Dosing and uses of Trisenox (arsenic trioxide)
Adult dosage forms and strengths
injectable solution
- 1mg/mL (10mg ampule)
Refractory or Relapsed Acute Promyelocytic Leukemia
0.15 mg/kg IV qDay infused over 1-2 hr until bone marrow remission; not to exceed 60 doses
Wait 3-6 weeks, THEn
0.15 mg/kg IV qDay x25 doses (administered over time period of up to 5 weeks)
Monitor: ECG, serum electrolytes
Orphan Indications
Treatment of myelocytic leukemia subtypes MO, M1, M2, M4, M5, M6, and M7
Treatment of chronic lymphocytic leukemia
Treatment of malignant glioma
Treatment of myelodysplastic syndrome
Treatment of multiple myeloma
Treatment of liver cancer
Treatment of chronic myeloid leukemia
Treatment of amyotrophic lateral sclerosis
Treatment of acute promyelocytic leukemia (oral capsule)
Orphan indications sponsors
- Cephalon Inc; 41 Moores Road, P. O. Box 4011; Frazer, PA 19355
- Terra Biological LLC; 3830 Valley Centre Drive, Suite 705-561; San Diego, California 92130
- Orsenix Holdings BV; 1105 North Market Street, Suite 1800; Wilmington, Delaware 19801
Pediatric dosage forms and strengths
injectable solution
- 1mg/mL (10mg ampule)
Refractory or Relapsed Acute Promyelocytic Leukemia
<4 years: Safety and efficacy not established
≥4 years: 0.15 mg/kg IV qDay infused over 1-2 hr until bone marrow remission; not to exceed 60 doses
Wait 3-6 weeks, THEn
0.15 mg/kg IV qDay for 25 doses (administered over time period of up to 5 weeks)
Monitor: ECG, serum electrolytes
Trisenox (arsenic trioxide) adverse (side) effects
>10%
Nausea (75%)
Cough (65%)
Fatigue (63%)
Pyrexia (63%)
Headache (60%)
Abdominal pain (58%)
Vomiting (58%)
Tachycardia (55%)
Diarrhea (53%)
Dyspnea (53%)
Leukocytosis (50%)
Pain (including bone pain, back pain, myalgia 50%)
Hypokalemia (50%)
Hypomagnesemia (45%)
Hyperglycemia (45%)
Insomnia (43%)
Edema (40%)
Sore throat (40%)
Prolonged QTc interval (38%)
Pruritus (33%)
Dermatitis (33%)
Parathesia (33%)
Arthralgia (33%)
Anxiety (30%)
Constipation (28%)
Chest pain (25%)
Epistaxis (25%)
Hypotension (25%)
Anorexia/decr appetite (23%)
Dizziness (23%)
Hypoxia (23%)
ALT increased (20%)
Depression (20%)
Pleural effusion (20%)
Sinusitis (20%)
Thrombocytopenia (19%)
Hyperkalemia (18%)
Injection site reactions (4-15%)
Anemia (14%)
Febrile neutropenia (13%)
Herpes simplex (13%)
Tremor (13%)
Upper respiratory infection (13%)
Vaginal hemorrhage (13%)
Weight gain (13%)
1-10%
Blurred vision (10%)
Crepitation (10%)
Eye irritation (10%)
Flushing (10%)
Hypertension (10%)
Hypocalcemia (10%)
Neutropenia (10%)
Pallor (10%)
Palpitations (10%)
Rales (10%)
Renal failure/impairment (8%)
Anxiety (30%)
Coma (5%)
Confusion (5%)
Tinnitus (5%)
Convulsion (5%)
Petechiae (8%)
Eyelid edema (5%)
Facial edema (8%)
GI hemorrhage (8%)
Hypoglycemia (8%)
Hyperpigmentation (8%)
Night sweats (8%)
Oral candidiasis (5%)
Urticaria (8%)
Earache (8%)
Warnings
Black box warnings
The drug should be administered under the supervision of an experienced cancer chemotherapy physician
May cause retinoic-acid-acute promyelocytic leukemia (RA-APL) syndrome or APL differentiation syndrome (may be fatal). APL syndrome is characterized by fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions with or without leukocytosis.
At first signs of APL, initiate high-dose steroids (dexamethasone IV 10 mg/kg q12hr for at least 3 days) until symptoms abate.
May prolong the QT interval. Increases the risk of torsade de pointes or complete AV block. Risk factors related to extent of QT prolongation, concurrent drug therapy (drugs that may prolong QT), history of torsade de pointes, concurrent potassium-wasting diuretics, hypokalemia, or hypomagnesemia.
Preexisting electrolyte abnormalities should be corrected prior to therapy. Perform baseline 12-lead ECG and obtain serum electrolytes (potassium, calcium, magnesium) and creatinine levels prior to treatment. Obtain ECG weekly and more frequently for unstable patients during induction and consolidation phases. Monitor electrolyte profiles at least twice weekly and more frequently for unstable patients during the induction phase and at least weekly during the consolidation phase.
Discontinue drugs known to prolong QT interval. If baseline QTc >500 msec, correct and reassess QTc prior to therapy initiation. Maintain potassium concentrations >4 mEq/L during therapy. Maintain magnesium concentrations >1.8 mg/dL. Absolute QT interval >500 msec necessitates reassessment.
Contraindications
Hypersensitivity
Cautions
Use caution in hepatic or renal impairment
Prolongs QTc intervaL
Risk of APL differentiation synd & hyperleukocytosis
Can cause fetal harm; advise of potential risk to a fetus and use of effective contraception
During therapy, maintain potassium, concentrations above 4 mEq/L and magnesium concentrations above 1.8 mg/dL to avoid cardiac conduction abnormalities
Arsenic trioxide is a human carcinogen; monitor patients for development of second primary malignancies
Monitor patient’s electrolyte, hematologic and coagulation profiles and obtain ECGs
Pregnancy and lactation
Pregnancy category: d
Lactation: Arsenic is excreted in milk. Because of the potential for serious adverse reactions in nursing infants from this drug, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Trisenox (arsenic trioxide)
Mechanism of action
Causes apoptosis of promyelocytic leukemia cells; damages fusion protein PML-RAR alpha
Pharmacokinetics
Half-life: 72 hr
Metabolism: Liver
Peak plasma time: 10-24 hr
Vd: 562 L
Excretion: Urine (15%)
Administration
IV Incompatibilities
Do not mix with other medications
IV Preparation
Dilute in 100-250 mL D5W or Ns
Does not contain a preservative; properly discard unused portion
IV Administration
Infuse over 1-2 hr
If acute vasomotor reactions occur, may infuse over a maximum of 4 hr
Does not require administration via a central venous catheter
Storage
Store at room temp; do not freeze
