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Arsenic Trioxide (Monograph)

Brand name: Trisenox
Drug class: Antineoplastic Agents
VA class: AN900
CAS number: 1327-53-3

Medically reviewed by Drugs.com on Dec 22, 2023. Written by ASHP.

Warning

    Experience of Supervising Clinician

  • Use under the supervision of a qualified clinician experienced in the management of acute leukemia.

    Acute Promyelocytic Leukemia (APL) Differentiation Syndrome

  • Risk of developing potentially fatal APL differentiation syndrome.

  • If signs or symptoms suggestive of APL differentiation syndrome (e.g., unexplained fever, dyspnea, weight gain, abnormal chest auscultatory findings, radiographic abnormalities) occur, initiate high-dose corticosteroid therapy (e.g., dexamethasone phosphate 10 mg IV twice daily for 3 days or longer until symptoms resolve) immediately regardless of the patient's leukocyte count; discontinuance of arsenic trioxide generally is not required.

    ECG Abnormalities

  • Risk of potentially fatal atypical ventricular tachycardia (torsades de pointes) and complete atrioventricular block, particularly in patients with a history of torsades de pointes, CHF, or preexisting QT interval prolongation, and in those receiving drugs that might prolong the QT interval or produce electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia).

    ECG and Electrolyte Monitoring

  • Prior to initiation of therapy, perform baseline ECG and determine serum electrolyte (potassium, calcium, and magnesium) and creatinine concentrations.

  • If baseline QTc interval >500 msec, institute appropriate corrective measures and reassess with serial ECGs prior to considering arsenic trioxide therapy.

  • Correct preexisting electrolyte abnormalities; if possible, discontinue drugs known to prolong the QT interval.

  • During therapy, maintain serum potassium concentrations >4 mEq/L and serum magnesium concentrations >1.8 mg/dL and monitor ECGs weekly (more frequently in clinically unstable patients).

  • If QT interval >500 msec during therapy, correct any concomitant risk factors immediately and weigh the risks/benefits of continued therapy.

  • If syncope and/or rapid or irregular heartbeat occurs, hospitalize patient for careful monitoring; discontinue arsenic trioxide until QTc interval decreases to <460 msec, electrolyte abnormalities are corrected, and syncope and irregular heartbeat resolve.

Introduction

Antineoplastic agent.

Uses for Arsenic Trioxide

Refractory or Relapsed Acute Promyelocytic Leukemia

Induction of remission and consolidation of acute promyelocytic leukemia (APL) that is refractory to retinoid and anthracycline therapy or has relapsed following such therapy; used in patients whose disease is characterized by the presence of the t(15;17) translocation or promyelocytic leukemia-retinoic acid receptor (PML-RAR)-α gene expression.

Actuarial 18-month relapse-free survival rate: 56%.

Newly Diagnosed Acute Promyelocytic Leukemia

As a component of therapy for newly diagnosed APL† [off-label] in combination with other agents and consolidation chemotherapy.

Combination therapy with arsenic trioxide and tretinoin has been used as an alternative to chemotherapy for induction and postremission therapy in newly diagnosed APL† [off-label]; may consider use of these regimens in select patients who cannot tolerate standard anthracycline-containing chemotherapy (e.g., geriatric patients with poor performance or patients with cardiac dysfunction).

Arsenic Trioxide Dosage and Administration

General

Administration

Administer by IV infusion.

IV Administration

For solution compatibility information, see Compatibility under Stability.

IV solutions of the drug contain no preservatives; discard any unused portion of single-use ampul.

Do not mix with other drugs.

Dilution

Immediately after withdrawing the appropriate dose of the drug from the ampul, dilute with 100–250 mL of 5% dextrose injection or 0.9% sodium chloride injection.

Rate of Administration

Administer by IV infusion over 1–2 hours; if acute vasomotor reactions occur, longer infusion periods (e.g., up to 4 hours) may be used.

Dosage

Pediatric Patients

Acute Promyelocytic Leukemia
Induction Therapy
IV

In children ≥5 years of age, 0.15 mg/kg daily. Continue until bone marrow remission occurs or for a maximum of 60 doses.

Consolidation Therapy
IV

In children ≥5 years of age, 0.15 mg/kg daily for 25 doses, administered over a period of up to 5 weeks. Initiate 3–6 weeks after completion of induction therapy.

Adults

Acute Promyelocytic Leukemia
Induction Therapy
IV

0.15 mg/kg daily. Continue until bone marrow remission occurs or for a maximum of 60 doses.

Consolidation Therapy
IV

0.15 mg/kg daily for 25 doses, administered over a period of up to 5 weeks. Initiate 3–6 weeks after completion of induction therapy.

Detailed Arsenic trioxide dosage information

Cautions for Arsenic Trioxide

Contraindications

Warnings/Precautions

Warnings

For warnings regarding experience of supervising clinician, APL differentiation syndrome, ECG abnormalities, and ECG and electrolyte monitoring, see Boxed Warning.

Hyperleukocytosis

Possible hyperleukocytosis (leukocyte count ≥10,000/mm3).

Carcinogenicity

Carcinogenicity studies not performed using IV arsenic trioxide; however, arsenic trioxide is a human carcinogen.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; avoid pregnancy during therapy. If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.

General Precautions

Adequate Patient Monitoring

Perform hematologic and coagulation tests and determine serum electrolyte concentrations at least twice weekly during induction therapy (more frequently in clinically unstable patients) and at least weekly during consolidation therapy.

Monitor ECG weekly (more frequently in clinically unstable patients) during induction and consolidation therapy.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Arsenic is distributed into milk in humans; discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children <5 years of age.

Used in 7 children 5–16 years of age with APL in one study and in 13 children and young adults 4–21 years of age with refractory or relapsed APL in another study; 5 and 11 achieved complete responses, respectively.

Hepatic Impairment

Not studied in patients with hepatic impairment.

Renal Impairment

Not studied in patients with renal impairment.

Potential for prolonged elimination. Use with caution in patients with renal failure.

Common Adverse Effects

Leukocytosis, GI effects (nausea, vomiting, diarrhea, abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, dizziness.

Drug Interactions

Extensively metabolized in the liver. Methyltransferases involved in metabolism of arsenic trioxide are not CYP isoenzymes.

Has no inhibitory effects on metabolism of substrates of major CYP isoenzymes (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, 4A9/11).

No formal drug interaction studies to date.

Drugs that Prolong the QT Interval

Potential pharmacologic interaction (additive effects on prolongation of the QT interval).

Drugs that May be Associated with Electrolyte Abnormalities

Potential pharmacologic interaction (additive effects on prolongation of the QT interval).

Specific Drugs

Drug

Interaction

Comments

Amphotericin B

Additive effects on prolongation of QT interval

Use with caution

Antiarrhythmics producing QT-interval prolongation

Additive effects on prolongation of QT interval

Use with caution

Diuretics (potassium-wasting)

Additive effects on prolongation of QT interval

Use with caution

Pimozide

Additive effects on prolongation of QT interval

Concomitant use not recommended

Thioridazine

Additive effects on prolongation of QT interval

Use with caution

Ziprasidone

Additive effects on prolongation of QT interval

Concomitant use not recommended

Arsenic trioxide drug interactions (more detail)

Arsenic Trioxide Pharmacokinetics

Pharmacokinetics of trivalent arsenic have not been characterized.

Distribution

Extent

Arsenic is stored mainly in liver, kidney, heart, lung, hair, and nails.

Inorganic arsenical preparations cross the placenta in animals.

Elimination

Metabolism

Arsenic trioxide is extensively metabolized via reduction by arsenate reductase and methylation (mainly in the liver) by methyltransferases.

Elimination Route

Trivalent arsenic is excreted in urine.

Stability

Storage

Parenteral

Solution

25°C (may be exposed to 15–30°C). Do not freeze.

Chemically and physically stable after dilution for 24 hours at room temperature and 48 hours when refrigerated.

Compatibility

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Arsenic Trioxide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV use only

1 mg/mL (10 mg)

Trisenox

Cephalon

AHFS DI Essentials™. © Copyright 2024, Selected Revisions January 1, 2010. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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