Adult: Induction: 150 mcg/kg once daily via infusion over 1-2 hr (up to 4 hr if acute vasomotor reactions occur) until remission. Max: 50 doses. Consolidation: 150 mcg/kg once daily for 25 doses given for 5 days wkly, followed by 2 days rest, repeated for 5 wk. Consolidation treatment must begin 3-4 wk after induction completion.
Severe (CrCl <30 mL/min): Dosage reduction may be necessary.
Dilute 10 mg of the drug w/ 100-250 mL dextrose 5% or NaCl 0.9% inj.
Patient w/ history of torsade de pointes, pre-existing QT interval prolongation, CHF, electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia). Hepatic and renal impairment. Pregnancy.
Leucocytosis, neutropenia, increased liver enzyme values, nausea, vomiting, diarrhoea, abdominal pain, fatigue, oedema, hyperglycaemia, hypokalaemia, dyspnoea, cough, rash, pruritus, pyrexia, headache, paraesthesia/dysesthesia, dizziness; haemorrhage, infection; atrial fibrillation/flutter. Potentially Fatal: APL differentiation syndrome (i.e. fever, dyspnoea, wt gain, pulmonary infiltrates, pleural/pericardial effusions, w/ or w/o leucocytosis); QT prolongation leading to torsade de pointes, complete AV block.
Monitor ECG, blood sugar, electrolytes (esp K and Mg), CBC w/ differential, serum creatinine, hepatic function, and coagulation parameters at baseline, then at least twice wkly during induction, and at least wkly during consolidation (more frequent for clinically unstable patients).
Symptoms: Convulsions, muscle weakness, confusion. Management: Treat acute toxicity w/ chelation therapy of IM dimercaprol 3 mg/kg 4 hrly until toxicity subsides, then oral penicillamine 250-1000 mg daily may be given. In the presence of coagulopathy, administer oral dimercaptosuccinic acid succimer (DCI) 10 mg/kg or 350 mg/m2 8 hrly for 5 days and then 12 hrly for 2 wk. Dialysis may be beneficial for severe acute toxicity.
Increased risk of hypokalaemia or hypomagnesaemia w/ diuretics and amphotericin B. Increased risk of QT prolongation w/ Class Ia/III antiarrhythmics (e.g. quinidine, amiodarone, sotalol, dofetilide), antipsychotics (e.g. thioridazine, ziprasidone, pimozide), antidepressants (e.g. amitriptyline), macrolides (e.g. erythromycin), antihistamines (e.g. terfenadine, astemizole), quinolones (e.g. sparfloxacin), and cisapride.
Description: Arsenic trioxide, an antineoplastic agent, induces apoptosis by causing morphological changes and DNA fragmentation in acute promyelocytic leukemia (APL) cells. It also damages and degrades promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-α fusion gene, a characteristic of APL. Pharmacokinetics: Absorption: Time to peak plasma concentration: 2 hr (AsIII); approx 10-24 hr (MMAV, DMAV). Distribution: Stored mainly in the liver, kidneys, heart, lungs, hair, and nails. Readily crosses the placenta and enters breast milk. Volume of distribution: >400 L (increases w/ increasing body wt). Metabolism: Immediately hydrolysed into its active form, arsenious acid (AsIII), which is hepatically metabolised via oxidative methylation by methyltransferases to the less active pentavalent metabolites, monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV); and via oxidation to the minor metabolite, arsenic acid (AsV). Excretion: Via urine (primarily as MMAV, DMAV; 15% as unchanged AsIII). Elimination half-life: 10-14 hr (AsIII); approx 32 hr (MMAV); approx 72 hr (DMAV).
L01XX27 - arsenic trioxide ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
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