thiotepa Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antineoplastics, thiotepa derivatives 2638 52-24-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • thio-tepa
  • triethylenethiophosphortriamide
  • thiotepa
  • oncotepa
  • phosphorothioic acid triethylenetriamide
  • tespamin
  • tespamine
  • thiophosphamide
  • tepadina
A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed).
  • Molecular weight: 189.22
  • Formula: C6H12N3PS
  • CLOGP: 0.52
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 0
  • TPSA: 9.03
  • ALOGS: -1.31
  • ROTB: 3

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 1.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 6.70 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.90 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 2.70 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
March 9, 1959 FDA

FDA Adverse Event Reporting System (Female)

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
Mucosal inflammation 483.16 127.34 95 662 5129 2352199
Human herpesvirus 6 infection 311.51 127.34 45 712 335 2356993
Febrile neutropenia 232.38 127.34 60 697 10822 2346506
Cytomegalovirus infection 229.16 127.34 46 711 2667 2354661
Neutropenia 204.57 127.34 63 694 21485 2335843
Acute graft versus host disease 181.42 127.34 30 727 572 2356756
Graft versus host disease in skin 173.70 127.34 26 731 250 2357078
Thrombocytopenia 156.40 127.34 50 707 19081 2338247
Pyrexia 155.10 127.34 65 692 53643 2303685
Venoocclusive liver disease 153.18 127.34 26 731 582 2356746

FDA Adverse Event Reporting System (Male)

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
Mucosal inflammation 494.53 98.22 103 724 4066 1741888
Cytomegalovirus infection 494.20 98.22 99 728 3202 1742752
Febrile neutropenia 217.54 98.22 65 762 11035 1734919
Epstein-Barr virus infection 204.97 98.22 40 787 1085 1744869
Human herpesvirus 6 infection 204.81 98.22 34 793 353 1745601
Acute graft versus host disease 197.13 98.22 37 790 810 1745144
Neutropenia 185.71 98.22 65 762 18195 1727759
Thrombocytopenia 183.56 98.22 67 760 21182 1724772
Venoocclusive liver disease 181.11 98.22 35 792 898 1745056
Viral haemorrhagic cystitis 155.10 98.22 22 805 67 1745887
Acute graft versus host disease in skin 152.20 98.22 28 799 544 1745410
Graft versus host disease in skin 146.97 98.22 26 801 401 1745553
Acute lymphocytic leukaemia recurrent 142.02 98.22 24 803 278 1745676
Adenovirus infection 138.41 98.22 25 802 436 1745518
Graft versus host disease 135.29 98.22 30 797 1523 1744431
Post transplant lymphoproliferative disorder 132.35 98.22 26 801 724 1745230
Off label use 117.14 98.22 58 769 38513 1707441
Autoimmune lymphoproliferative syndrome 114.68 98.22 14 813 4 1745950
Pyrexia 104.20 98.22 57 770 46343 1699611
Anaemia 100.34 98.22 48 779 29409 1716545

Pharmacologic Action:

SourceCodeDescription
ATC L01AC01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ALKYLATING AGENTS
Ethylene imines
FDA MoA N0000000236 Alkylating Activity
FDA EPC N0000175558 Alkylating Drug
MeSH PA D000477 Alkylating Agents
MeSH PA D000970 Antineoplastic Agents
MeSH PA D018906 Antineoplastic Agents, Alkylating
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
MeSH PA D019653 Myeloablative Agonists
MeSH PA D009676 Noxae

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Allogeneic bone marrow transplantation indication 58390007
Hodgkin's disease indication 118599009
Non-Hodgkin's lymphoma indication 118601006
Malignant tumor of ovary indication 363443007 DOID:2394
Malignant tumor of urinary bladder indication 399326009 DOID:11054
Carcinoma of female breast indication 447782002
Pericardial Malignant Effusions indication
Pleural Malignant Effusions indication
Peritoneal Malignant Effusions indication
Acute infectious disease contraindication 63171007
Blood coagulation disorder contraindication 64779008 DOID:1247
Leukopenia contraindication 84828003 DOID:615
Kidney disease contraindication 90708001 DOID:557
Disease of liver contraindication 235856003 DOID:409
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
100MG/VIAL TEPADINA ADIENNE SA N208264 Jan. 26, 2017 RX POWDER INTRAVENOUS Jan. 26, 2020 FOR REDUCING THE RISK OF GRAFT REJECTION WHEN USED WITH HIGH-DOSE BUSULFAN AND CYCLOPHOSPHAMIDE AS A PREPARATIVE REGIMEN FOR ALLOGENEIC HEMATOPOIETIC PROGENITOR (STEM) CELL TRANSPLANTATION FOR PEDIATRIC PATIENTS WITH CLASS 3 BETA-THALASSEMIA
15MG/VIAL TEPADINA ADIENNE SA N208264 Jan. 26, 2017 RX POWDER INTRAVENOUS Jan. 26, 2020 FOR REDUCING THE RISK OF GRAFT REJECTION WHEN USED WITH HIGH-DOSE BUSULFAN AND CYCLOPHOSPHAMIDE AS A PREPARATIVE REGIMEN FOR ALLOGENEIC HEMATOPOIETIC PROGENITOR (STEM) CELL TRANSPLANTATION FOR PEDIATRIC PATIENTS WITH CLASS 3 BETA-THALASSEMIA
100MG/VIAL TEPADINA ADIENNE SA N208264 Jan. 26, 2017 RX POWDER INTRAVENOUS Jan. 26, 2024 INDICATED FOR REDUCING THE RISK OF GRAFT REJECTION WHEN USED IN CONJUNCTION WITH HIGH-DOSE BUSULFAN & CYCLOPHOSPHAMIDE AS A PREPARATIVE REGIMEN FOR ALLOGENIC HEMATOPOIETIC PROGENITOR CELL TRANSPLANTATION FOR PEDS. PATIENTS WITH CLASS 3 BETA-THALASSEMIA
15MG/VIAL TEPADINA ADIENNE SA N208264 Jan. 26, 2017 RX POWDER INTRAVENOUS Jan. 26, 2024 INDICATED FOR REDUCING THE RISK OF GRAFT REJECTION WHEN USED IN CONJUNCTION WITH HIGH-DOSE BUSULFAN & CYCLOPHOSPHAMIDE AS A PREPARATIVE REGIMEN FOR ALLOGENIC HEMATOPOIETIC PROGENITOR CELL TRANSPLANTATION FOR PEDS. PATIENTS WITH CLASS 3 BETA-THALASSEMIA

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
DNA DNA OTHER CHEMBL CHEMBL

External reference:

IDSource
4017910 VUID
N0000146261 NUI
C0039871 UMLSCUI
D00583 KEGG_DRUG
88997008 SNOMEDCT_US
387508004 SNOMEDCT_US
4017910 VANDF
2134 MMSL
10473 RXNORM
5573 MMSL
d00390 MMSL
002637 NDDF
905Z5W3GKH UNII
881 INN_ID
5453 PUBCHEM_CID
CHEBI:9570 CHEBI
CHEMBL671 ChEMBL_ID
DB04572 DRUGBANK_ID
D013852 MESH_DESCRIPTOR_UI
7622 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 0143-9309 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 15 mg INTRACAVITARY ANDA 13 sections
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 0143-9565 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 15 mg INTRACAVITARY ANDA 13 sections
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 25021-246 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 15 mg INTRAVENOUS ANDA 13 sections
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 43598-650 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 15 mg INTRAVENOUS ANDA 12 sections
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 69539-123 INJECTION, POWDER, FOR SOLUTION 15 mg INTRAVENOUS ANDA 18 sections
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 69539-124 INJECTION, POWDER, FOR SOLUTION 100 mg INTRAVENOUS ANDA 18 sections
TEPADINA HUMAN PRESCRIPTION DRUG LABEL 1 70121-1630 INJECTION, POWDER, FOR SOLUTION 15 mg INTRAVENOUS NDA 18 sections
TEPADINA HUMAN PRESCRIPTION DRUG LABEL 1 70121-1631 INJECTION, POWDER, FOR SOLUTION 100 mg INTRAVENOUS NDA 18 sections
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 72205-045 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 15 mg INTRAVENOUS ANDA 18 sections
Thiotepa HUMAN PRESCRIPTION DRUG LABEL 1 72205-046 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 18 sections