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 23, 2024. Written by ASHP.

Introduction

Antineoplastic agent.¹

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;^{1 4 16 17} 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.^{1 5}

Actuarial 18-month relapse-free survival rate: 56%.¹⁷

Newly Diagnosed Acute Promyelocytic Leukemia

As a component of therapy for newly diagnosed APL^{† [off-label]} in combination with other agents and consolidation chemotherapy.^{17 20 25}

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).^{27 28 29}

Arsenic Trioxide Dosage and Administration

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.¹

Administration

Administer by IV infusion.¹

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.¹

Do not mix with other drugs.¹

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.¹

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.¹

Dosage

Pediatric Patients

Acute Promyelocytic Leukemia

Induction Therapy

IV

In children ≥5 years of age, 0.15 mg/kg daily.¹ Continue until bone marrow remission occurs or for a maximum of 60 doses.¹

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.¹ Initiate 3–6 weeks after completion of induction therapy.¹

Adults

Acute Promyelocytic Leukemia

Induction Therapy

IV

0.15 mg/kg daily.¹ Continue until bone marrow remission occurs or for a maximum of 60 doses.¹

Consolidation Therapy

IV

0.15 mg/kg daily for 25 doses, administered over a period of up to 5 weeks.¹ Initiate 3–6 weeks after completion of induction therapy.¹

Cautions for Arsenic Trioxide

Contraindications

• Known hypersensitivity to arsenic trioxide or any ingredient in the formulation.¹

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).^{1 11}

Carcinogenicity

Carcinogenicity studies not performed using IV arsenic trioxide; however, arsenic trioxide is a human carcinogen.¹

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; avoid pregnancy during therapy.¹ If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹

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.¹

Monitor ECG weekly (more frequently in clinically unstable patients) during induction and consolidation therapy.¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Arsenic is distributed into milk in humans;¹ discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children <5 years of age.¹

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.^{1 11 26}

Hepatic Impairment

Not studied in patients with hepatic impairment.¹

Renal Impairment

Not studied in patients with renal impairment.¹

Potential for prolonged elimination.¹ Use with caution in patients with renal failure.¹

Common Adverse Effects

Leukocytosis, GI effects (nausea, vomiting, diarrhea, abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, dizziness.¹

Drug Interactions

Extensively metabolized in the liver.¹ Methyltransferases involved in metabolism of arsenic trioxide are not CYP isoenzymes.¹

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

No formal drug interaction studies to date.¹

Drugs that Prolong the QT Interval

Potential pharmacologic interaction (additive effects on prolongation of the QT interval).^{14 15}

Drugs that May be Associated with Electrolyte Abnormalities

Potential pharmacologic interaction (additive effects on prolongation of the QT interval).¹

Specific Drugs

Arsenic Trioxide Pharmacokinetics

Pharmacokinetics of trivalent arsenic have not been characterized.¹

Distribution

Extent

Arsenic is stored mainly in liver, kidney, heart, lung, hair, and nails.¹

Inorganic arsenical preparations cross the placenta in animals.¹

Elimination

Metabolism

Arsenic trioxide is extensively metabolized via reduction by arsenate reductase and methylation (mainly in the liver) by methyltransferases.¹

Elimination Route

Trivalent arsenic is excreted in urine.¹

Stability

Storage

Parenteral

Solution

25°C (may be exposed to 15–30°C).¹ Do not freeze.¹

Chemically and physically stable after dilution for 24 hours at room temperature and 48 hours when refrigerated.¹

Compatibility

Parenteral

Solution CompatibilityHID

Actions

• Mechanism of action not fully elucidated.^{1 5}

• Believed to induce apoptosis (programmed cell death) of promyelocytic leukemia cells.^{1 5}

Advice to Patients

• Importance of informing clinicians if unexplained fever, dyspnea, or weight gain occurs.¹

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Boxed Warning and see Cautions.)

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.

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