arsenic trioxide

AR-sen-ik trye-OX-ide

Therapeutic Classification: antineoplastics

Pharmacologic Classification: heavy metals

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.

Alters DNA and fusion proteins in leukemic cells.

Therapeutic effects:

Improved hematologic parameters in patients with APL.

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.

(effect on hematologic parameters)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

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).

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

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).

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.

(Generic available)

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

Assess for APL differentiation syndrome (fever, dyspnea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or without leukocytosis). Syndrome can be fatal. If signs and symptoms of syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest sounds or radiologic abnormalities) occur, initiate high dose corticosteroids (dexamethasone 10 mg IV every 12 hr for at least 3 days until signs and symptoms resolve) irrespective of leukocyte count. Resume therapy at 50% dose. If symptoms do not recur, increase dose after 7 days. If symptoms recur, decrease dose to previous dose. Most patients do not require discontinuation of therapy.
Monitor ECG prior to starting therapy and weekly or more frequently for clinically unstable patients during induction or consolidation phase. May cause QT interval prolongation and may lead to a torsade de pointes-type arrhythmia, potentially fatal, and complete atrioventricular block. Risk of arrhythmia is increased with increased QT prolongation, concurrent administration of QT prolonging drugs, history of torsade de pointes, pre-existing QT interval prolongation, HF, administration of potassium-wasting diuretics, or other conditions resulting in hypokalemia or hypomagnesemia. For QTc >450 msec for men or >460 msec for women, discontinue drugs causing prolonged QT interval. Replace electrolytes. Once QTc normalizes, resume dose at 50% for 7 days. If no QTc prolongation, increase dose to 0.11 mg/kg daily for 7 days. If no QTc prolongation, increase dose to 0.15 mg/kg .
Monitor vital signs periodically throughout therapy. May cause hypotension or hypertension.
Monitor for signs and symptoms of encephalopathy (confusion, decreased level of consciousness, seizures, cognitive deficits, ataxia, visual symptoms, ocular motor dysfunction) during therapy. In patients at risk for thiamine deficiency (chronic alcohol use, malabsorption, nutritional deficiency, concomitant use of furosemide), monitor thiamine levels to prevent Wernicke's encephalopathy. May require IV thiamine.

Lab Test Considerations:

Verify negative pregnancy test prior to starting therapy.Monitor electrolyte, hematologic, and coagulation profiles at least twice weekly and more frequently for clinically unstable patients during induction phase and at least weekly during consolidation phase. May cause hypokalemia, hyperkalemia, hypomagnesemia, hyperglycemia, hypoglycemia, hypocalcemia, and acidosis. Keep potassium levels > 4 mEq/dL and magnesium concentrations > 1.8 mg/dL during therapy.
- May cause ↑ ALT and AST and total bilirubin concentrations. If total bilirubin >3 times upper limit of normal (ULN), AST >5 times ULN, or ALT >5 times ULN, hold therapy. When total bilirubin <1.5 times ULN and AST/ALT <3 times ULN, resume therapy at 50% dose. If no increased total bilirubin or AST/ALT levels after 7 days, return to initial dose. If hepatotoxicity returns, permanently discontinue therapy.
- May cause leukocytosis. If WBC >10,000/mm³, administer hydroxyurea. When WBC <10,000/mm³, discontinue hydroxyurea.
- May cause thrombocytopenia, febrile neutropenia, and neutropenia. If absolute neutrophil count (ANC) <1000/mm³ or platelet count <50,000/mm³, reduce dose to 0.11 mg/kg. If myelosuppression lasts ≥50 days or occurs on 2 consecutive cycles, assess remission status with marrow aspirate. If molecular remission, decrease dose to 0.10 mg/kg.
- May cause anemia and disseminated intravascular coagulation.

Toxicity and Overdose:

Symptoms of acute arsenic toxicity include convulsions, muscle weakness, and confusion. If symptoms occur, discontinue therapy immediately and consider chelation therapy.

Fatalities have occurred with chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings. Arsenic trioxide should be administered under the supervision of a physician experienced in the management of patients with acute leukemia.

IV Administration:

Rate: Administer over 2 hr; may be extended up to 4 hr if acute vasomotor reactions are observed. Does not require a central venous catheter.

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.

Improved hematologic parameters in patients with APL.

NDC Code

0220- Boiron
- 0220-0522- Arsenicum album
  - 0220-0522-41- 80 PELLET in 1 TUBE (0220-0522-41)

0220- Boiron
- 0220-0525- Arsenicum album
  - 0220-0525-41- 5 [hp_C] in 1 TUBE (0220-0525-41)

0220- Boiron
- 0220-0526- Arsenicum album
  - 0220-0526-41- 6 [hp_C] in 1 TUBE (0220-0526-41)

0220- Boiron
- 0220-0527- Arsenicum album
  - 0220-0527-41- 9 [hp_C] in 1 TUBE (0220-0527-41)

0220- Boiron
- 0220-0528- Arsenicum album
  - 0220-0528-41- 12 [hp_C] in 1 TUBE (0220-0528-41)

0220- Boiron
- 0220-0529- Arsenicum album
  - 0220-0529-41- 15 [hp_C] in 1 TUBE (0220-0529-41)

0220- Boiron
- 0220-0530- Arsenicum album
  - 0220-0530-41- 30 [hp_C] in 1 TUBE (0220-0530-41)

0220- Boiron
- 0220-0549- Arsenicum album
  - 0220-0549-41- 200 [kp_C] in 1 TUBE (0220-0549-41)

0220- Boiron
- 0220-0550- Arsenicum album
  - 0220-0550-41- 1 [hp_M] in 1 TUBE (0220-0550-41)

0220- Boiron
- 0220-0553- Arsenicum album
  - 0220-0553-41- 10 [hp_M] in 1 TUBE (0220-0553-41)

0220- Boiron
- 0220-0554- Arsenicum album
  - 0220-0554-41- 12 [hp_X] in 1 TUBE (0220-0554-41)

0220- Boiron
- 0220-0557- Arsenicum album
  - 0220-0557-41- 30 [hp_X] in 1 TUBE (0220-0557-41)

14789- Nexus Pharmaceuticals Inc
- 14789-600- Arsenic Trioxide
  - 14789-600-10- 10 VIAL, SINGLE-DOSE in 1 CARTON (14789-600-10) > 10 mL in 1 VIAL, SINGLE-DOSE

43406- Natural Creations, Inc.
- 43406-0168- Arsenicum Album 30C
  - 43406-0168-1- 30 mL in 1 BOTTLE, DROPPER (43406-0168-1)

43406- Natural Creations, Inc.
- 43406-0318- Arsenicum Album 200C
  - 43406-0318-1- 30 mL in 1 BOTTLE, DROPPER (43406-0318-1)

49315- Alidac Pharmaceuticals Limited
- 49315-005- Arsenic trioxide
  - 49315-005-10- 10 VIAL in 1 CARTON (49315-005-10) > 10 mL in 1 VIAL (49315-005-01)

49315- Alidac Pharmaceuticals Limited
- 49315-007- Arsenic trioxide
  - 49315-007-10- 10 VIAL in 1 CARTON (49315-007-10) > 6 mL in 1 VIAL (49315-007-01)

50742- Ingenus Pharmaceuticals, LLC
- 50742-438- ARSENIC TRIOXIDE
  - 50742-438-10- 1 VIAL, GLASS in 1 CARTON (50742-438-10) > 10 mL in 1 VIAL, GLASS

54879- STI Pharma LLC
- 54879-027- Arsenic Trioxide
  - 54879-027-11- 10 VIAL in 1 CARTON (54879-027-11) > 1 mL in 1 VIAL (54879-027-10)

54973- Hyland's
- 54973-0605- ARSENICUM ALBUM
  - 54973-0605-4- 250 TABLET in 1 BOTTLE, PLASTIC (54973-0605-4)

54973- Hyland's
- 54973-2905- ARSENICUM ALBUM
  - 54973-2905-4- 250 TABLET in 1 BOTTLE, PLASTIC (54973-2905-4)

62106- Seroyal USA
- 62106-4878- ARSENICUM ALBUM
  - 62106-4878-4- 10 TUBE in 1 CARTON (62106-4878-4) > 140 GRANULE in 1 TUBE

63323- Fresenius Kabi USA, LLC
- 63323-637- Arsenic Trioxide
  - 63323-637-10- 10 VIAL, SINGLE-DOSE in 1 CARTON (63323-637-10) > 10 mL in 1 VIAL, SINGLE-DOSE (63323-637-03)

63459- Cephalon, Inc.
- 63459-600- Trisenox
  - 63459-600-10- 10 AMPULE in 1 CARTON (63459-600-10) > 10 mL in 1 AMPULE (63459-600-01)

63459- Cephalon, Inc.
- 63459-601- Trisenox
  - 63459-601-06- 10 VIAL, SINGLE-DOSE in 1 CARTON (63459-601-06) > 6 mL in 1 VIAL, SINGLE-DOSE (63459-601-11)

68382- Zydus Pharmaceuticals (USA) Inc.
- 68382-997- Arsenic trioxide
  - 68382-997-10- 10 VIAL in 1 CARTON (68382-997-10) > 10 mL in 1 VIAL (68382-997-01)

68428- Washington Homeopathic Products
- 68428-033- Arsenicum Album Kit Refill
  - 68428-033-01- 750 PELLET in 1 VIAL, GLASS (68428-033-01)

68428- Washington Homeopathic Products
- 68428-083- Arsenicum Album Kit Refill
  - 68428-083-01- 750 PELLET in 1 VIAL, GLASS (68428-083-01)

68428- Washington Homeopathic Products
- 68428-225- Arsenicum album
  - 68428-225-03- 75 PELLET in 1 VIAL, GLASS (68428-225-03)

68428- Washington Homeopathic Products
- 68428-225- Arsenicum album
  - 68428-225-05- 150 PELLET in 1 VIAL, GLASS (68428-225-05)

68428- Washington Homeopathic Products
- 68428-225- Arsenicum album
  - 68428-225-06- 1200 PELLET in 1 BOTTLE, GLASS (68428-225-06)

68428- Washington Homeopathic Products
- 68428-225- Arsenicum album
  - 68428-225-11- 300 PELLET in 1 BOTTLE, GLASS (68428-225-11)

68428- Washington Homeopathic Products
- 68428-225- Arsenicum album
  - 68428-225-12- 600 PELLET in 1 BOTTLE, GLASS (68428-225-12)

69918- Amring Pharmaceuticals Inc.
- 69918-720- ARSENIC TRIOXIDE
  - 69918-720-02- 2 VIAL, GLASS in 1 CARTON (69918-720-02) > 10 mL in 1 VIAL, GLASS (69918-720-01)

69918- Amring Pharmaceuticals Inc.
- 69918-720- ARSENIC TRIOXIDE
  - 69918-720-10- 10 VIAL, GLASS in 1 CARTON (69918-720-10) > 10 mL in 1 VIAL, GLASS (69918-720-01)

70710- Zydus Pharmaceuticals (USA) Inc.
- 70710-1610- Arsenic trioxide
  - 70710-1610-6- 10 VIAL in 1 CARTON (70710-1610-6) > 6 mL in 1 VIAL (70710-1610-1)

71919- Washington Homeopathic Products
- 71919-083- Arsenicum album
  - 71919-083-07- 15 mL in 1 VIAL, GLASS (71919-083-07)

71919- Washington Homeopathic Products
- 71919-083- Arsenicum album
  - 71919-083-08- 30 mL in 1 VIAL, GLASS (71919-083-08)

71919- Washington Homeopathic Products
- 71919-083- Arsenicum album
  - 71919-083-09- 50 mL in 1 BOTTLE, GLASS (71919-083-09)

71919- Washington Homeopathic Products
- 71919-083- Arsenicum album
  - 71919-083-10- 100 mL in 1 BOTTLE, GLASS (71919-083-10)

76472- HBC NATURALS INC
- 76472-1132- Arsenicum Album 30c
  - 76472-1132-1- 80 PELLET in 1 CYLINDER (76472-1132-1)

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