arsenic trioxide indications/contra

Stem definitionDrug idCAS RN
244 1327-53-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • trisenox
  • arsenic trioxide
  • arsenic oxide
  • arsenious oxide
  • arsenious trioxide
  • white arsenic
Arsenic trioxide causes morphological changes and DNA fragmentation characteristic of apoptosis in NB4 human promyelocytic leukemia cells in vitro. Arsenic trioxide also causes damage or degradation of the fusion protein promyelocytic leukemia (PML)­ retinoic acid receptor (RAR)-alpha.
  • Molecular weight: 197.84
  • Formula: As2O3
  • CLOGP:
  • LIPINSKI: None
  • HAC: 3
  • HDO: 0
  • TPSA: 43.37
  • ALOGS:
  • ROTB: 2

Drug dosage:

None

Approvals:

DateAgencyCompanyOrphan
Sept. 25, 2000 FDA CEPHALON

FDA Adverse Event Reporting System

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MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Electrocardiogram QT prolonged 564.79 39.57 123 908 10672 3374156
Acute promyelocytic leukaemia differentiation syndrome 470.47 39.57 61 970 167 3384661
Alanine aminotransferase increased 243.04 39.57 74 957 23566 3361262
Febrile neutropenia 218.98 39.57 65 966 18910 3365918
Pleural effusion 193.55 39.57 59 972 18720 3366108
Aspartate aminotransferase increased 190.93 39.57 60 971 21053 3363775
Pyrexia 163.51 39.57 77 954 81038 3303790
White blood cell count decreased 153.33 39.57 53 978 24894 3359934
Pneumonia 148.62 39.57 69 962 70074 3314754
Disseminated intravascular coagulation 129.77 39.57 34 997 6183 3378645
Hepatic function abnormal 127.06 39.57 38 993 11189 3373639
Pancytopenia 123.31 39.57 42 989 18778 3366050
Hyperleukocytosis 122.41 39.57 15 1016 20 3384808
Leukocytosis 117.39 39.57 31 1000 5802 3379026
Pericardial effusion 116.21 39.57 31 1000 6030 3378798
Gamma-glutamyltransferase increased 108.02 39.57 32 999 9096 3375732
Platelet count decreased 93.78 39.57 38 993 27430 3357398
Hypotension 93.03 39.57 45 986 49469 3335359
Hyperglycaemia 87.93 39.57 27 1004 8641 3376187
Acute promyelocytic leukaemia 82.49 39.57 14 1017 302 3384526
Haemoglobin decreased 80.24 39.57 35 996 30259 3354569
Blood alkaline phosphatase increased 78.66 39.57 26 1005 10527 3374301
Sepsis 74.82 39.57 34 997 32339 3352489
Leukaemia recurrent 74.00 39.57 14 1017 566 3384262
Neutropenia 70.69 39.57 33 998 33353 3351475
Blood lactate dehydrogenase increased 69.15 39.57 21 1010 6459 3378369
Malignant neoplasm progression 65.40 39.57 26 1005 17767 3367061
Hypoxia 60.84 39.57 21 1010 9670 3375158
Lower respiratory tract infection fungal 59.47 39.57 9 1022 90 3384738
Ventricular extrasystoles 58.14 39.57 16 1015 3471 3381357

Pharmacologic Action:

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SourceCodeDescription
ATC L01XX27 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
CHEBI has role CHEBI:24852 insecticide
CHEBI has role CHEBI:35610 antineoplastic agent
MeSH PA D000970 Antineoplastic Agents

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Acute promyelocytic leukemia, FAB M3 indication 110004001 DOID:0060318
Acute myelomonocytic leukemia, FAB M4 indication 110005000
Hyperkalemia contraindication 14140009
Complete atrioventricular block contraindication 27885002
Torsades de pointes contraindication 31722008
Hypokalemia contraindication 43339004
Chronic heart failure contraindication 48447003
Kidney disease contraindication 90708001 DOID:2527
Prolonged QT interval contraindication 111975006
Hypomagnesemia contraindication 190855004
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001
Congenital long QT syndrome contraindication 442917000
Myelodysplastic syndrome off-label use 109995007

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6723351 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6723351 Nov. 10, 2018 TREATING 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
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6723351 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOGENOUS LEUKEMIA (APL)
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6855339 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6855339 Nov. 10, 2018 TREATING 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
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6855339 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOGENOUS LEUKEMIA (APL)
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6861076 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6861076 Nov. 10, 2018 TREATING 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
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6861076 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOGENOUS LEUKEMIA (APL)
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6884439 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6884439 Nov. 10, 2018 TREATING 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
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6884439 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APL)
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6982096 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6982096 Nov. 10, 2018 TREATING 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
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 6982096 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APL)
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 8273379 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 8273379 Nov. 10, 2018 TREATING 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
1MG/ML TRISENOX CEPHALON N021248 Sept. 25, 2000 RX INJECTABLE INJECTION 8273379 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APL) IN PATIENTS WHOSE APL IS CHARACTERIZED BY THE PRESENCE OF THE (15;17) TRANSLOCATION OR PML/RAR-ALPHA GENE EXPRESSION
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6723351 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6723351 Nov. 10, 2018 TREATING 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
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6723351 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOGENOUS LEUKEMIA (APL)
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6855339 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6855339 Nov. 10, 2018 TREATING 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
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6855339 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOGENOUS LEUKEMIA (APL)
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6861076 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6861076 Nov. 10, 2018 TREATING 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
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6861076 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOGENOUS LEUKEMIA (APL)
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6884439 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6884439 Nov. 10, 2018 TREATING 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
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6884439 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APL)
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6982096 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6982096 Nov. 10, 2018 TREATING 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
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 6982096 Nov. 10, 2018 TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA (APL)
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 8273379 Nov. 10, 2018 IN COMBINATION WITH TRETINOIN, TREATING ADULTS AND PEDIATRIC PATIENTS 1 YEAR AND OLDER WITH NEWLY-DIAGNOSED LOW-RISK ACUTE PROMYELOCYTIC LEUKEMIA (APL) CHARACTERIZED BY THE PRESENCE OF THE T(15;17) TRANSLOCATION OR PML/RAR-A GENE EXPRESSION
2MG/ML TRISENOX CEPHALON N021248 Oct. 13, 2017 RX INJECTABLE INJECTION 8273379 Nov. 10, 2018 TREATING 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

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Thioredoxin reductase 1, cytoplasmic Enzyme INHIBITOR CHEMBL CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.82 WOMBAT-PK

External reference:

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IDSource
CHEBI:30621 CHEBI
C1096917 UMLSCUI
D02106 KEGG_DRUG
4021238 VANDF
71831 MMSL
N0000148681 NDFRT
N0000179044 NDFRT
d04720 MMSL
15787 MMSL
18330 RXNORM
400907001 SNOMEDCT_US
72251000 SNOMEDCT_US
007172 NDDF
CHEMBL1200978 ChEMBL_ID
DB01169 DRUGBANK_ID
S7V92P67HO UNII
C006632 MESH_SUPPLEMENTAL_RECORD_UI
14888 PUBCHEM_CID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Trisenox HUMAN PRESCRIPTION DRUG LABEL 1 63459-600 INJECTION, SOLUTION 1 mg INTRAVENOUS NDA 19 sections
Trisenox HUMAN PRESCRIPTION DRUG LABEL 1 63459-601 INJECTION, SOLUTION 2 mg INTRAVENOUS NDA 19 sections
Emvita 6 HUMAN OTC DRUG LABEL 1 66343-018 LIQUID 18 [hp_M] ORAL UNAPPROVED HOMEOPATHIC 6 sections