Arsenic trioxide

Name: Arsenic trioxide

Side Effects of Arsenic Trioxide

Common side effects of arsenic trioxide include the following:

  • nausea
  • tiredness
  • fever
  • swelling
  • tremors
  • chest pain
  • diarrhea
  • vomiting
  • stomach pain
  • sore throat
  • constipation
  • imbalance of electrolytes
  • headache
  • difficulty falling asleep
  • sensations of burning or tingling in arms, hands, fingers, feet, legs, or toes
  • cough
  • difficulty breathing
  • nosebleeds
  • skin inflammation
  • itch
  • abnormal heart rhythm
  • fast heart beat
  • muscle and joint pain
  • high white blood cell count
  • anxiety
  • low blood pressure

This is not a complete list of this medication’s side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
 

Arsenic Trioxide Precautions

Serious side effects have been reported with use of arsenic trioxide:

  • Arsenic trioxide should be given only under the supervision of a doctor who has experience in treating people who have leukemia (cancer of the white blood cells).
  • Arsenic trioxide may cause a serious or life-threatening group of symptoms called APL differentiation syndrome. Your doctor will monitor you carefully to see whether you are developing this syndrome. Your doctor may ask you to weigh yourself every day during the first few weeks of your treatment because weight gain is a symptom of APL differentiation syndrome. If you experience any of the following symptoms, call your doctor immediately: fever, weight gain, shortness of breath, labored breathing, chest pain, or cough. At the first sign that you are developing APL differentiation syndrome, your doctor will prescribe one or more medications to treat the syndrome.
  • Arsenic trioxide may cause QT prolongation (heart muscles take longer to recharge between beats due to an electrical disturbance), which can cause serious or life-threatening heart rhythm problems. Before you begin treatment with arsenic trioxide, your doctor will order an electrocardiogram (ECG; test that records the electrical activity of the heart) and other tests to see whether you already have an electrical disturbance in your heart or are at higher than usual risk of developing this condition. Your doctor will monitor you closely and will order an ECG and other tests during your treatment with arsenic trioxide. Tell your doctor if you have or have ever had QT prolongation, heart failure, irregular heartbeat, or low levels of potassium or magnesium in your blood. Also tell your doctor if you are taking any of the following medications: amiodarone (Cordarone), amphotericin (Abelcet, Amphotec, Fungizone), cisapride (Propulsid), disopyramide (Norpace), diuretics ('water pills'), dofetilide (Tikosyn), erythromycin (E.E.S., E-Mycin, Erythrocin), moxifloxacin (Avelox), pimozide (Orap), procainamide (Procanbid, Pronestyl), quinidine (Quinidex), sotalol (Betapace, Betapace AF), sparfloxacin (Zagam), thioridazine (Mellaril), and ziprasidone (Geodon). Call your doctor immediately if you have an irregular or fast heartbeat or if you faint during your treatment with arsenic trioxide.

Do not take this medication if you are allergic to arsenic trioxide or to any of the inactive ingredients.

Arsenic Trioxide Food Interactions

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of this medication, there are no specific foods that you must exclude from your diet.

Inform MD

Before receiving arsenic trioxide injection,

  • tell your doctor and pharmacist if you are allergic to arsenic trioxide or any other medications
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.
  • tell your doctor if you have or have ever had kidney disease
  • tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. Talk to your doctor about using birth control to prevent pregnancy during your treatment with arsenic trioxide. If you become pregnant while receiving arsenic trioxide, call your doctor. Arsenic trioxide may harm the fetus.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you are receiving arsenic trioxide

What is arsenic trioxide?

Arsenic trioxide is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Arsenic trioxide is used to treat a cancer of the blood and bone marrow called acute promyelocytic (pro-MYE-loe-SIT-ik) leukemia, or APL.

Arsenic trioxide may also be used for other purposes not listed in this medication guide.

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

Brand Names U.S.

  • Trisenox

Dosing Pediatric

Note: Arsenic trioxide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011).

Acute promyelocytic leukemia (APL), relapsed or refractory: Children ≥4 years (US labeling) or ≥5 years (Canadian labeling): IV: Refer to adult dosing. Note: The Canadian labeling recommends dosing obese pediatric patients based on ideal body weight.

APL, newly diagnosed (off-label use): IV:

Induction, consolidation, and maintenance (Mathews 2006):

Induction: 0.15 mg/kg/day (maximum dose: 10 mg); administer daily until bone marrow remission; maximum: 60 doses for induction

Consolidation: 0.15 mg/kg/day (maximum dose: 10 mg) for 4 weeks, starting 4 weeks after completion of induction therapy

Maintenance: 0.15 mg/kg/dose (maximum dose: 10 mg) administered 10 days per month for 6 months, starting 4 weeks after completion of consolidation therapy

Children >1 year and Adolescents (APML 4 protocol; Iland 2012):

Induction: 0.15 mg/kg/day over 2 hours on days 9 to 36 (in combination with tretinoin and idarubicin)

Consolidation (2 cycles): 0.15 mg/kg/day on days 1 to 28 of consolidation cycle 1 (in combination with tretinoin); 0.15 mg/kg/day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33 of consolidation cycle 2 (in combination with tretinoin)

Dosing Renal Impairment

Mild-to-moderate impairment (CrCl ≥30 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling.

Severe renal impairment (CrCl <30 mL/minute): Use with caution (systemic exposure to metabolites may be higher); may require dosage reduction; monitor closely for toxicity.

Dialysis patients: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze. Following dilution in D5W or NS, solution for infusion is stable for 24 hours at room temperature or 48 hours when refrigerated.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Arsenic crosses the human placenta. In studies of women exposed to high levels of arsenic from drinking water, cord blood levels were similar to maternal serum levels. Dimethylarsinic acid (DMA) was the form of arsenic found in the fetus. An increased risk of low birth weight and still births were observed in women who ingested high levels of dietary arsenic. Women of childbearing potential should avoid pregnancy; effective contraception should be used during and after therapy. The Canadian labeling contraindicates use in pregnant women. It also recommends that women of childbearing potential avoid pregnancy, and male patients wear condoms during intercourse with women who are pregnant or of childbearing potential during therapy and for 3 months following therapy discontinuation.

In Summary

Commonly reported side effects of arsenic trioxide include: pleural effusion, dyspnea, fever, leukocytosis, palpitations, prolonged qt interval on ecg, tachycardia, and weight gain. Other side effects include: cardiac arrhythmia. See below for a comprehensive list of adverse effects.

For Healthcare Professionals

Applies to arsenic trioxide: compounding powder, intravenous solution

Gastrointestinal

Very common (10% or more): Nausea (75%), upper and lower abdominal pain (58%), vomiting (58%), diarrhea (53%), constipation (28%), loose stools (10%), dyspepsia (10%)
Common (1% to 10%): Oral blistering, fecal incontinence, gastrointestinal hemorrhage, dry mouth, abdominal tenderness, hemorrhagic diarrhea, abdominal distension, oral candidiasis
Frequency not reported: Dysphagia, mucosal inflammation/stomatitis, oropharyngeal pain, cecitis[Ref]

Respiratory

Very common (10% or more): Cough (65%), dyspnea (53%), sore throat (35%), APL differentiation syndrome (26.9%), epistaxis (25%), hypoxia (23%), pleural effusion (20%), sinusitis (20%), post nasal drip (13%), upper respiratory tract infection (13%), wheezing (13%), decreased breath sounds (10%), crepitations (10%), rales (10%)
Common (1% to 10%): Hemoptysis, tachypnea, rhonchi, nasopharyngitis, pleuritic pain, pulmonary alveolar hemorrhage
Frequency not reported: Acute respiratory distress syndrome, lung infiltration, pneumonitis, pulmonary edema, respiratory distress, capillary leak syndrome, pneumonia[Ref]

Other

Very common (10% or more): Fatigue (63%), pyrexia (63%), non-specific edema (40%), rigors (38%), chest pain (25%), non-specific pain (15%), herpes simplex (13%), vaginal hemorrhage (13%), weakness (10%)
Common (1% to 10%): Non-specific bacterial infection, herpes zoster, intermenstrual bleeding, sepsis, earache, tinnitus, chills
Frequency not reported: Death[Ref]

Nervous system

Very common (10% or more): Headache (60%), neuropathy (44%), paresthesia (33%), dizziness (23%), tremor (13%)
Common (1% to 10%): Convulsion, somnolence, coma, peripheral neuropathy, seizures
Uncommon (0.1% to 1%): Cerebrovascular accident
Frequency not reported: Neuralgia, cerebral hemorrhage[Ref]

Cardiovascular

Very common (10% or more): Tachycardia (55%), QT prolongation (40%), hypotension (25%), flushing (10%), hypertension (10%), pallor (10%), palpitations (10%), premature ventricular contractions (at least 10%)
Common (1% to 10%): Torsade de pointes, abnormal ECG, ventricular extrasystoles and ventricular tachycardia (both in association with QT prolongation), pericardial effusion, vasculitis
Frequency not reported: Complete heart block, cardiac failure[Ref]

Metabolic

Very common (10% or more): Hypokalemia (50%), hypomagnesemia (45%), hyperglycemia (45%), anorexia (23%), hyperkalemia (18%), decreased appetite (15%), weight gain (13%), hypocalcemia (10%)
Common (1% to 10%): Weight loss, hypoglycemia, acidosis, hypernatremia, ketoacidosis, hypermagnesemia, increased blood creatinine
Frequency not reported: Hyponatremia, hypoalbuminemia, hypophosphatemia, increased lipase, dehydration, fluid retention[Ref]

Hematologic

Very common (10% or more): Leukocytosis (50%), anemia (20%), thrombocytopenia (18%), febrile neutropenia (13%), neutropenia (10%)
Common (1% to 10%): Disseminated intravascular coagulation, lymphadenopathy, hemorrhage, thrombosis, pancytopenia
Uncommon (0.1% to 1%): Leucopenia vasculitis
Frequency not reported: Hyperleukocytosis, lymphopenia[Ref]

Dermatologic

Very common (10% or more): Tachycardia (55%), QT prolongation (40%), hypotension (25%), flushing (10%), hypertension (10%), pallor (10%), palpitations (10%), premature ventricular contractions (at least 10%)
Common (1% to 10%): Torsade de pointes, abnormal ECG, ventricular extrasystoles and ventricular tachycardia (both in association with QT prolongation), pericardial effusion, vasculitis
Frequency not reported: Complete heart block, cardiac failure[Ref]

Psychiatric

Very common (10% or more): Insomnia (43%), anxiety (30%), depression (20%)
Common (1% to 10%): Agitation, confusion, mood alteration[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (33%), myalgia (25%), bone pain (23%), back pain (18%), limb pain (13%), neck pain (13%)
Common (1% to 10%): Musculoskeletal pain[Ref]

Hepatic

Very common (10% or more): Increased ALT (20%), increased AST (13%), hepatotoxicity (at least 10%)
Common (1% to 10%): Increased gamma-glutamyltransferase, liver dysfunction, hyperbilirubinemia[Ref]

Local

Very common (10% or more): Injection site pain (20%), injection site erythema (13%), injection site edema (10%)[Ref]

Ocular

Very common (10% or more): Eye irritation (10%), blurred vision (10%)
Common (1% to 10%): Dry eye, painful red eye[Ref]

Hypersensitivity

Common (1% to 10%): Drug hypersensitivity[Ref]

Renal

Common (1% to 10%): Renal failure, renal impairment, oliguria, incontinence
Frequency not reported: Enuresis[Ref]

Some side effects of arsenic trioxide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Adult Dose for Acute Promyelocytic Leukemia

-Induction: IV infusion of 0.15 mg/kg over 1 to 2 hours once a day until bone marrow remission.
Maximum Dose (Induction): Not to exceed 60 doses.

-Consolidation: IV infusion of 0.15 mg/kg over 1 to 2 hours once a day; begin 3 to 6 weeks after completion of induction therapy.
Maximum Dose (Consolidation): 25 doses over a period up to 5 weeks.

Use: Induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

Usual Pediatric Dose for Acute Promyelocytic Leukemia

Age 4 Years and Older:
-Induction: IV infusion of 0.15 mg/kg over 1 to 2 hours once a day until bone marrow remission.
Maximum Dose (Induction): Not to exceed 60 doses.

-Consolidation: IV infusion of 0.15 mg/kg over 1 to 2 hours once a day; begin 3 to 6 weeks after completion of induction therapy.
Maximum Dose (Consolidation): 25 doses over a period up to 5 weeks.

Use: Induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.

Liver Dose Adjustments

-Mild and Moderate Hepatic Impairment (Child-Pugh A and B): Use with caution.
-Severe Hepatic Impairment (Child-Pugh C): Use with caution; monitor for toxicity.

(web3)