Trisenox (Arsenic Trioxide) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Clinical Studies Experience

Safety information was available for 52 patients with relapsed or refractory APL who participated in clinical trials of TRISENOX. Forty patients in the Phase 2 study received the recommended dose of 0.15 mg/kg of which 28 completed both induction and consolidation treatment cycles. An additional 12 patients with relapsed or refractory APL received doses generally similar to the recommended dose. Most patients experienced some drug-related toxicity, most commonly leukocytosis, gastrointestinal (nausea, vomiting, diarrhea, and abdominal pain), fatigue, edema, hyperglycemia, dyspnea, cough, rash or itching, headaches, and dizziness. These adverse effects have not been observed to be permanent or irreversible nor do they usually require interruption of therapy.

Serious adverse events (SAEs), grade 3 or 4 according to version 2 of the NCI Common Toxicity Criteria, were common. Those SAEs attributed 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 ≥ 500 msec (n=16, 1 with torsade de pointes), atrial dysrhythmias (n=2), and hyperglycemia (n=2).

The following table describes the adverse events that were observed in patients treated for APL with TRISENOX at the recommended dose at a rate of 5% or more. Similar adverse event profiles were seen in the other patient populations who received TRISENOX.

Adverse Events (any grade) Occurring in ≥ 5% of 40 Patients with APL who Received TRISENOX (arsenic trioxide) injection at a dose of 0.15 mg/kg/day

System organ class/Adverse Event		All Adverse Events, Any Grade		Grade 3 & 4 Events
		n	%	n	%
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
	Injection site edema	4	10
	Weakness	4	10	2	5
	Hemorrhage	3	8
	Weight gain	5	13
	Weight loss	3	8
	Drug hypersensitivity	2	5	1	3
Gastrointestinal disorders
	Nausea	30	75
	Anorexia	9	23
	Appetite decreased	6	15
	Diarrhea	21	53
	Vomiting	23	58
	Abdominal pain (lower & upper)	23	58	4	10
	Sore throat	14	35
	Constipation	11	28	1	3
	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
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
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
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
Skin & 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
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
Infections and infestations
	Sinusitis	8	20
	Herpes simplex	5	13
	Upper respiratory tract infection	5	13	1	3
	Bacterial infection - non-specific	3	8	1	3
	Herpes zoster	3	8
	Nasopharyngitis	2	5
	Oral candidiasis	2	5
	Sepsis	2	5	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
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
Vascular disorders
	Hypotension	10	25	2	5
	Flushing	4	10
	Hypertension	4	10
	Pallor	4	10
Psychiatric disorders
	Anxiety	12	30
	Depression	8	20
	Agitation	2	5
	Confusion	2	5
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
Reproductive system disorders
	Vaginal hemorrhage	5	13
	Intermenstrual bleeding	3	8
Ear disorders
	Earache	3	8
	Tinnitus	2	5

Post-Marketing Experience

The following reactions have been reported from clinical trials and/or world-wide post-marketing surveillance. Because they are reported from a population of unknown size, precise estimates of frequency cannot be made.

Cardiac disorders: ventricular extrasystoles in association with QT prolongation, and ventricular tachycardia in association with QT prolongation

Nervous system disorders: peripheral neuropathy

Hematologic disorders: pancytopenia

Respiratory, thoracic, and mediastinal disorders: A differentiation syndrome, like retinoic acid syndrome, has been reported with the use of TRISENOX for the treatment of malignancies other than APL.

REPORTS OF SUSPECTED TRISENOX SIDE EFFECTS / ADVERSE REACTIONS

Possible Trisenox side effects / adverse reactions in 5 year old male

Reported by a physician from Japan on 2011-10-05

Patient: 5 year old male

Reactions: Respiratory Disorder

Suspect drug(s):
Trisenox

Possible Trisenox side effects / adverse reactions in 64 year old female

Reported by a physician from United Kingdom on 2011-10-06

Patient: 64 year old female

Reactions: Gamma-Glutamyltransferase Increased

Suspect drug(s):
Gemtuzumab Ozogamicin
    Dosage: 6 mg unit dose at unknown frequency
    Indication: Acute Myeloid Leukaemia
    Start date: 2011-07-15
    End date: 2011-07-29

Atracurium Besylate
    Dosage: unk
    Indication: Acute Myeloid Leukaemia
    Start date: 2011-07-15
    End date: 2011-07-18

Atracurium Besylate
    Dosage: unk
    Indication: Myelodysplastic Syndrome
    Start date: 2011-08-04

Trisenox
    Dosage: unk
    Indication: Acute Myeloid Leukaemia
    Start date: 2011-07-15
    End date: 2011-07-29

Trisenox
    Indication: Myelodysplastic Syndrome

Gemtuzumab Ozogamicin
    Indication: Myelodysplastic Syndrome

Possible Trisenox side effects / adverse reactions in 64 year old female

Reported by a physician from United Kingdom on 2011-10-18

Patient: 64 year old female

Reactions: Gamma-Glutamyltransferase Increased

Suspect drug(s):
Atracurium Besylate
    Dosage: unk
    Indication: Acute Myeloid Leukaemia
    Start date: 2011-07-15
    End date: 2011-07-18

Gemtuzumab Ozogamicin
    Dosage: 6 mg unit dose at unknown frequency
    Indication: Acute Myeloid Leukaemia
    Start date: 2011-07-15
    End date: 2011-07-29

Gemtuzumab Ozogamicin
    Indication: Myelodysplastic Syndrome

Trisenox
    Indication: Myelodysplastic Syndrome

Atracurium Besylate
    Dosage: unk
    Indication: Myelodysplastic Syndrome
    Start date: 2011-08-04

Trisenox
    Dosage: unk
    Indication: Acute Myeloid Leukaemia
    Start date: 2011-07-15
    End date: 2011-07-29