Arsenic Trioxide
ARSENIC TRIOXIDE — arsenic trioxide
injection, solution
Fresenius Kabi USA, LLC
WARNING: DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES AND ENCEPHALOPATHY INCLUDING WERNICKE’S
Differentiation Syndrome: Patients with acute promyelocytic leukemia (APL) treated with Arsenic Trioxide Injection have experienced differentiation syndrome, which may be life-threatening or fatal. Signs and symptoms may include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy, and multi-organ dysfunction, in the presence or absence of leukocytosis. If differentiation syndrome is suspected, immediately initiate high-dose corticosteroids and hemodynamic monitoring until resolution. Temporarily withhold Arsenic Trioxide Injection [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].
Cardiac Conduction Abnormalities: Arsenic Trioxide Injection can cause QTc interval prolongation, complete atrioventricular block and torsade de pointes, which can be fatal. Before administering Arsenic Trioxide Injection, assess the QTc interval, correct electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer Arsenic Trioxide Injection to patients with a ventricular arrhythmia or prolonged QTc interval. Withhold Arsenic Trioxide Injection until resolution and resume at reduced dose for QTc prolongation [see Dosage and Administration (2.3), Warnings and Precautions (5.2)].
Encephalopathy: Serious encephalopathy, including Wernicke’s, has occurred with Arsenic Trioxide Injection. Wernicke’s is a neurologic emergency. Consider testing thiamine levels in patients at risk for thiamine deficiency. Administer parenteral thiamine in patients with or at risk for thiamine deficiency. Monitor patients for neurological symptoms and nutritional status while receiving Arsenic Trioxide Injection. If Wernicke’s encephalopathy is suspected, immediately interrupt Arsenic Trioxide Injection and initiate parenteral thiamine. Monitor until symptoms resolve or improve and thiamine levels normalize [see Warnings and Precautions (5.3)].
1. INDICATIONS AND USAGE
1.2 Relapsed or Refractory APL
Arsenic Trioxide Injection is indicated for induction of remission and consolidation in patients with 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
2.2 Recommended Dosage for Relapsed or Refractory APL
A treatment course for patients with relapsed or refractory APL consists of 1 induction cycle and 1 consolidation cycle [see Clinical Studies (14.2)].
- For the induction cycle, the recommended dosage of Arsenic Trioxide Injection is 0.15 mg/kg/day intravenously daily until bone marrow remission or up to a maximum of 60 days.
- For the consolidation cycle, the recommended dosage of Arsenic Trioxide Injection is 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks. Begin consolidation 3 to 6 weeks after completion of induction cycle.
2.3 Monitoring and Dosage Modifications for Adverse Reactions
During induction, monitor coagulation studies, blood counts, and chemistries at least 2-3 times per week through recovery. During consolidation, monitor coagulation studies, blood counts, and chemistries at least weekly.
Table 2 shows the dosage modifications for adverse reactions due to Arsenic Trioxide Injection when used alone.
Adverse Reaction | Dosage Modification |
Differentiation syndrome, defined by the presence of 2 or more of the following:
|
|
QTc (Framingham formula)Prolongation greater than 450 msec for men or greater than 460 msec for women[see Warnings and Precautions (5.2)] |
|
Hepatotoxicity, defined by 1 or more of the following:
|
|
Other severe or life-threatening (grade 3-4) nonhematologic reactions[see Adverse Reactions (6)] |
|
Moderate (grade 2) nonhematologic reactions[see Adverse Reactions (6)] |
|
Leukocytosis (WBC count greater than 10 Gi/L)[see Adverse Reactions (6.1)] |
|
Myelosuppression, defined by 1 or more of the following:
|
|
Dose Level | Arsenic Trioxide Injection mg/kg intravenously once daily |
Starting level | 0.15 |
-1 | 0.11 |
-2 | 0.10 |
-3 | 0.075 |
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.