Miscellaneous antineoplastics
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Trisenox Dosage

Drug Detail:Trisenox (Arsenic trioxide [ ar-sen-ik-trye-ox-ide ])

Generic Name: ARSENIC TRIOXIDE 2mg in 1mL

Dosage Form: injection, solution

Drug Class: Miscellaneous antineoplastics

Contents
Uses Warnings Before Taking Dosage Side effects Interactions

2.1 Recommended Dosage for 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 dosage of TRISENOX is 0.15 mg/kg/day 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 TRISENOX is 0.15 mg/kg/day 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.

Table 1: Recommended Dosage 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 cycle with TRISENOX and tretinoin is recommended.


2.2 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 [see Clinical Studies (14.2)].

  • For the induction cycle, the recommended dosage of TRISENOX 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 TRISENOX 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.

2.3 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 dosage modifications for adverse reactions due to TRISENOX when used alone or in combination with tretinoin.

Table 2: Dosage Modifications for Adverse Reactions of TRISENOX

Adverse Reaction Dosage 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

[see Warnings and Precautions (5.1)]
  • Temporarily withhold TRISENOX. Consider holding tretinoin if symptoms are severe.
  • Administer 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 one week in the absence of recurrence of symptoms of differentiation syndrome.
  • If symptoms re-appear, decrease TRISENOX and/or tretinoin to the previous dose.
QTc (Framingham formula) Prolongation greater than 450 msec for men or greater than 460 msec for women [see Warnings and Precautions (5.2)]
  • Withhold TRISENOX and any medication known to prolong the QTc interval.
  • Correct electrolyte abnormalities.
  • After the QTc normalizes and electrolyte abnormalities are corrected, resume treatment with TRISENOX at a 50% reduced dose (0.075 mg/kg/day daily) for one week after resolution.
  • If the 50% reduced dose is tolerated for one week (in the absence of QTc prolongation), increase the dose of TRISENOX to 0.11 mg/kg/day daily for the next week [see Dosage and Administration (2.1)].
  • The dose of TRISENOX can be increased to 0.15 mg/kg/day 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

[see Warnings and Precautions (5.4)]
  • Withhold 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 one week 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 [see Adverse Reactions (6)]
  • 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

[see Adverse Reactions (6)]
  • Reduce the dose of TRISENOX and/or tretinoin by 1 dose level (see Table 3 below).

Leukocytosis (WBC count greater than 10 Gi/L)

[see Adverse Reactions (6.1)]
  • 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

[see Adverse Reactions (6)]
  • 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

2.4 Preparation and 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, store TRISENOX for no more than 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 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.

The TRISENOX vial is single-dose and does not contain any preservatives. Discard unused portions of each vial properly. Do not mix TRISENOX with other medications.

Safe Handling Procedures

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

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