Arsenic trioxide

Intravenous
Acute promyelocytic leukaemia

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.

Lactation.

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:
Mechanism of Action: 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 (As^III); approx 10-24 hr (MMA^V, DMA^V).
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 (As^III), which is hepatically metabolised via oxidative methylation by methyltransferases to the less active pentavalent metabolites, monomethylarsonic acid (MMA^V) and dimethylarsinic acid (DMA^V); and via oxidation to the minor metabolite, arsenic acid (As^V).
Excretion: Via urine (primarily as MMA^V, DMA^V; 15% as unchanged As^III). Elimination half-life: 10-14 hr (As^III); approx 32 hr (MMA^V); approx 72 hr (DMA^V).

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)

Store between 15-30°C. Do not freeze.

Cytotoxic Chemotherapy

L01XX27 - arsenic trioxide ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.

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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.