Manageable monitoring profile
Proactive monitoring is essential for proper management of TRISENOX
® (arsenic trioxide)
injection therapy.
APL differentiation syndrome: Signs are subtle and easy to overlook
- Weigh patient daily to detect weight changes
- Instruct patient to immediately report fever, sudden weight gain, musculoskeletal pain, fluid retention, and/or dyspnea and other characteristics of the APL differentiation syndrome
- At first signs of syndrome, administer dexamethasone 10 mg IV BID for a minimum of 3 days or longer until signs and symptoms have abated
- In clinical trials, termination of TRISENOX was not required in the majority of patients1; interruption of therapy is necessary if symptoms of APL syndrome do not respond to steroid treatment
- Treat weight gain symptomatic of fluid overload (in absence of differentiation syndrome) with potassium-sparing diuretics
Electrolytes: Monitor throughout treatment
- Prior to initiating therapy, assess serum electrolytes (potassium, magnesium, calcium) and creatinine; pre-existing electrolyte abnormalities should be corrected
- Induction: Monitor at least twice weekly, and more frequently for clinically unstable patients
- Consolidation: Monitor at least weekly
- Supplement electrolytes as needed
- Maintain serum potassium > 4.0 mEq/L
- Maintain serum magnesium > 1.8 mg/dL
If rash occurs:
- Interruption of therapy with TRISENOX may not be necessary
- Topical steroids may be effective; use topical antihistamines for pruritus
Other blood tests
- Hematologic and coagulation profiles should be monitored at least twice weekly and more frequently for clinically unstable patients during induction, and at least weekly during consolidation
- TRISENOX may increase blood sugar levels
- Exercise caution in patients with renal and hepatic impairment
- Transient increases in transaminase levels may occur. These events typically do not require dose reduction or interruption of therapy
Monitor 12-lead ECGs at baseline, then weekly
- Monitor more frequently in patients at risk for a cardiac event, with electrolyte abnormalities, or if QT increases
- Avoid concomitant drugs that prolong QT interval; check online at www.azcert.org
- If absolute QT is > 500 msec, immediately correct risk factors such as electrolytes and concomitant drugs, while the risk/benefit of continuing versus suspending TRISENOX should be considered
- If syncope, or rapid or irregular heartbeat occurs, hospitalize and monitor continuously; assess and correct electrolytes
- Hold TRISENOX until QTc is < 460 msec and symptoms resolve
Hyperleukocytosis
- Usually self-limiting
- Additional chemotherapy may not be required
- Interruption of therapy with TRISENOX may not be necessary
>> Click here to review the safety profile for TRISENOX.
TRISENOX is indicated for induction of remission and consolidation 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.
Serious adverse events, grade 3 or 4, were common. Those events attributable to TRISENOX in the Phase 2
study of 40 patients with refractory or relapsed APL included APL differentiation syndrome (n=3), hyperleukocytosis (n=3), QTc
interval prolongation (n=16), atrial dysrhythmias (n=2), hyperglycemia (n=2), and torsades de pointes (n=1).
In addition to QT interval prolongation, the most common drug-related side effects included leukocytosis, gastrointestinal events (nausea, vomiting, diarrhea, and abdominal pain), fatigue, swelling, hyperglycemia (an abnormal increased content of sugar in the blood), shortness of breath, cough, rash or itching, headache, and dizziness. Have your doctor review side effects with you.
In clinical trials, most patients taking TRISENOX experienced some drug-related toxicity, most commonly leukocytosis, gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headache, and dizziness. These adverse effects have not been observed to be permanent or irreversible, nor do they usually require interruption of therapy.
To report an adverse event contact Cephalon Medical Services at 1-800-896-5855 or usmedinfo@cephalon.com.
WARNING
Experienced Physician and Institution:
TRISENOX® (arsenic trioxide) injection should be administered under the supervision
of a physician who is experienced in the management of patients with acute leukemia.
APL Differentiation Syndrome:
Some patients with APL treated with TRISENOX have experienced symptoms similar to a syndrome called
the retinoic-acid-acute promyelocytic leukemia (RA-APL) or APL differentiation syndrome, characterized
by fever, dyspnea, weight gain, pulmonary infiltrates and pleural or pericardial effusions, with or
without leukocytosis. This syndrome can be fatal. The management of the syndrome has not been fully
studied, but high-dose steroids have been used at the first suspicion of the APL differentiation
syndrome and appear to mitigate signs and symptoms. At the first signs that could suggest the syndrome
(unexplained fever, dyspnea and/or weight gain, abnormal chest auscultatory findings or radiographic
abnormalities), high-dose steroids (dexamethasone 10 mg intravenously BID) should be immediately
initiated, irrespective of the leukocyte count, and continued for at least 3 days or longer until
signs and symptoms have abated. The majority of patients do not require termination of TRISENOX therapy
during treatment of the APL differentiation syndrome.
ECG Abnormalities:
Arsenic trioxide can cause QT interval prolongation and complete atrioventricular block. QT prolongation can
lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal. The risk of torsade de pointes
is related to the extent of QT prolongation, concomitant administration of QT prolonging drugs, a history of
torsade de pointes, pre-existing QT interval prolongation, congestive heart failure, administration of
potassium-wasting diuretics, or other conditions that result in hypokalemia or hypomagnesemia. One patient
(also receiving amphotericin B) had torsade de pointes during induction therapy for relapsed APL with arsenic
trioxide.
ECG and Electrolyte Monitoring Recommendations:
Prior to initiating therapy with TRISENOX, a 12-lead ECG should be performed and serum electrolytes (potassium,
calcium, and magnesium) and creatinine should be assessed; pre-existing electrolyte abnormalities should be
corrected and, if possible, drugs that are known to prolong the QT interval should be discontinued. For QTc
greater than 500 msec, corrective measures should be completed and the QTc reassessed with serial ECGs prior
to considering using TRISENOX. During therapy with TRISENOX, potassium concentrations should be kept above 4 mEq/L
and magnesium concentrations should be kept above 1.8 mg/dL. Patients who reach an absolute QT interval value > 500
msec should be reassessed and immediate action should be taken to correct concomitant risk factors, if any, while
the risk/benefit of continuing versus suspending TRISENOX therapy should be considered. If syncope, rapid or irregular
heartbeat develops, the patient should be hospitalized for monitoring, serum electrolytes should be assessed, TRISENOX
therapy should be temporarily discontinued until the QTc interval regresses to below 460 msec, electrolyte abnormalities
are corrected, and the syncope and irregular heartbeat cease. There are no data on the effect of TRISENOX on the QTc
interval during the infusion.
1. TRISENOX® (arsenic trioxide) Injection [current approved prescribing information]. Frazer, PA: Cephalon, Inc.