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Trisenox Dosage

Generic name: ARSENIC TRIOXIDE 2mg in 1mL
Dosage form: injection, solution

Medically reviewed on January 19, 2018.

2.1 Recommended Dosage

Newly-Diagnosed Low-Risk Acute Promyelocytic Leukemia (APL)

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

  • For the induction cycle, the recommended dose of TRISENOX is 0.15 mg/kg intravenously daily in combination with tretinoin until bone marrow remission and not to exceed 60 days (see Table 1).
  • For the consolidation cycles, the recommended dose of TRISENOX is 0.15 mg/kg intravenously daily 5 days per week during weeks 1-4 of an 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.

Table 1: Recommended Dose of TRISENOX in Combination with Tretinoin

Induction (1 cycle)

TRISENOX

0.15 mg/kg once

daily intravenously

until marrow remission but not to exceed 60 days

Tretinoina

22.5 mg/m2 twice daily orally

until marrow remission but not to exceed 60 days

Consolidation (4 cycles)

Week 1

Week 2

Week 3

Week 4

Week 5

Week 6

Week 7

Week 8

TRISENOX

0.15 mg/kg once

daily intravenously

Days 1-5

Days 1-5

Days 1-5

Days 1-5

--

--

--

--

Tretinoina

22.5 mg/m2 twice daily orally

Days 1-7

Days 1-7

--

--

Daysb 1-7

Daysb 1-7

--

--

aRounded to the nearest 10 mg increment

bOmitted during the 4th cycle of consolidation

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

Relapsed or Refractory APL

A treatment course including TRISENOX monotherapy for patients with relapsed or refractory APL consists of 1 induction cycle and 1 consolidation cycle [see Clinical Studies (14.2)].

  • For the induction cycle, the recommended dose of TRISENOX is 0.15 mg/kg intravenously daily until bone marrow remission or up to a maximum of 60 days.
  • For the consolidation cycle, the recommended dose of TRISENOX is 0.15 mg/kg intravenously daily for 25 doses over a period of up to 5 weeks. Begin consolidation 3 to 6 weeks after completion of induction therapy.

2.2 Dose Modifications for Toxicities

During induction therapy, monitor coagulation studies, blood counts, and chemistries at least 2-3 times per week through recovery. During consolidation, monitor at least weekly. Management of some adverse reactions may require dose interruption, dose reduction, or permanent discontinuation of TRISENOX [see Warnings and Precautions (5) and Adverse Reactions (6)]. Table 2 shows the dose modifications for toxicity due to TRISENOX when used alone or in combination with tretinoin.

Table 2: Dose Adjustments for Adverse Reactions

Adverse Reaction(s) Dose Modification

Differentiation syndrome, defined by the presence of 2 or more of the following:

  • Unexplained fever
  • Dyspnea
  • Pleural and/or pericardial effusion
  • Pulmonary infiltrates
  • Renal failure
  • Hypotension
  • Weight gain greater than 5 kg
  • Temporarily withhold TRISENOX. Consider holding tretinoin if symptoms are severe.
  • Treat with dexamethasone 10 mg intravenously every 12 hours until the resolution of signs and symptoms for a minimum of 3 days.
  • Resume treatment when the clinical condition improves and reduce the dose of the withheld drug(s) by 50%.
  • Increase the dose of the withheld drug(s) to the recommended dosage after 7 days in the absence of recurrence of symptoms of differentiation syndrome.
  • If symptoms re-appear, decrease TRISENOX and/or tretinoin to the previous dose.
QTc Prolongation greater than 450 msec for men or greater than 460 msec for women:
  • Withhold treatment with TRISENOX and any medication known to prolong the QTc interval.
  • Replete electrolytes.
  • After the QTc normalizes, resume treatment with TRISENOX at a 50% reduced dose (0.075 mg/kg once daily) for 7 days.
  • If the 50% reduced dose is tolerated for 7 days (in the absence of QTc prolongation), increase the dose of TRISENOX to 0.11 mg/kg once daily for 7 days.
  • The dose of TRISENOX can be increased to 0.15 mg/kg in the absence of QTc prolongation during that 14-day dose-escalation period.

Hepatotoxicity, defined by 1 or more of the following:

  • Total bilirubin (TB) greater than 3 times the upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) greater than 5 times the ULN
  • Alkaline phosphatase (AP) greater than 5 times the ULN
  • Withhold treatment with TRISENOX and/or tretinoin.
  • Resume treatment at a 50% reduced dose of the withheld drug(s) when TB is less than 1.5 times the ULN and AP/AST are less than 3 times the ULN.
  • Increase the dose of the withheld drug(s) back to the recommended dosage after 7 days on the reduced dose in the absence of worsening of hepatotoxicity.
  • Discontinue the withheld drug(s) permanently if hepatotoxicity recurs.
Other severe or life-threatening (grade 3-4) nonhematologic reactions
  • Temporarily withhold TRISENOX and tretinoin.
  • When the adverse reaction resolves to no more than mild (grade 1), resume TRISENOX and tretinoin reduced by 2 dose levels (see Table 3 below).
Moderate (grade 2) nonhematologic reactions
  • Reduce the dose of TRISENOX and/or tretinoin by 1 dose level (see Table 3 below).
Leukocytosis (WBC count greater than 10 Gi/L)
  • Administer hydroxyurea.
  • Hydroxyurea may be discontinued when the WBC declines below 10 Gi/L.
Myelosuppression, defined by 1 or more of the following:
  • absolute neutrophil count less than 1 Gi/L
  • platelets less than 50 Gi/L lasting more than 5 weeks
  • Consider reducing the dose of TRISENOX and tretinoin by 1 dose level (see Table 3 below).
  • If myelosuppression lasts ≥ 50 days or occurs on 2 consecutive cycles, assess a marrow aspirate for remission status. In the case of molecular remission, resume TRISENOX and tretinoin at 1 dose level lower (see Table 3 below).

Table 3: Dose Reduction Levels for Hematologic and Nonhematologic Toxicities

Dose Level TRISENOX
mg/kg intravenously
once daily
Tretinoin*
mg/m2 orally
twice daily
Starting level 0.15 22.5
-1 0.11 18.75
-2 0.10 12.5
-3 0.075 10

*Rounded to the nearest 10 mg increment

2.3 Instructions for Preparation and Intravenous Administration

Reconstitution

Dilute TRISENOX with 100 to 250 mL 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP, using proper aseptic technique, immediately after withdrawal from the vial. Do not save any unused portions for later administration.

After dilution, TRISENOX is chemically and physically stable when stored for 24 hours at room temperature and 48 hours when refrigerated.

Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Administer TRISENOX intravenously 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.

The TRISENOX vial is single-dose and does not contain any preservatives. Unused portions of each vial should be discarded properly. Do not mix TRISENOX with other medications.

Safe Handling Procedures

TRISENOX is a cytotoxic drug. Follow applicable special handling and disposal procedures.1

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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