Trisenox

Other Antineoplastic Agents

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Moderate
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Nonvesicant

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Arsenic trioxide for injection is available as a 12 mg/6 mL (2 mg/mL) vial and a 10 mg/10 mL (1 mg/mL) vial.
Dilution:
Remove the calculated amount of arsenic trioxide from the 1 mg/mL or 2 mg/mL vial and dilute in 100 to 250 mL of 5% dextrose injection or 0.9% sodium chloride injection; discard any unused drug remaining in the vial.
Do NOT mix arsenic trioxide with other medications.
Storage following dilution: the diluted admixture is stable for 48 hours under refrigeration or for 24 hours at room temperature.
Intravenous (IV) infusion:
Administer the arsenic trioxide admixture IV over 2 hours. The infusion time may be extended up to 4 hours if acute vasomotor reactions occur.

Severe

thrombocytopenia / Delayed / 0-58.0
neutropenia / Delayed / 0-48.0
differentiation syndrome / Delayed / 16.0-23.0
pleural effusion / Delayed / 0-20.0
hyperkalemia / Delayed / 0-18.0
hypomagnesemia / Delayed / 0-13.0
hypokalemia / Delayed / 0-13.0
hyperglycemia / Delayed / 0-13.0
abdominal pain / Early / 0-10.0
hypoxia / Early / 0-10.0
dyspnea / Early / 0-10.0
bone pain / Delayed / 0-10.0
GI bleeding / Delayed / 0-8.0
seizures / Delayed / 0-8.0
arthralgia / Delayed / 0-8.0
disseminated intravascular coagulation (DIC) / Delayed / 8.0-8.0
renal failure (unspecified) / Delayed / 0-8.0
nephrotoxicity / Delayed / 0-8.0
hypotension / Rapid / 0-5.0
atrial flutter / Early / 0-5.0
atrial fibrillation / Early / 0-5.0
fever / Early / 0-5.0
elevated hepatic enzymes / Delayed / 2.0-5.0
paresthesias / Delayed / 0-5.0
coma / Early / 0-5.0
myalgia / Early / 0-5.0
anemia / Delayed / 0-5.0
oliguria / Early / 0-5.0
fatigue / Early / 0-5.0
weakness / Early / 0-5.0
constipation / Delayed / 0-3.0
pruritus / Rapid / 0-3.0
headache / Early / 0-3.0
insomnia / Early / 0-3.0
back pain / Delayed / 0-3.0
leukocytosis / Delayed / 0-3.0
heart failure / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
AV block / Early / Incidence not known
torsade de pointes / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known

Moderate

sinus tachycardia / Rapid / 0-55.0
QT prolongation / Rapid / 2.0-40.0
edema / Delayed / 40.0-40.0
chest pain (unspecified) / Early / 0-25.0
hypertriglyceridemia / Delayed / 0-22.0
depression / Delayed / 0-20.0
hypercholesterolemia / Delayed / 0-16.0
erythema / Early / 0-13.0
wheezing / Rapid / 0-13.0
vaginal bleeding / Delayed / 13.0-13.0
palpitations / Early / 0-10.0
hypertension / Early / 0-10.0
hypocalcemia / Delayed / 0-10.0
blurred vision / Early / 10.0-10.0
fecal incontinence / Early / 0-8.0
hypoglycemia / Early / 0-8.0
tachypnea / Early / 0-8.0
hemoptysis / Delayed / 0-8.0
lymphadenopathy / Delayed / 0-8.0
peripheral neuropathy / Delayed / 0-6.0
neurotoxicity / Early / 0-6.0
metabolic acidosis / Delayed / 0-5.0
candidiasis / Delayed / 0-5.0
confusion / Early / 0-5.0
urinary incontinence / Early / 0-5.0
paresis / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known

Mild

nausea / Early / 0-75.0
cough / Delayed / 0-65.0
vomiting / Early / 0-58.0
diarrhea / Early / 0-53.0
chills / Rapid / 0-38.0
anxiety / Delayed / 0-30.0
epistaxis / Delayed / 0-25.0
anorexia / Delayed / 0-23.0
infection / Delayed / 2.0-23.0
dizziness / Early / 0-23.0
ecchymosis / Delayed / 0-20.0
injection site reaction / Rapid / 0-20.0
sinusitis / Delayed / 0-20.0
xerosis / Delayed / 0-15.0
hyperhidrosis / Delayed / 0-13.0
tremor / Early / 0-13.0
weight gain / Delayed / 13.0-13.0
dyspepsia / Early / 0-10.0
pallor / Early / 10.0-10.0
flushing / Rapid / 10.0-10.0
ocular irritation / Rapid / 10.0-10.0
xerostomia / Early / 0-8.0
urticaria / Rapid / 0-8.0
night sweats / Early / 0-8.0
petechiae / Delayed / 0-8.0
skin hyperpigmentation / Delayed / 0-8.0
drowsiness / Early / 0-8.0
xerophthalmia / Early / 8.0-8.0
weight loss / Delayed / 8.0-8.0
pharyngitis / Delayed / 0-5.0
agitation / Early / 0-5.0
tinnitus / Delayed / 0-5.0
otalgia / Early / Incidence not known

Alcoholism, encephalopathy, malnutrition, thiamine deficiency

Serious encephalopathy including Wernicke encephalopathy, a neurologic emergency, has been reported with arsenic trioxide therapy. In all patients, monitor nutritional status and evaluate for neurological symptoms (e.g., confusion, decreased level of consciousness, seizures, cognitive deficits, ataxia, visual symptoms, and ocular motor dysfunction) during arsenic trioxide therapy. Patients with thiamine deficiency may be at increased risk for developing encephalopathy; consider obtaining thiamine levels in patients who are at risk for this deficiency (e.g., chronic alcohol use/alcoholism, malabsorption, nutritional deficiency/malnutrition, or concomitant use of furosemide). Administer IV thiamine in patients with or at risk for thiamine deficiency. Immediately stop arsenic trioxide therapy if Wernicke encephalopathy is suspected and start IV thiamine. Monitor patients until symptoms resolve or improve and thiamine levels normalize.[59438]

Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, electrolyte imbalance, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), torsade de pointes, ventricular arrhythmias

Life-threatening cardiac arrhythmias and conduction abnormalities such as QT prolongation, torsade de pointes-type ventricular arrhythmia, and complete AV block have been reported with arsenic trioxide. Prior to starting therapy, assess the QTc interval by electrocardiogram (ECG), correct any electrolyte imbalance, and discontinue other drugs known to prolong QTc interval (if possible); do not administer arsenic trioxide in patients with prolonged QTcF interval or ventricular arrhythmias. Monitor ECG weekly and more frequently in clinically unstable patients or patients who are receiving concomitant QT prolonging medications. In patients who develop a QTc interval greater than 450 milliseconds (msec) for men or greater than 460 msec for women (using the Framingham formula), hold arsenic trioxide and all other concomitant medications known to prolong the QTc interval and correct electrolyte abnormalities. Resume therapy at a reduced dose when the QTc normalizes and electrolyte abnormalities are corrected. Monitor serum electrolyte concentrations (e.g., magnesium, potassium, calcium) at least 2- to 3-times weekly during induction therapy and at least weekly during consolidation therapy. Maintain serum potassium concentrations greater than 4 mEq/L and serum magnesium concentrations greater than 1.8 mg/dL during arsenic trioxide therapy. The risk of torsade de pointes may increase with severe or pre-existing QTc prolongation (e.g., long QT syndrome), concomitant administration of QTc prolonging drugs or medications that may lead to electrolyte abnormalities (e.g., potassium-wasting diuretics, amphotericin B), a history of torsade de pointes or cardiac disease, congestive heart failure, or other conditions that result in hypokalemia or hypomagnesemia.[63753] [59438] Use arsenic trioxide with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.[28432] [28457] [56592]

Differentiation syndrome, leukocytosis

Differentiation syndrome (with or without leukocytosis) has been reported in patients with acute promyelocytic leukemia who received arsenic trioxide; some cases were life-threatening or fatal. When arsenic trioxide is given in combination with tretinoin, patients should receive differentiation syndrome prophylaxis with prednisone 0.5 mg/kg orally once daily during induction therapy. In patients with leukocytosis, administer hydroxyurea until the white blood cell count is less than 10 X 109 cells/L. Monitor patients for signs or symptoms of differentiation syndrome. If this syndrome develops or is suspected, hold arsenic trioxide, start hemodynamic monitoring, and administer dexamethasone 10 mg IV every 12 hours for a minimum of 3 days or until signs and symptoms resolve. Symptoms of differentiation syndrome may include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusion, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy, and/or multi-organ dysfunction.

Trisenox

Rx

Cytotoxic agent that promotes myeloid differentiation
Used for the treatment of acute promyelocytic leukemia
Cardiac arrhythmias and differentiation syndrome have been reported

For the treatment of acute promyelocytic leukemia (APL).
NOTE: The FDA has designated arsenic trioxide as an orphan drug for the treatment of APL.
For consolidation treatment in patients with newly diagnosed APL following remission induction with tretinoin (all-trans retinoic acid) plus anthracyline-based chemotherapy†. Intravenous dosage Adults and Adolescents 15 years and older

0.15 mg/kg IV daily given 5 days per week for 5 weeks for 2 cycles of consolidation therapy (separated by a 2-week rest) following induction therapy with all-trans retinoic acid (ATRA), cytarabine, and daunorubicin has been studied in a randomized, phase III trial (n = 481). All patients also received 2 consolidation cycles with ATRA plus daunorubicin, and patients who remained in complete remission received maintenance treatment with ATRA or ATRA plus oral mercaptopurine and methotrexate.

For induction and consolidation therapy in patients with APL who are refractory to or who have relapsed from retinoid and anthracycline therapy. Intravenous dosage Adults

0.15 mg/kg IV over 2 hours once daily until bone marrow remission or for up to a maximum of 60 days as induction therapy. At 3 to 6 weeks after the completion of induction therapy, give 1 cycle of consolidation therapy with arsenic trioxide 0.15 mg/kg IV over 2 hours daily for 25 doses over a period of up to 5 weeks (e.g., 5 days per week). Dose interruption, dose reduction, or permanent therapy discontinuation may be necessary in patients who develop severe toxicity. In a multicenter, single-arm study (n = 40; patients aged 18 to 59 years, n = 27; patients aged older than 60 years, n = 8), treatment with arsenic trioxide resulted in a clinical complete remission (CR) rate of 85% in patients with APL who had relapsed from or not achieved a response to induction chemotherapy using an anthracycline and at least 1 course of induction therapy with tretinoin (all-trans retinoic acid, ATRA). The median time to clinical CR was 59 days (range, 28 to 85 days); the median time to the elimination of all visible leukemic cells on bone marrow aspirate review (bone marrow remission) was 35 days (range, 20 to 85 days). Consolidation therapy was given to 28 of the 34 patients who achieved a clinical CR after induction therapy; 18 patients received up to 4 additional cycles of arsenic trioxide maintenance therapy at a dose schedule similar to that used for consolidation therapy. Following induction or consolidation therapy, 11 patients who achieved a remission with arsenic trioxide received an allogeneic or autologous bone marrow transplant. At a median follow-up time of 17.1 months, the estimated 18-month relapse-free survival and overall survival (OS) rates were 56% and 66%, respectively. The clinical CR rate (75% vs. 93%) and 18-month OS rate (38% vs. 73%) were lower in patients aged 60 years or older compared with patients aged 18 to 59 years.

Adolescents and Children 4 years and older

0.15 mg/kg IV over 2 hours once daily until bone marrow remission or for up to a maximum of 60 days as induction therapy. At 3 to 6 weeks after the completion of induction therapy, give 1 cycle of consolidation therapy with arsenic trioxide 0.15 mg/kg IV over 2 hours daily for 25 doses over a period of up to 5 weeks (e.g., 5 days per week). Dose interruption, dose reduction, or permanent therapy discontinuation may be necessary in patients who develop severe toxicity.[63753] [59438] In a multicenter, single-arm study (n = 40; patients younger than 18 years, n = 5), treatment with arsenic trioxide resulted in a clinical complete remission (CR) rate of 85% in patients with APL who had relapsed from or not achieved a response to induction chemotherapy using an anthracycline and at least 1 course of induction therapy with tretinoin (all-trans retinoic acid, ATRA). In the overall study population, the median time to clinical CR was 59 days (range, 28 to 85 days); the median time to the elimination of all visible leukemic cells on bone marrow aspirate review (bone marrow remission) was 35 days (range, 20 to 85 days). Consolidation therapy was given to 28 of the 34 patients who achieved a clinical CR after induction therapy; 18 patients received up to 4 additional cycles of arsenic trioxide maintenance therapy at a dose schedule similar to that used for consolidation therapy. Following induction or consolidation therapy, 11 patients who achieved a remission with arsenic trioxide received an allogeneic or autologous bone marrow transplant. At a median follow-up time of 17.1 months, the estimated 18-month relapse-free survival and overall survival (OS) rates were 56% and 66%, respectively. In the 5 patients who were less than 18 years of age, the estimated 18-month OS rate was 80%. In the 5 patients who were less than 18 years of age, the estimated 18-month OS rate was 80%.[38036] In a phase I study that evaluated 13 pediatric patients with relapsed or refractory APL (median age, 17 years; range, 4 to 21 years), a clinical CR was achieved in 85% of patients at a median of 20 arsenic trioxide doses (range, 17 to 20 doses). Arsenic trioxide 0.15 mg/kg IV was given 5 days/week for 20 doses followed by a 2-week break for up to 70 doses. [59468]

For induction and consolidation therapy in patients with newly-diagnosed, low-risk APL, in combination with tretinoin (all-trans retinoic acid). Intravenous dosage Adults

0.15 mg/kg IV over 2 hours once daily in combination with tretinoin 22.5 mg/m2 orally twice daily (dose rounded to the nearest 10-mg increment) until bone marrow remission or for up to a maximum of 60 days as induction therapy followed by consolidation therapy with arsenic trioxide 0.15 mg/kg IV daily given 5 days per week for 4 consecutive weeks (total of 20 doses/cycle) in combination with tretinoin 22.5 mg/m2 orally twice daily (dose rounded to the nearest 10-mg increment) as continuous therapy during weeks 1 and 2 (on all 4 cycles) and during weeks 5 and 6 (on cycles 1, 2, and 3 only). Consolidation therapy is repeated every 8 weeks for 4 cycles. During induction therapy, all patients should receive differentiation syndrome prophylaxis with prednisone 0.5 mg/kg orally once daily. Dose interruption, dose reduction, or permanent therapy discontinuation may be necessary in patients who develop severe toxicity. Treatment with arsenic trioxide plus tretinoin was noninferior to tretinoin plus anthracycline-containing chemotherapy for the primary endpoint of 2-year event-free survival (EFS) rate (98.15% vs. 85.95%; difference of 12.2%; 95% CI, 4.3% to 20.1%; p < 0.001 for noninferiority) in 229 adult patients (median age, 46.6 years; range, 18 to 71 years) with newly diagnosed, low-to-intermediate risk APL in a multinational, randomized, phase III trial (the APL0406 trial). After a median follow-up of 40.6 months, the estimated 50-month EFS (97.3% vs. 80%; p < 0.001) and overall survival (99.2% vs. 92.6%; p = 0.0073) rates were significantly higher in the arsenic trioxide plus tretinoin arm compared with the tretinoin plus anthracycline-containing chemotherapy arm in the intention-to-treat population (n = 263).

Hepatic Impairment

Baseline hepatic impairment: Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Treatment-Related Hepatotoxicity
For 1 or more signs or symptoms of hepatotoxicity (i.e., total bilirubin level greater than 3-times the upper limit of normal (ULN), AST level greater than 5-times the ULN, or alkaline phosphatase (AP) level greater than 5-times the ULN): Hold arsenic trioxide (and/or tretinoin) therapy. When the total bilirubin level is less than 1.5-times the ULN and AST/AP levels are less than 3-times the ULN, resume the withheld drug(s) at a 50% dose reduction; treatment may be increased back to the recommended doses after 1 week in the absence of worsening hepatotoxicity. If hepatotoxicity recurs, permanently discontinue the withheld drug(s).

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abarelix: (Contraindicated) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation, such as arsenic trioxide.
Abciximab: (Moderate) Abciximab is contraindicated for use in patients with a platelet count of less than 100,000 cells/microliter. Patients with thrombocytopenia are at increased risk of bleeding complications. Thus, antineoplastic agents that cause clinically significant thrombocytopenia could increase the bleeding risk associated with abciximab. An additive risk of bleeding may occur when abciximab is used with agents that cause clinically significant thrombocytopenia.
Acetazolamide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with arsenic trioxide.
Adagrasib: (Major) Concomitant use of adagrasib and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Albuterol; Budesonide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Alfuzosin: (Major) Arsenic trioxide administration is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Avoid the use of arsenic trioxide with other agents that may prolong the QT interval or increase the risk of torsades de pointes. If possible, drugs with potential to prolong the QT interval should be discontinued prior to beginning arsenic trioxide therapy. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg, but the effect with alfuzosin 40 mg was not as great as the QT prolongation observed with therapeutic doses of moxifloxacin. There have been no reports of torsades de pointes (TdP) in extensive post-marketing experience with alfuzosin outside the United States. There are no known pharmacokinetic/pharmacodynamic studies of the effect of other alpha-blockers on cardiac repolarization. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients with a known history of cardiac arrhythmias, QT prolongation (e.g., congenital or acquired QT prolongation), history of torsades de pointes, or patients who are taking medications known to prolong the QT interval.
Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Alteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Amiodarone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval should only be done after careful assessment of risks versus benefits. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. If possible, avoid coadministration or discontinue drugs that are known to prolong the QT interval prior to initiating arsenic trioxide therapy. Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Avoid coadministration of amisulpride and arsenic trioxide due to the potential for additive QT prolongation and torsade de pointes (TdP); discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Monitor ECG frequently if coadministration is required. Amisulpride causes dose- and concentration- dependent QT prolongation. QT interval prolongation, TdP, and complete atrioventricular block have been reported with arsenic trioxide use.
Amlodipine; Celecoxib: (Minor) Some antineoplastic agents cause thrombocytopenia, and patients with thrombocytopenia are at increased risk of bleeding complications. Celecoxib does not generally affect platelet counts, prothrombin time, or partial thromboplastin time, and does not inhibit platelet aggregation at indicated dosages. It is unclear if celecoxib is associated with less risk than other NSAIDs due to its lack of platelet inhibitory effects; bleeding events have occurred with celecoxib.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of arsenic trioxide and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Clarithromycin is associated with QT prolongation and TdP. QT prolongation, TdP, and complete atrioventricular block have also been reported with the administration of arsenic trioxide.
Amphotericin B: (Major) Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia. Examples of drugs that may cause electrolyte abnormalities include amphotericin B. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms. Torsade de pointes was reported in 1 patient who received arsenic trioxide during induction therapy for relapsed acute promyelocytic leukemia; this patient was also receiving amphotericin B.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported with use of anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include arsenic trioxide. In addition, anagrelide inhibits platelet aggregation at high doses. Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur.
Apomorphine: (Major) Concurrent use of arsenic trioxide and apomorphine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, apomorphine should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Artemether; Lumefantrine: (Major) Concurrent use of arsenic trioxide and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, artemether; lumefantrine should be discontinued prior to initiating arsenic trioxide therapy. Consider ECG monitoring if arsenic trioxide must be used with or after artemether; lumefantrine treatment. Administration of artemether; lumefantrine is associated with prolongation of the QT interval. QT prolongation should also be expected with the administration of arsenic trioxide. Additionally, TdP and complete atrioventricular block have been reported with arsenic trioxide.
Asenapine: (Major) If possible, drugs that are known to prolong the QT interval, such as asenapine, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
Aspirin, ASA; Dipyridamole: (Moderate) Concurrent use of dipyridamole and antineoplastic agents may lead to an increased risk of bleeding.
Atomoxetine: (Major) Concomitant use of atomoxetine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Azelastine; Fluticasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Azithromycin: (Major) Avoid coadministration of azithromycin with arsenic trioxide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Beclomethasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Bedaquiline: (Major) Concurrent use of arsenic trioxide and bedaquiline should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, bedaquiline should be discontinued prior to initiating arsenic trioxide therapy. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. QT prolongation should also be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported.
Betamethasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Budesonide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Budesonide; Formoterol: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Buprenorphine: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as buprenorphine. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Buprenorphine; Naloxone: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as buprenorphine. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Cabotegravir; Rilpivirine: (Major) Concurrent use of arsenic trioxide and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, rilpivirine should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Celecoxib: (Minor) Some antineoplastic agents cause thrombocytopenia, and patients with thrombocytopenia are at increased risk of bleeding complications. Celecoxib does not generally affect platelet counts, prothrombin time, or partial thromboplastin time, and does not inhibit platelet aggregation at indicated dosages. It is unclear if celecoxib is associated with less risk than other NSAIDs due to its lack of platelet inhibitory effects; bleeding events have occurred with celecoxib.
Celecoxib; Tramadol: (Minor) Some antineoplastic agents cause thrombocytopenia, and patients with thrombocytopenia are at increased risk of bleeding complications. Celecoxib does not generally affect platelet counts, prothrombin time, or partial thromboplastin time, and does not inhibit platelet aggregation at indicated dosages. It is unclear if celecoxib is associated with less risk than other NSAIDs due to its lack of platelet inhibitory effects; bleeding events have occurred with celecoxib.
Ceritinib: (Major) Avoid coadministration of arsenic trioxide with ceritinib due to the risk of QT interval prolongation; discontinue ceritinib or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Ceritinib also causes concentration-dependent prolongation of the QT interval.
Chloroquine: (Major) Avoid coadministration of chloroquine with arsenic trioxide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Chlorpromazine: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include chlorpromazine. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciclesonide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Cilostazol: (Moderate) Because cilostazol inhibits platelet aggregation, a potential additive risk for bleeding exists if cilostazol is given in combination with other drugs that affect hemostasis. Agents that cause clinically significant thrombocytopenia could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Because of the potential for TdP, use of arsenic trioxide with cisapride is contraindicated.
Cisplatin: (Major) Because electrolyte abnormalities increase the risk of QT interval prolongation and serious arrhythmias, avoid the concomitant use of arsenic trioxide with drugs that may cause electrolyte abnormalities, particularly hypokalemia and hypomagnesemia such as cisplatin. If concomitant drug use is unavoidable, frequently monitor serum electrolytes (and replace as necessary) and electrocardiograms. Additionally, closely monitor renal function if concomitant use is necessary. Both drugs can cause nephrotoxicity, which may be exacerbated with the use of additional nephrotoxins.
Citalopram: (Major) Avoid coadministration of citalopram and arsenic trioxide. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Citalopram causes dose-dependent QT interval prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Clarithromycin: (Major) Concurrent use of arsenic trioxide and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Clarithromycin is associated with QT prolongation and TdP. QT prolongation, TdP, and complete atrioventricular block have also been reported with the administration of arsenic trioxide.
Clofazimine: (Major) Concomitant use of clofazimine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clopidogrel: (Moderate) Because clopidogrel inhibits platelet aggregation, a potential additive risk for bleeding exists if clopidogrel is given in combination with other drugs that affect hemostasis. Clopidogrel should be used cautiously in patients with thrombocytopenia following the administration of myelosuppressive antineoplastic agents or other drugs that cause significant thrombocytopenia due to the increased risk of bleeding.
Clozapine: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include clozapine. In addition, it is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of promethazine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Corticosteroids: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Cortisone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Crizotinib: (Major) Avoid concomitant use of arsenic trioxide with crizotinib due to the risk of QT prolongation; discontinue crizotinib or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrocardiograms and electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Crizotinib has also been associated with concentration-dependent QT prolongation.
Dasatinib: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include arsenic trioxide.
Deflazacort: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Degarelix: (Major) Avoid concomitant use of arsenic trioxide and degarelix due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with arsenic trioxide. Halogenated anesthetics can prolong the QT interval. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Deutetrabenazine: (Major) Avoid concomitant use of arsenic trioxide and deutetrabenazine due to the potential for QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexamethasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Quinidine: (Major) If possible, quinidine should be discontinued prior to initiating arsenic trioxide therapy. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Diclofenac: (Minor) A theoretical increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia including myelosuppressive antineoplastic agents.
Diclofenac; Misoprostol: (Minor) A theoretical increased risk of bleeding may occur when NSAIDs are used with agents that cause clinically significant thrombocytopenia including myelosuppressive antineoplastic agents.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Dipyridamole: (Moderate) Concurrent use of dipyridamole and antineoplastic agents may lead to an increased risk of bleeding.
Disopyramide: (Major) If possible, disopyramide should be discontinued prior to initiating arsenic trioxide therapy. If coadministered, these drugs should be used cautiously and with close monitoring. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Dofetilide: (Major) Avoid concomitant use of arsenic trioxide and dofetilide due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP.
Dolasetron: (Major) Avoid concomitant use of arsenic trioxide with other drugs, such as dolasetron, that may cause QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Dolutegravir; Rilpivirine: (Major) Concurrent use of arsenic trioxide and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, rilpivirine should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include arsenic trioxide.
Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include arsenic trioxide.
Dronedarone: (Contraindicated) Coadministration of dronedarone and arsenic trioxide is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include arsenic trioxide.
Efavirenz: (Major) QT interval prolongation, TdP, and complete atrioventricular block have been reported with arsenic trioxide use. Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as efavirenz; select an alternative antiretroviral that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) QT interval prolongation, TdP, and complete atrioventricular block have been reported with arsenic trioxide use. Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as efavirenz; select an alternative antiretroviral that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) QT interval prolongation, TdP, and complete atrioventricular block have been reported with arsenic trioxide use. Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as efavirenz; select an alternative antiretroviral that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Eliglustat: (Major) Avoid coadministration of eliglustat and arsenic trioxide. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should be expected with the administration of arsenic trioxide.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concurrent use of arsenic trioxide and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, rilpivirine should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Concurrent use of arsenic trioxide and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, rilpivirine should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Encorafenib: (Major) Avoid coadministration of encorafenib and arsenic trioxide due to QT prolongation. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Monitor electrolytes and correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Entrectinib: (Major) Avoid coadministration of entrectinib with arsenic trioxide due to the risk of QT prolongation. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Entrectinib has been associated with QT prolongation.
Eptifibatide: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when eptifibatide is used concomitantly with agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Eribulin: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Concurrent use of arsenic trioxide and erythromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, erythromycin should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Erythromycin is also associated with QT prolongation and TdP.
Escitalopram: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as arsenic trioxide, should be done with caution and close monitoring.
Fingolimod: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of TdP. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fingolimod include arsenic trioxide.
Flecainide: (Major) Concurrent use of flecainide and arsenic trioxide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, flecainide should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Flecainide, a Class IC antiarrhythmic, is also associated with a possible risk for QT prolongation and/or TdP; although, the increase in QT interval is largely due to prolongation of the QRS interval. Causality for TdP has not been established for flecainide.
Fluconazole: (Major) Concurrent use of arsenic trioxide and fluconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, fluconazole should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Fluconazole has also been associated with QT prolongation and rare cases of TdP.
Fludrocortisone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Flunisolide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Fluoxetine: (Major) Avoid coadministration of fluoxetine and arsenic trioxide. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should be expected with the administration of arsenic trioxide.
Fluphenazine: (Minor) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously with arsenic trioxide include fluphenazine.
Fluticasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Fluticasone; Salmeterol: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Fluticasone; Vilanterol: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Fluvoxamine: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT prolongation such as fluvoxamine. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrocardiograms. Torsade de Pointes (TdP), QT prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
Formoterol; Mometasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as arsenic trioxide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes. Torsade de pointes, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fostemsavir: (Major) Avoid concomitant use of arsenic trioxide and fostemsavir due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Concurrent use of arsenic trioxide and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, gemifloxacin should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Gemifloxacin may also prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab ozogamicin with arsenic trioxide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Gilteritinib: (Major) Avoid concomitant use of arsenic trioxide with gilteritinib; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Gilteritinib has been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with arsenic trioxide due to the potential for additive QT prolongation. Discontinue glasdegib or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Goserelin: (Major) Avoid concomitant use of arsenic trioxide with goserelin; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
Granisetron: (Major) Avoid concomitant use of arsenic trioxide with granisetron. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Granisetron has also been associated with QT prolongation. Concurrent use may result in additive risk of QT prolongation.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with arsenic trioxide. Halogenated anesthetics can prolong the QT interval. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Haloperidol: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include haloperidol.
Histrelin: (Major) Avoid concomitant use of arsenic trioxide with histrelin; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
Hydrocortisone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Hydroxychloroquine: (Major) Avoid coadministration of arsenic trioxide and hydroxychloroquine due to the risk of increased QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Hydroxyzine: (Major) Avoid coadministration of hydroxyzine and arsenic trioxide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP); discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Monitor ECG frequently if coadministration is required. QT interval prolongation, TdP, and complete atrioventricular block have been reported with arsenic trioxide use. Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP.
Ibutilide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided with other agents also known to have this effect, such as arsenic trioxide.
Indapamide: (Moderate) Indapamide may induce hypokalemia, increasing the potential for proarrhythmic effects (e.g., torsade de pointes) of arsenic trioxide. Potassium levels should be within the normal range prior and during administration of these agents. In the absence of electrolyte imbalances, these agents can be used together safely.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with arsenic trioxide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. TdP, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Interferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Interferon Alfa-n3: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with arsenic trioxide. Halogenated anesthetics can prolong the QT interval. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Itraconazole: (Major) Avoid coadministration of itraconazole and arsenic trioxide. Itraconazole has been associated with prolongation of the QT interval. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should be expected with the administration of arsenic trioxide.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with arsenic trioxide due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and arsenic trioxide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concurrent use of arsenic trioxide and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Clarithromycin is associated with QT prolongation and TdP. QT prolongation, TdP, and complete atrioventricular block have also been reported with the administration of arsenic trioxide.
Lapatinib: (Major) Avoid coadministration of arsenic trioxide with lapatinib due to the risk of QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor ECGs for QT prolongation and monitor electrolytes; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Prolongation of the QT interval, TdP, and complete atrioventricular block have been reported with arsenic trioxide use.
Lefamulin: (Major) Avoid coadministration of lefamulin with arsenic trioxide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, ECG monitoring is recommended during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with arsenic trioxide due to the risk of QT prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Prolongation of the QT interval has also been reported with lenvatinib therapy.
Leuprolide: (Major) Avoid concomitant use of arsenic trioxide with leuprolide; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid concomitant use of arsenic trioxide with leuprolide; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levofloxacin: (Major) Concomitant use of levofloxacin and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and arsenic trioxide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lithium: (Major) Lithium should be used cautiously and with close monitoring with arsenic trioxide. Lithium has been associated with QT prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Lofexidine: (Major) Avoid coadministration of lofexidine and arsenic trioxide due to the potential for additive QT prolongation and torsade de pointes (TdP). Monitor ECG frequently if coadministration is required. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. QT interval prolongation, TdP, and complete atrioventricular block have been reported with arsenic trioxide use.
Loop diuretics: (Moderate) Use caution when using arsenic trioxide concomitantly with loop diuretics, as these can cause electrolyte abnormalities, which can increase the risk of QT prolongation.
Loperamide: (Major) Concomitant use of loperamide and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with arsenic trioxide due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs th

at prolong the QT interval, such as arsenic trioxide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Mannitol: (Major) Avoid concomitant use of arsenic trioxide with mannitol. Electrolyte abnormalities (e.g., hypokalemia) caused by mannitol may increase the risk for QT prolongation and torsade de pointes. Monitor electrocardiograms and serum electrolytes more frequently if concurrent use cannot be avoided.
Maprotiline: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include mefloquine. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Methadone: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include methadone. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Methazolamide: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and methazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with arsenic trioxide.
Methylprednisolone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Metronidazole: (Major) Concomitant use of metronidazole and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and arsenic trioxide; both drugs have been reported to increase the QT interval. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If use of these drugs together is unavoidable, frequently monitor electrocardiograms. In clinical trials, QT prolongation was reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Torsade de pointes, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Mifepristone: (Major) Concomitant use of arsenic trioxide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Major) Concomitant use of arsenic trioxide and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mobocertinib: (Major) Concomitant use of mobocertinib and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mometasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Moxifloxacin: (Major) Concurrent use of arsenic trioxide and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, moxifloxacin should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and arsenic trioxide; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Torsade de pointes, QT prolongation, and complete atrioventricular block have occurred with arsenic trioxide use.
Ofloxacin: (Major) Concomitant use of ofloxacin and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of fluoxetine and arsenic trioxide. QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should be expected with the administration of arsenic trioxide. (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Olanzapine; Samidorphan: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Olopatadine; Mometasone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Ondansetron: (Major) Concomitant use of ondansetron and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Avoid coadministration of osilodrostat and arsenic trioxide due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Monitor ECG frequently if coadministration is required. QT interval prolongation, torsade de pointes, and complete atrioventricular block have been reported with arsenic trioxide use. Osilodrostat is associated with dose-dependent QT prolongation.
Osimertinib: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation such as osimertinib; discontinue osimertinib or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Concomitant use may increase the risk of QT prolongation.
Oxaliplatin: (Major) Avoid concomitant use of arsenic trioxide and oxaliplatin due to the potential for QT prolongation. If concomitant drug use is unavoidable, frequently monitor electrocardiograms and electrolytes; correct electrolyte abnormalities prior to administration. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in post-marketing experience.
Ozanimod: (Major) Avoid concomitant use of arsenic trioxide and ozanimod due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, consult cardiology and frequently monitor ECGs. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Pacritinib: (Major) Concomitant use of pacritinib and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided with other agents also known to have this effect, such as arsenic trioxide. However, if coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include arsenic trioxide.
Pasireotide: (Major) Cautious use of pasireotide and arsenic trioxide is needed, as coadministration may have additive effects on the prolongation of the QT interval. If possible, drugs that are known to prolong the QT interval, such as pasireotide, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Pazopanib: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include pazopanib.
Peginterferon Alfa-2a: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Peginterferon Alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Pentamidine: (Major) If possible, drugs that are known to prolong the QT interval, like pentamidine, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Pentamidine-induced hypokalemia or hypomagnesemia can also potentiate the cardiac toxicity of arsenic trioxide.
Perphenazine: (Minor) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include perphenazine.
Perphenazine; Amitriptyline: (Minor) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include perphenazine.
Pimavanserin: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as pimavanserin. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of arsenic trioxide with pimozide is contraindicated.
Pitolisant: (Major) Avoid coadministration of pitolisant with arsenic trioxide as concurrent use may increase the risk of QT prolongation. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Pitolisant prolongs the QT interval. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Ponesimod: (Major) Avoid concomitant use of arsenic trioxide and ponesimod due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If concomitant drug use is unavoidable, frequently monitor ECGs and for signs and symptoms of infection. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Posaconazole: (Major) Concurrent use of arsenic trioxide and posaconazole should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, posaconazole should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide; TdP and complete atrioventricular block have been reported. Posaconazole has also been associated with QT prolongation and in rare cases, TdP.
Potassium-sparing diuretics: (Moderate) Use caution when using arsenic trioxide with potassium-sparing diuretics. Electrolyte abnormalities, such as increased potassium, may increase the risk for QT prolongation and torsade de pointes.
Prednisolone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Prednisone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include arsenic trioxide.
Procainamide: (Major) If possible, procainamide should be discontinued prior to initiating arsenic trioxide therapy. Procainamide administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Prochlorperazine: (Minor) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include prochlorperazine. If coadministration is necessary, then close monitoring is essential.
Promethazine: (Major) Concomitant use of promethazine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of quetiapine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) If possible, quinidine should be discontinued prior to initiating arsenic trioxide therapy. Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Quinine: (Major) Concurrent use of quinine and arsenic trioxide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should also be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported.
Quizartinib: (Major) Concomitant use of quizartinib and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include ranolazine. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported.
Relugolix: (Major) Avoid concomitant use of arsenic trioxide with relugolix due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of arsenic trioxide with relugolix due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Reteplase, r-PA: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Ribociclib: (Major) Avoid coadministration of ribociclib with arsenic trioxide due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Prolongation of the QT interval, TdP, and complete atrioventricular block have been reported with arsenic trioxide use. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with arsenic trioxide due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Prolongation of the QT interval, TdP, and complete atrioventricular block have been reported with arsenic trioxide use. Concomitant use may increase the risk for QT prolongation.
Rilpivirine: (Major) Concurrent use of arsenic trioxide and rilpivirine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If possible, rilpivirine should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include arsenic trioxide.
Romidepsin: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Romidepsin has been reported to prolong the QT interval. If romidepsin must be coadministered with arsenic trioxide, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
Ropeginterferon alfa-2b: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Saquinavir: (Major) Concurrent use of arsenic trioxide and saquinavir should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP. QT prolongation should also be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have been reported.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Major) Avoid coadministration of arsenic trioxide and selpercatinib due to the potential for additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Concentration-dependent QT prolongation has been observed with selpercatinib therapy.
Sertraline: (Major) Concomitant use of sertraline and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with arsenic trioxide. Halogenated anesthetics can prolong the QT interval. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported.
Siponimod: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation, such as siponimod. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Torsade de pointes, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) If possible, drugs that are known to prolong the QT interval, such as solifenacin, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
Sorafenib: (Major) Avoid coadministration of sorafenib with arsenic trioxide due to the risk of additive QT prolongation. If concomitant use is unavoidable, frequently monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Concomitant use of sotalol and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sunitinib: (Major) Avoid concomitant use of arsenic trioxide with sunitinib if possible due to the risk of QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor ECGs for QT prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
Tacrolimus: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include tacrolimus.
Tamoxifen: (Major) Concomitant use of tamoxifen and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Concurrent use of arsenic trioxide and telavancin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Telavancin has been associated with QT prolongation and should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. TdP and complete atrioventricular block have also been reported with arsenic trioxide.
Tenecteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Tetrabenazine: (Major) f possible, drugs that are known to prolong the QT interval, such as tetrabenazine, should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc.
Thiazide diuretics: (Moderate) Concomitant use of thiazide diuretics and arsenic trioxide should be done cautiously. Electrolyte abnormalities, such as hypokalemia and hypomagnesemia, may increase the risk for QT prolongation and torsade de pointes.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of arsenic trioxide with thioridazine is contraindicated.
Thrombolytic Agents: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Ticlopidine: (Moderate) Ticlopidine therapy is contraindicated in patients with hematopoietic disorders including myelosuppression and thrombocytopenia. Ticlopidine should be used cautiously, if at all, in patients with thrombocytopenia following the administration of myelosuppressive antineoplastic agents due to a potential increase in the risk of bleeding.
Tolterodine: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation that should be used cautiously and with close monitoring with arsenic trioxide include tolterodine. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. This should be taken into consideration when prescribing tolterodine to patients taking other drugs that are associated with QT prolongation.
Toremifene: (Major) Avoid coadministration of arsenic trioxide with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, frequently monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Toremifene has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
Trazodone: (Major) Concomitant use of trazodone and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triamcinolone: (Moderate) Caution is advisable during concurrent use of arsenic trioxide and corticosteroids as electrolyte imbalance caused by corticosteroids may increase the risk of QT prolongation with arsenic trioxide.
Triclabendazole: (Major) Concomitant use of triclabendazole and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include trifluoperazine.
Triptorelin: (Major) Avoid concomitant use of arsenic trioxide with triptorelin; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Vandetanib: (Major) Avoid coadministration of vandetanib with arsenic trioxide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, frequently monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Torsade de pointes, QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use.
Vardenafil: (Major) Concomitant use of vardenafil and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include vemurafenib.
Venlafaxine: (Major) Concomitant use of venlafaxine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voclosporin: (Major) Avoid concomitant use of arsenic trioxide and voclosporin due to the risk of additive QT prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concurrent use of arsenic trioxide and clarithromycin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Clarithromycin is associated with QT prolongation and TdP. QT prolongation, TdP, and complete atrioventricular block have also been reported with the administration of arsenic trioxide.
Voriconazole: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with arsenic trioxide include voriconazole.
Vorinostat: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with arsenic trioxide.
Ziprasidone: (Contraindicated) Ziprasidone is contraindicated for use with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs, including arsenic trioxide. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsade de pointes (TdP). Arsenic trioxide can cause QTc interval prolongation, complete atrioventricular block, and a TdP-type ventricular arrhythmia, which can be fatal.

Arsenic Trioxide/Trisenox Intravenous Inj Sol: 1mL, 1mg, 2mg

Adults

0.15 mg/kg IV daily.

Geriatric

0.15 mg/kg IV daily.

Adolescents

0.15 mg/kg IV daily.

Children

4 years and older: 0.15 mg/kg IV daily.
less than 4 years: Safety and efficacy not established.

Infants

Safety and efficacy not established.

Neonates

Safety and efficacy not established.

The mechanism of action of arsenic trioxide is not completely understood, but may be dependent to some degree on the dose administered and tumor type. Observations of arsenic trioxide in vitro have not completely correlated with in vivo results. Acute promyelocytic leukemia is caused by a genetic lesion that disrupts the alpha retinoic acid receptor (RAR-alpha). The fusion protein that is formed, PML-RAR-alpha, inhibits apoptotic pathways and blocks myeloid differentiation. Arsenic trioxide degrades the PML-RAR-alpha fusion protein; however, arsenic trioxide causes a different pattern of proteolysis than all-trans-retinoic acid (ATRA). By degrading the PML-RAR-alpha protein, arsenic trioxide therapy allows myeloid differentiation to continue and apoptosis to occur. Unlike ATRA, arsenic trioxide does not down regulate wild-type RAR-alpha. Effects of arsenic trioxide are concentration dependent: induction of nonterminal differentiation occurs at relatively low concentrations (0.1—0.5 M/L) and apoptosis occurs at higher concentrations (0.5—2 mcM/L). Other suggested actions include downregulation of Bcl-2, modification of the glutathione redox system, caspase activation, modulation of mitochondrial permeability transition pore, and inhibition of angiogenesis via decreases in vascular endothelial growth factor (VGEF).

Arsenic trioxide is administered as an intravenous infusion. It undergoes hydrolysis when placed into solution and forms arsenious acid, the pharmacologically active form of arsenic trioxide. Arsenious acid is metabolized via methylation in body tissues and in the liver via methyltransferases to form the 2 main (and less toxic) metabolites, monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV). Another metabolite, present at low levels in the plasma, is arsenic acid; it is formed by the oxidation of arsenious acid in tissues via enzymatic or nonenzymatic processes. The mean elimination half-life for arsenious acid is 10 to 14 hours, and the estimated mean terminal elimination half-lives for MMAV and DMAV are 32 hours and 72 hours, respectively. The arsenious acid volume of distribution at steady state is large (mean, 562 L); it is widely distributed throughout body tissues. The total clearance of arsenious acid is 49 L/hour; the renal clearance is 9 L/hour. Clearance is not dependent on the arsenic trioxide dose when it is given within the dose range of 7 mg to 32 mg. Following the administration of arsenic trioxide, about 15% of the dose is excreted as unchanged arsenious acid in the urine. MMAV and DMAV are excreted primarily in the urine.
 
Affected cytochrome P450 isoenzymes: none
Arsenic trioxide did not demonstrate human liver microsome inhibitory activity on cytochrome P450 (CYP) enzymes such as CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5, and CYP4A9/11 in vitro. Therefore, the pharmacokinetics parameters of drugs that are substrates for these CYP enzymes are not expected to be affected by concomitant use of arsenic trioxide.

Intravenous Route

After a single-dose of arsenic trioxide 0.15 mg/kg (range, 7 to 32 mg), systemic exposure (AUC) appears to be linear; clearance is not dependent on dose for this studied range. Following arsenic trioxide 0.15 mg/kg IV over 2 hours for 5 days per week, the arsenious acid Tmax was 2 hours, the mean AUC was 194 ng x hour/mL on day 1 of cycle 1, and the mean AUC was 332 ng x hour/mL on day 25 of cycle 1 (about a 2-fold accumulation from day 1) in a pharmacokinetic study in 6 patients with acute promyelocytic leukemia. Due to their longer half-lives, MMAV and DMAV accumulation ranged from 1.4-fold to 8-fold following multiple dosing compared with single dose administration.

Pregnancy

Arsenic trioxide may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant during arsenic trioxide therapy. Discuss the potential hazard to the fetus if arsenic trioxide is used during pregnancy or if a patient becomes pregnant while taking this drug. No studies have evaluated arsenic trioxide use in pregnant women. However, of 3 reports of arsenic trioxide exposure during pregnancy, 1 patient who became pregnant during therapy experienced a miscarriage. Increased resorption, neural-tube defects, anophthalmia, and microphthalmia were reported following administration of arsenic trioxide in female rats at a dose equivalent to 10-times the recommended human dose.

Arsenic trioxide is excreted into breast milk. Because of the potential for adverse reactions in nursing infants, women should discontinue breast-feeding during arsenic trioxide therapy and for at 2 weeks after the last dose.[63753] [59438]