Version May 2024
Arsenic trioxide can cause QTc interval prolongation, complete atrioventricular block, and torsade de pointes, which can be fatal. Before administering arsenic trioxide, assess the QTc interval, correct preexisting electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer arsenic trioxide to patients with a ventricular arrhythmia or prolonged QTc interval. Withhold arsenic trioxide until resolution and resume at reduced dose for QTc prolongation.
Patients with acute promyelocytic leukemia treated with arsenic trioxide have experienced differentiation syndrome, which may be life threatening or fatal. Signs and symptoms may include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy, and multiorgan dysfunction, in the presence or absence of leukocytosis. If differentiation syndrome is suspected, immediately initiate high-dose corticosteroids and hemodynamic monitoring until resolution. Temporarily withhold arsenic trioxide.
Serious encephalopathy, including Wernicke, has occurred with arsenic trioxide. Wernicke encephalopathy is a neurologic emergency. Consider testing thiamine levels in patients at risk for thiamine deficiency. Administer parenteral thiamine in patients with or at risk for thiamine deficiency. Monitor patients for neurological symptoms and nutritional status while receiving arsenic trioxide. If Wernicke encephalopathy is suspected, immediately interrupt arsenic trioxide and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize.
Note: Prior to treatment initiation, assess the QTc interval (by ECG), correct preexisting electrolyte abnormalities, and consider discontinuing concomitant medications known to prolong QTc interval. Do not administer arsenic trioxide to patients with a ventricular arrhythmia or prolonged QTc interval. Maintain serum potassium >4 mEq/L and magnesium >1.8 mg/dL during treatment. Consider testing thiamine levels in patients at risk for thiamine deficiency; administer parenteral thiamine in patients with or at risk for thiamine deficiency.
Acute promyelocytic leukemia, newly diagnosed:
Acute promyelocytic leukemia, newly diagnosed, low risk: Note: Prophylaxis for differentiation syndrome with prednisone 0.5 mg/kg/day is recommended starting on day 1 and continuing until the end of induction.
Induction (1 cycle): IV: 0.15 mg/kg once daily (in combination with tretinoin); continue until bone marrow remission, not to exceed 60 days (Ref).
Consolidation (4 cycles): IV: 0.15 mg/kg once daily for 5 days each week during weeks 1 to 4 of each 8-week consolidation cycle (in combination with tretinoin) for a total of 4 consolidation cycles (Ref).
Acute promyelocytic leukemia, newly diagnosed, including intermediate- and/or high-risk disease (off-label):
APL0406 protocol: Intermediate- risk (Ref):
Induction (1 cycle): IV: 0.15 mg/kg once daily (in combination with tretinoin); continue until bone marrow remission, not to exceed 60 days.
Consolidation (4 cycles): IV: 0.15 mg/kg once daily for 5 days each week during weeks 1 to 4 of each 8-week consolidation cycle (in combination with tretinoin) for a total of 4 consolidation cycles.
AML17 protocol (low-, intermediate-, or high-risk); in combination with tretinoin (Ref):
Induction (cycle 1): IV: 0.3 mg/kg once daily on days 1 to 5 in week 1, followed by 0.25 mg/kg twice a week during weeks 2 to 8; high-risk patients were also administered a single dose of gemtuzumab within the first 4 days of treatment.
Consolidation (cycles 2 to 5): IV: 0.3 mg/kg once daily on days 1 to 5 in week 1, followed by 0.25 mg/kg twice a week during weeks 2 to 4.
C9710 protocol (low-, intermediate-, or high-risk); following remission induction with tretinoin, daunorubicin, and cytarabine, and followed by tretinoin (Ref): Consolidation (2 courses): IV: 0.15 mg/kg once daily on days 1 to 5 in each week during weeks 1 to 5; each course is separated by 2 weeks.
Low-, intermediate-, or high-risk patients unable to tolerate anthracycline-based therapy; in combination with tretinoin (Ref):
Induction (1 cycle; beginning 10 days after initiation of tretinoin): IV: 0.15 mg/kg once daily until bone marrow remission; maximum: 75 doses for induction; high-risk patients were also administered gemtuzumab on day 1 of induction.
Consolidation (4 cycles): IV: 0.15 mg/kg once daily on Monday through Friday for 4 weeks of every 8-week treatment cycle for 4 cycles (weeks 1 to 4, 9 to 12, 17 to 20, and 25 to 28).
APML4 protocol (low-, intermediate- and high-risk) (Ref):
Induction (1 cycle): IV: 0.15 mg/kg once daily on days 9 to 36 (in combination with tretinoin and age-adjusted idarubicin).
Consolidation (2 cycles): IV: 0.15 mg/kg once daily on days 1 to 28 of consolidation cycle 1 (in combination with tretinoin); 0.15 mg/kg once daily 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).
Ac ute promyelocytic leukemia, relapsed or refractory:
Induction (1 cycle): IV: 0.15 mg/kg once daily until bone marrow remission; maximum: 60 doses for induction.
Consolidation (1 cycle): IV: 0.15 mg/kg once daily for 25 doses over a period of up to 5 weeks, beginning 3 to 6 weeks after completion of induction therapy.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
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).
Hepatic impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Patients with severe impairment (Child-Pugh class C) should be monitored closely for toxicity.
Hepatotoxicity during treatment (defined as 1 or more of the following: total bilirubin >3 times the ULN, AST >5 times ULN, alkaline phosphatase (AP) >5 times ULN): Withhold arsenic trioxide and/or tretinoin. When total bilirubin <1.5 times ULN and AST/AP <3 times ULN, resume treatment with the dose(s) reduced by 50%. After 7 days at the reduced dose(s), in the absence of worsening hepatotoxicity, increase the dose(s) back to the recommended dose(s). If hepatotoxicity recurs, discontinue permanently.
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
Dosage reduction levels (for hematologic and nonhematologic toxicities; tretinoin may also require dose reduction):
Initial dosage: 0.15 mg/kg once daily
First dose reduction level: 0.11 mg/kg once daily
Second dose reduction level: 0.1 mg/kg once daily
Third dose reduction level: 0.075 mg/kg once daily
Dosage adjustment when used alone or in combination with tretinoin:
Hematologic toxicities:
Leukocytosis (WBC >10,000/mm3 ): Administer hydroxyurea; may discontinue hydroxyurea when WBC declines to <10,000/mm 3.
ANC <1,000/mm3: Consider reducing the dose (arsenic trioxide and tretinoin) by 1 dose level. If myelosuppression lasts ≥50 days or occurs on 2 consecutive cycles, assess marrow aspirate for remission status. In the case of molecular remission, resume arsenic trioxide (and tretinoin) at 1 dose level lower.
Platelets <50,000/mm3 (lasting >5 weeks): Consider reducing the dose (arsenic trioxide and tretinoin) by 1 dose level. If myelosuppression lasts ≥50 days or occurs on 2 consecutive cycles, assess marrow aspirate for remission status. In the case of molecular remission, resume arsenic trioxide (and tretinoin) at 1 dose level lower.
Nonhematologic toxicities:
Differentiation syndrome (defined as the presence of 2 or more of the following: Unexplained fever, dyspnea, pleural and/or pericardial effusion, pulmonary infiltrates, renal failure, hypotension, weight gain >5 kg): Temporarily withhold arsenic trioxide (consider withholding tretinoin if symptoms are severe) and begin dexamethasone 10 mg IV every 12 hours until resolution of signs/symptoms for a minimum of 3 days. When clinical condition improves, resume treatment with the dose of the withheld drug(s) reduced by 50%. After 7 days, in the absence of recurrent symptoms, increase the dose to the recommended dosage. If symptoms recur, decrease arsenic and/or tretinoin to the previous dose.
Encephalopathy: If Wernicke encephalopathy is suspected, immediately interrupt arsenic trioxide and initiate parenteral thiamine; monitor until symptoms resolve or improve and thiamine levels normalize.
QTc (Framingham formula) prolongation >450 msec (for males) or >460 msec (for females): Withhold arsenic trioxide and any concomitant medication known to prolong the QTc interval. Correct electrolyte abnormalities. After the QTc normalizes and electrolyte abnormalities are corrected, resume arsenic trioxide with a 50% dose reduction (to 0.075 mg/kg once daily) for 7 days. If the 50% dose reduction is tolerated for 7 days, in the absence of QTc prolongation, increase the arsenic trioxide dose to 0.11 mg/kg once daily for 7 days. In the absence of QTc prolongation, the dose may be further increased to 0.15 mg/kg once daily during the 14-day dose escalation period.
Other nonhematologic reactions:
Moderate (grade 2): Reduce the dose (arsenic trioxide and/or tretinoin) by 1 dose level.
Severe or life-threatening (grade 3 or 4): Temporarily withhold arsenic trioxide and tretinoin. When the adverse reaction resolves to no more than mild (grade 1), resume arsenic trioxide and tretinoin with the dose reduced by 2 dose levels.
Refer to adult dosing.
(For additional information see "Arsenic trioxide: Pediatric drug information")
Note: Prior to treatment initiation, assess the QTc interval (by ECG), correct preexisting electrolyte abnormalities, and consider discontinuing concomitant medications known to prolong QTc interval. Do not administer arsenic trioxide to patients with a ventricular arrhythmia or prolonged QTc interval. Maintain serum potassium >4 mEq/L and magnesium >1.8 mg/dL during treatment. Consider testing thiamine levels in patients at risk for thiamine deficiency; administer parenteral thiamine in patients with or at risk for thiamine deficiency. Arsenic trioxide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Acute promyelocytic leukemia (APL), initial treatment: Limited data available:
Single-agent:
Children and Adolescents: Dosing based on experience available for children ≥3 years; however, age was not an exclusion criteria in clinical trial (Ref).
Induction: IV: 0.15 mg/kg/day (maximum dose: 10 mg/dose); administer daily until bone marrow remission; maximum induction: 60 doses (Ref).
Consolidation: IV: 0.15 mg/kg/day (maximum dose: 10 mg/dose) for 4 weeks, starting 4 weeks after completion of induction therapy (Ref).
Maintenance: IV: 0.15 mg/kg/dose (maximum dose: 10 mg/dose) administered 10 days per month for 6 months, starting 4 weeks after completion of consolidation therapy (Ref).
In combination with tretinoin and gemtuzumab in high-risk APL:
Children and Adolescents: Dosing based on experience available for adolescents ≥14 years; however, age was not an exclusion criteria in clinical trial (Ref).
Induction (beginning 10 days after initiation of tretinoin): IV: 0.15 mg/kg/day until bone marrow remission; maximum induction: 75 doses (Ref).
Consolidation: IV: 0.15 mg/kg/day Monday through Friday for 4 weeks every 8 weeks for 4 cycles (weeks 1 to 4, 9 to 12, 17 to 20, and 25 to 28) (Ref).
In combination with tretinoin, idarubicin, and prednisone (APML4 protocol):
Children >1 year and Adolescents:
Induction: IV: 0.15 mg/kg/day over 2 hours on days 9 to 36 (in combination with tretinoin and idarubicin) (Ref).
Consolidation: IV: 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); 2 cycles total (Ref).
Acute promyelocytic leukemia (APL), relapsed or refractory:
Children ≥4 years and Adolescents:
Induction: IV: 0.15 mg/kg/day; administer daily until bone marrow remission; maximum induction: 60 doses.
Consolidation: IV: 0.15 mg/kg/day starting 3 to 6 weeks after completion of induction therapy; maximum consolidation: 25 doses over a period of up to 5 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Acute promyelocytic leukemia (APL), relapsed or refractory:
Children ≥4 years and Adolescents:
Dosage reduction levels (for hematologic and nonhematologic toxicities):
Initial dosage: IV: 0.15 mg/kg once daily.
First dose reduction level: IV: 0.11 mg/kg once daily.
Second dose reduction level: IV: 0.1 mg/kg once daily.
Third dose reduction level: IV: 0.075 mg/kg once daily.
Dosage adjustment when used alone or in combination with tretinoin: Refer to tretinoin monograph for additional information.
Hematologic toxicities:
Leukocytosis (WBC >10,000/mm3): Administer hydroxyurea; may discontinue hydroxyurea when WBC declines to <10,000/mm3.
ANC <1,000/mm3: Consider reducing the arsenic trioxide dose by 1 dose level. If myelosuppression lasts ≥50 days or occurs on 2 consecutive cycles, assess marrow aspirate for remission status. In the case of molecular remission, resume arsenic trioxide at 1 dose level lower.
Platelets <50,000/mm3 (lasting >5 weeks): Consider reducing the arsenic trioxide dose by 1 dose level. If myelosuppression lasts ≥50 days or occurs on 2 consecutive cycles, assess marrow aspirate for remission status. In the case of molecular remission, resume arsenic trioxide at 1 dose level lower.
Nonhematologic toxicities:
Differentiation syndrome (defined as the presence of 2 or more of the following: Unexplained fever, dyspnea, pleural and/or pericardial effusion, pulmonary infiltrates, renal failure, hypotension, weight gain >5 kg): Temporarily withhold arsenic trioxide and begin IV dexamethasone (10 mg in adults) every 12 hours until resolution of signs/symptoms for a minimum of 3 days. When clinical condition improves, resume treatment with the dose reduced by 50%. After 7 days, in the absence of recurrent symptoms, increase the dose to the recommended dosage. If symptoms recur, decrease arsenic trioxide to the previous dose.
Encephalopathy: If Wernicke encephalopathy is suspected, immediately interrupt arsenic trioxide and initiate parenteral thiamine; monitor until symptoms resolve or improve and thiamine levels normalize.
QTc (Framingham formula) prolongation >450 msec (for males) or >460 msec (for females): Withhold arsenic trioxide and any other medication known to prolong the QTc interval. Correct electrolyte abnormalities. After the QTc normalizes and electrolyte abnormalities corrected, resume arsenic trioxide with a 50% dose reduction (to 0.075 mg/kg once daily) for 7 days. If the 50% dose reduction is tolerated for 7 days, in the absence of QTc prolongation, increase the arsenic trioxide dose to 0.11 mg/kg once daily for 7 days. In the absence of QTc prolongation, the dose may be further increased to 0.15 mg/kg once daily during the 14-day dose escalation period.
Other nonhematologic reactions:
Moderate (grade 2): Reduce the arsenic trioxide dose by 1 dose level.
Severe or life-threatening (grade 3 or 4): Temporarily withhold arsenic trioxide. When the adverse reaction resolves to no more than mild (grade 1), resume arsenic trioxide with the dose reduced by 2 dose levels.
Children and Adolescents:
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
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).
Children and Adolescents:
Baseline: There are no dosage adjustments provided in the manufacturer's labeling; use with caution. Patients with severe impairment should be monitored closely for toxicity.
Hepatic impairment during therapy (defined as one or more of the following: Total bilirubin >3 times the ULN, AST >5 times ULN, alkaline phosphatase [AP] >5 times ULN): Withhold arsenic trioxide. Once total bilirubin <1.5 times ULN and AST/AP <3 times ULN, resume treatment with the dose reduced by 50%. After 7 days at the reduced dose(s), in the absence of worsening hepatotoxicity, increase the dose back to the recommended dose. If hepatotoxicity recurs, discontinue permanently.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adult patients.
>10%:
Cardiovascular: Chest pain (25%), edema (40%), hypotension (25%), prolonged QT interval on ECG (40%; >500 msec), tachycardia (55%)
Dermatologic: Dermatitis (43%), diaphoresis (13%), ecchymoses (20%), erythema of skin (13%), pruritus (33%), xeroderma (15%)
Endocrine & metabolic: Hyperglycemia (45%), hyperkalemia (18%), hypokalemia (50%), hypomagnesemia (45%), weight gain (13%)
Gastrointestinal: Anorexia (23%), constipation (28%), decreased appetite (15%), diarrhea (53%), lower abdominal pain (≤58%), nausea (75%), sore throat (35%), upper abdominal pain (≤58%), vomiting (58%)
Genitourinary: Vaginal hemorrhage (13%)
Hematologic & oncologic: Anemia (20%; grades 3/4: 5%), differentiation syndrome (16% to 23%; can be serious), febrile neutropenia (13%; grades 3/4: 8%), leukocytosis (50%; grades 3/4: 3%), thrombocytopenia (18%; grades 3/4: 13%)
Hepatic: Increased serum alanine aminotransferase (20%), increased serum aspartate aminotransferase (13%)
Infection: Herpes simplex infection (13%)
Local: Erythema at injection site (13%), pain at injection site (20%)
Nervous system: Anxiety (30%), depression (20%), dizziness (23%), fatigue (63%), headache (60%), insomnia (43%), pain (15%), paresthesia (33%), rigors (38%)
Neuromuscular & skeletal: Arthralgia (33%), back pain (18%), limb pain (13%), myalgia (25%), neck pain (13%), ostealgia (23%), tremor (13%)
Respiratory: Cough (65%), dyspnea (53%), epistaxis (25%), hypoxia (23%), pleural effusion (20%), post nasal drip (13%), sinusitis (20%), upper respiratory tract infection (13%), wheezing (13%)
Miscellaneous: Fever (63%)
1% to 10%:
Cardiovascular: Atrial arrhythmia (5%), ECG abnormality (8%; non-QT prolongation), facial edema (8%), flushing (10%), hypertension (10%), palpitations (10%), torsades de pointes (3%)
Dermatologic: Hyperpigmentation (8%), night sweats (8%), pallor (10%), skin lesion (8%), urticaria (8%)
Endocrine & metabolic: Acidosis (5%), hypocalcemia (10%), hypoglycemia (8%), intermenstrual bleeding (8%), weight loss (8%)
Gastrointestinal: Abdominal distension (8%), abdominal tenderness (8%), bloody diarrhea (8%), dyspepsia (10%), fecal incontinence (8%), gastrointestinal hemorrhage (8%), loose stools (10%), oral bullae (8%), oral candidiasis (5%), xerostomia (8%)
Genitourinary: Oliguria (5%), urinary incontinence (5%)
Hematologic & oncologic: Disseminated intravascular coagulation (8%; grades 3/4: 8%), hemorrhage (8%), hyperleukocytosis (8%), lymphadenopathy (8%), neutropenia (10%; grades 3/4: 10%), petechia (8%)
Hypersensitivity: Hypersensitivity reaction (5%)
Infection: Bacterial infection (8%), herpes zoster infection (8%), sepsis (5%)
Local: Local skin exfoliation (5%), swelling at injection site (10%)
Nervous system: Agitation (5%), coma (5%), confusion (5%), drowsiness (8%), seizure (8%)
Neuromuscular & skeletal: Asthenia (10%)
Ophthalmic: Blurred vision (10%), eye irritation (10%), eye redness (with pain: 5%), eyelid edema (5%), xerophthalmia (8%)
Otic: Otalgia (8%), tinnitus (5%)
Renal: Renal failure syndrome (8%), renal insufficiency (8%)
Respiratory: Abnormal breath sounds (decreased: 10%), hemoptysis (8%), nasopharyngitis (5%), rales (10%), rhonchi (8%), tachypnea (8%)
Postmarketing:
Cardiovascular: Atrioventricular block, cardiac failure, ventricular premature contractions, ventricular tachycardia
Dermatologic: Toxic epidermal necrolysis
Endocrine & metabolic: Increased gamma-glutamyl transferase
Hematologic & oncologic: Bone marrow failure (necrosis), malignant melanoma, malignant neoplasm (including pancreatic), pancytopenia, squamous cell carcinoma
Nervous system: Encephalopathy (including Wernicke's), paresis, peripheral neuropathy, reversible posterior leukoencephalopathy syndrome
Neuromuscular & skeletal: Rhabdomyolysis
Otic: Deafness
Hypersensitivity to arsenic or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Pregnancy; breast-feeding
Concerns related to adverse effects:
• Cardiac conduction abnormalities: Arsenic trioxide may cause QTc interval prolongation, complete atrioventricular block, and torsade de pointes, which may be fatal. In newly diagnosed low-risk acute promyelocytic leukemia (APL) studies, some patients who received arsenic trioxide in combination with tretinoin experienced QTc (Framingham formula) prolongation >450 msec (for males) and >460 msec (for females) throughout treatment cycles. In studies for relapsed or refractory APL, over one-third of patients who received arsenic trioxide (as monotherapy) had at least one ECG with a QTc interval >500 msec. Prolonged QTc has been observed between 1 and 5 weeks after start of arsenic trioxide treatment, and usually resolved by 8 weeks after treatment. There are no data on the effect of arsenic trioxide on the QTc interval during the infusion. The risk of torsades de pointes is related to the extent of QTc prolongation, concurrent use of QTc prolonging medications, a history of torsade des pointes, preexisting QTc interval prolongation, heart failure, concurrent potassium-wasting diuretics, or other conditions associated with hypokalemia or hypomagnesemia. The risk may be increased when arsenic trioxide is coadministered with medications associated with electrolyte abnormalities (eg, diuretics, amphotericin B).
• Differentiation syndrome: Patients with APL treated with arsenic trioxide have experienced differentiation syndrome (may be life threatening or fatal). Signs and symptoms may include fever (unexplained), dyspnea, acute respiratory distress, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, weight gain or peripheral edema, hypotension, renal insufficiency, hepatopathy, or multiorgan dysfunction, occurring with or without leukocytosis. The onset of differentiation syndrome has occurred as early as day 1 of induction to as late as the second month of induction therapy. Prophylaxis with prednisone is recommended during induction cycle when arsenic trioxide is used in combination with tretinoin.
• Encephalopathy: Serious encephalopathy, including Wernicke, has been reported with use.
• Hepatotoxicity: In newly diagnosed low-risk APL studies, almost half of the patients treated with arsenic trioxide in combination with tretinoin experienced elevated AST, alkaline phosphatase, and/or serum bilirubin, which usually resolved with temporary discontinuation of arsenic trioxide and/or tretinoin. Long-term hepatic abnormalities may occur in patients with APL treated with arsenic trioxide in combination with tretinoin. Mild hepatic dysfunction and hepatic steatosis have been observed at a median of 7 years (range: up to 14 years) following arsenic trioxide and tretinoin combination therapy.
• Secondary malignancy: Arsenic trioxide is a human carcinogen.
Other warnings/precautions:
• Multiple concentrations: Arsenic trioxide is available in different concentrations; verify concentration prior to admixture to assure appropriate dose preparation.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 10 mg/10 mL (10 mL); 12 mg/6 mL (6 mL)
Solution, Intravenous [preservative free]:
Trisenox: 12 mg/6 mL (6 mL)
Generic: 10 mg/10 mL (10 mL); 12 mg/6 mL (6 mL)
Yes
Solution (Arsenic Trioxide Intravenous)
10 mg/10 mL (per mL): $25.20 - $71.28
12 mg/6 mL (per mL): $95.60 - $107.78
Solution (Trisenox Intravenous)
12 mg/6 mL (per mL): $233.32
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Trisenox: 10 mg/10 mL ([DSC]); 12 mg/6 mL ([DSC])
Generic: 10 mg/10 mL (10 mL)
IV: Infuse over 2 hours; arsenic trioxide has also been infused over 1 hour (Ref). If acute vasomotor reactions occur, the infusion duration may be extended to up to 4 hours. Arsenic trioxide does not require administration via a central venous catheter.
Arsenic trioxide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Parenteral: Do not mix with other medications. Infuse IV over 2 hours. In adolescents ≥15 years, doses have been infused over 1 hour (Ref). If acute vasomotor reactions occur, may infuse over a maximum of 4 hours. Does not require administration via a central venous catheter.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Acute promyelocytic leukemia, newly diagnosed, low-risk disease: Treatment of newly diagnosed low-risk acute promyelocytic leukemia (APL), in combination with tretinoin, in adults whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression
Acute promyelocytic leukemia, relapsed or refractory: Remission induction and consolidation treatment of APL in patients 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
Acute promyelocytic leukemia, newly diagnosed, including intermediate- or high-risk disease
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Multiple concentrations: Arsenic trioxide is available in different concentrations; verify concentration prior to admixture to assure appropriate dose preparation.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amiodarone: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification
Amphotericin B: May enhance the hypotensive effect of Arsenic Trioxide. Amphotericin B may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as amphotericin B. Risk D: Consider therapy modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Carbetocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination
Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
ClomiPRAMINE: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Dabrafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Dronedarone: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Dronedarone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
DroPERidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of DroPERidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Etelcalcetide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias (including TdP) with a continuous overnight ECG when fingolimod is combined with QT prolonging drugs. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Fluconazole: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluconazole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Fluorouracil Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Gemifloxacin: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification
Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
HydrOXYzine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Imipramine: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Miscellaneous Agents (Highest Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Loop Diuretics: May enhance the hypotensive effect of Arsenic Trioxide. Loop Diuretics may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the loop diuretics. Risk D: Consider therapy modification
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Meglumine Antimoniate: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Methadone: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Ondansetron: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Osmotic Diuretics: May enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the osmotic diuretics. Risk D: Consider therapy modification
Oxytocin: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pacritinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pacritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
PAZOPanib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of PAZOPanib. Risk X: Avoid combination
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination
Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination
Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Propofol: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Class III Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Miscellaneous Agents (Highest Risk): May enhance the QTc-prolonging effect of Arsenic Trioxide. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Highest Risk). Risk X: Avoid combination
QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quizartinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination
RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination
SUNItinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of SUNItinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Terbutaline: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Arsenic Trioxide. Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the thiazide and thiazide-like diuretics. Risk D: Consider therapy modification
Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Females should be advised against conceiving during treatment with arsenic trioxide (Sanz 2019). Verify pregnancy status in females of reproductive potential prior to initiating therapy. Females of reproductive potential should use effective contraception during treatment and for 6 months after the final arsenic trioxide dose. Males with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the final arsenic trioxide dose.
Arsenic trioxide crosses the placenta (Concha 1998).
Based on the mechanism of action and findings in animal reproduction studies, arsenic trioxide may cause fetal harm if administered during pregnancy.
Arsenic trioxide occurs naturally and toxicity varies between organic and inorganic forms (IOM 2000). 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 (Concha 1998; von Ehrenstein 2006; Yang 2003).
Available leukemia guidelines note arsenic trioxide is teratogenic and should not be used at any time during pregnancy (Lishner 2016; Sanz 2019).
Arsenic trioxide is present in breast milk.
Arsenic trioxide is naturally found in breast milk; concentrations range from 0.2 to 6 mcg/kg (IOM 2000). In studies of women exposed to high levels of arsenic from drinking water, breast milk concentrations were low (~3.1 mcg/kg) and did not correlate with maternal serum levels (Concha 1998). The possible effect of maternal arsenic trioxide therapy on breast milk concentrations is not known.
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends discontinuing breastfeeding during therapy and for 2 weeks after the final arsenic trioxide dose.
Monitor electrolytes (potassium, calcium, and magnesium), CBC with differential, renal function (serum creatinine), hepatic function, blood glucose, and coagulation parameters at baseline then at least 2 to 3 times a week during induction and at least weekly during consolidation; more frequent monitoring may be necessary in unstable patients. Consider testing thiamine levels in patients at risk for thiamine deficiency. Evaluate pregnancy status (prior to treatment in females of reproductive potential). Baseline then weekly 12-lead ECG (monitor more frequently in clinically unstable patients and in patients with concomitant medications associated with QTc prolongation that could not be discontinued). Monitor for signs/symptoms of APL differentiation syndrome (unexplained fever, dyspnea, and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities). Monitor for neurological symptoms (eg, Wernicke encephalopathy) and nutritional status. Monitor for the development of second primary malignancies.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Arsenic trioxide induces apoptosis in APL cells via morphological changes and DNA fragmentation; also damages or degrades the fusion protein promyelocytic leukemia (PML)-retinoic acid receptor (RAR) alpha
Distribution: Vdss: Arsenious acid (AsIII): 562 L; widely distributed throughout body tissues; dependent on body weight and increases as body weight increases; orally administered arsenic trioxide distributes into the CNS
Metabolism: Arsenic trioxide is immediately hydrolyzed to the active form, arsenious acid (AsIII) which is methylated (hepatically) to the less active pentavalent metabolites, monomethylarsonic acid (MMAv) and dimethylarsinic acid (DMAv) by methyltransferases; AsIII is also oxidized to the minor metabolite, arsenic acid (Asv)
Half-life elimination: AsIII: 10 to 14 hours; MMAv: ~32 hours; DMAv: ~72 hours
Time to peak: AsIII: At the end of infusion (2 hours); MMAv and DMAv; ~10 to 24 hours
Excretion: Urine (MMAv, DMAv, and ~15% of a dose as unchanged AsIII)
Altered kidney function: Results from a pharmacokinetic study in patients with advanced malignancies showed that mean AUC for AsIII was ~48% higher in patients with several renal impairment (CrCl <30 mL/minute) than in patients with normal renal function (CrCl >80 mL/minute). Systemic exposure to metabolites MMAV and DMAV may also be increased in patients with renal impairment.
Hepatic function impairment: A small pharmacokinetic study in patients with hepatocellular carcinoma showed that the mean dose-normalized AUC and Cmax values were 40% and 70% higher, respectively, in a patient with severe hepatic impairment (Child-Pugh class C) versus patients with normal hepatic function. Additionally, the mean dose-normalized trough plasma levels for metabolites MMAV and DMAV were 2.2-fold and 4.7-fold higher, respectively, than levels in patients with normal hepatic function.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
