Arsenic trioxide


Concise Prescribing Info
Indications/Uses
Acute promyelocytic leukaemia.
Dosage/Direction for Use
Adult : IV Induction: 150 mcg/kg once daily until remission. Max: 50 doses. Consolidation: 150 mcg/kg once daily for 5 days wkly, followed by 2 days rest, repeated for 5 wk; begin 3-4 wk after induction completion.
Dosage Details
Intravenous
Acute promyelocytic leukaemia
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.
Renal Impairment
Severe (CrCl <30 mL/min): Dosage reduction may be necessary.
Reconstitution
Dilute 10 mg of the drug w/ 100-250 mL dextrose 5% or NaCl 0.9% inj.
Contraindications
Lactation.
Special Precautions
Patient w/ history of torsade de pointes, pre-existing QT interval prolongation, CHF, electrolyte abnormalities (e.g. hypokalaemia, hypomagnesaemia). Hepatic and renal impairment. Pregnancy.
Adverse Reactions
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.
MonitoringParameters
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).
Overdosage
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.
Drug Interactions
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.
Action
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).
Chemical Structure

Chemical Structure Image
Arsenic trioxide

Source: National Center for Biotechnology Information. PubChem Database. CID 261004, CID=261004, https://pubchem.ncbi.nlm.nih.gov/compound/cid-261004 (accessed on Jan. 21, 2020)

Storage
Store between 15-30°C. Do not freeze.
ATC Classification
L01XX27 - arsenic trioxide ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Arsenic Trioxide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/10/2016.

Buckingham R (ed). Arsenic Trioxide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/10/2016.

Joint Formulary Committee. Arsenic Trioxide. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/10/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Arsenic Trioxide. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 04/10/2016.

Trisenox Injection, Solution (Cephalon, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/10/2016.

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