than 5% overall myeloblasts by morphological examination of the marrow. After induction of remission, consolidation cycles may be given, and maintenance therapy considered. For patients with white blood cell counts greater than 10 × 10⁹/L, Phenasen is dosed at 0.15 mg/kg/day from day 9 for 28 days during induction, 0.15 mg/kg/day from day 1 for 28 days during the first consolidation cycle, and 0.15 mg/kg/day for 5 days per week over 5 weeks during the second consolidation cycle. For patients with white blood cell counts of 10 × 10⁹/L or less, Phenasen is dosed at 0.15 mg/kg/day from day 1 until haematological complete remission or for a maximum of 60 days during induction, and 0.15 mg/kg/day 5 days per week over 4 weeks on and 4 weeks off for a total of 4 consolidation cycles.

Key safety warnings

Some patients with acute promyelocytic leukaemia treated with Phenasen experience symptoms similar to APL differentiation syndrome, characterised by fever, dyspnoea, weight gain, pulmonary infiltrates and pleural or pericardial effusions with or without leukocytosis. This syndrome can be fatal. The first signs that could suggest the development of APL differentiation syndrome are unexplained fever, dyspnoea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities. High dose steroids have been used at the first suspicion of APL differentiation syndrome and appear to mitigate signs and symptoms. Arsenic trioxide can cause QT interval prolongation and complete atrioventricular block. QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal. The risk of torsade de pointes is related to the extent of QT prolongation, concomitant administration of QT prolonging drugs, a history of torsade de pointes, pre-existing QT interval prolongation, congestive heart failure, administration of potassium-depleting diuretics, or other conditions that result in hypokalaemia or hypomagnesaemia. Prior to initiating therapy with Phenasen, a 12-lead electrocardiogram 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. Peripheral neuropathy has been associated with the use of arsenic trioxide. Patients should be monitored periodically for symptoms or signs of neuropathy.

Contraindications

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

Regulatory history

Phenasen arsenic trioxide 10 mg/10 mL injection vial was first registered on the Australian Register of Therapeutic Goods (ARTG 152760) on 13 May 2009. The TGA approved an extension of indications on 24 August 2015 for the treatment of previously untreated acute promyelocytic leukaemia (APL) in combination with all-trans retinoic acid (ATRA) and/or chemotherapy.