Drug reference

Arsenic Trioxide

Antineoplastic · Cancer Chemotherapy

Also known as Trisenox

AntineoplasticCancer ChemotherapyATC null

CDSCO approved

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Avoid (teratogenic and embryotoxic in animal studies)

FDA category + note

Top interactionssee all 12 →

XipamideContraindicatedTextbookG&G 14e · p567
PregnancySevereTextbookG&G 14e · p1390
AbarelixSevereDatabaseDDInter
AbirateroneSevereDatabaseDDInter

Mechanism

Arsenic trioxide functions as a differentiating agent primarily in acute promyelocytic leukemia (APL). It specifically targets the PML-RARA fusion protein, a molecular hallmark of APL resulting from the t(15;17) translocation. By promoting the degradation of this oncoprotein, it induces differentiation and apoptosis of leukemic cells, thereby treating the malignancy.

Indications

Acute promyelocytic leukaemia (specialist use only)Induction of remission and consolidation in adults with untreated, low-to-intermediate risk acute promyelocytic leukaemia (characterised by the t[15;17] translocation or the PML/RAR-alpha gene, with WBC count 10x10^3 per microlitre or less), when given with all-trans-retinoic acid (ATRA)Induction of remission and consolidation in adults with relapsed or refractory acute promyelocytic leukaemia, after a retinoid and chemotherapyRelapsed acute promyelocytic leukemia (APL)acute promyelocytic leukemia (APML) with a t(15;17) translocation that fuses PML to the retinoic acid receptor RAR-α (in combination with tretinoin)newly diagnosed, low-risk APMLAPML patients after relapse from retinoid or chemotherapyResistant/relapsed cases of APL (after tretinoin)First line therapy of APL (in combination with tretinoin + anthracycline)

Dosing

Adult: Consult product literature or local protocols

Pharmacokinetics

Half-life

10 to 14 h

Bioavailability

Well absorbed orally.

Metabolism

Primary mechanism of elimination is through enzymatic methylation.

Excretion

Less than 20% of administered drug is excreted unchanged in the urine. Multiple methylated metabolites form rapidly and are excreted in urine.

Contraindications

Simultaneous treatment with other QT-prolonging drugs
patients with ventricular arrhythmias or prolonged QTc

Side effects

Common

Abdominal painAlveolar haemorrhageAnaemiaArrhythmiasArthralgiaChest painChillsDiarrhoeaDizzinessDyspnoeaElectrolyte imbalanceFatigueFeverHeadacheHyperbilirubinaemiaHyperglycaemiaHypotensionHypoxiaIncreased risk of infectionKetoacidosisLeucocytosisMyalgiaNauseaNeutropeniaOedemaPainPancytopeniaParaesthesiaPericardial effusionQT interval prolongationRenal failureRespiratory disordersSeizureSkin reactionsThrombocytopeniaVasculitisVision blurredVomitingWeight increasedHyperglycemiaHepatic enzyme elevationsDysesthesiasLight-headednessdyspneapruritusMalaiseSensory disturbancesEffusionsBreathlessnessQ-T prolongationA-V block

Serious

Confusion
Decreased leucocytes
Encephalopathy
Fluid imbalance
Heart failure
Hepatotoxicity
Peripheral neuropathy
Sepsis
Differentiation syndrome (Leucocyte activation syndrome)
Leukocyte maturation syndrome (similar to ATRA, in fewer than 10% of patients, includes pulmonary distress, effusions, and mental status changes; reversible with oxygen, corticosteroids, and temporary discontinuation of the drug)
QT interval prolongation (occurs in 40% of patients)
Torsade de pointes (rarely)
differentiation syndrome (life-threatening, requires high-dose corticosteroids)
QTc interval prolongation
complete atrioventricular block
torsades de pointes (fatal)
encephalopathy (including Wernicke’s, requires parenteral thiamine treatment)
hepatic function abnormalities
new primary malignancies (carcinogenic effect)