Posology : מינונים

4.2 Posology and method of administration
ARSENIC TRIOXIDE S.K. 1MG/ML 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

ARSENIC TRIOXIDE S.K. 1MG/ML 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

ARSENIC TRIOXIDE S.K. 1MG/ML must be administered intravenously at a dose of 0.15 g/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
ARSENIC TRIOXIDE S.K. 1MG/ML 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. ARSENIC TRIOXIDE S.K. 1MG/ML 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 ARSENIC TRIOXIDE S.K. 1MG/ML 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 ARSENIC TRIOXIDE S.K. 1MG/ML treatment. Patients who experience such reactions that are considered ARSENIC TRIOXIDE S.K. 1MG/ML 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 ARSENIC TRIOXIDE S.K. 1MG/ML, caution is advised in the use of ARSENIC TRIOXIDE S.K. 1MG/ML in patients with hepatic impairment (see sections 4.4 and 4.8).

Renal impairment

Since no data are available across all renal impairment groups, caution is advised in the use of ARSENIC TRIOXIDE S.K. 1MG/ML in patients with renal impairment.

Pediatric population

ARSENIC TRIOXIDE S.K. 1MG/ML is not indicated in children and adolescence below 18 years old.
Method of administration
ARSENIC TRIOXIDE S.K. 1MG/ML 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.