cops [30:80 mL/min). Systemic exposure to metabolites MMA V and DMA V may also be increased in patients with renal impairment. Special Populations: Hepatic Function Impairment A small pharmacokinetic study in patients with hepatocellular carcinoma showed that the mean dose-normalized AUC and C max values were 40% and 70% higher, respectively, in a patient with severe hepatic impairment (Child-Pugh class C) versus patients with normal hepatic function. Additionally, the mean dose-normalized trough plasma levels for metabolites MMA V and DMA V were 2.2-fold and 4.7-fold higher, respectively, than levels in patients with normal hepatic function. Use: Labeled Indications Acute promyelocytic leukemia: Remission induction 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 Off Label Uses Acute promyelocytic leukemia (newly diagnosed) Data from a phase II and a phase III trial supports the use of arsenic trioxide (either single-agent or in combination with tretinoin and age-adjusted idarubicin) in the treatment of acute promyelocytic leukemia (APL) in children [Iland 2012] , [Mathews 2006] . Additionally, data from a phase III trial supports the use of arsenic in combination with tretinoin in the management of low-to-intermediate risk APL in adults [Lo-Coco 2013] . Data from multiple other trials supports the use of arsenic trioxide for induction and/or consolidation treatment of APL in adults [Estey 2006] , [Iland 2012] , [Powell 2010] , [Ravandi 2009] . Contraindications Hypersensitivity to arsenic or any component of the formulation Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breast-feeding Dosing: Adult Note: Arsenic trioxide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting. Acute promyelocytic leukemia (APL), relapsed or refractory: IV: Induction: 0.15 mg/kg once daily until bone marrow remission; maximum: 60 doses for induction Consolidation: 0.15 mg/kg once daily starting 3 to 6 weeks after completion of induction therapy; maximum: 25 doses over a period of up to 5 weeks for consolidation APL, newly diagnosed (off-label use): IV: Low/intermediate risk (Lo-Coco 2013): Induction: 0.15 mg/kg/day; administer daily until bone marrow remission (in combination with tretinoin) Consolidation: 0.15 mg/kg/day; administer 5 days/week for 4 weeks every 8 weeks for a total of 4 cycles (in combination with tretinoin) High-risk: Consolidation therapy after remission induction with tretinoin, daunorubicin and cytarabine (Powell 2010): Two consolidation courses (2 weeks apart): 0.15 mg/kg/day 5 days/week for 5 weeks In combination with tretinoin in patients unable to tolerate anthracycline-based therapy (Estey 2006; Ravandi 2009): Induction (beginning 10 days after initiation of tretinoin): 0.15 mg/kg/day until bone marrow remission; maximum: 75 doses for induction Consolidation: 0.15 mg/kg/day Monday through Friday for 4 weeks every 8 weeks for 4 cycles (weeks 1 to 4, 9 to 12, 17 to 20, and 25 to 28) APML 4 protocol (Iland 2012): Induction: 0.15 mg/kg/day over 2 hours on days 9 to 36 (in combination with tretinoin and age-adjusted idarubicin) Consolidation (2 cycles): 0.15 mg/kg/day on days 1 to 28 of consolidation cycle 1 (in combination with tretinoin); 0.15 mg/kg/day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33 of consolidation cycle 2 (in combination with tretinoin) Dosing: Pediatric Note: Arsenic trioxide is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011). Acute promyelocytic leukemia (APL), relapsed or refractory: Children 4 years (US labeling) or 5 years (Canadian labeling): IV: Refer to adult dosing. Note: The Canadian labeling recommends dosing obese pediatric patients based on ideal body weight. APL, newly diagnosed (off-label use): IV: Induction, consolidation, and maintenance (Mathews 2006): Induction: 0.15 mg/kg/day (maximum dose: 10 mg); administer daily until bone marrow remission; maximum: 60 doses for induction Consolidation: 0.15 mg/kg/day (maximum dose: 10 mg) for 4 weeks, starting 4 weeks after completion of induction therapy Maintenance: 0.15 mg/kg/dose (maximum dose: 10 mg) administered 10 days per month for 6 months, starting 4 weeks after completion of consolidation therapy Children >1 year and Adolescents (APML 4 protocol; Iland 2012): Induction: 0.15 mg/kg/day over 2 hours on days 9 to 36 (in combination with tretinoin and idarubicin) Consolidation (2 cycles): 0.15 mg/kg/day on days 1 to 28 of consolidation cycle 1 (in combination with tretinoin); 0.15 mg/kg/day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33 of consolidation cycle 2 (in combination with tretinoin) Dosing: Renal Impairment Mild-to-moderate impairment (CrCl 30 mL/minute): There are no dosage adjustments provided in the manufacturer s labeling. Severe renal impairment (CrCl] Drug Status Rx Availability Prescription only D Pregnancy Category Positive evidence of risk N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Arsenic trioxide Rating 1 User Review 9.0 /10 1 User Review 9.0 Rate it! Drug Class Miscellaneous antineoplastics Related Drugs miscellaneous antineoplastics tretinoin , Revlimid , Zytiga , Accutane , isotretinoin , irinotecan Acute Promyelocytic Leukemia tretinoin , Trisenox , Vesanoid , More... many differing kinds
time for supper Arsenic Trioxide of ethical
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