TRISENOX Concentrate for solution for infusion Ref.[6218] Active ingredients: Arsenic trioxide

TRISENOX must be administered under the supervision of a physician who is experienced in the management of acute leukaemias, and the special monitoring procedures described in section 4.4 must be followed.

Posology

The same dose is recommended for adults and elderly.

Newly diagnosed low-to-intermediate risk acute promyelocytic leukaemia (APL)

Induction treatment schedule

TRISENOX must be administered intravenously at a dose of 0.15 mg/kg/day, given daily until complete remission is achieved. If complete remission has not occurred by day 60, dosing must be discontinued.

Consolidation schedule

TRISENOX must be administered intravenously at a dose of 0.15 mg/kg/day, 5 days per week. Treatment should be continued for 4 weeks on and 4 weeks off, for a total of 4 cycles.

Relapsed/refractory acute promyelocytic leukaemia (APL)

Induction treatment schedule

TRISENOX must be administered intravenously at a fixed dose of 0.15 mg/kg/day given daily until complete remission is achieved (less than 5% blasts present in cellular bone marrow with no evidence of leukaemic cells). If complete remission has not occurred by day 50, dosing must be discontinued.

Consolidation schedule

Consolidation treatment must begin 3 to 4 weeks after completion of induction therapy. TRISENOX is to be administered intravenously at a dose of 0.15 mg/kg/day for 25 doses given 5 days per week, followed by 2 days interruption, repeated for 5 weeks.

Dose delay, modification and reinitiation

Treatment with TRISENOX must be temporarily interrupted before the scheduled end of therapy at any time that a toxicity grade 3 or greater on the National Cancer Institute Common Toxicity Criteria is observed and judged to be possibly related to TRISENOX treatment. Patients who experience such reactions that are considered TRISENOX related must resume treatment only after resolution of the toxic event or after recovery to baseline status of the abnormality that prompted the interruption. In such cases, treatment must resume at 50% of the preceding daily dose. If the toxic event does not recur within 7 days of restarting treatment at the reduced dose, the daily dose can be escalated back to 100% of the original dose. Patients who experience a recurrence of toxicity must be removed from treatment.

For ECG, electrolytes abnormalities and hepatotoxicity see section 4.4.

Special populations

Hepatic impairment

Since no data are available across all hepatic impairment groups and hepatotoxic effects may occur during the treatment with TRISENOX, caution is advised in the use of TRISENOX in patients with hepatic impairment (see section 4.4 and 4.8).

Renal impairment

Since no data are available across all renal impairment groups, caution is advised in the use of TRISENOX in patients with renal impairment.

Paediatric population

The safety and efficacy of TRISENOX in children aged up to 17 years has not been established. Currently available data for children aged 5 to 16 years are described in section 5.1 but no recommendation on a posology can be made. No data are available for children under 5 years.

Method of administration

TRISENOX must be administered intravenously over 1-2 hours. The infusion duration may be extended up to 4 hours if vasomotor reactions are observed. A central venous catheter is not required.

Patients must be hospitalised at the beginning of treatment due to symptoms of disease and to ensure adequate monitoring.

For instructions on preparation of the medicinal product before administration, see section 6.6.

If symptoms suggestive of serious acute arsenic toxicity (e.g. convulsions, muscle weakness and confusion) appear, TRISENOX must be immediately discontinued and chelating therapy with penicillamine at a daily dose ≤1 g per day may be considered. The duration of treatment with penicillamine must be evaluated taking into account the urinary arsenic laboratory values. For patients who cannot take oral medicinal product, dimercaprol administered at a dose of 3 mg/kg intramuscularly every 4 hours until any immediately life-threatening toxicity has subsided may be considered. Thereafter, penicillamine at a daily dose ≤1 g per day may be given. In the presence of coagulopathy, the oral administration of the chelating agent Dimercaptosuccinic Acid Succimer (DCI) 10 mg/kg or 350 mg/m² every 8 hours during 5 days and then every 12 hours during 2 weeks is recommended. For patients with severe, acute arsenic overdose, dialysis should be considered.

TRISENOX 1 mg/ml concentrate for solution for infusion: 4 years.

TRISENOX 2 mg/ml concentrate for solution for infusion: 3 years.

After dilution in intravenous solutions, TRISENOX is chemically and physically stable for 24 hours at 15-30°C and 72 hours at refrigerated (2-8°C) temperatures. From a microbiological point of view, the product must be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless dilution has taken place in controlled and validated aseptic conditions.

This medicinal product does not require any special storage conditions.

For storage conditions after dilution of the medicinal products, see section 6.3.

TRISENOX 1 mg/ml concentrate for solution for infusion: Type I borosilicate glass ampoule containing 10 ml of concentrate. Each pack contains 10 ampoules.

TRISENOX 2 mg/ml concentrate for solution for infusion: 6 ml concentrate in a clear, Type I borosilicate glass vial with a chlorobutyl rubber stopper (FluroTec coated plug) and an aluminium crimp cap with a plastic flip-top button. Each pack contains 10 vials.

Preparation of TRISENOX

Aseptic technique must be strictly observed throughout handling of TRISENOX since no preservative is present.

TRISENOX must be diluted with 100 to 250 ml of glucose 50 mg/ml (5 %) solution for injection or sodium chloride 9 mg/ml (0.9 %) solution for injection immediately after withdrawal from the ampoule or vial.

TRISENOX must not be mixed with or concomitantly administered in the same intravenous line with other medicinal products.

The diluted solution must be clear and colourless. All parenteral solutions must be inspected visually for particulate matter and discoloration prior to administration. Do not use the preparation if foreign particulate matter is present.

Procedure for proper disposal

TRISENOX is for single use only and any unused portions of each ampoule or of each vial must be discarded properly. Do not save any unused portions for later administration.

Any unused medicinal product, any items that come into contact with the product or waste material must be disposed of in accordance with local requirements.