Trisenox 12mg/6ml Inj, 6ml
WARNING: A health problem called differentiation syndrome has happened. This may cause organ problems and can be deadly. Call your doctor right away if you have bone pain, cough, fever, shortness of breath or other breathing problems, sudden weight gain, swelling in the arms or legs, or swollen gland. Call your doctor right away if you have signs of liver problems like dark urine or yellow skin or eyes; signs of kidney problems like unable to pass urine, change in amount of urine passed, or blood in the urine; or signs of low blood pressure like dizziness or passing out.This drug may cause a very bad and sometimes deadly type of heartbeat that is not normal (long QT on ECG, torsades de pointes). The chance may be raised if you take amphotericin B or some types of water pills (diuretics), if you have low potassium or magnesium levels, or if you have heart failure. If you have ever had a long QT on ECG or other abnormal heartbeat, talk with your doctor. This drug may not be right for you. If you have questions, talk with your doctor.Talk with your doctor if you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.You will need an ECG before starting this drug and during treatment. Talk with your doctor.You will need your blood work checked before starting this drug and during treatment. Talk with your doctor.Severe brain or nervous system problems, like Wernicke's encephalopathy, have happened with this drug. Talk with your doctor if you take furosemide, drink alcohol on a regular basis, have low thiamine levels, have poor nutrition, or if your body does not take in nutrients well. Call your doctor right away if you feel confused or very sleepy. Call your doctor right away if you have a change in balance, change in eyesight, trouble thinking or walking, or seizures. @ COMMON USES: It is used to treat a type of leukemia.
Drug Class
Antineoplastic agent
Pharmacologic Class
Apoptosis inducer; Differentiation agent; PML-RARΞ± degradation agent
Pregnancy Category
Category D
FDA Approved
Nov 2000
DEA Schedule
Not Controlled
Overview
What is this medicine?
Trisenox is a medicine used to treat a specific type of blood cancer called Acute Promyelocytic Leukemia (APL). It works by helping the cancer cells mature and die, or by stopping them from growing. It is given as an injection into a vein.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. It is essential to follow the instructions carefully. This medication is administered as an infusion into a vein over a specified period.
Storing and Disposing of Your Medication
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
Missing a Dose
If you miss a dose, contact your doctor to receive guidance on the next steps to take.
To use this medication correctly, follow your doctor's instructions and read all the information provided. It is essential to follow the instructions carefully. This medication is administered as an infusion into a vein over a specified period.
Storing and Disposing of Your Medication
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
Missing a Dose
If you miss a dose, contact your doctor to receive guidance on the next steps to take.
Lifestyle & Tips
- Maintain good hydration as instructed by your doctor.
- Report any new or worsening symptoms immediately.
- Avoid taking any new medications, including over-the-counter drugs, herbal remedies, or supplements, without consulting your doctor or pharmacist.
- Follow all dietary recommendations, especially regarding electrolyte intake (e.g., potassium, magnesium).
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Newly Diagnosed APL: 0.15 mg/kg/day IV until complete remission (CR) or up to 60 days. Consolidation: 0.15 mg/kg/day IV for 25 doses over 5 weeks, repeated for 4 cycles. Relapsed/Refractory APL: Induction: 0.15 mg/kg/day IV until CR or up to 50 doses. Consolidation: 0.15 mg/kg/day IV for 25 doses over 5 weeks, repeated for 4 cycles.
Dose Range:
0.15 - 0.15 mg
Condition-Specific Dosing:
Newly Diagnosed APL:
0.15 mg/kg/day IV until CR or up to 60 days (induction), then 0.15 mg/kg/day IV for 25 doses over 5 weeks (consolidation, 4 cycles).
Relapsed/Refractory APL:
0.15 mg/kg/day IV until CR or up to 50 doses (induction), then 0.15 mg/kg/day IV for 25 doses over 5 weeks (consolidation, 4 cycles).
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
0.15 mg/kg/day IV, similar to adult dosing, based on clinical trials in pediatric APL.
Adolescent:
0.15 mg/kg/day IV, similar to adult dosing, based on clinical trials in pediatric APL.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but use with caution and monitor closely.
Moderate:
No specific dose adjustment recommended, but use with caution and monitor closely.
Severe:
No specific dose adjustment recommended, but use with caution and monitor closely due to limited data.
Dialysis:
Not available; caution advised due to limited data.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended, but use with caution and monitor closely.
Moderate:
No specific dose adjustment recommended, but use with caution and monitor closely.
Severe:
No specific dose adjustment recommended, but use with caution and monitor closely due to limited data.
Pharmacology
Mechanism of Action
Arsenic trioxide induces apoptosis and inhibits proliferation of acute promyelocytic leukemia (APL) cells. It causes degradation of the PML-RARΞ± fusion protein, which is characteristic of APL, and induces differentiation of APL cells.
Pharmacokinetics
Absorption:
Bioavailability:
100% (IV administration)
Tmax:
Not applicable (IV)
FoodEffect:
Not applicable (IV)
Distribution:
Vd:
Not well characterized, distributes to tissues.
ProteinBinding:
Not well characterized.
CnssPenetration:
Limited, but some penetration has been observed.
Elimination:
HalfLife:
Plasma half-life of arsenic trioxide is short (10-15 hours); however, the elimination half-life of total arsenic from the body (primarily as methylated metabolites) is much longer, ranging from days to weeks.
Clearance:
Not well characterized.
ExcretionRoute:
Primarily renal excretion of methylated metabolites.
Unchanged:
Minimal unchanged drug excreted renally.
Pharmacodynamics
OnsetOfAction:
Clinical response (remission) typically observed within weeks of initiation.
PeakEffect:
Not directly applicable to a cytotoxic agent; peak effect is clinical remission.
DurationOfAction:
Duration of remission varies; treatment cycles are defined.
Safety & Warnings
BLACK BOX WARNING
Patients with APL treated with arsenic trioxide have experienced APL differentiation syndrome, QT prolongation, and sudden death. Patients should be closely monitored for these adverse reactions. Arsenic trioxide should be administered under the supervision of a physician experienced in the management of patients with acute leukemias.
Side Effects
Serious Side Effects: Seek Medical Help Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that enlarge
+ Uncontrollable bleeding
Signs of infection, such as:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or changed sputum production
+ Painful urination
+ Mouth sores
+ Wounds that do not heal
Signs of electrolyte problems, including:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Balance changes
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe nausea or vomiting
Signs of high or low blood pressure, such as:
+ Severe headache or dizziness
+ Fainting or near-fainting
+ Changes in vision
Chest pain or pressure
Rapid or abnormal heartbeat
Swollen glands
Depression
Abnormal sensations, such as burning, numbness, or tingling
Shakiness
Rapid breathing
Agitation
Ringing in the ears, hearing loss, or other changes in hearing
Swelling
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention if they bother you or persist:
Headache
Dizziness
Drowsiness
Fatigue
Weakness
Stomach pain
Constipation
Weight changes
Dry mouth, skin, or eyes
Sleep disturbances
Back, bone, joint, muscle, or neck pain
Excessive sweating
Pain, redness, or swelling at the injection site
Eye irritation
Anxiety
Arm or leg pain
Flushing
Pale skin
Skin irritation
* Ear pain
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that enlarge
+ Uncontrollable bleeding
Signs of infection, such as:
+ Fever
+ Chills
+ Severe sore throat
+ Ear or sinus pain
+ Cough
+ Increased or changed sputum production
+ Painful urination
+ Mouth sores
+ Wounds that do not heal
Signs of electrolyte problems, including:
+ Mood changes
+ Confusion
+ Muscle pain, cramps, or spasms
+ Weakness
+ Shakiness
+ Balance changes
+ Abnormal heartbeat
+ Seizures
+ Loss of appetite
+ Severe nausea or vomiting
Signs of high or low blood pressure, such as:
+ Severe headache or dizziness
+ Fainting or near-fainting
+ Changes in vision
Chest pain or pressure
Rapid or abnormal heartbeat
Swollen glands
Depression
Abnormal sensations, such as burning, numbness, or tingling
Shakiness
Rapid breathing
Agitation
Ringing in the ears, hearing loss, or other changes in hearing
Swelling
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention if they bother you or persist:
Headache
Dizziness
Drowsiness
Fatigue
Weakness
Stomach pain
Constipation
Weight changes
Dry mouth, skin, or eyes
Sleep disturbances
Back, bone, joint, muscle, or neck pain
Excessive sweating
Pain, redness, or swelling at the injection site
Eye irritation
Anxiety
Arm or leg pain
Flushing
Pale skin
Skin irritation
* Ear pain
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever, cough, difficulty breathing, rapid weight gain, swelling (signs of differentiation syndrome)
- Palpitations, dizziness, fainting (signs of heart rhythm problems)
- Numbness, tingling, burning pain, or weakness in hands or feet (signs of nerve damage)
- Yellowing of skin or eyes, dark urine, severe fatigue, abdominal pain (signs of liver problems)
- Unusual bleeding or bruising, signs of infection (fever, chills, sore throat)
- Severe nausea, vomiting, or diarrhea
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the symptoms you experienced.
If you are taking any medications that can disrupt electrolyte balances, as numerous drugs can cause this issue. If you are unsure, consult your doctor or pharmacist for guidance.
* If you are breastfeeding, as you should not breastfeed while taking this medication and for 2 weeks after your last dose.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. They will help determine if it is safe to take this medication in conjunction with your other treatments and health issues. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the symptoms you experienced.
If you are taking any medications that can disrupt electrolyte balances, as numerous drugs can cause this issue. If you are unsure, consult your doctor or pharmacist for guidance.
* If you are breastfeeding, as you should not breastfeed while taking this medication and for 2 weeks after your last dose.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health conditions with your doctor and pharmacist. They will help determine if it is safe to take this medication in conjunction with your other treatments and health issues. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
While taking this drug, you may be more susceptible to infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or the flu.
Be cautious, as this medication can increase your risk of bleeding easily. To reduce this risk, avoid injuries and use a soft toothbrush and an electric razor for shaving.
There is a potential increased risk of developing certain types of cancer associated with this medication. Discuss this risk with your doctor to understand it better.
Common side effects of this drug include diarrhea, vomiting, stomach upset, and decreased appetite. If you experience these side effects, consult your doctor for guidance on managing them. Immediately contact your doctor if these side effects are severe, persistent, or bothersome.
This medication may also cause elevated cholesterol and triglyceride levels. Discuss your lipid profile with your doctor and monitor it as advised.
If you have diabetes (high blood sugar), inform your doctor, as this medication may increase your blood sugar levels. Monitor your blood sugar levels as directed by your doctor and report any signs of high blood sugar, such as confusion, drowsiness, unusual thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
If you are 65 years or older, use this medication with caution, as you may be more prone to side effects.
This drug may affect sperm quality, potentially impacting fertility. Discuss this risk with your doctor if you are planning to father a child.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you or your partner may become pregnant, it is crucial to use effective birth control during treatment and for a specified period after the last dose. Consult your doctor to determine how long to continue using birth control. If pregnancy occurs, notify your doctor immediately.
While taking this drug, you may be more susceptible to infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or the flu.
Be cautious, as this medication can increase your risk of bleeding easily. To reduce this risk, avoid injuries and use a soft toothbrush and an electric razor for shaving.
There is a potential increased risk of developing certain types of cancer associated with this medication. Discuss this risk with your doctor to understand it better.
Common side effects of this drug include diarrhea, vomiting, stomach upset, and decreased appetite. If you experience these side effects, consult your doctor for guidance on managing them. Immediately contact your doctor if these side effects are severe, persistent, or bothersome.
This medication may also cause elevated cholesterol and triglyceride levels. Discuss your lipid profile with your doctor and monitor it as advised.
If you have diabetes (high blood sugar), inform your doctor, as this medication may increase your blood sugar levels. Monitor your blood sugar levels as directed by your doctor and report any signs of high blood sugar, such as confusion, drowsiness, unusual thirst or hunger, frequent urination, flushing, rapid breathing, or fruity-smelling breath.
If you are 65 years or older, use this medication with caution, as you may be more prone to side effects.
This drug may affect sperm quality, potentially impacting fertility. Discuss this risk with your doctor if you are planning to father a child.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you or your partner may become pregnant, it is crucial to use effective birth control during treatment and for a specified period after the last dose. Consult your doctor to determine how long to continue using birth control. If pregnancy occurs, notify your doctor immediately.
Overdose Information
Overdose Symptoms:
- Convulsions
- Muscle weakness
- Confusion
- Coma
- Severe gastrointestinal symptoms (nausea, vomiting, diarrhea)
- Cardiac arrhythmias
- Renal failure
- Liver failure
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. Contact Poison Control at 1-800-222-1222. Treatment is supportive and may include chelation therapy (e.g., dimercaprol).
Drug Interactions
Major Interactions
- Drugs that prolong the QT interval (e.g., Class IA and III antiarrhythmics, thioridazine, moxifloxacin, some macrolides, tricyclic antidepressants) - increased risk of Torsades de Pointes.
- Drugs that cause hypokalemia or hypomagnesemia (e.g., diuretics, amphotericin B) - increased risk of QT prolongation.
Moderate Interactions
- Hepatotoxic agents - potential for additive hepatotoxicity.
- Myelosuppressive agents - potential for additive myelosuppression.
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess baseline QT interval and identify pre-existing cardiac abnormalities, as arsenic trioxide can prolong the QT interval and lead to fatal arrhythmias.
Timing: Prior to initiation of therapy.
Serum Electrolytes (Potassium, Magnesium, Calcium)
Rationale: To correct any electrolyte abnormalities (especially hypokalemia and hypomagnesemia) prior to and during treatment, as these increase the risk of QT prolongation.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function and monitor for hepatotoxicity.
Timing: Prior to initiation of therapy.
Renal Function Tests (Creatinine, BUN)
Rationale: To assess baseline renal function.
Timing: Prior to initiation of therapy.
Complete Blood Count (CBC) with differential
Rationale: To assess baseline hematologic status and monitor for myelosuppression.
Timing: Prior to initiation of therapy.
APL-specific markers (e.g., PML-RARΞ± by PCR)
Rationale: To confirm diagnosis and monitor response to therapy.
Timing: Prior to initiation of therapy.
Routine Monitoring
Electrocardiogram (ECG)
Frequency: Weekly during induction and consolidation, more frequently if QT prolongation occurs.
Target: QTc < 500 ms (absolute); < 25% increase from baseline (relative).
Action Threshold: Hold dose if QTc > 500 ms or significant increase from baseline; resume when QTc < 480 ms and electrolytes corrected.
Serum Electrolytes (Potassium, Magnesium, Calcium)
Frequency: Twice weekly during induction, then weekly during consolidation. More frequently if abnormalities detected.
Target: Potassium > 4.0 mEq/L, Magnesium > 1.8 mg/dL, Calcium within normal limits.
Action Threshold: Correct abnormalities immediately; hold dose if not corrected.
Liver Function Tests (LFTs)
Frequency: Weekly during induction and consolidation.
Target: Within normal limits or acceptable elevation per protocol.
Action Threshold: Hold dose for significant elevations (e.g., > 5x ULN); resume when improved.
Complete Blood Count (CBC) with differential
Frequency: Twice weekly during induction, then weekly during consolidation.
Target: Maintain adequate counts.
Action Threshold: Manage myelosuppression per institutional guidelines; dose interruption may be required.
Symptom Monitoring
- APL differentiation syndrome (fever, dyspnea, weight gain, pulmonary infiltrates, pleural/pericardial effusions, hypotension, renal failure)
- Cardiac arrhythmias (palpitations, dizziness, syncope)
- Peripheral neuropathy (numbness, tingling, weakness)
- Hepatotoxicity (jaundice, dark urine, fatigue, abdominal pain)
- Myelosuppression (fever, signs of infection, unusual bleeding/bruising, severe fatigue)
- Hyperglycemia
- Rash, pruritus, edema
Special Patient Groups
Pregnancy
Contraindicated in pregnancy due to significant risk of fetal harm. Arsenic trioxide can cause embryo-fetal toxicity, including teratogenicity and embryolethality, based on animal studies.
Trimester-Specific Risks:
First Trimester:
High risk of major congenital malformations and embryolethality.
Second Trimester:
Risk of fetal toxicity and adverse developmental effects.
Third Trimester:
Risk of fetal toxicity and adverse developmental effects.
Lactation
Breastfeeding is contraindicated during treatment with arsenic trioxide and for a period after the last dose (e.g., 2 weeks) due to the potential for serious adverse reactions in the breastfed infant.
Infant Risk:
High risk of serious adverse effects due to potential excretion of arsenic into breast milk and its known toxicity.
Pediatric Use
Arsenic trioxide is used in pediatric patients with APL, with dosing typically weight-based and similar to adults. Close monitoring for adverse effects, particularly cardiac and neurological, is crucial.
Geriatric Use
No specific dose adjustment is generally required based on age alone. However, geriatric patients may have increased susceptibility to adverse effects due to age-related decline in renal or hepatic function, comorbidities, and concomitant medications. Close monitoring is recommended.
Clinical Information
Clinical Pearls
- Arsenic trioxide is highly effective in APL, particularly in combination with all-trans retinoic acid (ATRA).
- Close monitoring for APL differentiation syndrome is critical; prompt initiation of corticosteroids (e.g., dexamethasone) is essential for management.
- Rigorous electrolyte management (potassium, magnesium, calcium) is paramount to minimize the risk of QT prolongation and potentially fatal arrhythmias.
- Patients must be hospitalized for induction therapy due to the intensity of monitoring required.
- Peripheral neuropathy is a common and potentially dose-limiting toxicity; monitor for symptoms and consider dose modification if severe.
Alternative Therapies
- All-trans retinoic acid (ATRA) monotherapy (for certain APL subtypes or in specific contexts)
- Chemotherapy regimens (e.g., anthracycline-based regimens like idarubicin, cytarabine)
- Gemtuzumab ozogamicin (for CD33-positive AML, including some APL cases)
Cost & Coverage
Average Cost:
High (e.g., thousands of USD per vial) per 6ml vial
Insurance Coverage:
Specialty Tier (requires prior authorization, often covered by major medical plans for approved indications)
General Drug Facts
If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others, and do not take medication prescribed for someone else. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Dispose of unused or expired medications properly. Unless instructed otherwise, avoid flushing medications down the toilet or pouring them down the drain. If you are unsure about the correct disposal method, consult your pharmacist for guidance. Many communities have drug take-back programs, which your pharmacist can help you locate. Some medications may come with an additional patient information leaflet; check with your pharmacist to see if this applies to your prescription. If you have any questions or concerns about your medication, discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it was taken to ensure prompt and effective treatment.