ARSENIC TRIOXIDE-AFT CONCENTRATED SOLUTION FOR INJECTION FOR INFUSION 10MG/10ML [SIN16961P]

Product Info

ARSENIC TRIOXIDE-AFT CONCENTRATED SOLUTION FOR INJECTION FOR INFUSION 10MG/10ML

[SIN16961P]

4.1 THERAPEUTIC INDICATIONS

For the 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.

For the treatment of adults with newly-diagnosed low-to-intermediate risk acute promyelocytic leukemia (APL) in combination with tretinoin and whose APL is characterised by the presence of the t(15:17) translocation or PML/RAR-alpha gene expression.

4.2 DOSE AND METHOD OF ADMINISTRATION

Recommended Dosage for Newly Diagnosed Low-to-Intermediate-Risk Acute Promyelocytic Leukemia (APL)

A treatment course for patients with newly diagnosed low-to-intermediate-risk APL consists of 1 induction cycle and 4 consolidation cycles.

• For the induction cycle, the recommended dosage of arsenic trioxide is 0.15 mg/kg intravenously daily in combination with tretinoin until bone marrow remission but not to exceed 60 days (see Table 1)

• For the consolidation cycles, the recommended dosage of arsenic trioxide is 0.15 mg/kg intravenously daily 5 days per week during weeks 1–4 of each 8-week cycle for a total of 4 cycles in combination with tretinoin (see Table 1). Omit tretinoin during weeks 5–6 of the fourth cycle of consolidation.

Differentiation syndrome prophylaxis consisting of prednisone 0.5 mg/kg daily from day 1 until the end of induction therapy with arsenic trioxide and tretinoin is recommended.

Recommended Dosage for Relapsed or Refractory APL

A treatment course for patients with relapsed or refractory APL consists of 1 induction cycle and 1 consolidation cycle.

• For the induction cycle, the recommended dosage of arsenic trioxide is 0.15 mg/kg/day intravenously daily until bone marrow remission or up to a maximum of 60 days.

• For the consolidation cycle, the recommended dosage of arsenic trioxide is 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks. Begin consolidation 3 to 6 weeks after completion of induction cycle.

Monitoring and Dosage Modifications for Adverse Reactions

During induction monitor coagulation studies, blood counts, and chemistries at least 2–3 times per week through recovery. During consolidation, monitor coagulation studies, blood counts, and chemistries at least weekly.

Table 2 shows the dose modifications for adverse reactions due to arsenic trioxide when used alone or in combination with tretinoin.

Preparation and administration

Reconstitution

Dilute Arsenic trioxide-AFT with 100 or 250 mL 5% Dextrose Injection, or 0.9% Sodium Chloride Injection, using proper aseptic technique, immediately after withdrawal from the vial.

Once diluted the solution should be used as soon as possible. Product is for single use in one patient only and contains no antimicrobial preservative. Discard any residue. If storage is necessary, the prepared solution should be stored refrigerated between 2°C and 8°C for no longer than 48 hours or below 25 °C for no longer than 24 hours before discarding.

Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Administer Arsenic trioxide-AFT as an intravenous infusion over 2 hours. The infusion duration may be extended up to 4 hours if acute vasomotor reactions are observed. A central venous catheter is not required.

Do not mix Arsenic trioxide-AFT with other medications.

Safe Handling Procedures

Arsenic trioxide-AFT is a cytotoxic drug. Follow applicable special handling and disposal procedures.

Incompatibilities

In the absence of incompatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned above.

4.3 CONTRAINDICATIONS

Arsenic trioxide – AFT is contraindicated in patients who are hypersensitive to arsenic or any of the excipients (see Section 6.1 List of Excipients – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).