Trisenox

What Is Trisenox?

Trisenox (arsenic trioxide) is a cancer medication used to treat a cancer of the blood and bone marrow called acute promyelocytic leukemia, or APL.

What Are Side Effects of Trisenox?

Common side effects of Trisenox include:

• injection site reactions (pain, redness, or swelling),
• nausea,
• vomiting,
• diarrhea,
• stomach or abdominal pain,
• constipation,
• tiredness,
• cough,
• headache,
• dizziness,
• anxiety,
• depression,
• rash or itching,
• sleep problems (insomnia),
• numbness or tingly feeling,
• joint or muscle pain, or
• abnormal vaginal bleeding.

Tell your doctor if you have serious side effects of Trisenox including:

• sharp chest pain, wheezing, rapid breathing, shortness of breath;
• feeling weak, tired, or ill;
• fever, chills, swelling in your ankles or feet, weight gain;
• fainting, fast or pounding heartbeat;
• pale skin, easy bruising or bleeding (nosebleeds);
• high blood sugar (increased thirst, loss of appetite, fruity breath odor, increased urination, drowsiness, dry skin); or
• low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling).

Dosage for Trisenox

Trisenox is given intravenously under physician supervision at a dose of 0.15 mg/kg daily until bone marrow remission. Total induction dose should not exceed 60 doses. Consolidation treatment begins 3 to 6 weeks after completion of induction therapy and Trisenox is administered intravenously at a dose of 0.15 mg/kg daily for 25 doses for up to 5 weeks.

What Drugs, Substances, or Supplements Interact with Trisenox?

Trisenox may interact with droperidol, diuretics (water pills), antibiotics, antidepressants, anti-malaria medications, heart rhythm medicines, medicine to prevent or treat nausea and vomiting, medicines to treat psychiatric disorders, migraine headache medicines, or narcotics. Tell your doctor all medications you use.

Trisenox During Pregnancy and Breastfeeding

Trisenox should not be used during pregnancy. It may harm the fetus. If you become pregnant or think you may be pregnant, tell your doctor. Consult your doctor about birth control. This medication passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this drug is not recommended.

Additional Information

Our Trisenox (arsenic trioxide) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Trisenox Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Arsenic trioxide can cause a condition called differentiation syndrome, which affects blood cells and can be fatal if not treated. This condition may occur within 1 days to 2 months after you start taking this medicine.

Seek medical help right away if you have symptoms of differentiation syndrome:

• fever, cough, trouble breathing;
• dizziness;
• rash;
• decreased urination;
• rapid weight gain; or
• swelling in your arms or legs.

Also call your doctor right away if you have:

• fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
• confusion, decreased consciousness;
• problems with vision, balance, or muscle movement;
• a seizure;
• fever, tiredness, night sweats;
• easy bruising or bleeding;
• high blood sugar--increased thirst, increased urination, dry mouth, fruity breath odor;
• low magnesium--dizziness, irregular heartbeats, feeling jittery, muscle cramps, muscle spasms, cough or choking feeling; or
• low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

• stomach pain, nausea, vomiting, diarrhea;
• cough, sore throat, trouble breathing;
• fever, chills, tiredness, headache, joint pain;
• fast or irregular heartbeats;
• numbness or tingly feeling;
• low magnesium or potassium, high blood sugar;
• itching, rash;
• swelling;
• joint or muscle pain; or
• trouble sleeping.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Trisenox (Arsenic Trioxide Injection)

 

Trisenox Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Differentiation Syndrome [see WARNINGS AND PRECAUTIONS]
• Cardiac Conduction Abnormalities [see WARNINGS AND PRECAUTIONS]
• Encephalopathy [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Carcinogenesis [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Newly-Diagnosed Low-Risk APL

The safety of TRISENOX in combination with tretinoin was evaluated in Study APL0406, a randomized trial comparing TRISENOX plus tretinoin (n=129) versus chemotherapy plus tretinoin (n=137) in patients with newly-diagnosed APL [see Clinical Studies]. In the TRISENOX/tretinoin group, 98% of patients completed induction therapy and 89% completed at least three consolidation cycles. In the chemotherapy/tretinoin group, 96% completed induction therapy and 87% patients completed all three courses of consolidation therapy.

Serious adverse reactions were reported in 25% of patients on the TRISENOX/tretinoin arm and 24% on the chemotherapy/tretinoin arm. The serious adverse reactions reported in ≥ 2% of patients who received TRISENOX/tretinoin were abnormal liver tests, differentiation syndrome, dyspnea, pneumonia, and other infections. Fatal adverse reactions were reported in 1 (1%) patient on the TRISENOX/tretinoin arm and 8 (6%) patients on the chemotherapy/tretinoin arm.

TRISENOX/tretinoin was discontinued due to toxicity in 1 patient during induction and in 4 patients during the first three consolidation courses, whereas chemotherapy/tretinoin was discontinued due to toxicity in 4 patients during induction and in 6 patients during consolidation.

Selected hematologic and nonhematologic toxicities that occurred during induction or consolidation are presented in Table 4.

Table 4: Select Adverse Reactions of Trisenox in Combination with Tretinoin in Patients with Newly-Diagnosed APL in Study APL0406

Adverse Reaction	Induction n (%)	First Consolidation n (%)	Second Consolidation n (%)	Third Consolidation n (%)
Thrombocytopenia > 15 days (Grade 3-4)
TRISENOX/tretinoin	74 (58%)	6 (5%)	6 (5%)	8 (7%)
Chemotherapy/tretinoin	120 (88%)	17 (14%)	77 (63%)	26 (22%)
Neutropenia >15 days (Grade 3-4)
TRISENOX/tretinoin	61 (48%)	8 (7%)	7 (6%)	5 (4%)
Chemotherapy/tretinoin	109 (80%)	40 (32%)	90 (73%)	28 (24%)
Hepatic toxicity (Grade 3-4)
TRISENOX/tretinoin	51 (40%)	5 (4%)	1 (1%)	0 (0%)
Chemotherapy/tretinoin	4 (3%)	1 (1%)	0 (0%)	0 (0%)
Infection and fever of unknown origin
TRISENOX/tretinoin	30 (23%)	10 (8%)	4 (3%)	2 (2%)
Chemotherapy/tretinoin	75 (55%)	8 (6%)	46 (38%)	2 (2%)
Hypertriglyceridemia
TRISENOX/tretinoin	29 (22%)	22 (18%)	17 (14%)	16 (14%)
Chemotherapy/tretinoin	29 (22%)	19 (15%)	10 (8%)	13 (11%)
Hypercholesterolemia
TRISENOX/tretinoin	14 (10%)	19 (16%)	19 (16%)	16 (14%)
Chemotherapy/tretinoin	12 (9%)	12 (10%)	12 (10%)	11 (9%)
QT prolongation
TRISENOX/tretinoin	11 (9%)	3 (2%)	3 (2%)	2 (2%)
Chemotherapy/tretinoin	1 (1%)	0 (0%)	0 (0%)	0 (0%)
Gastrointestinal toxicity (Grade 3-4)
TRISENOX/tretinoin	3 (2%)	0 (0%)	0 (0%)	0 (0%)
Chemotherapy/tretinoin	25 (18%)	1 (1%)	6 (5%)	`0 (0%)
Neurotoxicity*
TRISENOX/tretinoin	1 (1%)	5 (4%)	6 (5%)	7 (6%)
Chemotherapy/tretinoin	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Cardiac function (Grade 3-4)
TRISENOX/tretinoin	0 (0%)	0 (0%)	0 (0%)	0 (0%)
Chemotherapy/tretinoin	5 (4%)	0 (0%)	0 (0%)	0 (0%)
*Mostly cases of reversible peripheral neuropathy

Relapsed Or Refractory APL

Safety information was available for 52 patients with relapsed or refractory APL who participated in clinical trials of TRISENOX. Forty patients in the Study PLRXAS01 received the recommended dose of 0.15 mg/kg, of whom 28 completed both induction and consolidation cycles. An additional 12 patients with relapsed or refractory APL received doses generally similar to the recommended dose.

Serious adverse reactions observed in the 40 patients with refractory or relapsed APL enrolled in Study PLRXAS01 included differentiation syndrome (n=3), hyperleukocytosis (n=3), QTc interval ≥ 500 msec (n=16, 1 with torsade de pointes), atrial dysrhythmias (n=2), and hyperglycemia (n=2).

The most common adverse reactions (> 30%) were 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, and pruritus.

Table 5 describes the adverse reactions in patients aged 5 to 73 years with APL who received TRISENOX at the recommended dose. Similar adverse reactions profiles were seen in the other patient populations who received TRISENOX.

Table 5: Adverse Reactions (≥ 5%) in Patients with Relapsed or Refractory APL Who Received TRISENOX in Study PLRXAS01

Body System Adverse reaction	Any Grade Adverse Reactions		Grade ≥3 Adverse Reactions
	n	%	n	%
Gastrointestinal disorders
Nausea	30	75
Abdominal pain (lower & upper)	23	58	4	10
Vomiting	23	58
Diarrhea	21	53
Sore throat	14	35
Constipation	11	28	1	3
Anorexia	9	23
Appetite decreased	6	15
Loose stools	4	10
Dyspepsia	4	10
Oral blistering	3	8
Fecal incontinence	3	8
Gastrointestinal hemorrhage	3	8
Dry mouth	3	8
Abdominal tenderness	3	8
Diarrhea hemorrhagic	3	8
Abdominal distension	3	8
Respiratory
Cough	26	65
Dyspnea	21	53	4	10
Epistaxis	10	25
Hypoxia	9	23	4	10
Pleural effusion	8	20	1	3
Post nasal drip	5	13
Wheezing	5	13
Decreased breath sounds	4	10
Crepitations	4	10
Rales	4	10
Hemoptysis	3	8
Tachypnea	3	8
Rhonchi	3	8
General disorders and administration site conditions
Fatigue	25	63	2	5
Pyrexia (fever)	25	63	2	5
Edema - non-specific	16	40
Rigors	15	38
Chest pain	10	25	2	5
Injection site pain	8	20
Pain - non-specific	6	15	1	3
Injection site erythema	5	13
Weight gain	5	13
Injection site edema	4	10
Weakness	4	10	2	5
Hemorrhage	3	8
Weight loss	3	8
Drug hypersensitivity	2	5	1	3
Nervous system disorders
Headache	24	60	1	3
Insomnia	17	43	1	3
Paresthesia	13	33	2	5
Dizziness (excluding vertigo)	9	23
Tremor	5	13
Convulsion	3	8	2	5
Somnolence	3	8
Coma	2	5	2	5
Cardiac disorders
Tachycardia	22	55
ECG QT corrected interval prolonged > 500 msec	16	40
Palpitations	4	10
ECG abnormal other than QT interval prolongation	3	8
Metabolism and nutrition disorders
Hypokalemia	20	50	5	13
Hypomagnesemia	18	45	5	13
Hyperglycemia	18	45	5	13
ALT increased	8	20	2	5
Hyperkalemia	7	18	2	5
AST increased	5	13	1	3
Hypocalcemia	4	10
Hypoglycemia	3	8
Acidosis	2	5
Hematologic disorders
Leukocytosis	20	50	1	3
Anemia	8	20	2	5
Thrombocytopenia	7	18	5	13
Febrile neutropenia	5	13	3	8
Neutropenia	4	10	4	10
Disseminated intravascular coagulation	3	8	3	8
Lymphadenopathy	3	8
Skin and subcutaneous tissue disorders
Dermatitis	17	43
Pruritus	13	33	1	3
Ecchymosis	8	20
Dry skin	6	15
Erythema - non-specific	5	13
Increased sweating	5	13
Facial edema	3	8
Night sweats	3	8
Petechiae	3	8
Hyperpigmentation	3	8
Non-specific skin lesions	3	8
Urticaria	3	8
Local exfoliation	2	5
Eyelid edema	2	5
Musculoskeletal, connective tissue, and bone disorders
Arthralgia	13	33	3	8
Myalgia	10	25	2	5
Bone pain	9	23	4	10
Back pain	7	18	1	3
Neck pain	5	13
Pain in limb	5	13	2	5
Psychiatric disorders
Anxiety	12	30
Depression	8	20
Agitation	2	5
Confusion	2	5
Vascular disorders
Hypotension	10	25	2	5
Flushing	4	10
Hypertension	4	10
Pallor	4	10
Infections and infestations
Sinusitis	8	20
Herpes simplex	5	13
Upper respiratory tract infection	5	13	1	3
Bacterial infection - nonspecific	3	8	1	3
Herpes zoster	3	8
Nasopharyngitis	2	5
Oral candidiasis	2	5
Sepsis	2	5	2	5
Reproductive system disorders
Vaginal hemorrhage	5	13
Intermenstrual bleeding	3	8
Ocular disorders
Eye irritation	4	10
Blurred vision	4	10
Dry eye	3	8
Painful red eye	2	5
Renal and urinary disorders
Renal failure	3	8	1	3
Renal impairment	3	8
Oliguria	2	5
Incontinence	2	5
Ear disorders
Earache	3	8
Tinnitus	2	5

Other Clinically Relevant Adverse Reactions

Leukocytosis

TRISENOX can induce proliferation of leukemic promyelocytes resulting in a rapid increase in white blood cell count. Leukocytosis greater than 10 Gi/L developed during induction therapy in 43% patients receiving TRISENOX/tretinoin for newly-diagnosed low-risk APL and in 50% of patients receiving TRISENOX monotherapy for relapsed/refractory APL. In the relapsed/refractory setting, a relationship did not exist between baseline WBC counts and development of hyperleukocytosis nor baseline WBC counts and peak WBC counts.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of TRISENOX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

Cardiac disorders: Ventricular extrasystoles in association with QT prolongation, ventricular tachycardia in association with QT prolongation, including torsade de pointes, atrioventricular block, and congestive heart failure

Ear and labyrinth disorders: Deafness

Hematologic disorders: Pancytopenia, bone marrow necrosis

Infections: Herpes zoster

Investigations: Gamma-glutamyltransferase increased

Musculoskeletal and connective tissue disorders: Bone pain, myalgia, rhabdomyolysis

Neoplasms benign, malignant and unspecified: Melanoma, pancreatic cancer, squamous cell carcinoma

Nervous system disorders: Peripheral neuropathy, paresis, seizures, confusion, encephalopathy, Wernicke's encephalopathy, posterior reversible encephalopathy syndrome

Skin and subcutaneous tissue disorders: Toxic epidermal necrolysis

DRUG INTERACTIONS

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 [see WARNINGS AND PRECAUTIONS]. Discontinue or replace with an alternative drug that does not prolong the QT/QTc interval while the 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 [see WARNINGS AND PRECAUTIONS]. Avoid concomitant use of drugs that can lead to electrolyte abnormalities. Monitor electrolytes more frequently in patients who must receive concomitant use of these drugs and TRISENOX.

Drugs That Can Lead To Hepatotoxicity

Concomitant use of these drugs and TRISENOX, particularly when given in combination with tretinoin, may increase the risk of serious hepatotoxicity [see WARNINGS AND PRECAUTIONS]. Discontinue or replace with an alternative drug that does not cause hepatotoxicity while the patient is using TRISENOX. Monitor liver function tests more frequently in patients when it is not feasible to avoid concomitant use.

Read the entire FDA prescribing information for Trisenox (Arsenic Trioxide Injection)