TRISENOX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRISENOX (TRISENOX).

How it works

Arsenic trioxide induces apoptosis in acute promyelocytic leukemia (APL) cells by targeting the PML-RARα fusion protein, leading to its degradation and subsequent differentiation and apoptosis. It also generates reactive oxygen species, disrupts mitochondrial function, and activates caspases.

What the body does with it

Metabolism	Arsenic trioxide undergoes hepatic methylation via arsenic(III) methyltransferase (AS3MT) to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). It is also converted to less toxic pentavalent forms. Excretion is primarily renal.
Excretion	Primarily renal excretion of unchanged arsenic (approximately 15-30% of the dose within 24 hours) with the remainder undergoing hepatic methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are excreted renally. Biliary and fecal elimination are minor (<5%).
Half-life	Terminal elimination half-life for inorganic arsenic is approximately 10-14 hours, with a mean of 12 hours. The methylated metabolites have longer half-lives, contributing to accumulation with repeated dosing. Clinical context: Supports daily dosing schedule with monitoring for toxicity.
Protein binding	Arsenic trioxide is 95-99% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution (Vd) is approximately 10-20 L/kg, indicating extensive tissue distribution, particularly to the liver, kidney, and skin. Clinical meaning: High Vd supports drug accumulation in tissues and prolonged elimination.
Bioavailability	Not applicable for oral route; only intravenous administration is approved. Bioavailability of oral formulation is approximately 85-90% but is not clinically used due to variable absorption and gastrointestinal toxicity.
Onset of Action	For intravenous administration (0.15 mg/kg/day): clinical response (e.g., reduction in peripheral blasts) may be observed within 7-14 days of treatment initiation.
Duration of Action	Duration of remission is variable; maintenance therapy may be required. Single course typically lasts 25-30 days with a 2-4 week rest period. Clinical notes: QTc prolongation can occur during treatment and may persist for several weeks after discontinuation.

Classification & Brands

Dosing & administration

0.15 mg/kg IV daily until bone marrow remission, then 0.15 mg/kg IV 5 days/week for 2 weeks with 2 weeks off for up to 6 cycles.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment recommended for GFR ≥ 30 mL/min. For GFR < 30 mL/min, use with caution; no specific guidelines.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use.
Pediatric use	Safety and effectiveness in children <5 years not established. For children ≥5 years, 0.15 mg/kg IV using same schedule as adults.
Geriatric use	No specific dose adjustment; use same dosing as younger adults due to similar exposure, monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRISENOX (TRISENOX).

Breastfeeding	Arsenic is excreted in human milk; M/P ratio unknown due to lack of data. Breastfeeding is contraindicated during TRISENOX therapy and for at least 2 weeks after last dose due to potential infant toxicity.
Teratogenic Risk	TRISENOX (arsenic trioxide) is embryotoxic and teratogenic in animals. In humans, first trimester exposure carries high risk of spontaneous abortion and congenital malformations (neural tube defects, cardiac anomalies). Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and perinatal death.

Warnings & precautions

■ FDA Black Box Warning

WARNING: APL DIFFERENTIATION SYNDROME. Arsenic trioxide can cause a syndrome of fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions, similar to retinoic acid syndrome. High-dose steroids should be initiated immediately if suspected.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to arsenic or any component of the formulation.","Patients with pre-existing prolonged QT interval (QTc > 500 ms) unless corrected.","Concurrent use of drugs that prolong QT interval (avoid or monitor closely)."]

Clinical Precautions

Precautions

["APL differentiation syndrome: May be life-threatening; treat with high-dose steroids at first suspicion.","QT interval prolongation: Risk of torsade de pointes; monitor electrolytes and ECG; avoid other QT-prolonging drugs.","Cardiac toxicity: Can cause atrioventricular block and ventricular arrhythmias; monitor cardiac function.","Hepatotoxicity: Can cause elevated liver enzymes; monitor liver function tests.","Electrolyte disturbances: Hypokalemia, hypomagnesemia, and hyperglycemia; correct before and during therapy.","Neurotoxicity: Peripheral neuropathy, encephalopathy; discontinue if severe.","Carcinogenicity: Arsenic is a known human carcinogen."]

Clinical Tips & Counseling

Drug interactions

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TRISENOX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for TRISENOX (TRISENOX).

How it works

What the body does with it

Metabolism	Arsenic trioxide undergoes hepatic methylation via arsenic(III) methyltransferase (AS3MT) to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). It is also converted to less toxic pentavalent forms. Excretion is primarily renal.
Excretion	Primarily renal excretion of unchanged arsenic (approximately 15-30% of the dose within 24 hours) with the remainder undergoing hepatic methylation to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), which are excreted renally. Biliary and fecal elimination are minor (<5%).
Half-life	Terminal elimination half-life for inorganic arsenic is approximately 10-14 hours, with a mean of 12 hours. The methylated metabolites have longer half-lives, contributing to accumulation with repeated dosing. Clinical context: Supports daily dosing schedule with monitoring for toxicity.
Protein binding	Arsenic trioxide is 95-99% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution (Vd) is approximately 10-20 L/kg, indicating extensive tissue distribution, particularly to the liver, kidney, and skin. Clinical meaning: High Vd supports drug accumulation in tissues and prolonged elimination.
Bioavailability	Not applicable for oral route; only intravenous administration is approved. Bioavailability of oral formulation is approximately 85-90% but is not clinically used due to variable absorption and gastrointestinal toxicity.
Onset of Action	For intravenous administration (0.15 mg/kg/day): clinical response (e.g., reduction in peripheral blasts) may be observed within 7-14 days of treatment initiation.
Duration of Action	Duration of remission is variable; maintenance therapy may be required. Single course typically lasts 25-30 days with a 2-4 week rest period. Clinical notes: QTc prolongation can occur during treatment and may persist for several weeks after discontinuation.

Classification & Brands

Dosing & administration

0.15 mg/kg IV daily until bone marrow remission, then 0.15 mg/kg IV 5 days/week for 2 weeks with 2 weeks off for up to 6 cycles.

Dosage form	INJECTABLE
Renal impairment	No dose adjustment recommended for GFR ≥ 30 mL/min. For GFR < 30 mL/min, use with caution; no specific guidelines.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use.
Pediatric use	Safety and effectiveness in children <5 years not established. For children ≥5 years, 0.15 mg/kg IV using same schedule as adults.
Geriatric use	No specific dose adjustment; use same dosing as younger adults due to similar exposure, monitor renal function closely.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for TRISENOX (TRISENOX).

Breastfeeding	Arsenic is excreted in human milk; M/P ratio unknown due to lack of data. Breastfeeding is contraindicated during TRISENOX therapy and for at least 2 weeks after last dose due to potential infant toxicity.
Teratogenic Risk	TRISENOX (arsenic trioxide) is embryotoxic and teratogenic in animals. In humans, first trimester exposure carries high risk of spontaneous abortion and congenital malformations (neural tube defects, cardiac anomalies). Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and perinatal death.