HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use - TRISENOX safely and effectively. See full prescribing information for - TRISENOX. TRISENOX® (arsenic trioxide ...
These highlights do not include all the information needed to use TRISENOX safely and effectively. See full prescribing information for TRISENOX.
TRISENOX® (arsenic trioxide) injection, for intravenous administration
Initial U.S. Approval: 2000
WARNING: APL DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES, AND ELECTROLYTE MONITORING
See full prescribing information for complete boxed warning.
-
•
-
Patients have experienced symptoms similar to retinoic-acid-Acute Promyelocytic Leukemia or APL differentiation syndrome, which can be fatal. If symptoms occur, initiate high-dose steroids immediately and continue for at least 3 days until symptoms have abated.
-
•
-
Arsenic trioxide can cause QT interval prolongation and complete atrioventricular block. QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal.
-
•
-
Before initiating therapy, perform a 12-lead ECG, assess serum electrolytes and creatinine, correct preexisting electrolyte abnormalities, and consider discontinuing drugs known to prolong QT interval.
INDICATIONS AND USAGE
TRISENOX is an arsenical indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
(1)
DOSAGE AND ADMINISTRATION
-
•
-
For induction therapy, administer intravenously at a dose of 0.15 mg/kg daily until bone marrow remission. Do not exceed 60 doses for total induction. ( 2.1)
-
•
-
Begin consolidation treatment 3 to 6 weeks after completion of induction therapy. Administer intravenously at a dose of 0.15 mg/kg daily for 25 doses over a period up to 5 weeks. ( 2.1)
-
•
-
Delay treatment for severe non-hematologic adverse reactions. ( 2.2)
-
•
-
Dilute prior to use. ( 2.3)
-
•
-
Administer intravenously over 1-2 hours. The infusion duration may be extended up to 4 hours if acute vasomotor reactions are observed. ( 2.3)
DOSAGE FORMS AND STRENGTHS
Injectable solution for intravenous administration supplied as 10 mg/10 ml of arsenic trioxide in single-use ampules. (3
CONTRAINDICATIONS
Hypersensitivity to arsenic. (4)
WARNINGS AND PRECAUTIONS
-
•
-
Cardiac Conduction Abnormalities: During TRISENOX therapy, maintain potassium concentrations above 4 mEq/L and magnesium concentrations above 1.8 mg/dL. ( 5.2)
-
•
-
Carcinogenesis: Arsenic trioxide is a human carcinogen. Monitor patients for the development of second primary malignancies. ( 5.3)
-
•
-
Embryo-Fetal Toxicity: Can cause fetal harm. Advise of potential risk to a fetus and use of effective contraception. ( 5.4, 8.1, 8.3)
-
•
-
Laboratory Tests: Monitor patient’s electrolyte, hematologic and coagulation profiles and obtain ECGs. ( 5.5)
ADVERSE REACTIONS
The most common adverse reactions in patients with relapsed or refractory APL were leukocytosis, gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, and dizziness. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals USA, Inc. at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
-
•
-
-
•
-
Lactation: Discontinue breastfeeding. ( 8.2)
-
•
-
Renal Impairment: Monitor patients with severe renal impairment (creatinine clearance less than 30 mL/min) for toxicity when treated with TRISENOX; dose reduction may be warranted. ( 8.6)
-
•
-
Hepatic Impairment: Monitor patients with severe hepatic impairment (Child-Pugh Class C) for toxicity when treated with TRISENOX. ( 8.7)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 9/2016
FULL PRESCRIBING INFORMATION: CONTENTS*
Table of Contents
1 INDICATIONS AND USAGE
TRISENOX is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and ...
TRISENOX is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (APL) who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage Induction Treatment Schedule: Administer TRISENOX intravenously at a dose of 0.15 mg/kg daily until bone marrow remission. Do not exceed 60 ...
2.1 Recommended Dosage
Induction Treatment Schedule: Administer TRISENOX intravenously at a dose of 0.15 mg/kg daily until bone marrow remission. Do not exceed 60 doses for induction.
Consolidation Treatment Schedule: Begin consolidation treatment 3 to 6 weeks after completion of induction therapy. Administer TRISENOX intravenously at a dose of 0.15 mg/kg daily for 25 doses over a period up to 5 weeks.
2.2 Dose Adjustment for Non-Hematologic Adverse Reactions
If a severe non-hematologic adverse reaction occurs (such as neurologic or dermatologic toxicity), consider delaying TRISENOX infusion until the event has resolved (≤ Grade 1).
2.3 Instructions for Preparation and Intravenous Administration
Administration
Administer TRISENOX intravenously over 1-2 hours. The infusion duration may be extended up to 4 hours if acute vasomotor reactions are observed. A central venous catheter is not required.
The TRISENOX ampule is single-use and does not contain any preservatives. Unused portions of each ampule should be discarded properly. Do not mix TRISENOX with other medications.
Reconstitution
Dilute TRISENOX with 100 to 250 mL 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP, using proper aseptic technique, immediately after withdrawal from the ampule. Do not save any unused portions for later administration.
Safe Handling Procedures
TRISENOX is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
2.4 Stability
After dilution, TRISENOX is chemically and physically stable when stored for 24 hours at room temperature and 48 hours when refrigerated.
3 DOSAGE FORMS AND STRENGTHS
TRISENOX is an injectable solution for intravenous administration supplied as 10 mg /10 mL of arsenic trioxide in single-use ampules.
TRISENOX is an injectable solution for intravenous administration supplied as 10 mg /10 mL of arsenic trioxide in single-use ampules.
4 CONTRAINDICATIONS
TRISENOX is contraindicated in patients who are hypersensitive to arsenic.
TRISENOX is contraindicated in patients who are hypersensitive to arsenic.
5 WARNINGS AND PRECAUTIONS
5.1 APL Differentiation Syndrome Nine of 40 patients with APL treated with TRISENOX, at a dose of 0.15 mg/kg, experienced the APL differentiation syndrome ...
5.1 APL Differentiation Syndrome
Nine of 40 patients with APL treated with TRISENOX, at a dose of 0.15 mg/kg, experienced the APL differentiation syndrome. High-dose steroids have been administered at the first suspicion of the APL differentiation syndrome and appear to mitigate signs and symptoms. At the first signs that could suggest the syndrome (unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic abnormalities), high-dose steroids (dexamethasone 10 mg intravenously BID) should be immediately initiated, irrespective of the leukocyte count, and continued for at least 3 days or longer until signs and symptoms have abated. The majority of patients do not require termination of TRISENOX therapy during treatment of the APL differentiation syndrome [see Adverse Reactions (6)].
5.2 Cardiac Conduction Abnormalities: Torsade de Pointes, Complete Heart Block, and QT Prolongation
Torsade de pointes and complete heart block have been reported. QT/QTc prolongation can occur. Sixteen of 40 patients (40%) had at least one ECG tracing with a QTc interval greater than 500 msec. Prolongation of the QTc was observed between 1 and 5 weeks after TRISENOX infusion, and then returned towards baseline by the end of 8 weeks after TRISENOX infusion.
Prior to initiating therapy with TRISENOX, a 12-lead ECG should be performed and serum electrolytes (potassium, calcium, and magnesium) and creatinine should be assessed. Preexisting electrolyte abnormalities should be corrected and, if possible, drugs that are known to prolong the QT interval should be discontinued. If it is not possible to discontinue the interacting drug, perform cardiac monitoring frequently [see Drug Interactions (7)].
Monitor ECG weekly, and more frequently for clinically unstable patients.
For QTc greater than 500 msec, complete corrective m
