arsenic trioxide

High Alert

Induction of remission and consolidation in patients with newly diagnosed low-risk acute promyelocytic leukemia (APL) whose disease is associated with the presence of the t(15; 17) translocation or PML/RAR-alpha gene expression (in combination with tretinoin).
Induction of remission and consolidation in patients with APL who do not respond to or tolerate retinoid and anthracycline chemotherapy and whose disease is associated with the presence of the t(15; 17) translocation or PML/RAR-alpha gene expression.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
OB: Pregnancy (may cause fetal harm);
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment (dose ↓ may be needed if CCr <30 mL/min);
Hepatic impairment;
History of torsade de pointes, QT interval prolongation, or HF, hypokalemia, hypomagenesemia or concurrent use of other drugs that cause QT interval prolongation;
Rep: Women of reproductive potential and men with female sexual partners of reproductive potential;
Pedi: Children <5 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation, atrial arrhythmias, COMPLETE HEART BLOCK, TORSADE DE POINTES

Derm: dermatitis

Endo: hyperglycemia, hypoglycemia

F and E: acidosis, hyperkalemia, hypocalcemia, hypokalemia, hypomagnesemia

GI: ↑liver enzymes, abdominal pain, constipation

GU: ↓fertility (males), renal failure

Hemat: differentiation syndrome, leukocytosis, anemia, DISSEMINATED INTRAVASCULAR COAGULATION, NEUTROPENIA, THROMBOCYTOPENIA

MS: back pain, arthralgia, bone pain, limb pain, myalgia, neck pain

Neuro: ENCEPHALOPATHY (INCLUDING WERNICKE'S ENCEPHALOPATHY), fatigue, headache, insomnia, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), weakness

Resp: hypoxia, dyspnea, pleural effusion

Misc: fever, hypersensitivity reactions, infection/sepsis, MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Use cautiously with other agents known to cause QT prolongation including some antiarrhythmics or thioridazine.
Concurrent use of amphotericin B, potassium- or magnesium-wasting diuretics (↑ risk of serious arrhythmias).

Availability ⬆ ⬇

(Generic available)

Solution for injection : 1 mg/mL; 2 mg/mL

Route/Dosage ⬆ ⬇

Newly Diagnosed Low-Risk APL

IV (Adults ): Induction: 0.15 mg/kg once daily until bone marrow remission (not to exceed 60 doses); Consolidation: 0.15 mg/kg once daily 5 days per wk during wk 1–4 of an 8–wk cycle for a total of 4 cycles.

Relapsed or Refractory APL

IV (Adults and Children ≥5 yr): Induction: 0.15 mg/kg once daily until bone marrow remission (not to exceed 60 doses); Consolidation: starting 3–6 wk after completion of induction; 0.15 mg/kg once daily for 25 doses over a period of 5 wk.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Alters DNA and fusion proteins in leukemic cells.

Therapeutic effects:

Improved hematologic parameters in patients with APL.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: heavy metals

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

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

Metabolism/Excretion: Converted from pentavalent arsenic to trivalent arsenic by arsenate reductase and further converted by methyltransferases in the liver. Methylated arsenic is excreted in urine.

Half-Life: Unknown.

Time/Action Profile ⬆ ⬇

(effect on hematologic parameters)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose of arsenic trioxide to patient.
Advise patient to notify health care professional immediately if signs and symptoms of differentiation syndrome (fever, sudden weight gain, dizziness/lightheadedness, labored breathing, accumulation of fluid in the lungs, heart, and chest), ECG abnormalities (fainting, irregular heartbeat), encephalopathy or other severe or persistent symptoms occur.
Rep: Caution women of reproductive potential to use effective contraception during therapy and for 6 mo following last dose of therapy. Advise males with female sexual partners of reproductive potential to use effective contraception for 3 mo following last dose. Advise patient to avoid breastfeeding during and for 2 wks following last dose. May impair fertility in males with reproductive potential.

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Indications ⬇