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

Stem definitionDrug idCAS RN
antineoplastic, alkylating agents, methanesulfonates 438 55-98-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • busilvex
  • busulfan
  • busulfex
  • busulphan
  • citosulfan
  • glyzophrol
  • leucosulfan
  • sulphabutin
An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
  • Molecular weight: 246.29
  • Formula: C6H14O6S2
  • CLOGP: -0.59
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 0
  • TPSA: 86.74
  • ALOGS: -1.68
  • ROTB: 7

  • 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 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.10 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 1 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.23 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 70 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.55 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.40 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 1 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.40 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
June 26, 1954 FDA ASPEN GLOBAL

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
Graft versus host disease 750.39 111.13 122 1647 837 2355479
Cytomegalovirus infection 654.53 111.13 127 1642 2586 2353730
Venoocclusive liver disease 610.46 111.13 96 1673 512 2355804
Acute graft versus host disease 559.92 111.13 89 1680 513 2355803
Chronic graft versus host disease 483.11 111.13 74 1695 319 2355997
Mucosal inflammation 388.78 111.13 93 1676 5131 2351185
Venoocclusive disease 371.13 111.13 56 1713 212 2356104
Acute graft versus host disease in skin 369.51 111.13 59 1710 348 2355968
Febrile neutropenia 277.00 111.13 83 1686 10799 2345517
Neutropenia 270.00 111.13 96 1673 21452 2334864
Ovarian failure 251.46 111.13 40 1729 228 2356088
Cystitis haemorrhagic 242.86 111.13 44 1725 592 2355724
Premature menopause 241.27 111.13 38 1731 201 2356115
Graft versus host disease in skin 221.43 111.13 36 1733 240 2356076
Ovarian atrophy 215.27 111.13 28 1741 18 2356298
Acute graft versus host disease in intestine 211.49 111.13 34 1735 209 2356107
Cytomegalovirus viraemia 208.61 111.13 37 1732 437 2355879
Primary hypogonadism 199.11 111.13 26 1743 18 2356298
Pyrexia 197.17 111.13 100 1669 53608 2302708
Adenovirus infection 193.49 111.13 33 1736 304 2356012
Thrombotic microangiopathy 186.98 111.13 40 1729 1307 2355009
Stomatitis 175.11 111.13 57 1712 9653 2346663
Acute myeloid leukaemia recurrent 173.04 111.13 28 1741 180 2356136
Off label use 170.25 111.13 101 1668 73497 2282819
Acute lymphocytic leukaemia recurrent 163.51 111.13 27 1742 200 2356116
Blood follicle stimulating hormone increased 161.45 111.13 24 1745 79 2356237
Multiple organ dysfunction syndrome 154.68 111.13 49 1720 7592 2348724
Thrombocytopenia 154.58 111.13 62 1707 19069 2337247
Blood luteinising hormone increased 153.95 111.13 22 1747 50 2356266
Post transplant lymphoproliferative disorder 153.43 111.13 29 1740 496 2355820
BK virus infection 148.71 111.13 26 1743 280 2356036
Idiopathic pneumonia syndrome 134.80 111.13 18 1751 18 2356298
Ascites 126.04 111.13 39 1730 5581 2350735
Product use in unapproved indication 125.08 111.13 46 1723 11154 2345162
Transplant failure 122.79 111.13 22 1747 275 2356041
Neoplasm recurrence 121.17 111.13 23 1746 402 2355914
Bacterial sepsis 118.00 111.13 23 1746 465 2355851
Acute myeloid leukaemia 115.43 111.13 31 1738 2679 2353637
Pancytopenia 113.13 111.13 43 1726 11409 2344907
Viral haemorrhagic cystitis 112.34 111.13 17 1752 65 2356251

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
Venoocclusive liver disease 808.23 80.46 143 1979 790 1743869
Cytomegalovirus infection 782.58 80.46 171 1951 3130 1741529
Graft versus host disease 747.85 80.46 145 1977 1408 1743251
Acute graft versus host disease 714.51 80.46 127 1995 720 1743939
Mucosal inflammation 626.03 80.46 149 1973 4020 1740639
Venoocclusive disease 487.20 80.46 81 2041 281 1744378
Acute graft versus host disease in skin 483.22 80.46 86 2036 486 1744173
Chronic graft versus host disease 354.71 80.46 66 2056 492 1744167
Cystitis haemorrhagic 324.49 80.46 63 2059 603 1744056
Epstein-Barr virus infection 274.71 80.46 60 2062 1065 1743594
Product use in unapproved indication 271.16 80.46 93 2029 9329 1735330
Off label use 256.88 80.46 134 1988 38437 1706222
Post transplant lymphoproliferative disorder 251.59 80.46 52 2070 698 1743961
Transplant failure 250.46 80.46 47 2075 367 1744292
Multiple organ dysfunction syndrome 245.64 80.46 86 2036 9156 1735503
Febrile neutropenia 226.59 80.46 85 2037 11015 1733644
BK virus infection 213.03 80.46 42 2080 436 1744223
Cytomegalovirus viraemia 205.51 80.46 42 2080 530 1744129
Pyrexia 204.37 80.46 123 1999 46277 1698382
Respiratory failure 201.13 80.46 84 2038 14421 1730238
Viral haemorrhagic cystitis 177.59 80.46 28 2094 61 1744598
Acute graft versus host disease in intestine 174.05 80.46 33 2089 273 1744386
Graft versus host disease in gastrointestinal tract 170.18 80.46 34 2088 379 1744280
Graft versus host disease in skin 163.08 80.46 33 2089 394 1744265
Adenovirus infection 160.56 80.46 33 2089 428 1744231
Bacteraemia 151.10 80.46 41 2081 1839 1742820
Thrombotic microangiopathy 146.23 80.46 37 2085 1258 1743401
Leukaemia recurrent 137.59 80.46 27 2095 272 1744387
Stomatitis 134.50 80.46 48 2074 5356 1739303
Renal failure 133.66 80.46 70 2052 19947 1724712
Sepsis 129.83 80.46 68 2054 19370 1725289
Pneumonia 128.24 80.46 92 2030 46090 1698569
Ascites 121.77 80.46 45 2077 5541 1739118
Septic shock 118.96 80.46 49 2073 8060 1736599
Blood follicle stimulating hormone increased 115.84 80.46 18 2104 34 1744625
Acute myeloid leukaemia recurrent 115.84 80.46 23 2099 247 1744412
Blood bilirubin increased 110.01 80.46 43 2079 6167 1738492
Herpes simplex 109.36 80.46 26 2096 677 1743982
Thrombocytopenia 107.75 80.46 62 2060 21187 1723472
Acute respiratory distress syndrome 105.43 80.46 36 2086 3515 1741144
Product administration error 103.81 80.46 34 2088 2919 1741740
Acute myeloid leukaemia 102.83 80.46 34 2088 3007 1741652
Neutropenia 102.59 80.46 57 2065 18203 1726456
Pneumonia cytomegaloviral 101.70 80.46 22 2100 369 1744290
Autoimmune lymphoproliferative syndrome 101.42 80.46 14 2108 4 1744655
Alanine aminotransferase increased 99.47 80.46 49 2073 12229 1732430
Bronchopulmonary aspergillosis 97.60 80.46 28 2094 1538 1743121
Diarrhoea 96.67 80.46 83 2039 53769 1690890
Acute lymphocytic leukaemia recurrent 95.70 80.46 20 2102 282 1744377
Hyperbilirubinaemia 95.41 80.46 30 2092 2257 1742402
Hepatic failure 94.48 80.46 38 2084 5865 1738794
Acute graft versus host disease in liver 93.52 80.46 18 2104 162 1744497
Stem cell transplant 92.39 80.46 21 2101 446 1744213
Bone marrow failure 88.51 80.46 35 2087 5165 1739494
Haematotoxicity 86.85 80.46 23 2099 935 1743724
Blood luteinising hormone increased 84.94 80.46 13 2109 21 1744638
Aspartate aminotransferase increased 81.37 80.46 41 2081 10715 1733944
Drug ineffective 80.83 80.46 81 2041 63720 1680939

Pharmacologic Action:

SourceCodeDescription
ATC L01AB01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ALKYLATING AGENTS
Alkyl sulfonates
FDA MoA N0000000236 Alkylating Activity
FDA EPC N0000175558 Alkylating Drug
MeSH PA D000477 Alkylating Agents
CHEBI has role CHEBI:67105 insect sterilant
CHEBI has role CHEBI:35610 antineoplastic agent
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
Philadelphia Chromosome Positive Chronic Myelocytic Leukemia indication
Mycosis contraindication 3218000 DOID:1564
Fanconi's anemia contraindication 30575002 DOID:13636
Viral disease contraindication 34014006 DOID:934
Hyperuricemia contraindication 35885006 DOID:1920
Hypokalemia contraindication 43339004
Fibrosis of lung contraindication 51615001 DOID:3770
Portal vein obstruction contraindication 57348003
Hyperglycemia contraindication 80394007 DOID:4195
Epilepsy contraindication 84757009 DOID:1826
Bacterial infectious disease contraindication 87628006
Radiation oncology AND/OR radiotherapy contraindication 108290001
Hypomagnesemia contraindication 190855004
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001
Severe Bone Marrow Depression contraindication

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)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Matrix metalloproteinase-9 Enzyme IC50 5.28 DRUG MATRIX
DNA DNA OTHER DRUG LABEL DRUG LABEL

External reference:

IDSource
D002066 MESH_DESCRIPTOR_UI
4018773 VUID
N0000147076 NUI
C0006463 UMLSCUI
D00248 KEGG_DRUG
2571007 SNOMEDCT_US
387138002 SNOMEDCT_US
4018773 VANDF
002638 NDDF
1828 RXNORM
4309 MMSL
d00183 MMSL
121305 MMSL
2478 PUBCHEM_CID
CHEBI:28901 CHEBI
CHEMBL820 ChEMBL_ID
DB01008 DRUGBANK_ID
G1LN9045DK UNII
564 INN_ID
7136 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
BUSULFAN HUMAN PRESCRIPTION DRUG LABEL 1 0409-1112 INJECTION, SOLUTION 6 mg INTRAVENOUS ANDA 19 sections
BUSULFAN HUMAN PRESCRIPTION DRUG LABEL 1 0517-0920 INJECTION 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 16729-351 INJECTION 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 25021-241 INJECTION, SOLUTION, CONCENTRATE 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 45963-640 INJECTION, SOLUTION, CONCENTRATE 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 51817-170 INJECTION 6 mg INTRAVENOUS ANDA 18 sections
BUSULFEX HUMAN PRESCRIPTION DRUG LABEL 1 59148-047 INJECTION 6 mg INTRAVENOUS NDA 19 sections
BUSULFEX HUMAN PRESCRIPTION DRUG LABEL 1 59148-070 INJECTION 6 mg INTRAVENOUS NDA 19 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 60505-6177 INJECTION 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 65219-160 INJECTION 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 67457-893 INJECTION 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 70121-1244 INJECTION 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 70860-216 INJECTION, SOLUTION, CONCENTRATE 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 72485-210 INJECTION, SOLUTION 6 mg INTRAVENOUS ANDA 18 sections
Busulfan HUMAN PRESCRIPTION DRUG LABEL 1 72606-559 INJECTION 6 mg INTRAVENOUS ANDA 17 sections
MYLERAN HUMAN PRESCRIPTION DRUG LABEL 1 76388-713 TABLET, FILM COATED 2 mg ORAL NDA 14 sections