What is the dosage of Trisenox?

Trisenox is available in 1 dosages, including 2 mg/ml Injection 6 ml

What does Trisenox treat?

Trisenox treats Leukemia, Promyelocytic, Acute

How is Trisenox administered?

Trisenox is administered as a Injectable

Trisenox

(arsenic trioxide)

Check Drug InteractionsCheck known drug interactions.

Check Drug Interactions

Financial Assistance Programs

Get Prior Authorization Forms

Dosage & Administration

Newly-diagnosed low-risk APL:

* Induction: Administer 0.15 mg/kg/day intravenously daily in combination with tretinoin until bone marrow remission. Do not exceed 60 days.

* Consolidation: Administer 0.15 mg/kg/day intravenously daily for 5 days per week during weeks 1-4 of each 8-week cycle for a total of 4 cycles in combination with tretinoin.

Relapsed or refractory APL:

* Induction: Administer 0.15 mg/kg/day intravenously daily until bone marrow remission. Do not exceed 60 days.
* Consolidation: Administer 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks.

PrescriberAI is currently offline. Try again later.

By using PrescriberAI, you agree to the AI Terms of Use.

This AI tool offers medical information for informational purposes only and is not a substitute for professional medical judgment or advice. Physicians and healthcare professionals should exercise their expertise and discretion when interpreting and applying the provided information to specific clinical situations.

Trisenox Prescribing Information

WARNING: DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES AND ENCEPHALOPATHY INCLUDING WERNICKE'S

Differentiation Syndrome: Patients with acute promyelocytic leukemia (APL) treated with TRISENOX have experienced differentiation syndrome, which may be life-threatening or fatal. Signs and symptoms may include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy, and multi-organ dysfunction, in the presence or absence of leukocytosis. If differentiation syndrome is suspected, immediately initiate high-dose corticosteroids and hemodynamic monitoring until resolution. Temporarily withhold TRISENOX [see Dosage and Administration , Warnings and Precautions ].

Cardiac Conduction Abnormalities: TRISENOX can cause QTc interval prolongation, complete atrioventricular block and torsade de pointes, which can be fatal. Before administering TRISENOX, assess the QTc interval, correct electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer TRISENOX to patients with a ventricular arrhythmia or prolonged QTc interval. Withhold TRISENOX until resolution and resume at reduced dose for QTc prolongation [see Dosage and Administration , Warnings and Precautions ].

Encephalopathy: Serious encephalopathy, including Wernicke's, has occurred with TRISENOX. Wernicke's is a neurologic emergency. Consider testing thiamine levels in patients at risk for thiamine deficiency. Administer parenteral thiamine in patients with or at risk for thiamine deficiency. Monitor patients for neurological symptoms and nutritional status while receiving TRISENOX. If Wernicke's encephalopathy is suspected, immediately interrupt TRISENOX and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize [see Warnings and Precautions ].

1.1 Newly-Diagnosed Low-Risk APL

TRISENOX is indicated in combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

1.2 Relapsed or Refractory APL

TRISENOX is indicated for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

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	--	--
a Rounded to the nearest 10 mg increment b Omitted 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 Dosagefor Relapsedor Refractory APL

A treatment course for patients with relapsed or refractory APL consists of 1 induction cycle and 1 consolidation cycle [see Clinical Studies ].

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 ]	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 ]	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 ]. 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 ]	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 ]	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 ]	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 ]	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 ]	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

8.1 Pregnancy

Risk Summary

Based on the mechanism of action [see Clinical Pharmacology ] and findings in animal studies, TRISENOX can cause fetal harm when administered to a pregnant woman. Arsenic trioxide was embryolethal and teratogenic in rats when administered on gestation day 9 at a dose approximately 10 times the recommended human daily dose on a mg/m2 basis (see Data). A related trivalent arsenic, sodium arsenite, produced teratogenicity when administered during gestation in mice at a dose approximately 5 times the projected human dose on a mg/m2 basis and in hamsters at an intravenous dose approximately equivalent to the projected human daily dose on a mg/m2 basis. There are no studies with the use of TRISENOX in pregnant women, and limited published data on arsenic trioxide use during pregnancy are insufficient to inform a drug-associated risk of major birth defects and miscarriage. Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data

Human Data

One patient was reported to deliver a live infant with no reported congenital anomalies after receiving arsenic trioxide during the first five months of pregnancy. A second patient became pregnant three months after discontinuing arsenic trioxide and was reported to have a normal pregnancy outcome. A third patient was a pregnant healthcare provider who experienced dermal contact with liquid arsenic trioxide and had a normal pregnancy outcome after treatment and monitoring. A fourth patient who became pregnant while receiving arsenic trioxide had a miscarriage.

Animal Data

Studies in pregnant mice, rats, hamsters, and primates have shown that inorganic arsenicals cross the placental barrier when given orally or by injection. An increase in resorptions, neural-tube defects, anophthalmia and microphthalmia were observed in rats administered 10 mg/kg of arsenic trioxide on gestation day 9 (approximately 10 times the recommended human daily dose on a mg/m2 basis). Similar findings occurred in mice administered a 10 mg/kg dose of a related trivalent arsenic, sodium arsenite (approximately 5 times the projected human dose on a mg/m2 basis), on gestation days 6, 7, 8, or 9. Intravenous injection of 2 mg/kg sodium arsenite (approximately equivalent to the projected human daily dose on a mg/m2 basis) on gestation day 7 (the lowest dose tested) resulted in neural-tube defects in hamsters.

8.2 Lactation

Risk Summary

Arsenic trioxide is excreted in human milk. There are no data on the effects of arsenic trioxide on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with TRISENOX and for 2 weeks after the final dose.

8.3 Females and Males of Reproductive Potential

TRISENOX can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ].

Pregnancy Testing

Conduct pregnancy testing in females of reproductive potential prior to initiation of TRISENOX.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with TRISENOX and for 6 months after the final dose.

Males

Advise males with female partners of reproductive potential to use effective contraception during treatment with TRISENOX and for 3 months after the final dose.

Infertility

Males

Based on testicular toxicities including decreased testicular weight and impaired spermatogenesis observed in animal studies, TRISENOX may impair fertility in males of reproductive potential [see Nonclinical Toxicology ].

8.4 Pediatric Use

The safety and efficacy of TRISENOX in combination with tretinoin in pediatric patients has not been established.

The safety and efficacy of TRISENOX as a single agent for treatment of pediatric patients with relapsed or refractory APL is supported by the pivotal phase 2 study in 40 patients with relapsed or refractory APL. Five patients below the age of 18 years (age range: 5 to 16 years) were treated with TRISENOX at the recommended dose of 0.15 mg/kg/day. A literature review included an additional 17 patients treated with arsenic trioxide for relapsed or refractory APL, with ages ranging from 4 to 21 years. No differences in efficacy and safety were observed by age.

8.5 Geriatric Use

Use of TRISENOX in combination with tretinoin in newly-diagnosed adult patients with low-risk APL is supported by a randomized, controlled trial that included 16 patients between the ages of 60 and 70 years. No overall differences in safety or effectiveness were observed between these patients and younger patients. A literature review included an additional 77 patients aged 60 to 84 years who were treated with arsenic trioxide in combination with tretinoin as part of induction and consolidation therapy for low- and high-risk APL. These studies showed lower survival rates in older patients. Monitor elderly patients frequently during treatment with TRISENOX.

Use of TRISENOX as monotherapy in patients with relapsed or refractory APL is supported by the open-label, single-arm trial that included 6 patients aged 65 and older (range: 65 to 73 years). A literature review included an additional 4 patients aged 69 to 72 years who were treated with arsenic trioxide for relapsed or refractory APL. No overall differences in safety or effectiveness were observed between these patients and younger patients.

8.6 Renal Impairment

Exposure of arsenic trioxide may be higher in patients with severe renal impairment [see Clinical Pharmacology ]. Monitor patients with severe renal impairment (creatinine clearance [CLcr] less than 30 mL/min) frequently for toxicity; a dose reduction may be warranted.

The use of TRISENOX in patients on dialysis has not been studied.

8.7 Hepatic Impairment

Since limited data are available across all hepatic impairment groups, caution is advised in the use of TRISENOX in patients with hepatic impairment [see Clinical Pharmacology ]. Monitor patients with severe hepatic impairment (Child-Pugh Class C) frequently for toxicity.