Adult Dosing

Acute promyelocytic leukemia

Induction treatment schedule

• 0.15 mg/kg IV daily until remission [Max: 60 doses]

Consolidation treatment schedule

• O.15 mg/kg IV qd for 25 doses over < 5 weeks
• Note: Treatment should begin 3 to 6 weeks after completion of induction therapy

Pediatric Dosing

• Safety and efficacy in pediatric patients (< 5yrs ) is not established

Acute promyelocytic leukemia

Child > = 5 yrs

• Induction treatment schedule: 0.15 mg/kg IV daily until remission [Max: 60 doses ]
• Consolidation treatment schedule: O.15 mg/kg IV daily for 25 doses over < 5 weeks; treatment should begin 3 to 6 weeks after completion of induction therapy

[Outline]

• Adult Dosing
• Pediatric Dosing

• Induction of remission and consolidation in Acute promyelocytic leukemia (APL) refractory to, or relapsed from, retinoid and anthracycline chemotherapy
• APL associated with t(15; 17) translocation/PML/RAR-alpha gene expression

• Hypersensitivity arsenic or to any of the ingredients of the product

• Arsenic trioxide should be used under the supervision of a qualified clinician experienced in the management of patients with acute leukemia
• The potentially fatal APL differentiation syndrome (also known as the retinoic acid-APL [RA-APL] syndrome) characterized by fever, dyspnea, weight gain, pulmonary infiltrates, pleural or pericardial effusions with or without leukocytosis has been reported. At the first signs of the syndrome, give dexamethasone 10 mg IV q12 hrs x 3 days or until signs and symptoms have abated. The majority of patients do not require termination of arsenic trioxide therapy during treatment of the APL differentiation syndrome
• Induces complete atrioventricular block, prolongs QT interval. Concomitant administration of QT prolonging drugs, history of torsade de pointes, pre-existing prolongation of QT interval, congestive heart failure, administration of potassium-wasting diuretics, or other conditions resulting in hypokalemia or hypomagnesemia may result in torsade de pointes- type of fatal ventricular arrhythmia. 12-lead ECG, serum electrolytes, creatinine should be done before initiation of therapy with arsenic trioxide Discontinue drugs that prolongs QT interval
• Correct pre-existing electrolyte abnormalities. For QTc > 500 msec corrective measures are required. Re-assess QTc with serial ECGs before initiating therapy. During treatment maintain potassium >4 mEq/L and magnesium >1.8 mg/dL. Re-assess patients reaching absolute QT interval value > 500 msec for other concomitant risk factors while analyzing risk to benefit ratio for termination of therapy vs. suspension of therapy
• If syncope or rapid or irregular heartbeat occurs during treatment, hospitalize patient and temporarily discontinue treatment until QTc interval <460 msec, electrolyte abnormalities are corrected, and the syncope and irregular heartbeat cease

Renal Dose Adjustment

• Severe renal impairment: Monitor patients for toxicity; dose adjustments recommended, but not defined

Hepatic Dose Adjustment

• Hepatic impairment: Use with caution
• Severe hepatic impairment: Monitor patients for toxicity; dose adjustments recommended, but not defined

• Administer under the supervision of a qualified clinician experienced in the management of patients with acute leukemia
• APL differentiation syndrome has occurred in patients treated with arsenic trioxide [US Black Box Warnings]
• Hyperleukocytosis unrelated to baseline WBC counts, has occurred in patients treated with this drug
• Risk of QT prolongation and complete AV block; monitor serial ECGs and correct pre-existing electrolyte imbalances
• Arsenic trioxide may cause fetal harm when administered to pregnant women. If a patient becomes pregnant during therapy, apprise her of the potential harm to the fetus
• Monitor BUN/creatinine, electrolytes at baseline then twice weekly or more frequently in unstable patients during induction, and qwk during consolidation
• Monitor CBC w/ diff, PT/aPTT twice weekly or more frequently in unstable patients during induction and qwk during consolidation

Cautions: Use cautiously in

• Renal impairment
• Hepatic impairment
• Pre-existing electrolyte abnormalities
• CHF
• Concomitant QT prolonging agents
• Concomitant potassium wasting diuretics
• Concomitant amphotericin
• Torsades de pointes history

Pregnancy Category:D

Breastfeeding: Unsafe; excreted in human milk. Manufacturer recommends discontinuation of breastfeeding or discontinuation of drug, considering the importance of the drug to the mother

• GI: Nausea, anorexia, diarrhea, loose motions, vomiting, abdominal pain, sore throat, constipation, dyspepsia, oral blistering, fecal incontinence, gastrointestinal hemorrhage, dry mouth, abdominal tenderness, hemorrhagic diarrhea, abdominal distension
• METABOLIC: Hypokalemia, hypomagnesemia, hyperglycemia, hyperkalemia, hypocalcemia, hypoglycemia, acidosis, ALT and AST increased
• CNS: Headache, insomnia, dizziness (excluding vertigo), tremor, convulsion, somnolence, coma
• NEURO: Paresthesia
• PSYCHIATRIC: Anxiety, depression, agitation, confusion
• RESP: URTI, Cough, dyspnea, epistaxis, hypoxia, pleural effusion, post nasal drip, decreased breath sounds, wheezing, crepitations, rales, tachypnea, hemoptysis, rhonchi
• DERM: Dermatitis, pruritus, ecchymosis, dry skin, erythema, increased sweating, facial edema, night sweats, petechiae, hyperpigmentation, urticaria, local exfoliation, eyelid edema
• CV: Chest Pain, Tachycardia, prolonged QTc, torsades de pointes, AV block, atrial arrhythmias, palpitations, ECG abnormalities, hypotension, flushing, hypertension
• MUSC: Arthralgia, myalgia, bone pain, back pain, neck pain, limb pain
• HEMA: Leukocytosis, anemia, thrombocytopenia, febrile neutropenia, neutropenia, neutropenia, lymphadenopathy, disseminated intravascular coagulation
• EENT: Sinusitis, nasopharyngitis, ocular irritation, blurred vision, dry eye, ocular redness, earache, tinnitus, oral candidiasis
• GU: Vaginal hemorrhage, intermenstrual bleeding, renal failure, renal impairment, oliguria, incontinence
• LOCAL: Injection site reaction
• MISC: Hypersensitivity, fever/rigors, hemorrhage, drug related toxicity, HSV infections, sepsis, bacterial infection, APL differentiation syndrome

• Antineoplastic agent; precise mechanism of action unknown, induces morphological changes and DNA fragmentation associated with apoptosis, degradation of the fusion protein PML/RAR-alpha
• Metabolized by liver; CYP450: none
• Primarily excreted in urine (15% unchanged)
• Half-life: 10-14 hrs

US Trade Name(s)

• Trisenox

US Availability

Trisenox

• INJ: 1 mg/mL (10 mL amp)

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• Trisenox

UK Availability

Trisenox

• INJ: 1 mg/mL (10 mL amp)

Australian Trade Name(s)

• Phenasen

Australian Availability

Phenasen

• INJ: 10 mg/10 mL

[Outline]

Hematology/Oncology

Antineoplastics

Miscellaneous Agents