Arsenic trioxide

What is Arsenic trioxide?

• Arsenic trioxide (Trisenox) an arsenical used to treat acute promyelocytic leukemia (APL) that has a certain chromosome abnormality or a fusion gene called PML/RAR-alpha. It is used with tretinoin in some newly diagnosed patients.

Arsenic-trioxide-3D-balls

What are the uses of this medicine?

Arsenic trioxide (Trisenox) is used:

• in combination with tretinoin for treatment of adults with newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
• 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.

How does this medicine work?

Arsenic trioxide - mechanism of action

• Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro.
• Arsenic trioxide also causes damage or degradation of the fusion protein promyelocytic leukemia (PML)-retinoic acid receptor (RAR)-alpha.

Who Should Not Use this medicine ?

This medicine cannot be used in patients:

• with hypersensitivity to arsenic.

What drug interactions can this medicine cause?

• Concomitant use of drugs that can prolong the QT/QTc interval and Trisenox may increase the risk of serious QT/QTc interval prolongation.
• Avoid concomitant use of drugs that can lead to electrolyte abnormalities.
• Concomitant use of drugs that can lead to hepatotoxicity and Trisenox, particularly when given in combination with tretinoin, may increase the risk of serious hepatotoxicity.

Is this medicine FDA approved?

• Arsenic trioxide was approved for medical use in the United States in 2000.

How should this medicine be used?

Recommended Dosage for Newly-Diagnosed Low-Risk Acute Promyelocytic Leukemia (APL):

• A treatment course for patients with newly-diagnosed low-risk APL consists of 1 induction cycle and 4 consolidation cycles.

Induction:

• Administer 0.15 mg/kg/day intravenously daily in combination with tretinoin until bone marrow remission.
• Do not exceed 60 days.

Consolidation:

• Administer 0.15 mg/kg/day intravenously daily for 5 days per week during weeks 1-4 of each 8-week cycle for a total of 4 cycles in combination with tretinoin.

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.

• Induction: Administer 0.15 mg/kg/day intravenously daily until bone marrow remission. Do not exceed 60 days.
• Consolidation: Administer 0.15 mg/kg/day intravenously daily for 25 doses over a period of up to 5 weeks.

Administration:

• Administer Trisenox as an intravenous infusion over 2 hours.
• The infusion duration may be extended up to 4 hours if acute vasomotor reactions are observed.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 12 mg/6 mL (2 mg/mL) arsenic trioxide in single-dose vial.

This medicine is available in fallowing brand namesː

• Trisenox

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea
• cough
• fatigue
• pyrexia
• headache
• abdominal pain
• vomiting
• tachycardia
• diarrhea
• dyspnea
• hypokalemia
• leukocytosis
• hyperglycemia
• hypomagnesemia
• insomnia
• dermatitis
• edema
• QTc prolongation
• rigors
• sore throat
• arthralgia
• paresthesia
• pruritus

What special precautions should I follow?

• Elevated aspartate aminotransferase (AST), alkaline phosphatase and serum bilirubin have occurred in patients with newly-diagnosed low-risk APL treated with Trisenox in combination with tretinoin. Monitor hepatic function tests at least twice weekly during induction and at least once weekly during consolidation. Withhold Trisenox for certain elevations in AST, alkaline phosphatase and bilirubin and resume at reduced dose upon resolution.
• Arsenic trioxide is a human carcinogen. Monitor patients for the development of second primary malignancies.
• Trisenox can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trisenox and for 6 months after the last dose.
• Serious encephalopathies were reported in patients receiving Trisenox. Monitor patients for neurological symptoms, such as confusion, decreased level of consciousness, seizures, cognitive deficits, ataxia, visual symptoms and ocular motor dysfunction. Advise patients and caregivers of the need for close observation.
• Differentiation syndrome, which may be life-threatening or fatal, has been observed in patients with acute promyelocytic leukemia (APL) treated with Trisenox. If differentiation syndrome is suspected, temporarily withhold Trisenox and immediately initiate dexamethasone 10 mg intravenously every 12 hours and hemodynamic monitoring until resolution of signs and symptoms for a minimum of 3 days.

What to do in case of emergency/overdose?

Symptoms of overdosage may:

• convulsions, muscle weakness, and confusion

Treatment of overdosage:

• For symptoms of Trisenox (arsenic trioxide) overdosage, immediately discontinue Trisenox and consider chelation therapy.
• Dimercaprol administered at a dose of 3 mg/kg intramuscularly every 4 hours until immediate life-threatening toxicity has subsided.
• Thereafter, penicillamine at a dose of 250 mg orally, up to a maximum frequency of four times per day (≤ 1 g per day), may be given.

Can this medicine be used in pregnancy?

• Based on the mechanism of action and findings in animal studies, Trisenox can cause fetal harm when administered to a pregnant woman.
• Advise pregnant women of the potential risk to a fetus.

Can this medicine be used in children?

• The safety and efficacy of Trisenox in combination with tretinoin in pediatric patients has not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• ARSENIC TRIOXIDE

Inactive ingredients:

• WATER
• SODIUM HYDROXIDE
• HYDROCHLORIC ACID

Who manufactures and distributes this medicine?

Distributed by:

• Teva Pharmaceuticals USA, Inc.
• Parsippany, NJ

What should I know about storage and disposal of this medication?

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
• Do not freeze.
• Trisenox is a hazardous drug.
• Follow applicable special handling and disposal procedures.

• Dailymed label info on Arsenic trioxide
• FDA Arsenic trioxide