Trisenox

>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%)

Since this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.
 

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Antineoplastic agent.1

Refractory or Relapsed Acute Promyelocytic Leukemia

Induction of remission and consolidation of acute promyelocytic leukemia (APL) that is refractory to retinoid and anthracycline therapy or has relapsed following such therapy;1 4 16 17 used in patients whose disease is characterized by the presence of the t(15;17) translocation or promyelocytic leukemia-retinoic acid receptor (PML-RAR)-α gene expression.1 5

Actuarial 18-month relapse-free survival rate: 56%.17

Newly Diagnosed Acute Promyelocytic Leukemia

As a component of therapy for newly diagnosed APL† in combination with other agents and consolidation chemotherapy.17 20 25

Combination therapy with arsenic trioxide and tretinoin has been used as an alternative to chemotherapy for induction and postremission therapy in newly diagnosed APL†; may consider use of these regimens in select patients who cannot tolerate standard anthracycline-containing chemotherapy (e.g., geriatric patients with poor performance or patients with cardiac dysfunction).27 28 29

Contraindications

• Known hypersensitivity to arsenic trioxide or any ingredient in the formulation.1

Warnings/Precautions

Warnings

For warnings regarding experience of supervising clinician, APL differentiation syndrome, ECG abnormalities, and ECG and electrolyte monitoring, see Boxed Warning.

Possible hyperleukocytosis (leukocyte count ≥10,000/mm3).1 11

Carcinogenicity studies not performed using IV arsenic trioxide; however, arsenic trioxide is a human carcinogen.1

May cause fetal harm; avoid pregnancy during therapy.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.1

General Precautions

Perform hematologic and coagulation tests and determine serum electrolyte concentrations at least twice weekly during induction therapy (more frequently in clinically unstable patients) and at least weekly during consolidation therapy.1

Monitor ECG weekly (more frequently in clinically unstable patients) during induction and consolidation therapy.1

Specific Populations

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Arsenic is distributed into milk in humans;1 discontinue nursing or the drug.1

Safety and efficacy not established in children <5 years of age.1

Used in 7 children 5–16 years of age with APL in one study and in 13 children and young adults 4–21 years of age with refractory or relapsed APL in another study; 5 and 11 achieved complete responses, respectively.1 11 26

Not studied in patients with hepatic impairment.1

Not studied in patients with renal impairment.1

Potential for prolonged elimination.1 Use with caution in patients with renal failure.1

Common Adverse Effects

Leukocytosis, GI effects (nausea, vomiting, diarrhea, abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, dizziness.1

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Chills
• convulsions (seizures)
• cough
• decreased urine output
• dry mouth
• eye pain
• general feeling of illness
• headache
• increased thirst
• irregular heartbeat
• loss of appetite
• mood changes
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in hands, feet, or lips
• sore throat
• trouble breathing
• unusual tiredness or weakness

• Abdominal or stomach cramps
• black, tarry stools
• bluish lips or skin
• blurred vision
• chest pain
• dizziness or lightheadedness
• fever
• flushed, dry skin
• fruit-like breath odor
• increased hunger
• increased urine output
• irregular or pounding heartbeat or pulse
• painful or difficult urination
• sores, ulcers, or white spots on the lips or in the mouth
• stomachache
• sweating
• swollen glands
• unexplained weight loss
• unusual bleeding or bruising
• unusual weight gain

• Anxiety
• behavior changes similar to drunkenness
• bleeding
• blood in the urine or stools
• bluish fingernails, palms, or nailbeds
• bruising
• cloudy urine
• cold sweats
• cool pale skin
• drowsiness
• headache
• large hives or rash
• persistent bleeding or oozing from puncture sites, mouth, or nose
• severe nausea
• shakiness
• sore mouth or tongue
• swelling of the eyelids, lips, or face
• vomiting of blood or material that looks like coffee grounds
• white patches in the mouth or on the tongue

Get emergency help immediately if any of the following symptoms of overdose occur:

• Confusion
• convulsions (seizures)
• muscle weakness, severe

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea

• Acid or sour stomach
• back pain
• belching
• bloating or swelling of the face, hands, lower legs, or feet
• bone pain
• constipation
• flushing
• heartburn
• heavy non-menstrual vaginal bleeding
• indigestion
• injection site pain, redness, or swelling
• itching
• itchy, red skin
• joint or muscle pain
• limb pain
• loss of appetite
• mental depression
• neck pain
• nosebleeds
• pale skin
• shivering chills
• trouble sleeping or getting to sleep
• weight gain

• Agitation
• blisters inside the mouth
• coughing or spitting up blood
• earache
• eye dryness, redness, or pain
• loss of bowel or bladder control
• night sweats
• rapid, shallow breathing
• ringing in the ears
• small red or purple spots on skin
• swelling of the abdominal or stomach area
• swelling or puffiness of the face or eyelids
• swollen, painful, or tender lymph glands in the neck, armpit, or groin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Trisenox is indicated for induction of remission and consolidation in patients with acute promyelocytic leukemia (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.

Trisenox is an injectable solution for intravenous administration supplied as 10 mg /10 mL of arsenic trioxide in single-use ampules.

Drugs That Can Prolong the QT/QTc Interval Concomitant use of these drugs and Trisenox may increase the risk of serious QT/QTc interval prolongation. Discontinue or replace with an alternative drug that does not prolong the QT/QTc interval while patient is using Trisenox. Monitor ECGs more frequently in patients when it is not feasible to avoid concomitant use.

Drugs That Can Lead to Electrolyte Abnormalities Electrolyte abnormalities increase the risk of serious QT/QTc interval prolongation. Avoid concomitant administration of drugs that can lead to electrolyte abnormalities. Monitor electrolytes more frequently in patients who must receive concomitant use of these drugs and Trisenox.

Trisenox is a sterile injectable solution of arsenic trioxide. The molecular formula of the drug substance in the solid state is As2O3, with a molecular weight of 197.8 and has the following structural formula:

Trisenox is available in 10 mL, single-use ampules containing 10 mg of arsenic trioxide. Trisenox is formulated as a sterile, nonpyrogenic, clear solution of arsenic trioxide in water for injection using sodium hydroxide and dilute hydrochloric acid to adjust to pH 8. Trisenox is preservative-free. Arsenic trioxide, the active ingredient, is present at a concentration of 1.0 mg/mL. Inactive ingredients and their respective approximate concentrations are sodium hydroxide (1.2 mg/mL) and hydrochloric acid, which is used to adjust the pH to 7.5 - 8.5.

Applies to arsenic trioxide: intravenous solution

Along with its needed effects, arsenic trioxide (the active ingredient contained in Trisenox) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking arsenic trioxide:

• Chills
• convulsions (seizures)
• cough
• decreased urine output
• dry mouth
• eye pain
• general feeling of illness
• headache
• increased thirst
• irregular heartbeat
• loss of appetite
• mood changes
• muscle pain or cramps
• nausea or vomiting
• numbness or tingling in hands, feet, or lips
• sore throat
• trouble breathing
• unusual tiredness or weakness

• Abdominal or stomach cramps
• black, tarry stools
• bluish lips or skin
• blurred vision
• chest pain
• dizziness or lightheadedness
• fever
• flushed, dry skin
• fruit-like breath odor
• increased hunger
• increased urine output
• irregular or pounding heartbeat or pulse
• painful or difficult urination
• sores, ulcers, or white spots on the lips or in the mouth
• stomachache
• sweating
• swollen glands
• unexplained weight loss
• unusual bleeding or bruising
• unusual weight gain

• Anxiety
• behavior changes similar to drunkenness
• bleeding
• blood in the urine or stools
• bluish fingernails, palms, or nailbeds
• bruising
• cloudy urine
• cold sweats
• cool pale skin
• drowsiness
• headache
• large hives or rash
• persistent bleeding or oozing from puncture sites, mouth, or nose
• severe nausea
• shakiness
• sore mouth or tongue
• swelling of the eyelids, lips, or face
• vomiting of blood or material that looks like coffee grounds
• white patches in the mouth or on the tongue

Get emergency help immediately if any of the following symptoms of overdose occur while taking arsenic trioxide:

• Confusion
• convulsions (seizures)
• muscle weakness, severe

Some side effects of arsenic trioxide may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea

• Acid or sour stomach
• back pain
• belching
• bloating or swelling of the face, hands, lower legs, or feet
• bone pain
• constipation
• flushing
• heartburn
• heavy non-menstrual vaginal bleeding
• indigestion
• injection site pain, redness, or swelling
• itching
• itchy, red skin
• joint or muscle pain
• limb pain
• loss of appetite
• mental depression
• neck pain
• nosebleeds
• pale skin
• shivering chills
• trouble sleeping or getting to sleep
• weight gain

• Agitation
• blisters inside the mouth
• coughing or spitting up blood
• earache
• eye dryness, redness, or pain
• loss of bowel or bladder control
• night sweats
• rapid, shallow breathing
• ringing in the ears
• small red or purple spots on skin
• swelling of the abdominal or stomach area
• swelling or puffiness of the face or eyelids
• swollen, painful, or tender lymph glands in the neck, armpit, or groin